Evidence review for exercise for chronic primary pain

National Guideline Centre (UK)

Evidence review for exercise for chronic primary pain

Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain

Evidence review E

NICE Guideline, No. 193

Authors

National Guideline Centre (UK).

London: National Institute for Health and Care Excellence (NICE); 2021 Apr.

ISBN-13: 978-1-4731-4066-0

1. Exercise interventions for chronic primary pain

1.1. Review question: What is the clinical and cost effectiveness of exercise interventions for the management of chronic primary pain?

1.2. Introduction

Exercise, or physical activity, is an important part of a healthy lifestyle. Activities associated with daily living such as walking, housework and gardening can be supplemented by activities typically considered to be exercise such as sporting activities and attendance at gyms. Exercise is particularly important for people with a variety of health conditions including musculoskeletal and cardiovascular, and is increasingly seen to be important in managing mental health problems. Increased physical activity is often recommended for people with chronic pain. A challenge for people with pain is to identify the amount and type of exercise that will reduce the impact pain has on their lives, set up healthy exercise habits, and enable them to enjoy the wider health benefits of maintaining an active lifestyle. Remaining motivated to continue exercising can also be more challenging for people living with pain.

Exercise can be carried out alone or as part of social interaction in groups and with teams. Supervised exercise can often be delivered in group settings. The emphasis is usually on encouraging and supporting the person to carry out the exercise independently and regularly.

A growing body of research shows exercise has an impact on many biological systems, including the nervous system, leading to a focus on exercise as a means to pain reduction. Exercise therapy can helpfully be framed in this context.

Although the variety of exercise types is vast, they can broadly be classified into one or more of four categories:

Cardiovascular/aerobic/conditioning
Resistance/anaerobic/strength
Flexibility including stretching
Proprioceptive including balance and movement awareness.

More recently terms like mind-body have emerged to define exercises that include movement with an emphasis on focussed awareness and often with connection to metaphysical and cultural philosophies. Examples include the various forms of Yoga and Tai Chi. These exercises can also be classified using the existing classification system above. This evidence review will look at the effectiveness of these types of exercise for people with chronic primary pain, including its effects on quality of life and function.

1.3. PICO table

For full details see the review protocol in appendix A.

Table 1

PICO characteristics of review question.

1.4. Clinical evidence

1.4.1. Included studies

91 studies were included in the review; these are summarised in the tables below. Evidence from these studies is summarised in the clinical evidence summary below.

3 Cochrane reviews that were relevant to this review question were identified and included in the review.³³^, ⁴⁹^, ²⁵⁰ These covered the following:

Mind-body therapy for fibromyalgia
Aerobic exercise for fibromyalgia
Strength training for fibromyalgia.

Evidence that had been published since the Cochrane publication dates were added to the original analyses, as were additional populations, interventions, comparisons and outcomes relevant to this review protocol.

Two Cochrane reviews relevant to this review question were identified after this review had been conducted. These reviews were not included, however references were cross-referenced against this review³²^, ¹⁵⁰.

Evidence was identified for the following populations:

Fibromyalgia (58 studies)
Chronic neck pain (31 studies)
Complex regional pain syndrome (1 study)
Masticatory pain (1 study)
Chronic pelvic pain syndrome (1 study)

Evidence was identified for the following comparisons:

Aerobic exercise versus usual care
Strength training versus usual care
Aerobic exercise and strength training versus usual care
Aerobic, strength and flexibility versus usual care
Strength training and flexibility versus usual care
Strength, proprioception and flexibility versus usual care
Proprioception versus usual care
Mind-body exercise versus usual care
Flexibility versus usual care
Aerobic exercise versus strength training
Aerobic exercise versus flexibility
Aerobic exercise versus biomechanical exercise
Aerobic exercise and strength training versus aerobic exercise
Aerobic exercise and strength training versus flexibility
Aerobic exercise and flexibility versus mind-body exercise
Aerobic exercise and flexibility versus aerobic exercise
Aerobic, strength, mind-body and proprioception versus flexibility
Strength training versus mind-body exercise
Strength training versus biomechanical exercise
Strength training versus flexibility
Strength and flexibility versus flexibility
Strength and flexibility versus mind-body exercise
Strength, flexibility and proprioception versus mind-body exercise
Strength versus proprioception
Mind-body exercise versus flexibility
Mind-body exercise versus biomechanical exercise
Flexibility and proprioception versus flexibility
Flexibility and relaxation versus aerobic exercise
Exercise versus psychological therapies
Manual therapy and exercise versus manual therapy
Manual therapy and exercise versus exercise
Exercise versus manual therapy.

See also the study selection flow chart in appendix C, study evidence tables in appendix D, forest plots in appendix E and GRADE tables in appendix F.

1.4.2. Excluded studies

See the excluded studies list in appendix I.

1.4.3. Summary of clinical studies included in the evidence review

1.4.3.1. Aerobic exercise versus usual care

Table 2

Summary of studies included in the evidence review.

1.4.3.2. Strength training versus usual care

Table 3

Summary of studies included in the evidence review.

1.4.3.3. Aerobic exercise and strength training versus usual care

Table 4

Summary of studies included in the evidence review.

1.4.3.4. Aerobic exercise, Strength and flexibility versus usual care

Table 5

Summary of studies included in the evidence review.

1.4.3.5. Strength and flexibility combination versus usual care

Table 6

Summary of studies included in the evidence review.

1.4.3.6. Strength, proprioception and flexibility versus usual care

Table 7

Summary of studies included in the evidence review.

1.4.3.7. Proprioception versus usual care

Table 8

Summary of studies included in the evidence review.

1.4.3.8. Mind-body versus usual care

Table 9

Summary of studies included in the evidence review.

1.4.3.9. Flexibility versus usual care

Table 10

Summary of studies included in the evidence review.

1.4.3.10. Aerobic exercise versus strength training

Table 11

Summary of studies included in the evidence review.

1.4.3.11. Aerobic exercise versus flexibility

Table 12

Summary of studies included in the evidence review.

1.4.3.12. Aerobic exercise versus biomechanical exercise

Table 13

Summary of studies included in the evidence review.

1.4.3.13. Aerobic and strength versus aerobic exercise

Table 14

Summary of studies included in the evidence review.

1.4.3.14. Aerobic and Strength versus flexibility

Table 15

Summary of studies included in the evidence review.

1.4.3.15. Aerobic and flexibility versus mind-body exercise

Table 16

Summary of studies included in the evidence review.

1.4.3.16. Aerobic exercise and flexibility versus aerobic exercise

Table 17

Summary of studies included in the evidence review.

1.4.3.17. Aerobic, strength, mind-body and proprioception versus flexibility

Table 18

Summary of studies included in the evidence review.

1.4.3.18. Strength training versus mind-body exercise

Table 19

Summary of studies included in the evidence review.

1.4.3.19. Strength versus biomechanical

Table 20

Summary of studies included in the evidence review.

1.4.3.20. Strength training versus flexibility

Table 21

Summary of studies included in the evidence review.

1.4.3.21. Strength and flexibility versus flexibility

Table 22

Summary of studies included in the evidence review.

1.4.3.22. Strength and flexibility versus mind-body exercises

Table 23

Summary of studies included in the evidence review.

1.4.3.23. Strength, flexibility and proprioception versus mind-body exercises

Table 24

Summary of studies included in the evidence review.

1.4.3.24. Strength versus proprioceptive training

Table 25

Summary of studies included in the evidence review.

1.4.3.25. Mind-body versus flexibility

Table 26

Summary of studies included in the evidence review.

1.4.3.26. Mind-body versus biomechanical

Table 27

Summary of studies included in the evidence review.

1.4.3.27. Flexibility and relaxation versus aerobic exercise

Table 28

Summary of studies included in the evidence review.

1.4.3.28. Flexibility and proprioception versus flexibility

Table 29

Summary of studies included in the evidence review.

1.4.3.29. Exercise versus psychological therapies

Table 30

Summary of studies included in the evidence review.

1.4.3.30. Manual therapy and exercise versus exercise

Table 31

Summary of studies included in the evidence review.

1.4.3.31. Manual therapy and exercise versus manual therapy alone

Table 32

Summary of studies included in the evidence review.

1.4.3.32. Exercise versus manual therapy

Table 33

Summary of studies included in the evidence review.

See appendix D for full evidence tables.

1.4.4. Quality assessment of clinical studies included in the evidence review

Table 34

Clinical evidence summary: Aerobic exercise versus usual care.

Table 35

Clinical evidence summary: Strength training versus usual care.

Table 36

Clinical evidence summary Aerobic and strength versus usual care.

Table 37

Clinical evidence summary: Aerobic, strength and flexibility versus usual care.

Table 38

Clinical evidence summary: Strength and flexibility versus usual care.

Table 39

Clinical evidence summary: Strength, proprioception and flexibility versus usual care.

Table 40

Clinical evidence summary: Proprioception versus usual care.

Table 41

Clinical evidence summary: Mind-body exercise versus usual care.

Table 42

Clinical evidence summary: Flexibility versus usual care.

Table 43

Clinical evidence summary: Aerobic exercise versus strength.

Table 44

Clinical evidence summary: Aerobic exercise versus flexibility.

Table 45

Clinical evidence summary: Aerobic exercise versus biomechanical exercise.

Table 46

Clinical evidence summary: Aerobic and strength versus aerobic exercise.

Table 47

Clinical evidence summary: Aerobic and strength versus flexibility.

Table 48

Clinical evidence summary: Aerobic and flexibility versus mind-body exercise.

Table 49

Clinical evidence summary: Aerobic exercise and flexibility versus aerobic exercise.

Table 50

Clinical evidence summary: Aerobic, strength, mind-body and proprioception versus flexibility.

Table 51

Clinical evidence summary: Strength versus mind-body.

Table 52

Clinical evidence summary: Strength versus biomechanical.

Table 53

Clinical evidence summary: Strength versus flexibility.

Table 54

Clinical evidence summary: Strength and flexibility versus flexibility.

Table 55

Clinical evidence summary: Strength and flexibility versus mind-body.

Table 56

Clinical evidence summary: Strength, flexibility and proprioception versus mind-body.

Table 57

Clinical evidence summary: Strength versus proprioception.

Table 58

Clinical evidence summary: Mind-body versus flexibility.

Table 59

Clinical evidence summary: Mind-body versus biomechanical.

Table 60

Clinical evidence summary: Flexibility and proprioception versus flexibility.

Table 61

Clinical evidence summary: Flexibility and relaxation versus aerobic exercise.

Table 62

Clinical evidence summary: Exercise versus psychological therapies.

Table 63

Clinical evidence summary: Manual therapy and exercise versus manual therapy.

Table 64

Clinical evidence summary: Manual therapy and exercise versus exercise.

Table 65

Clinical evidence summary: Exercise versus manual therapy.

See appendix F for full GRADE tables.

1.5. Economic evidence

1.5.1. Included studies

Two health economic studies were identified with the relevant comparisons and have been included in this review. This is summarised in the health economic evidence profile below and the health economic evidence tables in appendix H.

1.5.2. Excluded studies

Three additional health economic studies were identified as relevant to this question, but were selectively excluded as the committee judged that other available evidence was of greater applicability and methodological quality.¹⁸¹^,²⁶³^,²⁶⁴ These are listed in appendix I, with reason for exclusion given.

See also the health economic study selection flow chart in appendix G.

1.5.3. Summary of studies included in the economic evidence review

Note that Table 66 includes only the relevant comparisons for this review, although the evidence table in Appendix H: includes all comparators in the study.

Table 66

Health economic evidence profile: Aerobic exercise therapy vs. psychological therapy or usual care.

Table 67

Health economic evidence profile: Aquatic based aerobic exercise + usual care versus usual care.

1.5.4. Health economic modelling

This area was prioritised for new economic modelling. The rationale, methods and results are summarised below. Full details are available in the ‘Exercise modelling report’.

Methods

The clinical review showed a benefit of exercise compared to usual care in reducing pain and improving quality of life. When comparing types of exercise to each other, there was less evidence and it was difficult to draw conclusions about a hierarchy of types of exercise.

Two economic evaluations were identified for this review comparing exercise to treatment as usual. One was a UK within trial analysis (cost utility analysis) looking at a gym based exercise program (gym membership provided), and 6 fitness instructor-led monthly sessions, for a duration of 6 months. The committee view was that this study was quite different to most of the other studies in the clinical review, which tended to be structured class-based interventions, generally group based, with varying frequency/intensity. The study found exercise was not cost effective in the base case analysis using complete case data, but it was cost effective when using imputed data. The second economic evaluation was a Spanish within trial analysis (cost utility analysis, comparing 8 months of group pool-based exercised to usual care. This found exercise to be cost effective. Pool-based exercises are not considered to be current practice in the UK because they have higher costs. This was an older study than the UK one (2008), and had limitations like the costs of the staff involved seem very low compared to UK costs, which is likely to increase the ICER.

Uncertainty remained about the cost effectiveness of exercise from the included data, therefore, a lifetime cost utility analysis was undertaken, from the NHS perspective, that compared exercise with no exercise (both groups had usual care therefore this was not included in the model). The analysis is based on studies from the clinical review that reported utilities (EQ-5D), or the SF-36 that could be mapped to utilities (12 studies). All exercise types were pooled. All studies except one used supervised exercise, and most were group based (or assumed to be).

For each study, the difference between follow up EQ-5D (whether this was at the end of treatment or later) and the baseline EQ-5D was taken for the intervention and usual care group, to take account of any baseline differences between the two groups. The difference in EQ-5D was then taken between the intervention and usual care group for each study. Therefore, the treatment benefit is the EQ-5D gain from exercise compared to usual care, taking into account baseline differences. Where there were several studies that reported quality of life at the same time point, these were pooled in a meta-analysis. A linear trend line was fitted to the QoL gain points over time, based on weighted least squares regression to attach more weight to time points where there was more certainty about the treatment effect. The available data on the difference in utility between the comparators were combined with assumptions about what is likely to happen to treatment effect beyond the follow-up in the trials (treatment effect was extrapolated), to calculate the average QALY gain with exercise compared to no exercise. Extrapolation assumptions were based on committee opinion, and different assumptions were needed for different scenarios that occurred in probabilistic analyses. Note the treatment effect was extrapolated only until there was no additional quality of life benefit from exercise. Two base cases were analysed; one with a lifetime horizon and one where treatment effect is not extrapolated beyond the trial data.

The key difference in costs was agreed to be those related to delivering an exercise programme. No other costs were incorporated in the analysis. The average resource use from the interventions in each study were identified and costed, and a weighted average cost calculated, weighting by the number of participants in the studies.

Results

The probabilistic and deterministic base case results can be seen in the table below. Results are presented for both base cases. Both analyses show the ICER is below the NICE threshold of £20,000, and therefore exercise would be considered cost effective. The probability of exercise being cost effective is also high.

Table 68

Base case results (discounted).

The deterministic results are slightly different to the probabilistic in the lifetime analysis because there is a larger incremental QALY gain in the probabilistic analysis from the QALY gains having a skewed distribution, as there are some simulations with quite flat slopes which lead to a large QALY gain because of the extrapolation assumptions exacerbating the gain, and the point at which there is no longer a difference in treatment effect from exercise being far into the future. This was proven by looking at the distribution of the QALY gains in a probabilistic analysis and plotting them graphically. Additionally, when looking at the analysis where no extrapolation of the data was assumed, then the probabilistic and deterministic results are very close, proving that the extrapolation assumptions and the nature of the data in the probabilistic analysis is creating this discord between the types of results, and both types of results are still well below the NICE threshold.

Various sensitivity analyses were undertaken for both base cases, where long term data points were included that were not included in the base case, and also data points that followed a ‘de-training’ period were also only used in a sensitivity analysis. Sensitivity analysis also tested using final QoL values in the meta-analysis as opposed to changes from baseline. Assumptions were also made about less staff and lower staff bands, as the most conservative assumptions about resource use were made in the base case. All sensitivity analyses did not change the conclusions.

Limitations of the analysis include that data was pooled from different studies that had different interventions of different intensities. This is likely to affect costs but also treatment effect. There is uncertainty around whether the costs that have been pooled appropriately correspond to/or are leading to the pooled treatment effect. This is because it is unclear what it is about exercise that causes a benefit. The analysis only used a subset of studies from the clinical review. The linear trend line representing treatment effect over time is a simplification of how people’s quality of life would fluctuate in reality. The quality of life gain taken from the studies could also be an overestimate because it is likely that people who respond to follow up questionnaires or that have not dropped out of a trial are more engaged with the intervention. Additionally, it is uncertain what was happening after the intervention and whether people were continuing the intervention so assumptions were made. No other costs have been accounted for in the analysis except for intervention costs.

Overall, this analysis has pooled a subset of data from the clinical review that reported quality of life, to estimate the potential cost effectiveness of supervised exercise in general, not being specific to a particular type of exercise. Given the differences between the studies and how few studies were used compared to the review as a whole, this analysis should be interpreted carefully.

1.6. Evidence statements

1.6.1. Clinical evidence statements

1.6.1.1. Aerobic exercise versus usual care

Pain reduction

Very low quality evidence from 1 study with 40 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Very low quality evidence from 9 studies with 528 participants showed no clinically important difference between exercise and usual care at >3 months. Very low quality evidence from 1 study with 95 participants showed no clinically important difference between exercise and usual care at >3 months.

Health related quality of life

Very low quality evidence from 5 studies with 372 participants showed a clinically important benefit of exercise compared to usual care at >3 months. Very low to low quality evidence from 1 study with 54 participants showed a clinically important benefit of exercise compared to usual care at >3 months. Very low to low quality evidence from 1 study with 95 participants showed usual care to lead to a clinically important benefit compared to exercise at ≤3 months. Very low quality evidence from 2 studies with 259 participants showed a clinically important benefit of exercise compared to usual care at >3 months. Very low quality evidence from 1 study 95 participants showed no clinically important difference between exercise and usual care at ≤3 months or at >3 months.

Physical function

Very low quality evidence from 2 studies with 155 participants showed no clinically important difference between exercise and usual care at ≤3 months and very low quality evidence from 1 study with 95 participants showed no clinically important difference between exercise and usual care at >3 months. Very low quality evidence from 3 studies with 169 participants showed a clinically important benefit of exercise compared to usual care at >3 months. Very low quality evidence from 3 studies with 246 participants showed a clinically important benefit of exercise compared to usual care at >3 months.

Psychological distress

Low quality evidence from 1 study with 60 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Low quality evidence from 3 studies with 123 participants showed no clinically important difference between exercise and usual care at >3 months. Low quality evidence from 4 studies with 306 participants showed no clinically important difference between exercise and usual care at >3 months. Low quality evidence from 4 studies with 320 participants showed no clinically important difference between exercise and usual care at >3 months. Very low quality evidence from 1 study with 50 participants showed no clinically important difference between exercise and usual care at >3 months. Very low quality evidence from 1 study with 95 participants showed no clinically important difference between exercise and usual care at >3 months.

Use of healthcare services

Very low to low quality evidence from 1 study with 95 participants was identified but clinical importance could not be determined (unclear if high or low healthcare service use is a clinically important benefit).

Sleep

Very low quality evidence from 5 studies with 414 participants showed no clinically important difference between exercise and usual care at >3 months.

Discontinuation

Very low quality evidence from 9 studies with 607 participants showed more people discontinued from exercise compared to usual care.

1.6.1.2. Strength training versus usual care

Pain reduction

Very low quality evidence from 3 studies with 156 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Very low quality evidence from 3 studies with 251 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Very low quality evidence from 4 studies with 449 participants showed a clinically important benefit of exercise compared to usual care at >3 months.

Health related quality of life

Very low quality evidence from 2 studies with 102 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Low quality evidence from 1 study with 42 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Very low quality evidence from 2 studies with 52 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months.

Physical function

Low quality evidence from 3 studies with 146 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Very low quality evidence from 2 studies with 151 participants showed no clinically important difference between exercise and usual care at ≤3 months. Very low quality evidence from 1 study with 20 participants showed no clinically important difference between exercise and usual care at ≤3 months. Low quality evidence from 2 studies with 163 participants showed no clinically important difference between exercise and usual care at >3 months. Very low quality evidence from 3 studies with 105 participants showed a clinically important benefit of exercise compared to usual care at >3 months.

Psychological distress

Very low quality evidence from 1 study with 25 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Low quality evidence from 1 study with 21 participants showed a clinically important benefit of exercise compared to usual care at >3 months.

Use of healthcare services

Very low to low quality evidence from 1 study with 179 participants was identified but clinical importance could not be determined (unclear if high or low healthcare service use is a clinically important benefit).

Sleep

Low quality evidence from 1 study with 21 participants showed no clinically important difference between exercise and usual care at >3 months.

Discontinuation

Low quality evidence from 4 studies with 252 participants showed no clinically important difference between exercise and usual care at >3 months.

1.6.1.3. Aerobic and strength exercise versus usual care

Pain reduction

Low quality evidence from 2 studes with 129 participants showed no clinically important difference between between exercise and usual care at ≤3 months. Very low quality evidence from 3 studies with 161 participants showed a clinically important benefit of exercise compared to usual care at >3 months.

Health related quality of life

Low quality evidence from 1 study with 30 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months and >3 months. Low quality evidence from 2 studies with 54 participants showed no clinically important difference between exercise and usual care at ≤3 months. Very low quality evidence from 4 studies with 171 participants showed a clinically important benefit of exercise compared to usual care at >3 months. Low quality evidence from 1 study with 42 participants showed both a clinically important benefit of exercise compared to usual care and no clinically important difference at >3 months (various subscales).

Physical function

Low quality evidence from 1 study with 32 participants showed no clinically important difference between exercise and usual care at ≤3 months. Low quality evidence from 1 study with 16 participants showed a clinically important benefit of exercise compared to usual care at >3 months. Low quality evidence from 1 study with 37 participants showed a clinically important benefit of exercise compared to usual care at >3 months. Very low quality evidence from 1 study with 30 participants showed a clinically important benefit of exercise compared to usual care at >3 months.

Psychological distress

Low quality evidence from 2 studies with 54 participants showed no clinically important difference between exercise and usual care at ≤3 months. Very low quality evidence from 1 study with 58 participants showed no clinically important difference between exercise and usual care at ≤3 months. Low quality evidence from 1 study wih 32 participants showed no clinically important difference between between exercise and usual care at ≤3 months. Low quality evidence from 4 studies with 125 participants showed no clinically important difference between exercise and usual care at >3 months. Very low quality evidence from 2 studies with 83 participants showed a clinically important of exercise compared to usual care at >3 months.

Use of healthcare services

Very low quality evidence from 1 study with 78 participants showed no clinically important difference between exercise and usual care at >3 months.

Sleep

Low quality evidence from 1 study with 58 participants showed a clinically important benefit of exercise compared to usual care at >3 months.

Discontinuation

Low quality evidence from 4 studies with 125 participants showed no clinically important difference between exercise and usual care at ≤3 months. Very low quality evidence from 7 studies with 230 participants showed no clinically important difference between exercise and usual care at >3 months.

1.6.1.4. Aerobic, strength and flexibility versus usual care

Low quality evidence from 1 study with 25 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months for quality of life.

No other evidence identified.

1.6.1.5. Strength and flexibility versus usual care

Pain reduction

Low quality evidence from 2 studies with 110 participants showed no clinically important difference between exercise and usual care at ≤3 months. Low quality evidence from 2 studies with 144 participants showed a clinically important benefit of exercise compared to usual care at >3 months.

Health related quality of life

Low quality evidence from 1 study with 70 participants showed no clinically important difference between exercise and usual care at ≤3 months. Low quality evidence from 1 study with 144 participants showed no clinically important difference between exercise and usual care at >3 months.

Physical function

Low quality evidence from 1 study with 70 participants showed no clinically important difference between exercise and usual care at ≤3 months. Moderate quality evidence from 2 studies with 144 participants showed no clinically important difference between exercise and usual care at >3 months.

Psychological distress

Low quality evidence from 1 study with 70 participants showed no clinically important difference between exercise and usual care at ≤3 months or >3 months.

Use of healthcare services

No evidence identified.

Sleep

No evidence identified.

Discontinuation

Very low quality evidence from 2 studies with 157 participants showed no clinically important difference between exercise and usual care at >3 months.

1.6.1.6. Strength, proprioception and flexibility versus usual care

Pain reduction

Low quality evidence from 1 study with 76 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months and >3 months

Health related quality of life

Low quality evidence from 1 study with 76 participants showed both a clinically important benefit of exercise compared to usual care and no clinically important difference at ≤3 months and >3 months (various subscales).

Physical function

Low quality evidence from 1 study with 76 participants showed no clinically important difference between exercise compared to usual care at ≤3 months and >3 months.

Psychological distress

Low quality evidence from 1 study with 76 participants showed no clinically important difference between exercise compared to usual care at ≤3 months and >3 months.

Use of healthcare services

Sleep

No evidence identified.

Discontinuation

Low quality evidence from 1 study with 76 participants showed more people discontinued from exercise compared to usual care at ≤3 months.

1.6.1.7. Proprioception versus usual care

Low to very low quality evidence from 1 study with 46 participants showed no clinically important difference between exercise and usual care at ≤3 months and >3 months for pain or quality of life. Low quality evidence from the same study showed a clinically important benefit of exercise compared to usual care at ≤3 months and >3 months for psychological distress, and a clinically important benefit at ≤3 months for physical function, but no clinically important difference at >3 months.

No other evidence identified.

1.6.1.8. Mind-body exercise versus usual care

Pain reduction

Very low quality evidence from 8 studies with 393 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Low quality evidence from 1 study with 117 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Very low quality evidence from 1 study with 117 participants showed a clinically important benefit of exercise compared to usual care at >3 months. Low quality evidence from 1 study with 80 participants showed a clinically important benefit of exercise compared to usual care at >3 months. Low quality evidence from 3 studies with 221 participants showed a clinically important benefit of exercise compared to usual care at >3 months.

Health related quality of life

Low quality evidence from 1 study with 57 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Very low quality evidence from 3 studies with 106 participants showed no clinically important difference between exercise and usual care at ≤3 months. Moderate quality evidence from 3 studies with 220 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Very low quality evidence from 3 studies with 220 participants showed no clinically important difference between exercise and usual care at ≤3 months. Very low quality evidence from 3 studies with 221 participants showed no clinically important difference between exercise and usual care at >3 months. Very low quality evidence from 1 study with 80 participants showed a clinically important benefit of exercise compared to usual care at >3 months.

Physical function

Very low quality evidence from 7 studies with 363 participants showed no clinically important difference between exercise and usual care at >3 months. Low quality evidence from 3 studies with 225 participants showed no clinically important difference between exercise and usual care at >3 months. Low quality evidence from 1 study with 80 participants showed a clinically important benefit of exercise compared to usual care at >3 months.

Psychological distress

Very low quality evidence from 5 studies with 306 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Low quality evidence from 1 study with 57 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months. Low quality evidence from 2 studies with 77 participants showed no clinically important difference between exercise and usual care at ≤3 months. Moderate quality evidence from 3 studies with 223 participants showed no clinically important difference between exercise and usual care at >3 months. Low quality evidence from 1 study with 77 participants showed no clinically important difference between exercise and usual care at >3 months.

Use of healthcare services

No evidence identified.

Sleep

Very low quality evidence from 2 studies with 60 participants showed no clinically important difference between exercise and usual care at ≤3 months.

Discontinuation

Very low quality evidence from 12 studies with 784 participants showed no clinically important difference between exercise and usual care at >3 months.

1.6.1.9. Flexibility versus usual care

Pain reduction

Very low quality evidence from 1 study with 28 participants showed a clinically important benefit of exercise compared to usual care at ≤3 months.

Health related quality of life

No evidence identified.

Physical function

Very low quality evidence from 1 study with 28 participants showed no clinically important difference between exercise and usual care at ≤3 months.

Psychological distress

No evidence identified.

Use of healthcare services

No evidence identified.

Sleep

No evidence identified.

Discontinuation

Very low quality evidence from 1 study with 34 participants showed more people discontinued from exercise compared to usual care at ≤3 months.

1.6.1.10. Aerobic versus strength

Pain reduction

Very low quality evidence from 4 studies with 199 participants showed no clinically important difference between aerobic and strength at ≤3 months. Very low quality evidence from 1 study with 60 participants showed no clinically important difference between aerobic and strength at >3 months.

Health related quality of life

Very low quality evidence from 3 studies with 127 participants showed a clinically important benefit of aerobic compared to strength at ≤3 months.

Physical function

Very low quality evidence from 1 study with 26 participants showed no clinically important difference between aerobic and strength at ≤3 months. Moderate quality evidence from 1 study with 75 participants showed no clinically important difference between aerobic and strength at ≤3 months. Low quality evidence from 2 studies with 86 participants showed no clinically important difference between aerobic and strength at >3 months.

Psychological distress

Very low quality evidence from 2 studies with 52 participants showed no clinically important difference between aerobic and strength at ≤3 months. Very low quality evidence from 1 study with 75 participants showed a clinically important benefit of aerobic compared to strength at ≤3 months.

Use of healthcare services

No evidence identified.

Sleep

Very low quality evidence from 1 study with 26 participants showed no clinically important difference between aerobic and strength at ≤3 months.

Discontinuation

Low quality evidence from 4 studies with 196 participants showed no clinically important difference between aerobic and strength at ≤3 months.

1.6.1.11. Aerobic exercise versus flexibility

Pain reduction

Very low quality evidence from 1 study with 60 participants showed no clinically important difference between aerobic and flexibility at ≤3 months. Very low quality evidence from 1 study with 60 participants showed a clinically important benefit of aerobic compared to flexibility at >3 months.

Health related quality of life

Very low quality evidence from 1 study with 60 participants showed a clinically important benefit of aerobic compared to flexibility at ≤3 months and >3 months.

Physical function

No evidence identified.

Psychological distress

Very low quality evidence from 1 study with 60 participants showed no clinically important difference between aerobic and flexibility at ≤3 months, and both clinically important benefit of aerobic (for depression subscale) and no clinically important difference (for anxiety subscale) at >3 months.

Use of healthcare services

No evidence identified.

Sleep

No evidence identified.

Discontinuation

Very low quality evidence from 1 study with 76 participants showed more people discontinued from aerobic compared to flexibility at >3 months.

1.6.1.12. Aerobic exercise versus biomechanical exercise

Moderate to very low quality evidence from 1 study with 42 participants showed a clinically important benefit of aerobic exercise compared with biomechanical exercise for quality of life at ≤3 months, but no clinically important difference between aerobic and biomechanical exercise for pain reduction, psychological distress or sleep. More people discontinued from biomechanical exercise than aerobic exercise.

No other evidence identified.

1.6.1.13. Aerobic and strength versus aerobic exercise

Low to very low quality evidence from 1 study with 43 participants showed no clinically important difference between aerobic and strength and aerobic at >3 months for quality of life, psychological distress or discontinuation.

No other evidence identified.

1.6.1.14. Aerobic and strength versus flexibility

Very low quality evidence from 1 study with 85 participants showed no clinically important difference between aerobic and strength and flexibility at ≤3 months for pain or psychological distress but a benefit or aerobic and strength for quality of life. Very low quality evidence from 1 study with 76 participants showed a clinically important benefit of aerobic and strength compared to flexibility at >3 months for pain and quality and life but not clinically important difference for psychological distress. Very low quality evidence from 2 studies with 103 participants showed more people discontinued from aerobic and strength compared to flexibility at ≤3 months.

No other evidence identified.

1.6.1.15. Aerobic and flexibility versus mind-body exercise

Very low to low quality evidence from 1 study with 111 participants showed no clinically important difference between aerobic and flexibility and mind-body at ≤3 months and >3 months for quality of life, physical function, psychological distress and sleep (other than a benefit of aerobic and flexibility for a mental quality of life subscale at ≤3 months and a physical quality of life subscale at >3 months. Very low quality evidence from the same study showed more people discontinued from aerobic and flexibility compared to mind-body exercise at ≤3 months.

No other evidence identified.

1.6.1.16. Aerobic and flexibility versus aerobic exercise

Moderate quality evidence from 1 study with 64 participants showed a clinically important benefit of aerobic and flexibility exercise compared with aerobic exercise alone for quality of life and sleep at ≤3 months and >3 months, but no clinically important difference between aerobic and flexibility exercise and aerobic exercise alone for pain reduction at either time point, or discontinuation.

No other evidence identified.

1.6.1.17. Aerobic, strength, mind-body and proprioception versus flexibility

Low quality evidence from 1 study with 21 participants showed a clinically important benefit of aerobic, strength, mind-body and proprioception exercise compared with flexibility for quality of life and discontinuation, but no clinically important difference for physical function at ≤3 months.

No other evidence identified.

1.6.1.18. Strength training versus mind-body exercise

Pain reduction

Very low quality evidence from 1 study with 36 participants showed a clinically important benefit of mind-body exercise compared to strength training at ≤3 months.

Health related quality of life

Very low quality evidence from 1 study with 36 participants showed no clinically important difference between strength training and mind-body exercise at ≤3 months.

Physical function

Very low quality evidence from 1 study with 36 participants showed a clinically important benefit of mind-body exercise compared to strength training at ≤3 months.

Psychological distress

Very low quality evidence from 1 study with 36 participants showed a clinically important benefit of mind-body exercise compared to strength training at ≤3 months.

Use of healthcare services

No evidence identified.

Sleep

No evidence identified.

Discontinuation

Very low quality evidence from 1 study showed more people discontinued from strength compared to mind-body exercise at ≤3 months.

1.6.1.19. Strength training versus biomechanical exercise

Pain reduction

Very low quality evidence from 1 study with 38 participants showed a clinically important benefit of biomechanical exercise compared to strength training at ≤3 months.

Health related quality of life

Very low quality evidence from 1 study with 38 participants showed no clinically important difference between strength training and biomechanical exercise at ≤3 months.

Physical function

Very low quality evidence from 1 study with 38 participants showed no clinically important difference between strength training and biomechanical exercise at ≤3 months.

Psychological distress

Very low quality evidence from 1 study with 38 participants showed no clinically important difference between strength training and biomechanical exercise at ≤3 months.

Use of healthcare services

No evidence identified.

Sleep

No evidence identified.

Discontinuation

No evidence identified.

1.6.1.20. Strength training versus flexibility

Pain reduction

Moderate quality evidence from 2 studies with 86 participants showed no clinically important difference between strength and flexibility at ≤3 months.

Health related quality of life

Very low quality evidence from 1 study with 60 participants showed both a clinically important benefit and no clinically important difference of/between strength compared to flexibility at >3 months.

Physical function

Very low quality evidence from 1 study with 30 participants showed clinically important benefit of flexibility compared to strength at ≤3 months.

Psychological distress

Low quality evidence from 1 study with 56 participants showed clinically important benefit of flexibility compared to strength (anxiety subscale) and no clinically important difference between strength and flexibility (depression subscale) at ≤3 months.

Use of healthcare services

No evidence identified.

Sleep

Moderate quality evidence from 1 study with 56 participants showed a clinically important benefit of strength compared to flexibility at ≤3 months.

Discontinuation

Very low quality evidence from 3 studies with 157 participants showed a clinically important benefit of strength compared to flexibility at >3 months.

1.6.1.21. Strength and flexibility versus flexibility

Very low quality evidence from 1 study with 86 participants showed both a clinically important benefit of strength and flexibility compared to flexibility and no clinically important difference at >3 months (various subscales). Very low quality evidence from the same study showed a clinically important benefit of strength and flexibility compared to flexibility for discontinuation at >3 months.

No other evidence identified.

1.6.1.22. Strength and flexibility versus mind-body exercise

Pain reduction

Very low quality evidence from 2 studies with 117 participants showed a clinically important benefit of strength and flexibility compared to mind-body at ≤3 months. Moderate quality evidence from 2 studies with 140 participants showed no clinically important difference between strength and flexibility compared to mind-body at >3 months.

Health related quality of life

Moderate quality evidence from 2 studies with 117 participants showed no clinically important difference between strength and flexibility compared to mind-body at ≤3 months. Moderate to low quality evidence from 2 studies with 140 participants showed no clinically important difference between strength and flexibility compared to mind-body at >3 months.

Physical function

Low quality evidence from 2 studies with 117 participants showed no clinically important difference between strength and flexibility compared to mind-body at ≤3 months. Moderate to low quality evidence from 2 studies with 140 participants showed no clinically important difference between strength and flexibility compared to mind-body at >3 months.

Psychological distress

Low quality evidence from 1 study with 66 participants showed no clinically important difference between strength and flexibility compared to mind-body at ≤3 months.

Use of healthcare services

No evidence identified.

Sleep

No evidence identified.

Discontinuation

Very low quality evidence from 3 studies with 209 participants showed no clinically important difference between strength and flexibility compared to mind-body at >3 months.

1.6.1.23. Strength, flexibility and proprioception versus mind-body exercise

Very low to moderate quality evidence from 1 study with 75 participants showed no clinically important difference between strength and flexibility and flexibility at ≤3 months and >3 months for pain, quality of life, physical function and psychological distress. High quality evidence from the same study showed clinically important benefit of mind-body compared to strength, flexibility and proprioception at ≤3 months for discontinuation.

No other evidence identified.

1.6.1.24. Strength training versus proprioception

Moderate quality evidence from 1 study with 26 participants showed no clinically important difference between strength and proprioception at ≤3 months for physical function.

No other evidence identified.

1.6.1.25. Mind-body exercise versus flexibility

Very low quality evidence from 1 study with 55 participants showed no clinically important difference between mind-body and flexibility at ≤3 months for pain, but a clinically important benefit of mind-body for quality of life. Very low quality evidence from 1 study with 81 participants showed no clinically important difference between mind-body and flexibility at ≤3 months for sleep. Very low quality evidence from 1 study with 62 participants showed more people discontinued from mind-body at ≤3 months.

No other evidence identified.

1.6.1.26. Mind-body exercise versus biomechanical exericse

Pain reduction

Very low quality evidence from 1 study with 38 participants showed no clinically important difference between mind-body and biomechanical exercise at ≤3 months.

Health related quality of life

Very low quality evidence from 1 study with 38 participants showed no clinically important difference between mind-body and biomechanical exercise at ≤3 months.

Physical function

Very low quality evidence from 1 study with 38 participants showed no clinically important difference between mind-body and biomechanical exercise at ≤3 months.

Psychological distress

Very low quality evidence from 1 study with 38 participants showed no clinically important difference between mind-body and biomechanical exercise at ≤3 months.

Use of healthcare services

No evidence identified.

Sleep

No evidence identified.

Discontinuation

No evidence identified.

1.6.1.27. Flexibility and proprioception versus flexibility

Very low quality evidence from 1 study with 57 participants showed a clinically important benefit of flexibility and proprioception compared to flexibility for quality of life and psychological distress at ≤3 months, but no clinically important difference for discontinuation.

No other evidence identified.

1.6.1.28. Flexibility and relaxation versus aerobic

Very low to moderate quality evidence from 1 study with 136 participants showed no clinically important difference between flexibility and relaxation and aerobic at >3 months for quality of life or discontinuation.

1.6.1.29. Exercise versus psychological therapies

Pain reduction

Very low quality evidence from 4 studies with 251 participants showed no clinically important difference between exercise and psychological therapies at ≤3 months. Low quality evidence from 4 studies with 468 participants showed no clinically important difference between exercise and psychological therapies at >3 months.

Health related quality of life

Moderate quality evidence from 4 studies with 292 participants showed no clinically important difference between exercise and psychological therapies at ≤3 months. Very low quality evidence from 1 study with 60 participants showed a clinically important benefit of exercise compared with psychological therapies at ≤3 months . Low quality evidence from 1 study with 152 participants showed no clinically important difference between exercise and psychological therapies at >3 months.

Physical function

Very low quality evidence from 1 study with 98 participants showed a clinically important benefit of exercise compared to psychological therapies at ≤3 months. Low quality evidence from 3 studies with 199 participants showed no clinically important difference between exercise and psychological therapies at ≤3 months. Low quality evidence from 1 study with 105 participants showed a clinically important benefit of exercise compared to psychological therapies at >3 months.

Psychological distress

Low quality evidence from 1 study with 62 participants showed a clinically important benefit of exercise compared to psychological therapies at ≤3 months. Low quality evidence from 1 study with 105 participants showed no clinically important difference between exercise and psychological therapies at >3 months.

Use of healthcare services

No evidence identified.

Sleep

Moderate quality evidence from 1 study with 190 participants showed no clinically important difference between exercise and psychological therapies at >3 months. Low quality evidence from 1 study with 105 participants showed no clinically important difference between exercise and psychological therapies at >3 months.

Discontinuation

Low quality evidence from 10 studies with 1062 participants showed no clinically important difference between exercise and psychological therapies at >3 months.

1.6.1.30. Manual therapy and exercise versus manual therapy

Low quality evidence from 1 study with 101 participants showed no clinically important difference between manual therapy and exercise versus manual therapy for pain at ≤3 months and >3 months, but a clinically important benefit of manual therapy and exercise compared to manual therapy at ≤3 months and >3 months. Very low quality evidence from the same study with 127 participants showed no clinically important difference between the manual therapy and exercise compared to manual therapy for discontinuation.

1.6.1.31. Manual therapy and exercise versus exercise

Pain reduction

Moderate quality evidence from 6 studies with 542 participants showed a clinically important benefit of manual therapy and exercise compared with exercise alone at ≤3 months. Low quality evidence from 3 studies with 394 participants showed no clinically important difference between manual therapy and exercise versus exercise at >3 months.

Health related quality of life

Very low quality evidence from 1 study with 21 participants showed no clinically important difference between manual therapy and exercise versus exercise at >3 months. Moderate quality evidence from 1 study with 180 participants showed no clinically important difference between manual therapy and exercise versus exercise at ≤3 months and >3 months.

Physical function

Low quality evidence from 2 studies with 86 participants showed a clinically important benefit of manual therapy and exercise compared with exercise alone at ≤3 months. Very low quality evidence from 5 studies with 477 participants showed no clinically important difference between manual therapy and exercise versus exercise at ≤3 months. Moderate quality evidence from 3 studies with 394 participants showed no clinically important difference between manual therapy and exercise versus exercise at ≤3 months.

Psychological distress

No evidence identified.

Use of healthcare services

No evidence identified.

Sleep

No evidence identified.

Discontinuation

Very low quality evidence from 6 studies with 542 participants showed no clinically important difference between manual therapy and exercise versus exercise at >3 months.

1.6.1.32. Exercise versus manual therapy

Pain reduction

Low quality evidence from 1 study with 101 participants showed a clinically important benefit of exercise compared to psychological therapies at ≤3 months but no clinically important difference between exercise and manual therapies at >3 months.

Health related quality of life

No evidence identified.

Physical function

Low quality evidence from 1 study with 94 participants showed no clinically important difference between exercise and manual therapies at ≤3 months but a clinically important benefit of exercise compared to manual therapies at >3 months.

Psychological distress

No evidence identified.

Use of healthcare services

No evidence identified.

Sleep

No evidence identified.

Discontinuation

Very low quality evidence from 1 study with 127 participants showed more people discontinued from exercise compared to manual therapies at ≤3 months.

1.6.2. Health economic evidence statements

One cost–utility analysis found that gym-based aerobic exercise therapy was:
- not cost effective compared to treatment as usual for treating chronic primary pain when using complete case analysis (ICER: £76,960 per QALY). It also found that telephone-delivered cognitive behavioural therapy (TCBT) was dominant (less costly and more effective) compared to exercise therapy.
- cost effective compared to treatment as usual for treating chronic primary pain when using multiple imputation analysis (ICER: £17,690 per QALY gained). It also found that telephone-delivered cognitive behavioural therapy (TCBT) was dominant (less costly and more effective) compared to exercise therapy.
This analysis was assessed as directly applicable with potentially serious limitations.
One cost-utility analysis found that aquatic exercise therapy was cost effective in addition to usual care, compared to usual care (ICER: £3,630 per QALY gained). This analysis was assessed as partially applicable with potentially serious limitations.
One original cost-utility analysis found that exercise therapy was cost effective compared to no exercise therapy for treating chronic primary pain (probabilistic ICERs: £9,121 per QALY gained (lifetime analysis), £12,683 per QALY gained (no extrapolation analysis), deterministic ICERS: £12,327 per QALY gained (lifetime analysis), £12,739 per QALY gained (no extrapolation analysis). This analysis was assessed as directly applicable with minor limitations.

1.7. The committee’s discussion of the evidence

1.7.1. Interpreting the evidence

1.7.1.1. The outcomes that matter most

The committee considered pain reduction, health-related quality of life, physical function and psychological distress to be critical outcomes for decision-making. Use of healthcare services, sleep and discontinuation were also considered to be important outcomes. The critical and important outcomes agreed by the committee were adapted by consensus from relevant core outcome sets registered under the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. This included the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations.

Evidence was identified for all critical and important outcomes.

1.7.1.2. The quality of the evidence

Evidence from 91 randomised controlled trials was identified for 32 different comparisons in this review. Comparisons against usual care with the most evidence were mind-body, aerobic, aerobic plus strength and strength. There were several comparisons of mixed modality exercise versus usual care. A small amount of evidence for some head-to-head comparisons of different types of exercise was also identified. No evidence was identified for graded motor imagery.

The majority of the evidence was of low to very low quality, mainly due to risk of bias and imprecision. There was a lack of blinding in the studies due to the nature of the interventions; this combined with the mostly subjective outcomes resulted in a high risk of performance bias. The majority of the studies had small sample sizes, which increased the uncertainty around the point estimates. Another factor that could have contributed to imprecision was variation in the interventions within the evidence. There were a broad range of exercise programmes which varied in their duration, frequency, intensity, types of exercises and amount of contact with supervisors. This could have influenced the observed effectiveness of each individual intervention within the evidence, leading to greater uncertainty around the point estimates. The committee took into account the low quality evidence, including the uncertainty in their interpretation of the evidence, particularly when considering the small amount of evidence for comparisons between different types of exercise.

The committee noted that the definition of usual care varied across studies or was not clearly reported, which was a general limitation of the review. Usual care generally included: no additional interventions, participants being asked not change their activity levels or to continue normal activities, waiting list controls, low intensity interventions such as advice to stretch or interventions deemed appropriate by the healthcare professionals involved in the study (not including interventions similar to those in the intervention arm of the study).

1.7.1.3. Benefits and harms

The evidence base in general suggested a benefit of exercise therapies over usual care. Although there was uncertainty around the effect estimates for many of the outcomes, the committee agreed that the direction of effect on the whole was positive. Evidence comparing different types of exercise showed little difference in effectiveness between therapies. The majority of evidence involved supervised group exercise.

Exercise versus usual care

Evidence showed that, compared with usual care, there was generally a benefit of both single-modality and mixed-modality exercise therapies for pain reduction and quality of life.

Single-modality exercises

Most types of exercise showed a benefit in terms of improving critical outcomes for people with chronic primary pain (including quality of life, pain, physical function and psychological distress) both in the short-term (less than 3 months) and long-term (more than 3 months), although there was serious uncertainty around the effect estimates for many of the outcomes and in some cases, very serious uncertainty the direction of effect indicated a benefit. Interventions that were shown to be effective include aerobic exercise, strength exercise and mind-body exercises.

Evidence for flexibility alone (for example stretching) or proprioception alone (for example balance exercise) was more limited. Evidence for flexibility exercise was very low quality and was limited to one small study with a short-term follow up and small sample size. This evidence showed a benefit of flexibility in terms of pain, but no difference for physical function. Evidence for other critical outcomes such as psychological distress and quality of life was not available. Similarly evidence for proprioception versus usual care was very low quality and limited to one study with a small number of participants. This showed no benefit of proprioception in the short or long term for pain reduction, quality of life and physical function, and a benefit for psychological distress. The committee agreed that this evidence was not sufficient to determine the effectiveness of flexibility or proprioception exercises alone.

Mixed-modality exercises

Comparisons of mixed-modality exercises versus usual care included:

Aerobic and strength versus usual care
Aerobic, strength and flexibility versus usual care
Strength and flexibility versus usual care
Strength, proprioception and flexibility versus usual care

Evidence was available for all critical outcomes and generally showed a benefit of these types of exercise for quality of life and pain, although there was uncertainty around the effect estimates for many of the outcomes and in some cases, very serious uncertainty. Evidence for psychological distress and physical function varied across different types of exercise, with some exercise interventions showing a benefit whilst others showed mixed results, again with some uncertainty. There was less evidence for the outcome of sleep, with the majority showing no difference. Evidence for discontinuation was mixed, with some evidence to suggest that more people dropped out of the exercise interventions compared to usual care. However, the committee found the evidence about discontinuation difficult to interpret because usual care was often poorly defined.

Generally, the evidence showed a benefit of mixed-modality exercises for chronic primary pain. No evidence was available to compare mixed-modality exercises to each other, and the committee agreed that evidence was therefore not sufficient to determine whether one type of exercise was more beneficial than another. The committee instead considered that despite the uncertainty, the evidence reflected an overall benefit of exercise therapies, particularly for reducing pain and improving quality of life, in combination with the lack of negative effects other than discontinuation from the therapy and decided to make a recommendation for exercise.

Head-to-head comparisons (types of exercise compared to each other)

There were 17 different comparisons of different types of exercise compared to each other. The committee found it difficult to draw any firm conclusions regarding a hierarchical order of effectiveness. This was because the evidence was based on small sample sizes, had a high degree of uncertainty and was generally low to very low quality. This contributed to the committee decision not to make a recommendation for one type of exercise over another. When considered alongside the evidence demonstrating that discontinuation from exercise programmes is often an issue, the committee agreed that the choice of type of exercise should be made on an individualised basis, as people are more likely to adhere to an exercise programme that is suited to their needs and preferences.

Exercise versus psychological therapies

Evidence comparing various exercises to psychological therapies was limited, with only a small number of studies available, all of which had small sample sizes. Evidence was available for all critical outcomes but a consistent benefit of either exercise or psychological therapies was not demonstrated. Some outcomes suggested a benefit of exercise in terms of quality of life, physical function and psychological distress. However, there was serious uncertainty around the effect estimates and results were mixed with some evidence suggesting no difference between the two types of interventions (for pain, quality of life, physical function, psychological distress and sleep). Overall, the committee agreed that the evidence was insufficient to determine whether exercise as a whole is more or less effective than psychological therapies. The committee acknowledged that the effects observed with this comparison could have been affected by the type of exercise or psychological therapy in the individual studies contributing to each outcome.

Exercise versus manual therapies

Evidence that directly compared exercise with manual therapies was very limited and inconclusive. When exercise and manual therapies in combination were compared with manual therapies alone, there was a benefit of the addition of exercise for physical function, but no difference in pain or discontinuation. When exercise and manual therapies in combination were compared with exercise therapies alone, evidence showed no difference for pain, quality of life or discontinuation. Evidence for physical function was conflicting, with one outcome based on one small study showing a benefit of exercise and manual therapies in combination, but no difference in any other outcome measures. Overall, the evidence, suggested no benefit of the addition of manual therapy. No evidence was identified for psychological distress, sleep or use of healthcare services for exercise compared with manual therapies.

Summary across comparisons

The committee discussed the applicability of the evidence to the review population and the generalisability to all people with chronic primary pain as the vast majority of the evidence was based on women with fibromyalgia and people with chronic neck pain. The populations were pooled in the clinical review. Where heterogeneity was observed in the effect estimate, this was not explained by subgroup analysis by type of chronic primary pain and therefore the committee agreed that there was no reason recommendations made based on this evidence should not apply for all types of chronic primary pain conditions. The committee considered that despite the uncertainty around the effect estimates, the evidence base was large and benefits were shown across many of the critical and important outcomes, with very little evidence of negative effects except more people discontinuing from exercise interventions when compared to usual care. There was a clear indication that exercise is beneficial, but the most appropriate type of exercise may depend on the type of pain condition and it should be tailored to individual needs and preferences. This contributed to the committee decision not to make a recommendation about the type of exercise. The committee also noted that the majority of the evidence was based on supervised exercise interventions. In the absence of evidence on unsupervised exercise, the committee agreed to recommend only supervised exercise therapies.

1.7.2. Cost effectiveness and resource use

Two relevant published economic evaluations were identified that compared exercise with usual care. Original economic modelling was also undertaken.

One study was a UK within-trial analysis, looking at a leisure-facility-and-gym-based exercise programme. The comparators included treatment as usual and telephone-delivered cognitive behavioural therapy (TCBT). [NB. The TCBT comparison with usual care is reviewed in the psychological therapies review]. The exercise programme had an ICER of £76,960 per QALY gained compared to treatment as usual using complete case data (the primary analysis in the study) and would therefore not be considered cost effective. When using imputed outcome data, the study found that exercise versus treatment as usual had an ICER of £17,690 per QALY gained and therefore would be considered cost effective. The committee expressed concern over the disparity between the two ICERs, as it is difficult to tell which is a more accurate reflection of the true cost effectiveness of the programme, without knowing the nature of the missing data from the original study. A large amount of data was missing at the follow up 24 months after the intervention ended. This study was rated as directly applicable as it was a UK study from the NHS perspective using the EQ-5D, but with potentially serious methodological limitations such as the fact that the imputed outcomes led to a different conclusion to the complete case data, and the economic evaluation was based on a single RCT. Participation in the study was also based on self-reported symptoms. The committee noted that the cost-effectiveness analysis in the paper would be specific to the exercise programme as described in that particular trial (6 fitness instructor-led monthly sessions, plus a gym membership), which was not typical of the interventions in the other included studies in the review which were more class-based with higher frequency.

The second economic evaluation was a Spanish within-trial analysis, comparing 8 months of group pool-based exercises to usual care. This found exercise to be cost effective with an ICER of £3,630. Pool-based exercises are not considered to be current practice in the UK because they have higher costs. This study was rated as partially applicable with potentially serious limitations because although it uses the EQ-5D, it is not a UK study, it is more out of date than the UK study, and also the costs of the staff involved seem very low compared to UK costs, which is likely to increase the ICER in a UK setting. It is uncertain if this would increase the ICER to above £20,000 per QALY gained.

As both studies had limitations regarding their generalisability because of the types of interventions analysed, and significant uncertainties around cost effectiveness, this question was identified as being a high priority for an original economic analysis.

A cost-utility analysis using a lifetime horizon was undertaken comparing exercise with no exercise. The clinical review looked at each type of exercise separately (for example aerobics, mind body), however the committee agreed they could not infer if one type of exercise had more benefit than another. Therefore, this rationale was also applied to the economic modelling, meaning all the evidence on different types of exercise could be pooled together to make a general recommendation on exercise interventions as a whole. The interventions between studies also varied by intensity, which impacted resource use, however as the clinical review did not stratify by intensity, this supported the committee’s decision to pool all the studies for economic analysis.

Treatment effects were based on trials in the review that reported quality of life data, with the model pooling all available quality of life data that reported outcomes at the same time points, to derive an average treatment effect over time. Twelve studies were identified from the review that reported quality of life, either using EQ-5D or SF-36 that could be mapped to the EQ-5D. Differences in quality of life between the exercise and no exercise group in each study were calculated, taking into account the change from baseline in each arm, to derive the quality of life gain from exercise compared to no exercise for each study. A linear trend line was fitted to the pooled quality of life gain at each time point, and this was used to determine the QALY gain of the area under this line. The average treatment effect was also extrapolated beyond the available trial data, based on committee assumptions. Costs included only the costs of the staff time involved in providing an exercise programme. The total resource use from each study being used for treatment effect was identified and costed up, and a weighted average was taken based on the number of participants analysed in the intervention arm of each trial. All studies were looking at supervised exercise, and the majority were assumed to be group based (either because this was stated, or using their description of the intervention, or committee judgement) except one study known to be individual treatment.

Two base cases were modelled, one using a lifetime horizon and the other assuming no extrapolation beyond the trial data. Both base cases showed that exercise was cost effective compared with no exercise, with probabilistic ICERs of £9,121 (86% probability of exercise being cost effective at a threshold of £20,000 per QALY gained), and £12,683 (93% probability) respectively, and deterministic ICERS of £12,327 and £12,739 respectively. Various sensitivity analyses were undertaken, including varying costs, and including data omitted from the base case. The overall conclusion was robust to all sensitivity analyses tested.

The committee discussed the limitations of the analysis, which included how this was only based on a small proportion of studies from the clinical review as a whole (around 12%). However, they agreed that the studies used in the economic analysis were generally representative of the populations in the review as a whole and the populations that would be seen in practice with chronic primary pain (in other words, a mix of people with fibromyalgia and other chronic pain conditions). There was also a wide heterogeneity in the data being used in the model, as studies had very different populations, interventions, and intensities, and these were pooled together in the model. There is also uncertainty around the relationship between resource use and treatment benefit, and this needs to be considered then interpreting the results. It was not considered appropriate to explore this relationship more formally in the model (such as by modelling each study separately), as the clinical review did not establish which characteristics of exercise interventions improve outcomes.

The committee agreed that they had reservations about the two economic evaluations found in the literature, and that the economic analysis undertaken as part of the guideline pooled more data and was therefore considered more robust. The quality of life data from the identified UK economic evaluation was also included in the original economic analysis. The differences in results between the guideline original analysis and the UK economic evaluation are probably attributable to the fact that treatment effects were larger in the other trials included in the model, and additionally the UK economic evaluation found much higher health service costs in the exercise group at 18–24 months after intervention (i.e. they were using more health services). However it is difficult to know if the longer term health service costs were anything to do with the intervention after such long follow up.

Given that the clinical evidence showed there was some benefit from exercise, and taking that into account alongside the highly likely cost effectiveness of exercise, the committee decided to make a strong recommendation to offer exercise.

1.7.3. Other factors the committee took into account

The committee discussed that this review covered the use of exercise interventions to manage chronic primary pain. The committee’s experience was that many people with chronic primary pain find it difficult to be physically active. The UK Chief Medical Officers’ ‘Physical Activity Guidelines’ (2019) highlights that sedentary behaviour is an independent risk factor for poor health outcomes, including cardiovascular and cancer mortality, and obesity-related morbidity. NICE has published a range of guidance on physical activity. NICE also published guidance to ensure that interventions, including staff training, to improve population health and wellbeing meet individual needs: Behaviour change: individual approaches.

The committee therefore wished to highlight that there are important public health benefits to engaging in any physical activity for people with chronic primary pain, particularly if they are inactive or sedentary. The committee agreed that, for the chronic primary pain population, it was important to recommend continuing physical activity beyond the end of a formal exercise programme in a manner that is sustainable for the person. The committee discussed that if costs are incurred by engaging in physical activity after a formal exercise programme for management of chronic primary pain ends, this would be a personal cost, and would not fall to the NHS. Therefore, there were no implementation costs attributable to this recommendation.

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Appendices

Appendix A. Review protocols

Review protocol for exercise (PDF, 208K)

Table 69. Health economic review protocol

Appendix B. Literature search strategies

The literature searches for this review are detailed below and complied with the methodology outlined in Developing NICE guidelines: the manual.²⁰¹

For more information, please see the Methods Report published as part of the accompanying documents for this guideline.

B.1. Clinical search literature search strategy

Searches were constructed using a PICO framework where population (P) terms were combined with Intervention (I) and in some cases Comparison (C) terms. Outcomes (O) are rarely used in search strategies for interventions as these concepts may not be well described in title, abstract or indexes and therefore difficult to retrieve. Search filters were applied to the search where appropriate.

Table

Exclusions Randomised controlled trials

Medline (Ovid) search terms

Embase (Ovid) search terms

Cochrane Library (Wiley) search terms

B.2. Health Economics literature search strategy

Health economic evidence was identified by conducting a broad search relating to a Chronic Pain population in NHS Economic Evaluation Database (NHS EED – this ceased to be updated after March 2015) and the Health Technology Assessment database (HTA) with no date restrictions. NHS EED and HTA databases are hosted by the Centre for Research and Dissemination (CRD). Additional searches were run on Medline and Embase for health economics and economic modelling.

Table 70. Database date parameters and filters used

Medline search terms

Embase (Ovid) search terms

NHS EED and HTA (CRD) search terms

Appendix C. Clinical evidence selection

Figure 1. Flow chart of clinical study selection for the review of exercise

Appendix D. Clinical evidence tables

D.1. Evidence tables

Download PDF (2.1M)

D.2. Cochrane evidence tables

D.2.1. Bidonde 2017 (PDF, 560K)

D.2.2. Busch 2013 (PDF, 461K)

D.2.3. Theodom 2015 (PDF, 431K)

Appendix E. Forest plots

Appendix I. Excluded studies

I.1. Excluded clinical studies

Table 103. Studies excluded from the clinical review

I.2. Excluded health economic studies

Table 104. Studies excluded from the health economic review

Appendix J. MIDs for continuous outcomes

Table 105. MIDs for continuous outcomes: Aerobic exercise versus usual care

Table 106. MIDs for continuous outcomes: Strength training versus usual care

Table 107. MIDs for continuous outcomes: Aerobic and strength versus usual care

Table 108. MIDs for continuous outcomes: Strength and flexibility versus usual care

Table 109. MIDs for continuous outcomes: Strength, proprioception and flexibility versus usual care

Table 110. MIDs for continuous outcomes: Proprioception versus usual care

Table 111. MIDs for continuous outcomes: Mind-body exercise versus usual care

Table 112. MIDs for continuous outcomes: Flexibility versus usual care

Table 113. MIDs for continuous outcomes: Aerobic exercise versus strength

Table 114. MIDs for continuous outcomes: Aerobic exercise versus flexibility

Table 115. MIDs for continuous outcomes: Aerobic exercise versus biomechanical exercise

Table 116. MIDs for continuous outcomes: Aerobic and strength versus aerobic exercise

Table 117. MIDs for continuous outcomes: Aerobic and strength versus flexibility

Table 118. MIDs for continuous outcomes: Aerobic and flexibility versus mind-body exercise

Table 119. MIDS for continuous outcomes: Aerobic exercise and flexibility versus aerobic exercise

Table 120. MIDs for continuous outcomes: Aerobic, strength, mind-body and proprioception versus flexibility

Table 121. MIDs for continuous outcomes: Strength versus mind-body

Table 122. MIDs for continuous outcomes: Mind-body versus biomechanical

Table 123. MIDs for continuous outcomes: Strength versus flexibility

Table 124. MIDs for continuous outcomes: Strength and flexibility versus mind-body

Table 125. MIDs for continuous outcomes: Strength, flexibility and proprioception versus mind-body

Table 126. MIDs for continuous outcomes: Strength versus proprioception

Table 127. MIDs for continuous outcomes: Mind-body versus flexibility

Table 128. MIDs for continuous outcomes: Mind-body versus biomechanical

Table 129. MIDs for continuous outcomes: Flexibility and proprioception versus flexibility

Table 130. MIDs for continuous outcomes: Flexibility and relaxation versus aerobic exercise

Table 131. MIDs for continuous outcomes: Exercise versus psychological therapies

Table 132. MIDs for continuous outcomes: Manual therapy and exercise versus manual therapy

Table 133. MIDs for continuous outcomes: Manual therapy and exercise versus exercise

Table 134. MIDs for continuous outcomes: Exercise versus manual therapy

Intervention evidence review underpinning recommendations 1.2.1 to 1.2.2 in the NICE guideline

This evidence review was developed by the National Guideline Centre based at the Royal College of Physicians

Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and, where appropriate, their carer or guardian.

Local commissioners and providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.

NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.

Bookshelf ID: NBK569982PMID: 33939358

Table 1PICO characteristics of review question

Population	People, aged 16 years and over, with chronic primary pain (whose pain management is not addressed by existing NICE guidance) (chronic widespread pain, complex regional pain syndrome, chronic visceral pain, chronic orofacial pain, chronic musculoskeletal pain other than orofacial) Chronic pain in one or more anatomical regions that is characterized by significant emotional distress (anxiety, anger/frustration or depressed mood) and functional disability (interference in daily life activities and reduced participation in social roles). The diagnosis is appropriate independently of identified biological or psychological contributors unless another diagnosis would better account for the presenting symptoms.
Interventions	Interventions: Mind-body exercise (e.g. yoga, Tai Chi) Biomechanical (e.g. pilates) exercise Proprioceptive exercise Strength training Flexibility Aerobic (e.g. swimming, walking programme, aerobic exercise) Graded motor imagery Mixed modality exercise (aerobics and/or mind-body and/or biomechanical).
Comparisons	Comparators: Each other Usual care Psychological therapies Other physical therapies (e.g. manual therapy) Manual therapy + exercise.
Outcomes	CRITICAL: Pain reduction (any validated scale) Health related quality of life (including meaningful activity) Physical function (e.g. 6minute walk, sit to stand, Roland Morris Disability Questionnaire, Oswestry Disability Index, Canadian Occupational Performance Measure) Psychological distress (depression/anxiety) (preferably Hospital Anxiety and Depression Scale) IMPORTANT: Use of healthcare services Sleep Discontinuation. Outcomes will be extracted at the longest time point up to 3 months and at the longest time point after 3 months.
Study design	Randomised controlled trials (RCTs) and systematic reviews of RCTs Cross-over RCTs will be considered if no non-cross-over RCT evidence is identified.

Table 2Summary of studies included in the evidence review

Study	Intervention and comparison	Population	Outcomes	Comments
Andrade 2019¹⁷	16 week interventions. Intervention 1: Aerobic exercise (n=27) 32 aerobic pool sessions, 45 minutes each, twice a week. Conducted in groups of 5 and supervised by three physiotherapists. Progression of exercises was adjusted throughout in order to maintain optimum heart rate and reach the established perceived exertion threshold for each participant. Intervention 2: Usual care (n=27) No treatment; no further details	Women with fibromyalgia (n=54) Mean age 47.5(8) years Mean pain duration 7.5 years	At 16 weeks (post-intervention): Quality of life Pain reduction Psychological distress Sleep Discontinuation
Da costa 2005⁶⁷	12 week interventions. Intervention 1: Aerobic exercise (n=39) Meeting four times with an exercise physiologist. Visits were 90 minutes with 30 minute follow ups. Exercises were individualised for each participant and following the American college of sports medicine guidelines. Exercise focused mainly on aerobic fitness with exercises at heart rate intensity of 60–70% initially then to 75–85% depending on progress, and duration of exercise depended on the intensity although the guidelines suggested individuals should perform 60–120minutes per week. Stretching and strength exercises were also prescribed with the amount depending on the needs of each participant. Participants were provided with a heart rate monitor. Intervention 2: Usual care (n=41) Usual care control group	Women with fibromyalgia (n=80) Mean age 51.2 years Mean pain duration 11 years	At 12 months follow up (including 3 months intervention): Quality of life
Gowans 2001¹¹³ (Gowans 2002¹¹⁰)	23 week interventions. Intervention 1: Aerobic exercise (n=27) Water walking/running progressing to land walking/running. Classes for the first 6 weeks were conducted in a warm therapeutic pool; then progressed to 2 walking classes in a gym and 1 pool class. Classes were three times per week for 30 minutes (5 minutes stretching, 20 minutes aerobic activity, and 5 minutes stretching). Designed to generate a heart rate of 60–75% of age adjusted maximum heart rate. Intervention 2: Usual care (n=23) Continue ad libitum activity.	Fibromyalgia (n=50) Female:Male: 44:6 Mean age: 44.6 (8.7); 49.8 (7.3) years Duration of pain: 9.6 (8.6); 8.4 (7.6) years	At 23 weeks (post intervention): Quality of life Physical function Psychological distress Discontinuation	In Cochrane review (Bidonde 2017)
Kayo 2011¹⁴²	16 week interventions. Intervention 1: Aerobic exercise (n=30) Supervised indoor or outdoor walking, three times a week for 60 minutes (5–10 minutes stretching, walking and 5 minutes cool down). Intervention 3: Usual care (n=30) Control conditions not specified. Participants in all 3 groups were asked to discontinue tricyclic antidepressants but were allowed to use acetaminophen (paracetamol) for pain.	Fibromyalgia (n=60) All female Mean age: 47.7 (5.3); 46.7 (6.3); 46.1 (6.4) years Duration of pain: 4.0 (3.1); 4.7 (5.7); 5.4 (3.5) years	At 28 weeks (follow up, including 16 weeks intervention): Quality of life Pain Physical function Discontinuation	In Cochrane review (Bidonde 2017)
King 2002¹⁵²	12 week interventions. Intervention 1: Aerobic exercise (n=42) Walking, aquacise (deep and shallow water), or low impact aerobics. Three times a week starting at 10–15 minutes and progressing to 20–40 minutes. Intervention 2: Usual care (n=34) Waitlist control. Participants received written instructions for basic stretches and 5 items related to general coping strategies.	Fibromyalgia (n=170; third arm of study reported under exercise versus psychological therapy comparison) Females only Mean age: 45.2 (9.4); 44.9 (10); 47.4 (9); 47.3 (7.3) years Duration of pain: 7.8; 10.9; 8.9; 9.6 years	At 24 weeks (follow up including 12 week intervention): Quality of life Physical function Pain	In Cochrane review (Bidonde 2017)
Mengshoel 1992¹⁸⁹	20 week interventions. Intervention 1: Aerobic exercise (n=11) Modified low-impact aerobic dance; exercise for upper extremities performed at intervals between periods of rest; exercises modified to prevent pain, fatigue, and static muscle work. Twice a week for 60 minutes. Intervention 2: Usual care (n=14) Participants instructed to not change their habits regarding physical activities.	Fibromyalgia (n=25) All female Mean age: 33.5 (21 to 42); 34 (25 to 38) years Duration of pain: 8.5 (3 to 20), 8 (3 to 23) years	At 20 weeks (post intervention): Pain Discontinuation	In Cochrane review (Bidonde 2017)
McBeth 2012¹⁸¹ (Beasley 2015²⁸)	6 month intervention Intervention 1: Aerobic exercise (n=109) Gym based programme with monthly assessments led by instructors to reassess the programme. Exercise intensity increased until exercise levels achieved 40–85% maximum heart rate; recommended session length 20 to 60 minutes 3–5 times a week). Intervention 3: Usual care (n=109) Usual care from family physician, although precise care delivered, if any, was not recorded	Chronic widespread pain (n=330; third arm of study reported under exercise versus psychological therapy comparison) Mean age 55.7(12.5) years Duration of pain not stated	At 9 months: Quality of life Sleep Discontinuation (6 months)	Gym sessions were not supervised (70% finished the exercise intervention, those that finished reached the compliance threshold of at least 2 sessions per week. 16.2% didn’t complete sessions other than the monthly fitness instructor sessions.
Nichols 1994²⁰⁴	8 week interventions. Intervention 1: Aerobic exercise (n=10) Fast paced walking on an indoor track. Each session included a warm up and cool down regimen of stretching exercises, 1 warm up and cool down lap of slow paced walking. Three times a week. Intervention 2: Usual care (n=9) Daily activities as usual not involving physical activity.	Fibromyalgia (n=19) Female:Male: 17:2 Mean age: 47.8 (11.1); 50.8 (11.8) years Duration of pain: > 10; > 10 years except for a person who had 4	At 8 weeks (post intervention): Discontinuation	In Cochrane review (Bidonde 2017)
Norouzi 2019²⁰⁶	12 week interventions. Intervention 1: Aerobic exercise (n=40) Half of participants took part in walking on a treadmill. Walking was at an intensity of 60–75% estimated maximum heart rate. The other half of particpants took part in Zumba dancing. Each session consisted of a warm up followed by active upper and lower body movements, followed by a cool down and stretching. Three times a week for 60 minutes. Intervention 2: Usual care (n=20) Current daily activity levels were maintained and participants were asked to refrain from additional exercise or sport activities.	Fibromyagia (n=60) All female Mean age: 35.5 (2.42); 35.4 (2.80) years Duration of pain: 2.28 (0.3); 2.83 (0.29) years	At 12 weeks (post intervention) Psychological distress Physical function Discontinuation	3 armed trial; ‘aerobic exercise’ arm and ‘Zumba dancing’ arm combined for analysis
Sanudo 2010²³⁴	24 week interventions. Intervention 1: Aerobic exercise (n=22) Warm-up included slow walks, easy movements of progressive intensity, steady state aerobics included continuous walking with arm movements and jogging, interval training included aerobic dance and jogging, cool-down included slow walks, easy movements, relaxation training. Twice a week for 45–60 minutes (10 minutes warm-up, 5–10 minutes cool down, 15–20 minutes steady aerobics, 15 minutes interval training). Intervention 3: Usual care (n=21) Medical treatment for fibromyalgia and continued normal daily activities, which did not include structured exercise.	Fibromyalgia (n=64 ; third arm of study reported under aerobic and strength versus aerobic comparison) Females only Mean age: 55.9 (1.6); 55.9 (1.7); 56.6 (1.9) years Duration of pain: not specified	At 24 weeks (post intervention): Pain Quality of life Physical function Discontinuation (additional outcome)	In Cochrane review (Bidonde 2017)
Sanudo 2015²³²	24 week interventions Intervention 1: Aerobic exercise (n=16) Two sessions per week of 45–60 minutes duration. Each session included 10 minutes of warm up activities (easy movements and slow walking), 15–20 minutes of steady state exercise at 60–65% of predicted maximum heart rate (including continuous walking with arm movements and jogging) and 15 minutes of interval training at 75–80% (six repetitions of 1.5 minutes with 1 minute interpolated rest intervals), and 5–10 minutes of cool-down activities (slow walks, easy movements, relaxation training). Exercise intensity was monitored by a heart rate telemetric system. The intensity progressively increased as participants improved their exercise capacity to maintain the heart rate in the prescribed range. Intervention 2: Usual care (n=16) Participants continued their normal daily activities which did not include structured exercise.	Women with fibromyalgia (n=32) Mean age 56.5 years Mean pain duration not stated	At 24 weeks (post-intervention): Pain reduction Psychological distress Sleep Discontinuation
Schachter 2003²³⁹	16 week interventions. Intervention 1: Aerobic exercise (n=51) Home programme of low impact aerobics (long bout) with rhythmical movements designed to use all major muscle groups of the lower extremities performed to music. Three-five times a week for 10–30 minutes, increasing in intensity over the first 10 weeks. Intervention 2: Aerobic exercise (n=56) Home program of low-impact aerobics (short bout) to videotaped instructor and music, rhythmical movements of lower body muscles. Three to five times a week, twice a day for 5–15 minutes, increasing in intensity over the first 10 weeks. NB Aerobic exercise interventions pooled in the analysis. Intervention 3: Usual care (n=36) Participants were asked to refrain from starting any new regular physical activity or exercise programs or other non-pharmacological interventions.	Fibromyalgia (n=143) Females only Mean age: 41.3 (8.7); 41.9 (8.6); 42.5 (6.7) years Duration of pain: not specified	At 16 weeks (post intervention): Quality of life Pain Physical function Psychological distress	In Cochrane review (Bidonde 2017)
Sencan 2004²⁴¹	6 week interventions. Intervention 1: Aerobic exercise (n=20) Supervision unclear. Cycle ergometry 3 times a week for 40 minutes. Intervention 2: Usual care (n=20) Placebo group received sham transcutaneous electrical stimulation 3 times a week for 20 minutes each; electrodes applied on the 2 most painful tender points (with no current)	Women with fibromyalgia (n=60) Mean age 35.4 years Mean duration of pain 4.7 years	At 6 weeks post intervention and 26 weeks follow up: Pain reduction
Van eijk-hustings 2013²⁶⁴	12 week interventions. Intervention 1: Aerobic exercise (n=47) Sessions twice a week by a trained physiotherapist in a community gym (groups of 9 to 10 participants). Every session started with a 10-min warm up, comprising aerobic and stretching, followed by 30 minutes of aerobic exercise. The low- intensity aerobic part aimed to reach 55–64 % of the predicted maximum heart rate. Then, resistance training was applied during 15 min to strengthen major muscle groups. Finally, every session was finished with a 5-min cool down. Participants received a digital video disc presenting exercises to do at home, and they were advised to perform these once a week. Intervention 2: Usual care (n=48) Usual care involved GP appointments and at least some individualised education about fibromyalgia.	Fibromyalgia (n=96*) Mean age 42 years Mean duration of pain not reported	At 12 weeks (post-intervention) and 18 months (follow-up): Pain reduction Quality of life Physical function Psychological distress Use of healthcare services Sleep Discontinuation	*Third arm of RCT included in pain management programme evidence review.
Wigers 1996²⁷⁶	14 week interventions. Intervention 1: Aerobic exercise (n=20) Aerobic exercise, focusing on the whole body and aimed at minimizing eccentric muscle strain. Exercise involved movement to music and games. Three times a week for 45 minutes (23 minute music session including warming up and 2 peaks of high intensity training, 15 minutes of aerobic games with 2 high intensity periods). Intervention 2: Usual care (n=20) Continued treatments being used at baseline.	Fibromyalgia (n=40) Mean age: 43 (9); 44 (12); 46 (9) years Duration of pain: 9 (5); 11 (10); 11 (9) years	At 14 weeks (post intervention) and 4 years (follow-up): Pain Sleep Psychological distress Discontinuation (additional outcome)	In Cochrane review (Bidonde 2017)

Table 3Summary of studies included in the evidence review

Study	Intervention and comparison	Population	Outcomes	Comments
Assumpcao 2018²³	12 week interventions Intervention 1: Strength training (n=19) 12 week supervised resistance training programme of 40-minute sessions performed twice a week with progressive overload. Equipment included dumbbells, shin pads. No load was used in the first 2 sessions, after which time 0.5kg was added each week if the patient identified the effort as slightly intense on the Borg scale. 8 repetitions for: triceps, quadriceps, hip adductors and abductors, hip flexors, elbow flexors and extensors, pectoralis major and rhomboids. Intervention 2: Usual care (n=16) After 12 weeks patients were reassessed and offered physical therapy based on stretching and resistance training.	Women with fibromyalgia (n=35) Mean age 47 years Mean pain duration not stated	At 12 weeks (post-intervention): Pain reduction Physical function Discontinuation	60% were taking concomitant medication for fibromyalgia (antidepressants, analgesics, anti-inflammatories or psychotropic medication)
Borisut 2013³⁹	12 week interventions Intervention 1: Strength exercise (n=25) A progressive resistance exercise program for the neck muscles, especially the superficial neck flexor and extensor muscles. Neck flexion and extension were performed in the supine and prone positions. The first 4 weeks involved 12–15 repetitions, and the next 8 weeks involved 3 sets of 15 repetitions. Intervention 2: Strength exercise (n=25) A craniocervical flexion exercises which consisted of a low load exercise for the cranio-cervical flexor muscles. Participants moved to increase air pressure on a sensor and held for 10 seconds in 15 repetitions. Intervention 3: Strength exercise (n=25) A combination of progressive resistance exercise and craniocervical flexion exercise. NB Strength exercise interventions pooled in the analysis. Intervention 2: Usual care (n=25) After the data collection period, participants were advised to perform both the strength progressive resistance and cranio-cervical exercises	Women with chronic neck pain (n=100) Mean age: 31.1 (3.38); 30.40 (3.54) Mean pain duration not reported	At 12 weeks: Pain Physical function
Chiu 2005⁵⁹	Intervention 1: Strength training (n=67) There were 2 training sessions per week for a period of 6 weeks. The exercise program began with a warm up which involved one set (10 minutes) of activation of the deep neck, then 15 repetitions of flexion and extension of the neck. The resistance used during the warm up was set at approximately 20% of the maximum intensity. After the warm up, dynamic training started, which consisted of 3 sets of variable resistance load allowing 8–12 repetitions of full flexion and extension within pain tolerance. A 5 minute rest between sessions was given. The weight load was increased approximately 5% when a set of 12 or more repetitions had been achieved. Intervention 2: Usual care (n=78) The control group received infrared irradiation twice a week for 6 weeks. The irradiation time was 20 minutes.	Chronic neck pain for longer than 3 months (n=145) Mean age 43.3 years 61% had pain for over 12 months	At 6 weeks (post intervention): Pain reduction Physical function Discontinuation	Infrared irradiation was given to both the exercise group and the control group. For the exercise group, irradiation was given before the exercise program.
Falla 2013⁹⁰	8 week interventions Intervention 1: Strength training (n=23) Progressive exercise programme for the neck flexors and extensor muscles. Participants received personal instruction and supervision by a physiotherapist for 30 minutes once per week for 8 weeks. The therapist examined the exercises and progressed the participant if appropriate. The programme consisted of 2 stages. The first stage was 6 weeks duration. The principal exercise task during this period was flexion in a relaxed supine lying position and patients were guided by a pressure unit. The second stage was 2 weeks and involved higher load exercise with head weight as the load. During this stage, participants performed up to 15 repetitions of a head lift for flexors and neck extension for the extensor group. Participants practiced twice per day, and the programme was 10–20 minutes/day. Intervention 2: Usual care (n=23) The control group did not receive any intervention, however they patients were not asked to refrain from seeking treatment.	Chronic non-specific neck pain (n=46) Mean age 38.9 years Mean duration of pain 9.1 years	At 8 weeks (post-intervention): Pain reduction Quality of life Physical function Discontinuation
Glasgow 2017¹⁰⁷	8 week interventions Intervention 1: Strength training (n=14) Supervised resistance exercises twice a week for 8 weeks, each lasting 30 minutes. 3 sets of 8–12 repetitions followed by 90 second rest periods between each set. Exercises were chest presses, leg extensions, leg curls and seated rows, initially at a training intensity of 50–60% of maximum. Resistance was increased when participants could complete 12 repetitions on all 3 sets over 2 consecutive training days. Intervention 2: Usual care (n=12) Control group (non-exercising, no further details).	Women with fibromyalgia (n=26) Mean age 51 years Mean pain duration not specified	At 8 weeks (post-intervention): Quality of life Psychological distress Discontinuation
Hakkinen 2001¹¹⁹	21 week interventions. Intervention 1: Strength training (n=11) Resistance training including 6–8 dynamic resisted exercises using David 200 dynamometer to upper extremity, lower extremity, and trunk muscle groups. Twice a week. Intervention 2: Usual care (n=10) Controls maintained their normal low-intensity recreational physical activities but did not participate in the strength training.	Fibromyalgia (n= 21) All female Mean age: 37 (6) to 39 (6) years Duration of pain: 12 (4) years	At 21 weeks (post intervention): Pain Sleep Physical function Psychological distress	In Cochrane review (Busch 2013)
Kayo 2011¹⁴²	16 week interventions. Intervention 1: Strength training (n=30) Supervised exercise protocol consisting of 11 free active exercises for upper and lower limbs and trunk muscles, with free weights and body weight performed in the standing, sitting, and lying positions. Sessions were three times a week for 60 minutes. Exercise load and intensity increased every 2 weeks. Intervention 2: Usual care (n=30) Control conditions not specified. Participants in all 3 groups were asked to discontinue tricyclic antidepressants but were allowed to use acetaminophen (paracetamol) for pain.	Fibromyalgia (n=60) All female Mean age: 47.7 (5.3); 46.7 (6.3); 46.1 (6.4) years Duration of pain: 4.0 (3.1); 4.7 (5.7); 5.4 (3.5) years	At 28 weeks (follow up, including 16 weeks intervention): Quality of life Pain	In Cochrane review (Bidonde 2017)
Kingsley 2005¹⁵³	12 week interventions Intervention 1: Strength training (n=15) Twice a week sessions for 30 minutes. Sessions consisted of 11 exercises. Resistance machine exercises included chest press, leg extension, standing leg curl, shoulder press, lumbar extension and abdominal crunch. The cable exercises included low pulley biceps curl, high pulley triceps extension, and the mid pulley standing row. Body weight was used for the standing calf raises and body weight Swiss ball squats. Before and after workouts, participants performed 5 minutes of warm up and cool down that included stretching and walking. Participants began training at 40% of their 1-RM. Once 12 repetitions were performed in proper form, weight was increased by 2.3 to 4.5kg (5–10lb). Intervention 2: Usual care (n=14) Participants were asked not to change their activity levels during the 12 week intervention period.	Women with fibromyalgia (n=29) Mean age 46.2 years Mean pain duration 8 years	At 12 weeks (post-intervention) Quality of life Physical function Discontinuation
Suvarnnato 2019²⁴⁷	6 week interventions Intervention 1: Strength training (n=18) Semispinalis cervicis-training group. Exercises involved a physical therapist applying resistance to the posterior vertebral arches of the participant’s C2 vertebra whilst participants pushed against the resistance. Exercises were held for 10 seconds, 10 times per set, 3 sets per day (30 second rest between sets). Exercises performed twice per week over the 6 week period. Intervention 2: Strength training (n=18) Deep cervical flexor-training group. Low-load exercises focused on activating the deep flexor muscles of the cervical region. Exercises performed 10 times per set, 3 sets at a time with a 30 second rest between sets. Performed under supervision twice per week and advised to perform twice per day at home. NB Strength training interventions pooled in the analysis Intervention 3: Usual care (n=18) Usual care deemed appropriate by physical therapists other than strength exercises, e.g. stretching, manual therapy. 10–12 appointments within 6 weeks.	Chronic neck pain (n=54) Mean age 42.94 years Mean duration of pain 12.86 months	At 6 weeks (post-intervention) and 16 weeks (follow up): Pain reduction Physical function
Valkeinen 2004²⁶⁰	21 week interventions. Intervention 1: Strength training (n=13) Resisted dynamic exercise to knee extensors x 2 plus 5–6 exercises for other main muscle groups of body. Twice a week for 60–90 minutes. Intervention 2: Usual care Control conditions were treatment as usual and physical activity as usual.	Fibromyalgia (n-26) All females Mean age: 59.1 (3.5) to 60.2 (2.5) years Duration of pain: 8.5 (4.3) to 6.6 (4.1) years	At 21 weeks (post intervention): Physical function Discontinuation	In Cochrane review (Busch 2013)
Viljanen 2003²⁶⁷	12 week interventions Intervention 1: Strength training (n=135) Led by trained physiotherapist 3 times a week sessions for 30 minutes each, followed by on week of reinforcement training 6 months after randomisation. Dumbbells were used for dynamic muscle training (weight 1–3kg each according to maximum repetitions with a test weight of 7.5 kg). The Exercises, conducted in the same order in each session, were chosen to activate large muscle groups in the neck and shoulder region. After the 5thweek participants were taught 3 exercises from the program with stretches, after the 9th week they were asked to perform the full training program by themselves. Intervention 2: Usual care (n=130) Usual care, no change to physical activity or means of relaxation during the 12 months of follow up.	Chronic non-specific neck pain (n=393; third arm of study reported under exercise versus psychological therapy comparison) Mean age 44 years Mean pain duration 10.8 years	At 12 months follow up (including 12 week intervention): Pain reduction Discontinuation	All participants were office workers
Von trott 2009²⁷¹	12 week interventions (Intervention 1: Strength and flexibility n=39) 24 sessions at 45 minutes each held over 12 weeks, with 6–12 participants in each group. A standardised programme for computer and workplace related neck pain. It included repeated active cervical rotations as well and strength and flexibility exercises. Special intention as paid so that the patients’ individual pain limits were not exceeded. About 90% of the exercises were repeated in each lesion; some 10% was exchanged regularly Intervention 2: Usual care (n=40) Waiting list control participants did not receive Qigong or exercise therapy.	Office workers with chronic neck pain (n=79) Mean age 76 years Mean pain duration 18.6 years	At 12 weeks (post-intervention) and 24 weeks follow up: Pain reduction Quality of life Physical function Psychological distress Discontinuation

Table 4Summary of studies included in the evidence review

Study	Intervention and comparison	Population	Outcomes	Comments
Espi-lopez 2016⁸³	8 week interventions. Intervention 1: Aerobic, Strength training (n=13) Low-impact aerobic exercise with low impact strength exercises. Two sessions per week. Each session consisted of 60min and was divided into three parts: warm up (15 min); games, group dynamics and aerobics (30 min); and cool down with stretching for 15 min. The warm up consisted of combined low impact aerobic exercises, free range of motion exercises of limbs and spine, and coordination exercises plus stretching. This was followed by active low load resistance exercises involving arms and legs, followed by a circuit of coordination and agility exercises and then low-impact strength exercises of the trunk. This was followed by a cool down with stretches. Intervention 2: Usual care (n=9) No intervention, no further details	Fibromyalgia (n=22) Mean age 53.6(8.1) years Mean pain duration not stated	At 8 weeks (post-intervention): Quality of life Psychological distress Discontinuation
Etnier 2009⁸⁴	18 week interventions. Intervention 1: Aerobic, Strength exercise (n=8) The exercise sessions were 60 minutes in duration 3 days a week. During the sessions, participants walked, performed light resistance exercises, and performed static bridging and stretching exercises. All sessions were conducted and directly supervised by one of the authors. In terms of the walking portion, participants were encouraged to walk a comfortable/brisk pace (55–65% of maximal heart rate reserve) for 15 minutes. Over the course of the intervention, they were encouraged to try to walk a greater distance in the 15 minute period and used this as a self-measure of aerobic fitness. In terms of the light resistance exercises, participants moved through an 8 station light resistance exercise circuit. When subjects were able to easily complete the required number of repetitions for a certain exercise, resistance was increased by 1 pound. Often, this caused participants to reduce the number of repetitions for a short time followed by slowly working back to the required number. Static-bridging exercises require that the exerciser support her body (holding the body very still) in various positions to increase core (abdominal, back and pelvic), muscle strength/endurance. Usually 10 repetitions of approximately 3 seconds were completed in each session. Intervention 2: Usual care (n=8) No treatment control condition.	Women with fibromyalgia (n=16) Mean age not reported Mean duration of pain not reported	At 18 weeks (post-intervention): Quality of life Physical function Psychological distress Discontinuation	Most participants reported having symptoms as teenagers and received a medical diagnosis within the last 1–10 years.
Izquierdo-Alventosa 2020¹³²	8 week interventions. Intervention 1: Aerobic, Strength training (n=16) Low intensity physical exercise combing endurance training (aerobic and low-load resistance exercises aimed at improving endurance) and coordination. Each session consisted of a warm up of walking at a slow pace (10–15 minutes), training which involved 10 exercises (25–40 minutes), and a cool down of walking, stretching, and breathing (10–20 minutes). Twice a week for 60 minutes. Intervention 2: Usual care (n=16) No treatment control condition.	Women with fibromyalgia (n=32) Mean age: 53.06 (8.4); 55.13 (7.35) years Mean pain duration not stated	At 8 weeks (post-intervention) Pain reduction Physical functioning Psychological functioning Quality of life Discontinuation
Latorre roman 2015¹⁵⁹	18 week interventions. Intervention 1: Aerobic, Strength training (n=20) Sixty-minute sessions of functional training 3 times a week. Of those 3 weekly sessions, 2 consistent of exercise in water and 1 of exercise on land. A specialist instructed both groups. Each session included a warm up (5 minutes) and exercises of muscular strengthening and balance (40 minutes), and a cool down (5 minutes). Exercise intensity was increased during the whole programme by modifying the number of reps per set, by introducing weights (in on land exercises, 0.5–2kg per exercise) and materials that raised the resistance offered by water. Strength training consisted in 1–3 sets of 8–12 reps per exercise and circuit training. On land, multiple functional exercises were performed individually and on a circuit, for example, climbing stairs using weights as the external load (medicine ball). Intervention 2: Usual care (n=19) Participants continued with their daily activities that did not include any kind of physical exercise similar to that of the study group.	Women with fibromyalgia (n=39) Mean age 51.7 years Mean pain duration not stated	At 18 weeks (post-intervention) Pain reduction Quality of life Discontinuation
Munguia-izquierdo 2007²⁰⁰ (Munguia-izquierdo 2008¹⁹⁹)	16 week intervention Intervention 1: Aerobic, Strength training (n=35) The exercise group trained in a chest-high warm pool (32°C) 3 times a week for 16 weeks. Each session included 10 minutes of warming up with slow walks and mobility exercises, 10 to 20 minutes of strength exercises developed at a slow pace using water and aquatic materials as a means of resistance including a stepped progression during the program, 20 to 30 minutes of aerobic exercises developed progressively at intensity sufficient to achieve 50% to 80% of the age predicted maximum heart rate equation (220 – age), and 10 minutes of cooling down with low-intensity and relaxation exercises. Heart rate was monitored with a pulse meter. Intervention 2: Usual care (n=25) The control group was instructed not to change their habits regarding physical activities during the period. Usual activities and medication allowed.	Fibromyalgia (n=60) Mean age 48 years Mean pain duration 14 years	At 16 weeks (post-intervention): Quality of life Psychological distress Sleep Discontinuation
Sanudo 2011²³⁵	24 week interventions Intervention 1: Aerobic, Strength training (n=21) Twice weekly sessions of combined aerobic and muscle strength training for 24 weeks. 10 minute warm up followed by 10–15 minutes of aerobic exercises at 65–70% of maximum heart rate. Participants were in small groups and performed continuous walking with arm movements and jogging. This was followed by 15–20 minutes of muscle strengthening exercises with a circuit of 8 exercises using multiple muscles. Participants carried out 1 set of 8–10 repetitions and resistance was increased according to the patient’s tolerance. This was followed by a cool-down of 10 minutes which consisted of flexibility exercises. Duration 24 weeks. Concurrent medication/care: 81.25% were taking medication for FMS (analgesic or NSAID, antidepressant or other combination). Intervention 2: Usual care (n=21) Participants continued their usual treatment and daily activities which did not include any structured exercise.	Fibromyalgia (n=42) Mean age 55.87 years Mean pain duration not specified	At 24 weeks (post-intervention): Quality of life Psychological distress Discontinuation	81.25–84.2% were taking concurrent medication for fibromyalgia
Sanudo 2012²³³	24 week interventions Intervention 1: Strength training and aerobic exercise (n=21) Exercise was twice weekly for 45–60 minutes. Each session included 10 minutes of warm up activities (slow walking and gently movements of progressive intensity e.g. arm swinging); 10–15 minutes of aerobic exercise at 65% to 70% of maximal heart rate, 15–20 minutes of muscle strengthening exercises (one set of 8–10 repetitions for 8 different muscle groups, with a load of 1–3kg), and 10 minutes of flexibility exercises (1 set of 3 repetitions for 8–9 different exercises, maintaining the stretched position for 30 seconds). Strengthening and flexibility exercises focused on the main areas of pain in patients with FM (deltoids, biceps, neck, hips, back and chest). Intervention 2: Usual care (n=20) Usual medical treatment of fibromyalgia and continued normal daily activities which did not include structured exercise.	Fibromyalgia (n=41) Mean age not reported Mean pain duration not reported	At 24 weeks (post-intervention): Physical function Psychological distress Discontinuation
Tomas-carus 2008²⁵² (Tomas-carus 2007²⁵⁴, Tomas-carus 2009²⁵³^, ¹¹⁶)	8 month interventions Intervention 1: Aerobic and strength exercise (n=18) Supervised training in waist high pool of warm water 3 times per week during an 8 month period. Each session 1 hour, 10 minutes warming up with slow walks and easy movements of progressive intensity, 10 minutes of aerobic exercises (60–65% maximal heart rate), 20 minutes of strength exercises using water resistance (4 sets of 10 repetitions), 10 minutes of cooling down with low intensity exercises. Intervention 2: Usual care (n=17) Control group continuing daily activities which did not include any form of physical exercise similar to those in the therapy.	Women with fibromyalgia (n=34) Mean age 50.8 years Mean pain duration 19.8 years	At 3 months and 8 months (post-intervention): Pain reduction Quality of life Psychological distress Physical function Psychological distress Discontinuation
Waling 2002²⁷³	10 week interventions Intervention 1: Aerobic exercise (n=34) Endurance training of the shoulder muscles consisted of arm-cycling and arm exercises with rubber band resistance on the endurance level (30 RM repetition maximum). Intervention 2: Strength exercise (n=34) Strength training consisted of neck and shoulder exercises with individualized loads of 10 to 12 maximal voluntary contractions in three sets. NB Aerobic and strength exercise interventions pooled in the analysis. Intervention 2: Usual care (n=27) Participants, led by an occupational nurse, studied stress management once a week, 2 hours at a time, for 10 weeks. No exercises were performed in this group.	Women with work-related trapezius myalgia Mean age: 37.7 (5.6); 31.1 (15.8) years Pain duration: 6.3 (4.0); 7.3 (4.34) years	At post-intervention: Pain At 3 years (follow up): Pain Use of healthcare services
Ylinen 2003²⁸⁴ (Ylinen 2007²⁸¹, Ylinen 2006²⁸⁵)	2 week interventions Intervention 1: Strength training (n=60) 10 patients in each group, 12 day program with 5 sessions per week, each lasting 45 minutes. Exercises aimed to strengthen neck flexor muscles by using an elastic rubber band to train the muscles at a resistance of 80% of maximum (15 repetitions in each direction). Following this the group performed dynamic exercises for the shoulders and upper extremities, with an individually adjusted single dumbbell, performing only 1 set for each exercise with the highest load possible to perform 15 repetitions. This was followed by exercises for the trunk and leg muscles in the same format, which was then concluded by stretching exercises for 20 minutes. Intervention 2: Strength training (n=60) 10 patients in each group, 12 day program with 5 sessions per week, each lasting 45 minutes. Exercises aimed to strengthen neck flexor muscles by lifting head up from the supine position in 3 series of 20 repetitions. Following this the group performed dynamic exercises for the shoulders and upper extremities, at 3 sets of 20 repetitions for each exercise with a pair of dumbbells each weighing 2 kg. This was followed by exercises for the trunk and leg muscles in the same format, which was then concluded by stretching exercises for 20 minutes. NB: Strength training interventions pooled in the analysis Intervention 3: Usual care (n=60) Performed recreational activities on assessment days. Received written information about the same stretching exercises and were advised to practice these 20 minutes 3 times a week. They were also advised to perform aerobic exercise 3 times a week.	Office workers with chronic neck pain (n=180) Mean age 46 years Mean pain duration not stated (but minimum 6 months)	At 12 month follow up: Use of healthcare services

Table 5Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Garcia-martinez 2012⁹⁹

12 week interventions

Intervention 1: Aerobic, strength and flexibility exercise (n=14)

3 times a week sessions for 12 weeks. Each session was 60 min long and included 10 min of warming-up with slow walks and easy movements of progressive intensity, 20 min of aerobic exercise that began at 60–70% of maximal heart rate and was gradually increased to as high as 75–85% maximum, depending on the subjects’ adaptation, 20 min of stretching and strength exercise and 10 min of cooling down with low-intensity exercises.

Intervention 2: Usual care (n=14)

Subjects continued their daily activities which did not include any physical exercise.

Fibromyalgia (n=28)

Mean age 58.9 years

Mean duration of pain 10.3 years

Quality of life at 12 weeks (post-intervention)

Table 6Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Acar 2012¹

2 week intervention

Intervention 1: Strength and stretching combination (n=20)

Strength exercises for multiple muscles and neck stretching exercises. 10 sessions 5 days a week, supervised by physiotherapists.

Intervention 2: Usual care (n=20)

No details.

Chronic cervical pain (n=40)

Mean age 38(11.75) years

Mean pain duration 46.5 years

Pain reduction at 2 weeks (post-intervention)

Rendant 2011²²²

6 month interventions

Intervention 1: Strength and flexibility (n=39)

Exercise therapy was carried out by 6 qualified therapists. The exercises were based on a standard programme for chronic pain. Each lesson started with a warm up using a softball and was followed by repeated active cervical rotations and strengthening and flexibility exercises. The individual’s pain level was not exceeded. There were 18 sessions over a period of 6 months (1 session per week in the first 3 months, and biweekly sessions in the following 3 months).

Intervention 2: Usual care (n=41)

Waiting list control participants received no intervention.

Chronic non-specific neck pain (n=123; third arm of study reported under strength and flexibility versus mind-body and mind-body versus usual care comparisons)

Mean age 44.6 years

Mean pain duration 3.1 years

At 6 months (post-intervention)

Pain reduction
Quality of life
Physical function
Discontinuation

Pain rating of 40 or more required at baseline (VAS 0–100)

Third arm of study reported under separate comparisons (Qi-gong).

Table 7Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Lauche 2016¹⁶⁰

12 week interventions

Intervention 1: Strength, proprioception and flexibility (n=37)

Participants in the neck exercise group met once weekly for a 60- to 75-minute session for 12 weeks in total. This group was instructed in neck exercises, which were similar to those taught in rehabilitation programs containing exercises and education for a healthy back. Classes contained basic training of ergonomic principles (bodily alignment while standing), proprioceptive exercises, and isometric and dynamic mobilization, stretching, and strengthening neck and core exercises. The sessions opened with 5 to 10 minutes of warm-up exercises and ended with relaxation exercises. Participants also received illustrated and written information that covered the most important exercises, and they were asked to execute the exercises for at least 15 minutes each day.

Intervention 2: Usual care (n=39)

Participants in this group were advised to continue their usual activities and therapies, but not to initiate any new therapeutic regimen for symptom management.

Chronic non-specific neck pain (n=114; third arm of study reported under mind-body versus usual care and strength, proprioception and flexibility versus mind-body comparisons)

Mean age 48.49 years

Mean pain duration not specified

At 12 weeks (post-intervention) and 24 weeks (follow up):

Pain reduction
Quality of life
Physical function
Psychological distress
Discontinuation

VAS score of 45 or higher (0–100) inclusion criteria.

Table 8Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Altan 2004⁹

12-week interventions

Intervention 1: Proprioception (pool-based) (n= 24)

All patients were given two educational sessions of 1 h each for 2 days by a physiatrist about the description and available diagnosis and treatment methods of FMS. Next, they were assigned randomly into two groups by the researcher other than the one who performed the evaluation throughout the study.

In group 1, a pool-based exercise program was given by a physiotherapist to 25 patients in a therapeutic pool at 37°C for 35 min a day three times a week for 12 weeks. The program included warming (walking back and forth in the pool), activity (jumping in the pool and active joint motion range and stretching of the neck and the extremities), relaxation (lying supine on the water and slow swimming), and out-of-pool exercises (bending back and forth, squatting, and relaxing with deep breaths) for a period of 35 min.

Intervention 2: Usual care (n=22)

Warm balneotherapy pool sessions of 35 minutes 3 times a week for 12 weeks.

Fibromyalgia

Mean 43.5 (6.32) years, 43.91

Duration of pain not described

At 12 weeks (post-intervention) and 24 weeks follow up:

Pain reduction
Quality of life
Physical function
Psychological distress
Discontinuation

Table 9Summary of studies included in the evidence review

Study	Intervention and comparison	Population	Outcomes	Comments
Baptista 2012²⁷	16 week interventions: Intervention 1: Mind-body exercise (n=40) 1 hour belly dance class twice a week for 16 weeks. Each class had a maximum of 8 students and was led by physiotherapists. Classes began with warm up, followed by movements for the day, choreography and a cool-down exercise. Participants also received a disc with music and an exercise book with all movements for the programme. From the 4th week a set sequence of movements in the form of choreography was established for training at home. Intervention 2: Usual care (n=40) Offered intervention at the end of study.	Women with fibromyalgia (n=80) Mean age 49.3 years Pain duration not stated	At 32 weeks (follow up, including 16 week intervention): Pain reduction Quality of life Physical function Psychological distress Discontinuation
Bojner-Horwitz, 2003³⁸	12 week interventions. Intervention 1: Mind-body exercise (n=20) Dance and movement therapy consisted of four main themes including; awareness of the body; movement expressions; movement, feeling, image; and differentiation of feelings and integration 1 hour session, held weekly for 6 months. Intervention 2: Usual care (n=16) Participants received the intervention on completion of the study.	Women with fibromyalgia (n=36) Mean age 57 years Duration of pain not stated	Discontinuation at 6 months
Carson 2010⁵³	8 week interventions. Intervention 1: Mind-body exercise (n=25) Yoga consisted of 2 hour sessions, held weekly for 8 weeks in a group based format led by a certified, experienced yoga teacher. The intervention included meditation, breathing exercises, study of the application of yoga principles to optimal coping and gentle stretching poses and group discussions. Intervention 2: Usual care (n=28) Wait list.	Fibromyalgia (n=53) All females Mean age: 53.7 (SD 11.5) years Duration of pain: not reported	At 8 weeks (post intervention): Quality of life Physical function (additional outcome) Discontinuation (additional outcome)	In Cochrane review (Theadom 2015)
Carson 2012⁵⁴	8 week interventions. Intervention 1: Mind-body exercise (n=25) Yoga delivered within group sessions by a certified yoga instructor 120 minute sessions, delivered weekly over 8 weeks. Intervention 2: Usual care (n=28) Wait list.	Fibromyalgia (n=53) All females Mean age: not reported Duration of pain: not reported	At 8 weeks (post-intervention): Quality of life Pain (additional outcome) Discontinuation (additional outcome)	In Cochrane review (Theadom 2015)
Haak 2008¹¹⁸	7 week interventions Intervention 1: Mind-body exercise – Qigong (n=29) Total Qigong time 711.5 hours. Participants were instructed to practice Qigong at home with the support of a free instruction tape, twice a day for 20 minutes. Supervisors of the intervention were experienced Qigong masters. The sessions included internal and external methods of Qigong (influenced by oneself and influenced by the Qigong master). Intervention 2: Usual care (n=28)	Women with fibromyalgia (n=57) Mean age 53 years Mean duration of symptoms 15 years	At 7 weeks (follow up, including 4 week intervention): Pain reduction Quality of life Psychological
Holmer 2004¹²⁴	12 week interventions. Intervention 1: Mind-body exercise -Yoga (n=11) Delivered by a certified yoga instructor. No further details Intervention 2: Usual care (n=17) No further details.	Fibromyalgia (n=28) Age range 18 to 65 years Pain duration not specified	At 12 weeks (post-intervention): Pain Physical function Psychological distress Sleep
Lauche 2016¹⁶⁰	12 week interventions Intervention 1: Mind-body exercise - Tai Chi (n=38) Participants in the Tai Chi group met once weekly for a 75- to 90-minute session. The Tai Chi intervention was on the basis of a popular and internationally recognized Yang style (13 forms from Mantak Chia). Each session included a warm-up of 5 to 10 minutes, the Tai Chi form practice, and 5 to 10 minutes of relaxation at the end. Tai Chi forms followed explicit protocols outlined in a training manual, as required during teacher training certification. Sessions also included educational units and breathing exercises, and they were accompanied by relaxation music. Participants received illustrated written information that covered movement sequences learned in the previous session. They were asked to practice Tai Chi outside of classes for at least 15 minutes each day. Intervention 2: Usual care (n=39) Participants in this group were advised to continue their usual activities and therapies, but not to initiate any new therapeutic regimen for symptom management.	Chronic non-specific neck pain (n=114; third arm of study reported under strength, proprioception and flexibility versus mind-body and strength, proprioception and flexibility versus usual care comparisons) Mean age 50.94 years Mean pain duration not stated.	At 12 weeks (post-intervention) and 24 weeks (follow up): Pain reduction Quality of life Physical function Psychological distress Discontinuation	VAS score of 45 or higher (0–100) inclusion criteria.
Liu 2012¹⁶⁶	6 week interventions. Intervention 1: Mind-body exercise (n=7) Qi-gong delivered in a group based format with home practice in between sessions 15 to 20 minute sessions, held weekly for 6 weeks. Intervention 2: Usual care (n=7) Sham qi-gong delivered in a group based format with no meditation or healing sounds 15 to 20 minute sessions, held weekly for 6 weeks.	Fibromyalgia (n=14) Sex not reported Age: 18–70 years Duration of pain: not reported	At 6 weeks (post-intervention): Discontinuation	In Cochrane review (Theadom 2015) Query sham qi-gong
Lynch 2012¹⁷²	8 week interventions. Intervention 1: Mind-body exercise (n=53) Qi-gong delivered by a psychologist in a group based format in the community 3.5 day workshops held weekly with additional refresher sessions. Intervention 2: Usual care (n=47) Wait-list control.	Fibromyalgia (n=100) Sex not reported Age: not reported Duration of pain: not reported	At post-intervention (8 weeks) and 6 month follow-up: Pain Discontinuation (additional outcome)	In Cochrane review (Theadom 2015)
Mannerkorpi 2004¹⁷⁴	14 week interventions. Intervention 1: Mind-body exercise (n=19) Qi-gong + relaxation, 14 group sessions of 1.5 hours, were held weekly, delivered by a physiotherapist. The treatment included various breathing, relaxation and concentration techniques conducted in a supine or standing position including qi-gong movements. The movements were individually modified to match the functional limitations of the patients and there was an opportunity for discussion about the movements with the therapist. Participants were encouraged to practice the movements in between sessions. Intervention 2: Usual care (n=17) No further details.	Fibromyalgia (n=36) All females Age: 18–65 years Duration of pain: not reported	At 14 weeks (post intervention): Quality of life Physical function Discontinuation (additional outcome)	In Cochrane review (Theadom 2015)
Michalsen 2012¹⁹²	9 week interventions Intervention 1: Mind-body exercise – Yoga (n=38) Weekly 90 minute yoga classes using a wide range of postures to enhance flexibility, alignment, stability and mobility in muscles joints and tendons, run by a certified yoga instructor and physician. The exercises specifically addressed neck pain complaints and each class built up on the previous one. Subjects were requested to practice at home for 10–15 minutes, 2 to 3 times a week. Intervention 2: Usual care (n=39) Waiting list control. A standard self-care manual about exercise and education for chronic neck pain was given. The manual described exercises that could be carried out to aid chronic neck pain and participants were asked to practice at home for 10–15 minutes at least 3 times a week.	Chronic non-specific neck pain (n=77) Mean age 47.9 years Mean pain duration 6.55 years	At 10 weeks (post-intervention) Pain reduction Quality of life Physical function Psychological distress Discontinuation	Pain score of at least 4 on VAS 0–10 scale.
Rendant 2011²²²	6 month interventions Intervention 1: Mind-body exercise – Qigong (n=42) Qigong was performed by three qualified teachers certified by the German Qigong Society. Each session of qigong took 90 minutes. Neiyanggong, a special silent and slow form of qigong was chosen by the therapist in a consensus process. The lessons started with up to 12 neck exercises followed by 9 exercises for the shoulder and finished with breathing and moving exercises. There were 18 sessions over a period of 6 months (1 session per week in the first 3 months, and biweekly sessions in the following 3 months) Intervention 2: Usual care (n=41) Waiting list control participants received no intervention.	Chronic non-specific neck pain (n=123; third arm of study reported under strength and flexibility versus usual care and strength and flexibility versus mind-body comparisons) Mean age 44.6 years Mean pain duration 3.1 years	At 6 months (post-intervention) Pain reduction Quality of life Physical function Discontinuation	Pain rating of 40 or more required at baseline (VAS 0–100)
Von trott 2009²⁷¹	12 week interventions (n=38) Intervention 1: Mind-body exercise - Qigong. Twenty-four sessions (each 45 minutes), held over a period of 12 weeks, in groups of 6–12 participants. Qigong lessons started with about 10 minutes of typical qigong ‘opening’ exercises, continued with up to 4 exercises of Dantian Qigong, and finished with about 10 minutes of ‘closing’ exercises. (n=40) Intervention 2: Usual care Waiting list control participants did not receive Qigong or exercise therapy.	Office workers with chronic neck pain (n=78) Mean age 76 years Mean pain duration 18.6 years	At 12 weeks (post-intervention) and 24 weeks follow up: Pain reduction Quality of life Physical function Psychological distress Discontinuation
Wong 2018²⁷⁸	12 week interventions Intervention 1: Mind-body exercise - Tai Chi (n=18) Supervised sessions 3 times a week for 12 weeks. In the first session, the instructor explained the theory behind tai chi and its procedures providing participants with printed materials on its principles and techniques. In subsequent sessions, participants practiced 10 forms from the classic Yang style of tai chi. The sessions lasted approximately 55 minutes and included a 10 minute warm up, 40 minutes of practice and exercise finalising with a final 5 minute cool down period. During the sessions, the participants’ heart rate was 40–50% of the HR reserve as they imitated the instructors’ motion at the same speed. HR during training sessions was monitored using a polar device. Intervention 2: Usual care (n=19) Participants did not participate in any supervised or unsupervised exercise protocol and were asked to maintain their regular lifestyle habits for the duration of the study.	Women with fibromyalgia (n=37) Mean age 51 years Mean pain duration 27.5 years	At 12 weeks (post-intervention): Pain reduction Sleep Discontinuation
Wu 1999²⁷⁹	10 week interventions Intervention 1: Mind-body exercise – Qigong (n=13) 6 sessions of qigong training with 2 recognised qigong masters. Sessions included musical compositions and visual images which were coded to represent specific organ systems which qi is believed to stimulate. Each session lasted 40 minutes twice a week for 3 weeks, followed by 7 weeks of home exercises on a daily basis. Intervention 2: Usual care (n=13) Involving sham qigong. 6 sessions of simulated qigong training led by a simulated qigong master, in order to maximise nonspecific treatment effects. Participants were shown visual images and listened to recorded music similar to that in the qigong group. After this time a simulated qi adjustment was performed by the facilitator. Each session lasted for 40 minutes. This was followed by 7 weeks of home exercises.	Complex regional pain syndrome type I (late-stage) (n=26) Mean age 38.5 years Duration of pain not reported	At 10 weeks (post-intervention) Pain reduction	Participants were required to have failed to achieve 50% pain reduction through drug therapy or palliative physical or chiropractic therapy

Table 10Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Assumpcao 2018²³

12 week interventions

Intervention 2: Flexibility (n=18)

Patients underwent a 12 week supervised exercise program of 40-minute sessions performed twice a week. Segmental active muscle stretching was conducted without therapist assistance. Large muscles were chosen for their role in the muscular chains of global posture. Patients started with three repetitions up to a maximum of 5 by week 9. The stretch was held until the point of moderate discomfort, for 30 seconds

Intervention 3: Usual care (n=16)

Usual medical treatment. After 12 weeks patients were reassessed and offered physical therapy based on stretching and resistance training.

Women with fibromyalgia (n=36)

Mean age 47 years

Mean pain duration not stated

At 12 weeks (post-intervention):

Pain reduction
Physical function
Discontinuation

60% were taking concomitant medication for fibromyalgia (antidepressants, analgesics, anti-inflammatories or psychotropic medication)

Table 11Summary of studies included in the evidence review

Study	Intervention and comparison	Population	Outcomes	Comments
Bircan 2008³⁴	8 week interventions. Intervention 1: Aerobic exercise (n=15) Aerobic exercise program comprised walking on treadmill, initially for 20 min and increasing up to 30 min as the patient tolerated. Exercise intensity was adjusted to generate heart rates equivalent to 60–70% of age-adjusted maxi- mum heart rates (220 ¡ age in years). Heart rate monitoring was performed by using a pulse oximeter (Nonin Medical, Inc., MN, USA). At the beginning and end of each session mild stretches were included for 5 min. Intervention 2: Strength training (n=15) Patients received a supervised, progressive physical training program in a group setting with muscle strength exercises performed in the standing, sitting, and lying positions. Exercises strengthened the upper and lower limb muscles and trunk muscles, initially with 4–5 repetitions and progressing to 12 repetitions gradually. Free weights and body weight were used for strength. Patients began with resistance levels they could do easily, and weight was increased gradually according to patient’s tolerance. Exercise sessions began with a low intensity warm up of marching in place and gentle stretching for 5 min, followed by 30 min of muscle strength, and concluded with 5 min of cool down and stretching.	Fibromyalgia (n=30) All female Mean age 47.2 years Mean pain duration 4.2 years	At 8 weeks (post intervention): Pain reduction Quality of life Psychological distress Sleep Discontinuation (additional outcome)	In Cochrane review (Bidonde 2017)
Ericsson 2016⁸⁰	12 week interventions Intervention 1: Aerobic exercise (n=17) Pool exercise programme. 50 minute sessions in groups of 6–8 participants twice a week for 12 weeks, supervised by a physiotherapist. Sessions included aerobic exercise with endurance, strength, flexibility, coordination and relaxation. Patients were instructed to exercise at their own rhythm and modify exercises with respect to thresholds of pain and fatigue. They were encouraged to increase intensity and resistance with or without water equipment, based on the rate of perceived exertion on the Borg scale. (n=17) Intervention 2: Strength training Twice a week sessions for 12 weeks with free weights and resistance machines in groups of 8–10 patients, supervised by a physiotherapist. The sessions lasted approximately 1 hour and include exercises for multiple main muscle groups. Load was increased from 40% to 80% of one repetition maximum established at baseline. Participants performed 3 sets with 15–20 repetitions of each exercise, when the load increased they performed 2 sets but fewer repetitions. All sessions started with 10 minute warm up on an ergometer bicycle.	Fibromyalgia (n=34) All male Mean age 59 years Mean pain duration 5.3 years	At 12 weeks (post intervention): Pain reduction Quality of life Physical function Psychological distress Discontinuation
Hooten 2012¹²⁵	3 week interventions. Intervention 1: Aerobic exercise (n=36) Stationary bicycle exercises supervised by a physical therapist. Sessions also had a warm up and cool down and intensity of exercises was gradually increased to achieve 70–75% of maximal heart rate based on age. Exercise started at 10 minutes daily during week 1 (5 times a week), 15 minutes in week 2 and up to 20 to 30 minutes daily during week 3. Intervention 2: Strength training (n=36) Upper and lower body strengthening exercises were performed daily using resistive techniques, all supervised by a physical therapist with experience in treating patients with fibromyalgia. Each daily strength training session was 25–30 minutes in duration and also involved a warm up and cool down period. Participants were encouraged to train at the maximal amount of load tolerated, using one set of 10 repetitions.	Fibromyalgia (n=72) Mean age 46.5 years Mean pain duration 12.5 years	At 3 weeks (post-intervention): Pain reduction Discontinuation
Kayo 2011¹⁴²	16 week interventions. Intervention 1: Aerobic exercise (n=30) Supervised indoor or outdoor walking, three times a week for 60 minutes (5–10 minutes stretching, walking and 5 minutes cool down). Intervention 2: Strength training (n=30) Supervised exercise protocol consisting of 11 free active exercises for upper and lower limbs and trunk muscles, with free weights and body weight performed in the standing, sitting, and lying positions. Sessions were three times a week for 60 minutes. Exercise load and intensity increased every 2 weeks. Participants in all groups were asked to discontinue tricyclic antidepressants but were allowed to use acetaminophen (paracetamol) for pain	Fibromyalgia (n=60) All female Mean age: 47.7 (5.3); 46.7 (6.3); 46.1 (6.4) years Duration of pain: 4.0 (3.1); 4.7 (5.7); 5.4 (3.5) years	At 28 weeks (follow up, including 16 weeks intervention): Quality of life Pain	In Cochrane review (Bidonde 2017)
Sevimli 2015²⁴²	12-week interventions. Intervention 1 and 2 pooled. Intervention 1: Aerobic exercise – Swimming (n=25) Pool based aquatic aerobic exercise programme with group therapy 2 times a week. Duration was 40 minutes in the first month, 45 in the second month and 50 minutes in the final month. Intervention 2: Aerobic exercise - Other aerobic exercise (n=25) Gymnastic-based aerobic exercise programme with group therapy 2 times a week. Duration was 40 minutes in the first month, 45 in the second month and 50 minutes in the final month. No further details. NB Aerobic exercise interventions pooled in the analysis. Intervention 3: Strength training (n=25) Isometric strength and stretching exercise program lasting 15 minutes per day. Three minute loadings with 30 seconds rest between 3 sets of low to moderate intensity were repeated in the first month of the exercise programme, and in the second month this was increased to high intensity loadings of 4 sets, and in the third month rest intervals were reduced to 10 seconds with 5 sets of 3 minute loadings.	Women with fibromyalgia (n=75) Mean age 35 years Mean pain duration not specified	At 12 weeks (post-intervention) Pain reduction Quality of life Physical function Psychological distress

Table 12Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Mannerkorpi 2009¹⁷⁶

20 week interventions

Intervention 1: Aerobic exercise (n=20)

60 minutes 3 times weekly. After a 10-minute preliminary warm-up exercise, patients were subjected to sustained heart rate elevation training through the use of a bicycle ergometer. Heart rates were maintained in excess of 150 beats per minute for gradually increasing time periods, and were monitored with a Sanyo HRM-97E digital pulse meter.

(n=20) Intervention 2: Flexibility.

Participants met at similar intervals but at different times over the same 20-week observation period. Instruction was administered in a group setting by the same instructors as for CVR training, but consisted only of flexibility manoeuvres, such that sustained heart rate responses greater than 115 beats per minute were not attained.

Women with fibromyalgia (n=40)

Mean age 42 years

Duration of pain not specified

At 20 weeks post-intervention):

Pain reduction

Medication for pain discontinued at least 3 weeks before entry into the trial (patients receiving amitriptyline within the previous 3 months were excluded).

Paracetamol allowed if required.

Mccain 1986¹⁸² ¹⁸³

20 week interventions

Intervention 1: Aerobic exercise (n=18)

Three times a week programme. Participants had sustained heart rate elevated training via a bicycle ergometer. Heart rates were maintained in excess of 150 beats per minute for gradually incremental durations.

(n=16) Intervention 2: Flexibility

Participants met at similar intervals to the aerobic group. Exercise consisted of flexibility manoeuvres such that sustained heart rate responses were over 115 beats per minute were not attained.

Fibromyalgia (n=34)

Mean age 43 years

Duration of pain not specified

At 20 weeks (post-intervention):

Pain reduction

Valim 2003²⁵⁹

20 week interventions

Intervention 1: Aerobic exercise (n=38)

Walking programme monitored and supervised by a physiotherapist 3 times a week, with 45 minute duration for 20 weeks. Speed was determined by the training heart rate Patients cool down after each session consisted of making rhythmic movements to promote cooling off for 5 minutes.

Intervention 2: Flexibility (n=38)

3 sessions a week of 45 minute duration including 17 stretching exercises using both muscles and joints. Each position sustained for maximum 30 seconds (supervised by physiotherapist).

Women with fibromyalgia (n=76)

Mean age 46.8 years

Pain duration not specified

At 10 and 20 weeks (post-intervention):

Pain reduction
Quality of life
Psychological distress
Discontinuation

Acetaminophen allowed as rescue treatment.

Table 13Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

de Medeiros 2020⁶⁹

12 week interventions.

Intervention 1: Aerobic exercise (n=21)

Aquatic aerobics involved six main exercises lasting 30 min with different intensities. Two warm-up exercises and two cool-down exercises were performed before and after the program. Each session lasted 40 minutes.

Intervention 2: Biomechanical exercise (n=21)

Mat Pilates was used in groups of up to 4 women. The focus of the sessions was on centralization, concentration, control, precision, breathing and flow. Nine exercises were performed for the main muscle groups with progressions each month. The exercises were initially performed in 1 series of 8 repetitions in the first month. Then they were performed in 2 sets of 10 repetitions in the second month. Finally, they were performed in 3 sets of 8 repetitions in the last month. Three Swiss ball relaxation exercises were performed in 1 set of 30 s each (Fig. 2a.10 to a.12) at the end of each session. Each session lasted 50 minutes.

Women with fibromyalgia (n=42)

Mean age: 50.7 (9.7); 45.5 (10.6) years

Duration of pain not reported

At 12 weeks (post-intervention)

Pain
Quality of life
Psychological distress
Sleep
Discontinuation

Table 14Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Sanudo 2010²³⁴

24 week interventions.

Intervention 2: Mixed modality exercise (n=21)

Combined supervised aerobic exercise and resistance exercise. Resistance included 1 set of 8–10 reps for 8 different muscle groups with a load of 1–3 kg, flexibility included 1 set of 3 reps of 8–9 different exercises, maintaining stretch position for 30 seconds. The exercises focused on main areas of pain in patients with fibromyalgia (deltoids, biceps, neck (trapezius), hops (gluteus, quadriceps), back/chest/torso (latissimus dorsi, pectoralis major, and abdominals)). Twice a week, each session including 10 minutes warm-up, 10–15 minutes aerobic exercise, 15–20 minutes resistance, 10 minutes flexibility.

Intervention 1: Aerobic exercise (n=22)

Warm-up included slow walks, easy movements of progressive intensity, steady state aerobics included continuous walking with arm movements and jogging, interval training included aerobic dance and jogging, cool-down included slow walks, easy movements, relaxation training. Twice a week for 45–60 minutes (10 minutes warm-up, 5–10 minutes cool down, 15–20 minutes steady aerobics, 15 minutes interval training).

Fibromyalgia (n=64 ; third arm of study reported under aerobic versus usual care comparison)

Females only

Mean age: 55.9 (1.6); 55.9 (1.7); 56.6 (1.9) years

Duration of pain: not specified

At 24 weeks (post intervention):

Quality of life
Psychological distress
Discontinuation

In Cochrane review (Bidonde 2017)

Table 15Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Giubilei 2007¹⁰⁶

18 week interventions

Intervention 1: Aerobic and Strength exercise (n=52)

18 week walking program, 3 times per week. Each exercise session included a warm up and cool down regimen of slow paced walking, specific postural muscle and isometric strengthening exercises, and 40 minutes of fast paced walking on in-outdoor track, at 70–80% of maximum heart rate

Intervention 2: Flexibility (n=51)

Participants participated in a flexibility and motion exercise program for the same period of time and frequency as the aerobic group. Patients were instructed about the correct exercise execution and were advised to maintain their heart rate under 110bpm. Exercises were simply stretches with some motion exercises such as leg lifts.

Men with chronic prostatitis/chronic pelvic pain syndrome (n=103)

Mean age 36.7 years

Mean pain duration 5.72 years

At 6 weeks and18 weeks (post-intervention):

Pain reduction
Quality of life
Psychological distress
Discontinuation

Table 16Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Wang 2018²⁷⁴

24 week interventions

Intervention 1: Aerobic exercise and flexibility (n=75)

Each session lasted 60 minutes and ran twice a week for 24 weeks. Participants were encouraged to integrate at least 30 minutes of aerobic exercise into their daily routine during the intervention, and to continue this throughout the 52 week follow up. Sessions were closely supervised in a group format and were moderate intensity. Each session consisted of an active warm-up, choreographed aerobic training that progressed gradually from low to moderate intensity and a cool down involving low intensity movements and dynamic and static stretching. During the first week there was a 15 minute warm up, 20 minutes of aerobic training and 25 minutes of cool-down, which increased to 40 minutes of aerobic training by week 10 to (at 60–70% of estimated maximum heart rate).

Intervention 2: Mind-body exercise - Tai Chi (n=36)

Each session lasted 60 minutes and ran twice a week for 24 weeks. Participants were encouraged to integrate at least 30 minutes of tai chi into their daily routine during the intervention, and to continue this throughout the 52 week follow up. Sessions were run by experienced instructors and sessions were recorded to monitor quality and provide feedback to instructors. Participants also received printed materials on tai chi principles and fibromyalgia. The sessions included warm up, meditative movements, breathing techniques and various relaxation methods.

Fibromyalgia (n=111)

Mean age 51 years

Duration of pain 12.5 years

At 1 year follow up (including 24 week intervention):

Quality of life
Pain reduction
Physical function
Psychological distress
Sleep
Discontinuation

Table 17Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Gomez-Hernandez 2020¹⁰⁸

12 week interventions.

Intervention 1: Aerobic exercise and stretching (n=32)

Aerobic exercise was identical to intervention 2 (as described). Additionally, 45 minutes of stretching was carried out once per week. Each session consisted of three repetitions of 10 seconds for each trunk muscle and two repetitions of 10 seconds for each extremity muscle. After each repetition, there was a 10-second pause.

Intervention 2: Aerobic exercise (n=32)

Supervised cycling, with each session consisting of 2-minute cycling warm-up and 10 minutes of moderateintensity cycling (50%–70% of predicted maximum heart rate). Three times per week for 12 minutes.

Women with fibromyalgia (n=64)

Mean age: 54.27 (6.94) years

Duration of pain not reported

At 4 weeks and 12 weeks (post-intervention)

Pain
Quality of life
Sleep
Discontinuation

4 week outcomes are measured before end of intervention.

Table 18Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Carvalho 2020⁵⁵

7 week interventions

Intervention 1: Aerobic, strength, mind-body and proprioception (n=16)

An exergame programme performed on a Nintendo Wii system. The programme consisted of 6 sub games, which included jogging, a game involving active movement of the upper limbs in isolation from weight and balance training, yoga, a Hula Hoop game involving action of the trunk muscles and balance control, a step game involving alternating movements of lower limbs and balance, and a stationary walking game. This was performed three times per week for 1 hour.

Intervention 2: Flexibility (n=19)

Chain muscle stretching technique, which involved 9 stretching positions, held for 4 deep and prolonged breaths. These positions were chosen to include standing, sitting and lying positions, and to engage all muscle groups. The sessions were performed 3 times per week for 1 hour.

Women with fibromyalgia (n=35)

Mean age: 55.64 (9.16); 47.70 (15.46) years

Duration of pain: 9.91 (7.29); 14.65 (12.14) years

At 7 weeks (post-intervention)

Qualtiy of life
Physical function
Discontinuation

Table 19Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Lansinger 2013¹⁵⁷

12 week interventions

Intervention 1: Strength training (n=62)

Exercise therapy was performed individually and the training programme was adjusted for each participant. A physiotherapist instructed the participants throughout the training programme, which focused mainly on the cervical and shoulder/thoracic region. Each training session started with a warm up on a stationary bicycle for about 10 minutes, followed by 40 minutes of dynamic exercises. These exercises consisted of active movements aimed to increase range of motion in all neck directions and muscle exercises aimed to maintain/increase circulation, endurance and strength. The amount of load was individualised and was maintained within pain tolerance (aimed not to increase pain). The load at the muscle exercises was to achieve between 30% and 70% of maximum muscle capacity and was gradually increased as endurance and strength were gained. The exercises were performed with low resistance, allowing 20–30 repetitions of maximal voluntary contractions in three sets. 12 sessions in 3 months.

Intervention 2: Mind-body exercise – Qigong (n=60)

10–12 1 hour sessions conducted on a weekly or biweekly basis over 3 months. Qigong was performed according to medical qigong which is a modality of traditional Chinese medicine and is a way of affecting and directing qi (energy) for medical benefit. Each qigong exercise includes body posture and gentle movement, meditation (concentration) and purposeful relaxation, breathing regulation practice and self-administered massage. Qigong was conducted in groups of 10–15 participants.12 sessions in 3 months.

Non-specific neck pain for at least 12 weeks (n=122)

Mean age 43.8 years

Duration of pain: 60% for 1–10 years

At 12 weeks post-intervention):

Discontinuation

Inclusion criteria minimum VAS rating of 20 (0–100 scale)

Both groups received verbal ergonomic advice for both work and free time, as well as an information pamphlet on neck pain

Ulug 2018²⁵⁷

6 week interventions.

Intervention 1: Strength exercise (n=20)

Isometric exercise. In the sitting position, participants were instructed to place their hands firstly on the front (then the other sides) of their heads and push forward, but resist any movement of the head while maintaining the head and neck in the neutral position for 5 s. They were encouraged to do these exercises in 2 sets of 30 repetitions per day.

Intervention 2: Mind-body exercise (n=20)

Four Iyengar yoga exercises were taught to participants. They were told to maintain each yoga posture starting from at least 10–20 s in the following days. They were encouraged to do these exercises in 2 sets of 10 repetitions per day.

Chronic neck pain (>3 months) (n=60)

Mean age: 44.6 (4.3); 35.9 (9.8)

Duration of pain: 58.8 (63.3); 56 (60.1) months

At 6 weeks (follow-up):

Pain

All participants also received physical therapy 5 days a wweek for 3 weeks, including hot pack, ultrasound and conventional transcutaneous electrical nerve stimulation (TENS)

Table 20Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Ulug 2018²⁵⁷

6 week interventions.

Intervention 1: Strength exercise (n=20)

Intervention 2: Biomechanical (n=20)

Pilates involved participants being taught how to activate their deep abdominal muscles (transversus abdominis and multifidus) using visual imagery, verbal cueing or demonstrations. Five key elements of Pilates, including lateral costal breathing, centering (pelvic placement), ribcage placement, shoulder blade placement, head and neck placement, were taught. Four Pilates beginner mat exercises, including double-leg stretch level, shoulder bridge level, arm openings level and breast stroke level, were taught and patients were encouraged to perform these exercises in 2 sets of 10 repetitions per day.

Chronic neck pain (>3 months) (n=60)

Mean age: 44.6 (4.3); 38.7 (7.9)

Duration of pain: 58.8 (63.3); 55.1 (47) months

At 6 weeks (follow-up):

Pain

All participants also received physical therapy 5 days a week for 3 weeks, including hot pack, ultrasound and conventional transcutaneous electrical nerve stimulation (TENS)

Table 21Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Assumpcao 2018²³

12 week interventions

Intervention 1: Strength training (n=19)

12 week supervised resistance training programme of 40-minute sessions performed twice a week with progressive overload. Equipment included dumbbells, shin pads. No load was used in the first 2 sessions, after which time 0.5kg was added each week if the patient identified the effort as slightly intense on the Borg scale. 8 repetitions for: triceps, quadriceps, hip adductors and abductors, hip flexors, elbow flexors and extensors, pectoralis major and rhomboids.

Intervention 2: Flexibility (n=18)

Women with fibromyalgia (n=37)

Mean age 47 years

Mean pain duration not stated

At 12 weeks (post-intervention):

Pain reduction
Physical function
Discontinuation

60% were taking concomitant medication for fibromyalgia (antidepressants, analgesics, anti-inflammatories or psychotropic medication)

Gavi 2014¹⁰⁰

16 week interventions

Intervention 1: Strength training (n=40)

45 minute sessions 2 times a week for 16 weeks. Supervised progressive training in standing and sitting positions using weight machines. Moderate intensity with load of 45% the estimated maximum. Multiple muscle groups were trained in 12 different exercises, with 3 sets of 12 repetitions

Intervention 2: Flexibility (n=40)

45 minute sessions 2 times a week for 16 weeks. Stretching of the major muscles. No further details.

Women with fibromyalgia (n=80)

Mean age 47.61 years

Mean pain duration not specified

At 16 weeks (post-intervention):

Quality of life
Discontinuation

7% were taking benzodiazepines or amitriptyline concurrently

Jones 2002¹³⁶

12 week interventions.

Intervention 1: Strength training (n=28)

Supervised dynamic resistance exercise for lower and upper limbs and trunk using hand weight (1–3 lb (0.45–1.36 kg)) and elastic tubing; minimization of eccentric work (a videotape to guide home practice of the strengthening exercise regimen was provided to participants). Twice a week for 60 minutes, progressing from 4–12 reps.

Intervention 2: Flexibility (n=28)

Supervised static stretches (a videotape to guide home practice of the flexibility exercise regimen was provided to participants). Twice a week for 60 minutes.

Fibromyalgia (n=56)

All females

Mean age: 46.4 (8.6) to 49.2 (6.3) years

Duration of pain: 6.9 (6.6) to 7.7 (5.5) years

At 12 weeks (post intervention):

Pain
Physical function
Psychological distress
Sleep

In Cochrane review (Busch 2013)

Table 22Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Salo 2012²³⁰

12-month interventions

Intervention 1: Combined strength training and flexibility (n=49)

Participants used elastic rubber bands attached around the head for the isometric neck strength exercises. During each session they performed a series of 15 repetitions directly forward, obliquely toward the right and left and directly backwards. The aim was to reach the level of resistance that was 80% of the patient’s maximum isometric neck strength. In each exercise session, the patients also performed a single series of 15 repetitions of dynamic exercises for the shoulders and upper extremities with an individually adjusted highest load. These exercises involved shrugs, presses, curls, bent over rows, flyers and pullovers using dumbbells. The training programme also involved a single series of squats, sit ups and back extension exercises that used only the patient’s own body weight; these exercises were performed until muscle tiredness. The training session included stretching exercises for the neck, shoulder, and upper limb muscles with the exercise for each muscle lasting 30 seconds and repeated 3 times. Supervised meetings were conducted once a week for 6 weeks, then one session was conducted every second month for a total of 10 sessions over the 12 month period. Each group had 6–8 participants.

Intervention 2: Flexibility (n=52)

Those in the stretching group performed the same stretching exercises to the other group.

Chronic non-specific neck pain (n=101)

Mean age 40.5 years

Duration of pain 62 months

At 12 months post-intervention):

Quality of life
Discontinuation

Both groups were instructed to perform their exercises at home regularly three times a week and to keep a weekly exercise diary throughout the year. Both groups received written information about the exercises.

Table 23Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Cramer 2013⁶⁵

9 week interventions.

Intervention 1: Strength and flexibility exercise (manual based) (n=26)

Participants received a self-care manual to relieve neck pain and stiffness. The manual described and depicted a staged seated exercise program for the neck and shoulder region. The program began with taking a proper upright sitting posture, followed by stretching exercises for the neck and shoulders. Then, strength exercises and isometric exercises for the neck-shoulder region were performed. Patients were required to practice at home for 10 minutes each day and to record their practice in a diary.

Intervention 2: Mind-body exercise – Yoga (n=25)

90 minute weekly classes of 10–15 participants over 9 weeks. Designed for patients with chronic neck pain without previous experience in yoga. Each class consisted of 8 to 11 yoga postures chosen from a pool of 14 standing, sitting and supine postures, starting with relatively simple postures and succeeding to more complex ones. The focus of postures was given on lengthening and strength muscles of the neck and shoulder region and to improve stability and posture. Patients were required to practice at home for 10 minutes each day. Patients received a manual describing and depicting 3 basic standing and 3 basic sitting postures.

Non-specific neck pain for at least the previous 12 weeks (n=51)

Mean age 47.8 years

Duration of pain 8.1 years

At 9 weeks (post intervention):

Pain reduction
Quality of life
Physical function
Discontinuation

Participants in both groups were allowed to continue their usual pain medication and physical activity. They were asked not to change their treatment regimen during the course of the study and to daily record pain medications and other treatments for neck pain in their diaries.

Rendant 2011²²²

6 month interventions

Intervention 1: Strength and flexibility training (n=39)

Exercise therapy was carried out by 6 qualified therapists. The exercises was based on a standard programme for chronic pain. Each lesson started with a warm up using a softball and was followed by repeated active cervical rotations and strengthening and flexibility exercises. The individual’s pain level was not exceeded. There were 18 sessions over a period of 6 months (1 session per week in the first 3 months, and biweekly sessions in the following 3 months).

Intervention 2: Mind-body exercise – Qigong (n=42)

Qigong was performed by three qualified teachers certified by the German Qigong Society. Each session of qigong took 90 minutes. Neiyanggong, a special silent and slow form of qigong was chosen by the therapist in a consensus process. The lessons started with up to 12 neck exercises followed by 9 exercises for the shoulder and finished with breathing and moving exercises. There were 18 sessions over a period of 6 months (1 session per week in the first 3 months, and biweekly sessions in the following 3 months).

Chronic non-specific neck pain (n=123; third arm of study reported under strength and flexibility versus usual care and mind-body versus usual care comparisons)

Mean age 44.6 years

Mean pain duration 3.3 years

At 6 months (post-intervention)

Pain reduction
Quality of life
Physical function
Discontinuation

Pain rating of 40 or more required at baseline (VAS 0–100)

Von trott 2009²⁷¹

12 week interventions

Intervention 1: Strength and flexibility training (n=39)

24 sessions (each 45 minutes) at 2 sessions per week with groups of 6–12. A standardised programme for computer and workplace related neck pain. It included repeated active cervical rotations as well and strength and flexibility exercises. Special intention as paid so that the patients’ individual pain limits were not exceeded. About 90% of the exercises were repeated in each lesion; some 10% was exchanged regularly.

Intervention 2: Mind-body exercises – Qigong (n=38)

Twenty-four sessions (each 45 minutes), held over a period of 12 weeks, in groups of 6–12 participants. Qigong lessons started with about 10 minutes of typical qigong ‘opening’ exercises, continued with up to 4 exercises of Dantian Qigong, and finished with about 10 minutes of ‘closing’ exercises.

Office workers with chronic neck pain (n=77)

Mean age 76 years

Mean pain duration 18.6 years

At 12 weeks (post-intervention) and 24 weeks follow up:

Pain reduction
Quality of life
Physical function
Psychological distress
Discontinuation

Table 24Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Lauche 2016¹⁶⁰

12 week interventions

Intervention 1: Strength, proprioception and flexibility training (n=37)

Intervention 2: Mind-body exercise - Tai Chi (n=38)

Participants in the Tai Chi group met once weekly for a 75- to 90-minute session. The Tai Chi intervention was on the basis of a popular and internationally recognized Yang style (13 forms from Mantak Chia). Each session included a warm-up of 5 to 10 minutes, the Tai Chi form practice, and 5 to 10 minutes of relaxation at the end. Tai Chi forms followed explicit protocols outlined in a training manual, as required during teacher training certification. Sessions also included educational units and breathing exercises, and they were accompanied by relaxation music. Participants received illustrated written information that covered movement sequences learned in the previous session. They were asked to practice Tai Chi outside of classes for at least 15 minutes each day.

Chronic non-specific neck pain (n=114; third arm of study reported under mind-body versus usual care and strength, proprioception and flexibility versus mind-body comparisons)

Mean age 49.53 years

Mean pain duration not stated

At 12 weeks (post-intervention) and 24 weeks (follow up):

Pain reduction
Quality of life
Physical function
Psychological distress
Discontinuation

VAS score of 45 or higher (0–100) inclusion criteria.

Table 25Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Gallego Izquierdo 2016⁹⁷

8 week interventions

Intervention 1: Strength training (n=14)

Cranio-cervical flexion training led by physiotherapists. Low load training of flexor muscles to target deep flexors and aiming to minimize the activation of the superficial flexor muscles. The patient initially performed CCF to sequentially reach 5 pressure targets in 2 mmHg increments from a baseline of 20 mmHg to the final level of 30 mmHg. Once one set of 10 repetitions of 10 s was achieved at one target level, the exercise was progressed to train at the next target level up to the final target of 10 repetitions of 10 s at 30 mmHg. The exercise load prescribed to each patient was based on their assessment performance. Participants were taught to do exercises at home without biofeedback

Intervention 2: Proprioceptive exercise (n=14)

Participants trained in cervical proprioception following the protocol described by Revel et al. This regime consisted of exercises of head relocation, eye-follow, gaze stability and eye-head coordination. All active movements of the cervical spine (flexion, extension, rotation, lateral flexion) were performed. All exercises were progressed by increasing the speed and range of motion of the target and with participants in a standing position.

Chronic non-specific neck pain for at least 3 months (n=28)

Mean age 29.2 years

Mean duration of pain not specified

At 8 weeks (post-intervention):

Pain reduction
Physical function

Table 26Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Calandre 2009⁵⁰

6 week interventions.

Intervention 1: Mind-body exercise (n=39)

Tai chi was performed in a pool with water heated at 36 ° and was preceded by a shower with warm water to condition patients’ bodies. A trained physiotherapist adjusted the movement intensity to meet individual needs and participants were taught the 16 movements which constitute tai chi therapy. Both groups received 18 sessions of 60 minutes, delivered 3 times per week for 6 weeks.

Intervention 2: Flexibility (n=42)

Stretching was facilitated using supportive aids such as long wooden sticks, flexible strings and tubes to stretch muscles in the cervical, upper and lower extremities and trunk. Both groups received 18 sessions of 60 minutes, delivered 3 times per week for 6 weeks.

Fibromyalgia (n=81)

Female:Male 73:8

Age: 32 to 69 years

Duration of pain: not reported

At 3 months (follow-up):

Quality of life
Psychological distress
Sleep
Discontinuation (additional outcome)

In Cochrane review (Theadom 2015)

Table 27Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Ulug 2018²⁵⁷

6 week interventions.

Intervention 1: Mind-body exercise (n=20)

Intervention 2: Biomechanical (n=20)

Chronic neck pain (>3 months) (n=60)

Mean age: 35.9 (9.8); 38.7 (7.9)

Duration of pain: 56 (60.1); 55.1 (47) months

At 6 weeks (follow-up):

Pain

All participants also received physical therapy 5 days a week for 3 weeks, including hot pack, ultrasound and conventional transcutaneous electrical nerve stimulation (TENS)

Table 28Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Richards 2002²²⁴

12 week interventions

Intervention 1: Flexibility and relaxation (n=67)

Comprised of upper and lower limb stretches and relaxation techniques based on the published regimen by Ost. As the classes continued more techniques were introduced progressing through progressive muscle relaxation, release only relaxation and visualisation, cue controlled relaxation, and differential relaxation. This occupied the whole one hour class. The sessions were carried out twice weekly.

Intervention 2: Aerobic exercise (n=69)

Both groups met in hour-long classes of up to 18 individuals twice weekly for 12 weeks. The interventions were carried out by personal trainers. Exercise therapy comprised an individualised aerobic exercise programme, mostly walking on treadmills and cycling on exercise bicycles. Each individual was encouraged to increase the amount of exercise steadily as tolerated. When people first started classes they usually did two periods of exercise per class lasting six minutes. By 12 weeks they were doing two periods of 25 minutes at an intensity that made them sweat slightly while being able to talk comfortably in complete sentences.

Fibromyalgia (n=136)

Mean age 46.5 years

Duration of pain 5 years (median)

Quality of life (12 months)
Discontinuation (12 weeks, post-intervention)

Participants continued their medication at entry. They received standardised advice including an explanation of fibromyalgia and encouragement and were told that the exercise offered through prescription would improve their condition. Each week at the classes all individuals received an information leaflet covering an aspect of their condition.

Table 29Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Kibar 2015¹⁴⁷

6 week interventions

Intervention 1: Flexibility and proprioception exercises (n=35)

Balance exercises included postures that gradually reduced the base of support, dynamic movements that disturbed the centre of gravity, exercises that stressed the postural muscle groups and exercises that reduced sensory input (standing with eyes closed). Training was provided by an experienced physiotherapist for 20 sessions over a 4 week period (20 minutes for each session, 5 days/week). The group also received 5 minutes of static and 5 minutes of dynamic balance training with a KAT device 3 days/week. For flexibility, active static exercises were performed in order to enable compliance to exercise and its maintenance without being forced. Exercises were performed in 8 large muscle groups in three 60-second static stretching repetitions. Ten minutes of walking in place was also recommended as warm up.

(n=33) Intervention 2: Flexibility

As per the flexibility section of the combined intervention described above.

Fibromyalgia (n=68)

Mean age 48.14 years

Duration of pain not reported

At 6 weeks (post-intervention):

Quality of life
Psychological distress
Discontinuation

Table 30Summary of studies included in the evidence review

Study	Intervention and comparison	Population	Outcomes	Comments
Ericsson 2016⁸¹	15 week interventions Intervention 1: Strength training (n=67) Exercise sessions were twice a week for 15 weeks at physiotherapy premises and at a local gym and were supervised by experienced physiotherapists. The exercise program was standardized and performed in groups of five to seven participants but the load was adjusted individually. The exercise session started with 10 minutes of warm up followed by 50 minutes of resistance exercises focused on large muscle groups in all four extremities and trunk. The resistance exercise was initiated at 40 % of 1 repetition maximum (RM) and progressed up to 80 % of 1 RM during the 15 weeks. Possibilities for progression of loads were evaluated every 3–4 weeks. Forty-two participants (62.7 %) in the resistance exercise group reached exercise loads of 80 % of 1 RM while seven participants (10.4 %) reached exercise loads of 60 % of 1 RMv. This was followed by 10 minutes of stretching exercises (n=63) Intervention 2: Relaxation therapy Performed twice a week for 15 weeks, guided by experienced physiotherapists and conducted at physiotherapy premises in groups of five to eight participants. It was performed as autogenic training. which refers to a series of mental exercises including autosuggestion and relaxation. The relaxation therapy lasted for approximately 25 minutes, followed by stretching exercises.	Fibromyalgia (n=130) Aged 22 to 64 years Mean pain duration not specified	At 15 weeks (post-intervention): Pain reduction Quality of life Physical function Psychological distress Discontinuation
Fontaine 2010⁹⁴	12 week interventions. Intervention 1: Aerobic exercise (n=43) Walking (the most common form of life physical activity) and other forms (e.g., gardening/mowing the lawn) of household activity (e.g., vacuuming); and sports activity (e.g., cycling, swimming, field hockey). Frequency of 5–7 times per week for 60 minutes. Intervention 2: Education (n=26) Education, question and answer, and social support. Frequency of once per month for 90–120 minutes.	Fibromyalgia (n=69) All female Mean age: 46.4 (11.6); 49 (10.2) years Duration of pain: 5.9 (5.1); 9.6 (6.8) years	At 12 weeks (post intervention): Quality of life Pain Physical function Psychological distress Discontinuation	In Cochrane review (Bidonde 2017)
Gavish 2006¹⁰¹	8 week interventions Intervention 1: Strength training (n=10) Chewing exercise. Two units of sugarless chewing gum were chewed three times daily for 10 minutes (weeks 1 and 2), increasing to 15 minutes three times daily (weeks 5 and 6), and 30 minutes 3 times daily (weeks 7 and 8). Patients were instructed to chew at their own rate. All patients received a detailed explanation of their disorder, its cyclic nature and possible aetiology at the initial examination. They then received a detailed description of the chewing exercise protocol (at session 1). Sessions 2, 3, and 4 were to report patient’s condition, reassurance, support, and encouragement. They also reported their performance. Intervention 2: Pain education (n=10) All patients received a detailed explanation of their disorder, its cyclic nature and possible aetiology at the initial examination. Sessions 2, 3, and 4 were to report patient’s condition, reassurance, support, and encouragement.	Masticatory muscle pain for at least 6 months (n=20) Mean age 27.2 years Duration of pain not reported	At 8 weeks (post-intervention): Pain reduction Discontinuation	Inclusion criteria of age 20–45 years
Jones 2012¹³⁶	12 week interventions. Intervention 1: Mind-body exercise (n=51) Tai chi delivered in a group based format 90 minute sessions delivered twice weekly for 12 weeks. Intervention 2: Education (n=50) Education sessions delivered in a group based format on fibromyalgia, healthy eating, education based CBT strategies, sleep hygiene and lifestyle management 90 minute sessions delivered twice weekly for 12 weeks.	Fibromyalgia (n=101) Mean age 51.4 years Mean duration of pain 18.4 years	At 12 weeks (post-intervention): Pain Quality of life Physical function (additional outcome) Discontinuation (additional outcome)	In Cochrane review (Theadom 2015)
King 2002¹⁵²	12 week interventions. Intervention 1: Aerobic exercise (n=42) Walking, aquacise (deep and shallow water), or low impact aerobics. Three times a week starting at 10–15 minutes and progressing to 20–40 minutes. Intervention 2: Education (n=41) Educational session provided by a multidisciplinary team. Topics focused on potential causes of fibromyalgia, principles of self-management (goal setting, maximizing energy for household chores or personal activities, pain or fatigue coping strategies, benefits of exercise, evaluating alternative therapies, and barriers to behaviour change). Once a week for 1.5–2 hours.	Fibromyalgia (n=170; third arm of study reported under aerobic versus usual care comparison) Females only Mean age: 45.2 (9.4); 44.9 (10); 47.4 (9); 47.3 (7.3) years Duration of pain: 7.8; 10.9; 8.9; 9.6 years	At 24 weeks (follow up including 12 week intervention): Quality of life Physical function Pain Discontinuation	In Cochrane review (Bidonde 2017)
Martin 1996¹⁷⁹	6 week interventions Intervention 1: Aerobic, Strength training (n=30) Participants met 3 times a week for 6 weeks and participated in 1 h supervised exercise program. The program included 20 minutes walking at a pace sufficient to raise heart rate to 60–80% of maximum, 20 minutes of flexibility and strength training for multiple muscles. Intervention 2: Relaxation (n=30) 3 times per week for 6 week, supervised relaxation program for 1 hour in a quiet room. Patients were taught visualization, yoga and autogenic relaxation by experienced instructors.	Fibromyalgia (n=60) Mean age 44.8 years Duration of pain 9.2 years	At 6 weeks post-intervention): Quality of life Discontinuation
McBeth 2012¹⁸¹ (Beasley 2015²⁸)	6 month intervention Intervention 1: Aerobic exercise (n=109) Gym based programme with monthly assessments led by instructors to reassess the programme. Exercise intensity increased until exercise levels achieved 40–85% maximum heart rate; recommended session length 20 to 60 minutes 3–5 times a week) Intervention 2: Cognitive behavioural therapy (n=112) Telephone delivered, 7 weekly sessions (30–45 minutes each) plus initial assessment, followed by 1 session at 3 months and 1 session at 6 months. Delivered by 4 therapists. Intervention 3: Usual care (n=109) Usual care from family physician, although precise care delivered, if any, was not record3ed	Chronic widespread pain (n=330) Duration of pain not stated Mean age 55.7(12.5) years	At 9 months: Quality of life Sleep Discontinuation (6 months)
Silva 2019²⁴³	12 week interventions Intervention 1: Strength training (n=30) Resistance training, which consisted of 3 sets of 12 repetitions, alternating lower limbs. Loads were 60% of the 1 rep maximum in the first month, increasing to 80% in the third month. The following muscles were trained: biceps brachial, triceps, pectoralis, trapezius, knee extensors, knee flexors and hip abductors. Twice a week for 40 minutes. Intervention 2: Relaxation (n=30) Body relaxation sessions, which involved lying down with relaxing movement. Participants were invited to think about their illness, their life, imagining positive and negative points and to analyze everything. The physiotherapist also asked them to focus on the negative aspects and concentrate on these negative points, and they were asked to try to see good aspects of each point. Twice a week for 40 minutes.	Women with fibromyalgia (n=60) Mean age: 44.93 (10.30); 49.40 (8.30) years Duration of pain not reported	At 8 and 12 weeks (end of intervention) Pain reduction Physical function Quality of life Discontinuation	Only pain reduction reported at 8 weeks. Intervention not finished at 8 weeks so outcome measured before end of intervention.
Viljanen 2003²⁶⁷	12 week interventions Intervention 1: Strength training (n=135) Led by trained physiotherapist 3 times a week sessions for 30 minutes each, followed by on week of reinforcement training 6 months after randomisation. Dumbbells were used for dynamic muscle training (weight 1–3kg each according to maximum repetitions with a test weight of 7.5 kg). The Exercises, conducted in the same order in each session, were chosen to activate large muscle groups in the neck and shoulder region. After the 5thweek participants were taught 3 exercises from the program with stretches, after the 9th week they were asked to perform the full training program by themselves. Intervention 2: Relaxation (n=128) Led by trained physiotherapist 3 times a week sessions for 30 minutes each, followed by on week of reinforcement training 6 months after randomisation. Exercises aimed to teach participants to activate only those muscles needed for different daily activities and to relax other muscles. Participants were taught to perform the exercises alone from the 5th week.	Chronic non-specific neck pain (n=393; third arm of study reported under strength versus usual care comparison) Mean age 44 years Mean pain duration 10.8 years	At 12 months follow up (including 12 week intervention): Pain reduction Discontinuation	All participants were office workers
Wigers 1996²⁷⁶	14 week interventions. Intervention 1: Aerobic exercise (n=20) Aerobic exercise, focusing on the whole body and aimed at minimizing eccentric muscle strain. Exercise involved movement to music and games. Three times a week for 45 minutes (23 minute music session including warming up and 2 peaks of high intensity training, 15 minutes of aerobic games with 2 high intensity periods). Intervention 2: Stress management training (n=20) Stress management training with 2 treatment groups of 10, with each totalling 20 sessions and 30 hours of active treatment (twice a week for 6 weeks, and once a week for 8 weeks, each session 90 minutes).	Fibromyalgia (n=40) Female:Male: 55:5 Mean age: 43 (9); 44 (12); 46 (9) years Duration of pain: 9 (5); 11 (10); 11 (9) years	At 14 weeks (post intervention) and 4 years (follow-up): Pain Sleep Psychological distress Discontinuation	In Cochrane review (Bidonde 2017)

Table 31Summary of studies included in the evidence review

Study	Intervention and comparison	Population	Outcomes	Comments
Akhter 2014⁵	12 week interventions Intervention 1: Manual therapy, Strength and stretching (n=31) Manual therapy: (Maitland’s approach Grade V, High velocity thrust, low amplitude application, rotation/lateral flexion technique on painful and stiff cervical spinal segments in supine position, maximum 6 sessions in 3 weeks). Exercise: regime included a set of strength exercises consisted of isometric, concentric and eccentric exercises with rest in between and a set of stretching exercises of cervical spine and stretches 10 repetitions each. Intervention 2: Strength and flexibility (n=31) Participants performed supervised exercise regime same as the other group, and also followed the same home exercise programme.	People with a history of neck pain for 3 months with no related medical dysfunction (n=62) Mean age 38.8 years Mean duration of pain 4.45 years	At 12 weeks (post intervention): Pain reduction Physical function	After 3 weeks intervention both groups taught and practiced a home exercise program. A printed exercise sheet was provided with frequency and repetition details: twice a day, 7 days a week, for 3 months. This home exercise program consisted of strength exercises for neck/scapular stability, stretching exercises and general range of motion exercises for neck with advice regarding posture awareness and correction
Bronfort 2001⁴³	11 week interventions Intervention 1: Aerobic & Strength exercise (n=60) Warm up of stretching and upper body strength followed by 15 to 20 minutes of aerobic exercise using a stationary bike. Resistance exercises were performed on the MedX cervical extension and rotation machines, and resistance was increased periodically, with patients performing approximately 20 repetitions of each exercise. Duration 11 weeks. Intervention 2: Manual therapy and strength exercise (n=63) Spinal manipulation therapy and exercise plus strength exercises for the neck and upper body preceded by a short aerobic warm up of the upper body and light stretching. 2 sets of 15–30 repetitions were conducted and resistance was increased gradually over time.	Mechanical neck pain (no specific identified cause) (n=123) Mean age 44.3 years Mean pain duration 5 years	At 11 weeks post intervention and 12 months follow up: Pain reduction Physical function Discontinuation
El-Gendy 2019⁷⁸	4 week interventions Intervention 1: Manual therapy and stretching (n=20) Myofacial release therapy applied from sitting position after exact determination of the pain location. Superficial stroke massage was performed for 2–3 minutes on the back region to the neck and shoulders in reciprocating and transverse way. Then the therapist focused on the pain region locally and applied myofascial release technique. At the end of the treatment session, about 2–3-minute surface stroke massage was performed again. There were 3 sessions per week for 20 minutes. Stretching was also performed as identical to the stretching group (as described). Intervention 2: Stretching exercise (n=20) Stretching involved gentle stretching of the pectoral muscle, trapezius muscle, scaleni muscles, levator scapulae muscle, the suboccipital muscle. Also included some strengthening exercises including cervical flexion and extension, shoulder retraction exercise, upright rowing with resistance tubing and push ups if tolerated. Three sessions per week.	Chronic mechanical neck pain (n=40) Gender not reported Mean age: 33.9 (5.51); 33.65 (5.7) years Duration of pain not reported	At 4 weeks (post intervention) Pain Physical function Discontinuation	Three armed trial; third arm electrotherapy not included in the analysis
Evans 2002⁸⁵	12 week interventions Intervention 1: Manual therapy and Strength exercise (n=64) Spinal manipulation combined with rehabilitative exercise. Spinal manipulation treatment included manual spinal manipulation with light soft tissue massage as facilitate the spinal manipulative therapy. Rehabilitative exercise began each session with a warm up on a stationary bike with arm levers and light stretching, followed by upper body strengthening exercises including push-ups and dumbbell shoulder exercises. Dynamic neck extension, flexion, and rotation exercises were performed with the patient lying on a therapy table wearing headgear with variable weight attachments. Weights were determined by baseline strength performance and were increased gradually during the treatment phase. Each session was 1 hour and there were 20 sessions. Intervention 2: Strength exercise (n=63) 20 sessions. Warm up of stretching and aerobic exercise using a stationary bike, followed by strengthening exercises of the shoulders and upper back using variable resistance equipment. Patients were stabilized with torso restraints to isolate and specifically exercise the cervical musculature. They were encouraged to perform repetitions to volitional muscle fatigue (maximum 20 reps) even if the pain was exacerbated, and resistance was increased periodically.	Chronic mechanical neck pain for 12 weeks or more (n=127) Mean age 44.7 years Median pain duration 6 years	At 12 weeks (post-intervention) and 2 years (follow up): Pain reduction Quality of life Physical function Discontinuation
Evans 2012⁸⁶	12 week interventions Intervention 1: Manual therapy and Strength exercise (n=91) Identical exercises as strength intervention (as described) which was preceded by a 15–20 minute session with a licensed chiropractor who administered spinal manipulation therapy. Sessions focused mainly on manual manipulation to the cervical and thoracic spines using high velocity, low amplitude pressure applied to the joints. Up to 5 minutes of light soft tissue massage was also used Intervention 2: Strength exercise (n=89) Predominantly upper body and neck exercises that were partially individualised in terms of intensity, according to the participants’ abilities. One-on-one supervision in 20 1 hour sessions. The main focus was cervical strength exercises using low-tech methods performed with the patient lying on a therapy table, wearing headgear with variable weight attachments. 3 sets of 15–25 repetitions were conducted. There was also light aerobic warm up (5 minutes) and stretching before and after strength training.	Chronic nonspecific neck pain for at least 12 weeks (Grade I or II classification according to the Neck Pain Task Force) (n=180) Mean age 46.3 years Mean duration of pain 9.4 years	At 12 weeks (post-intervention) and 52 weeks (follow up): Pain reduction Quality of life Physical function Discontinuation
Lee 2016¹⁶³	10 week interventions Intervention 1: Manual therapy and strength exercise (n=16) Thoracic manipulation for 10 minutes plus deep craniocervical flexors training for 15 minutes, plus self-stretching of the levator scapulae and upper trapezius muscles as cool-down exercises for 10 minutes. Intervention 2: Strength (n=15) Deep craniocervical flexors training for 25 minutes, with self-stretching of the levator scapulae and upper trapezius muscles as cool-down exercises for 10 minutes. Intervention 3: Strength (n=15) Active ROM self-exercise, including neck flexion, extension, lateral flexion, and rotation without provocation of pain) for 35 minutes. NB Strength interventions were pooled in the analysis	People with chronic neck pain (n=46) Mean age not reported Mean pain duration not reported	At 10 weeks (post-intervention) Pain Physical function
Panton 2009 ²¹⁰	16 week interventions Intervention 1: Manual therapy and strength exercise (n=12) Exercise as in the strength group (below), plus manual therapy. Participants met twice a week for exercise, and twice a week for chiropractic treatment. Chiropractic treatment began with 5 minutes of ischemic compression to tender points on the back of the neck and spine. Pressure was applied with thumbs over tender points until the patient reacted to the pressure. The pressure was sustained for 10 seconds. This technique was continued throughout the 16 weeks with increasing pressure until an application of 4kg of digital pressure was reached. This 4kg of pressure was continued until the completion of the study. The next 5 minutes consisted of diversified chiropractic spinal adjustments. These adjustments consisted of short lever, low amplitude, high velocity thrusts. Cervical, thoracic and lumbar adjustments were performed. Target joints were determined at each visit through static and motion palpitation. Intervention 2: Strength training (n=15) Resistance training. Participants met twice a week. Resistance training was chosen to maximise strength gains. Participants performed one set of 8–12 repetitions twice a week on 10 exercises. Participants began training at approximately 50% of their initial 1-RM measurement and were slowly progressed to approximately 100% of their initial 1RM by the end of the 16 weeks. Once 12 repetitions were completed on 2 consecutive workouts, weights were increased by 5–10 pounds for upper and lower body respectively.	Women with fibromyalgia (n=27) Mean age 48.5 years Mean pain duration 5.5 years	At 16 weeks (post-intervention): Quality of life Physical function Discontinuation
Toprak celenay 2017²⁵⁶	6 week interventions Intervention 1: Aerobic & Strength exercise (n=24) The combined exercise programme was carried out 2 days a week for 6 weeks and took 1 hour. It was composed of 10 minute warm up exercises, 40 minutes aerobic and strengthening exercises including neck, trunk, upper and lower limb muscles. The aerobic exercise consisted of 20 minutes walking on a treadmill. The target heart rate was initially adjusted to 65–70% of the maximal heart rate and to 75–80% of the maximal heart rate in the advanced programme. Muscle strengthening exercises were then performed with elastic resistive bands for 20 minutes where multiple muscles were strengthened. When they performed 15 repetitions without serious pain or fatigue, they progressed to the next colour resistance band. They had 10 repetitions with a holding period of 10 seconds. Intervention 2: Manual therapy and exercise (n=25) Connective tissue massage was applied 2 days per week for a total of 12 sessions. While patients were in a sitting position, starting from the lumbosacral region, the lower thoracic, scapular, interscapular, and cervical regions were included in the treatment, respectively. For creating traction between cutaneous tissues, the middle fingers of both hands were used during the application. Each session lasted around 5–20 minutes. Exercise the same as above.	Women with fibromyalgia (n=49) Mean age 41 years Duration of pain not specified	At 6 weeks post-intervention): Discontinuation

Table 32Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Evans 2002⁸⁵

12 week interventions

Intervention 1: Manual therapy and Strength training (n=64)

Spinal manipulation combined with rehabilitative exercise. Spinal manipulation treatment included manual spinal manipulation with light soft tissue massage as facilitate the spinal manipulative therapy. Rehabilitative exercise began each session with a warm up on a stationary bike with arm levers and light stretching, followed by upper body strengthening exercises including push-ups and dumbbell shoulder exercises. Dynamic neck extension, flexion, and rotation exercises were performed with the patient lying on a therapy table wearing headgear with variable weight attachments. Weights were determined by baseline strength performance and were increased gradually during the treatment phase. Each session was 1 hour and there were 20 sessions.

Intervention 2: Manual therapy (n=64)

Patients received the same spinal manipulation treatment as in the combined treatment group. Duration 11 weeks. Concurrent medication/care: Patients were also given 45 minutes of micronutrient therapy (sham) to minimise the effects of attention bias.

Chronic mechanical neck pain for 12 weeks or more (n=128)

Mean age 44.7 years

Median pain duration 6 years

At 12 weeks (post-intervention) and 2 years (follow up):

Pain reduction
Quality of life
Physical function
Discontinuation

Table 33Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

Evans 2002⁸⁵

12 week interventions

Intervention 1: Strength training (n=61)

20 sessions. Warm up of stretching and aerobic exercise using a stationary bike, followed by strengthening exercises of the shoulders and upper back using variable resistance equipment. Patients were stabilized with torso restraints to isolate and specifically exercise the cervical musculature. They were encouraged to perform repetitions to volitional muscle fatigue (maximum 20 reps) even if the pain was exacerbated, and resistance was increased periodically.

Intervention 2: Manual therapy (n=64)

Chronic mechanical neck pain for 12 weeks or more (n=125)

Mean age 44.7 years

Median pain duration 6 years

At 12 weeks (post-intervention) and 2 years (follow up):

Pain reduction
Quality of life
Physical function
Discontinuation

Table 34Clinical evidence summary: Aerobic exercise versus usual care

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Control

Risk difference with Aerobic exercise versus control (95% CI)

Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)

(1 study)

6 weeks

⊕⊕⊝

MODERATE¹

due to risk of bias

The mean pain score in the control group was 62

The mean pain score at in the intervention groups was 21.5 lower

(30.38 to 12.62 lower)

Pain at >3 months (VAS, FIQ pain subscale, 0–100, final values, high is poor outcome)

528

(9 studies)

12–24 weeks

⊕⊕⊝⊝

LOW¹

due to risk of bias

The mean pain score in the control groups was 66.5

The mean pain score in the intervention groups was 6.97 lower

(10.77 to 3.17 lower)

Pain at >3 months (FIQ pain subscale, 0–100, high is poor outcome)

(1 study)

18 months

⊕⊕⊝⊝

LOW¹

due to risk of bias

The mean pain score in the control groups was

The mean pain score in the intervention groups was 1 lower

(10.34 lower to 8.34 higher)

Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)

372

(5 studies)

12–24 weeks

⊕⊝⊝⊝

VERY LOW¹^,²^,³

due to risk of bias, imprecision, inconsistency

The mean quality of life score in the control groups was 56.5

The mean quality of life score in the intervention groups was 7.89 lower

(13.23 to 2.55 lower)

Quality of life at >3 months (SF-36 functional capacity subscale, 0–100, final values, high is good outcome)

(1 study)

16 weeks

⊕⊕⊝⊝

LOW¹

due to risk of bias

The mean quality of life score in the control groups was 38

The mean quality of life score in the intervention groups was

12.5 higher

(3.85 to 21.15 higher)

Quality of life at >3 months (SF-36 physical appearance subscale, 0–100, final values, high is good outcome)

(1 study)

16 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 13.8

The mean quality of life score in the intervention groups was

16 higher

(2.68 lower to 34.68 higher)

Quality of life at >3 months (SF-36 pain subscale, 0–100, final values, high is good outcome)

(1 study)

16 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 29.2

The mean quality of life score in the intervention groups was

7.5 higher

(8.62 lower to 23.62 higher)

Quality of life at >3 months (SF-36 vitality subscale, 0–100, final values, high is good outcome)

(1 study)

16 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 30.2

The mean quality of life score in the intervention groups was

7.7 higher

(2.49 lower to 17.89 higher)

Quality of life at >3 months (SF-36 social aspects subscale, 0–100, final values, high is good outcome)

(1 study)

16 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 45.4

The mean quality of life score in the intervention groups was

8.9 higher

(3.16 lower to 20.96 higher)

Quality of life at >3 months (SF-36 emotional aspects subscale, 0–100, final values, high is good outcome)

(1 study)

16 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 22.4

The mean quality of life score in the intervention groups was

9.7 higher

(10.7 lower to 30.1 higher)

Quality of life at >3 months (SF-36 mental health subscale, 0–100, final values, high is good outcome)

(1 study)

16 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 43.4

The mean quality of life score in the intervention groups was

3.4 higher

(7.46 lower to 14.26 higher)

Quality of life at ≤3 months (EQ-5D, −0.594–1, high is good outcome, final values)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 0.5

The mean quality of life score in the intervention groups was

0.03 lower

(0.15 lower to 0.09 higher)

Quality of life at >3 months (EQ-5D, −0.594–1, high is good outcome, final values)

259

(2 studies)

9–18 months

⊕⊝⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 0.57

The mean quality of life score in the intervention groups was

0.06 higher

(0.01 lower to 0.13 higher)

Quality of life at ≤3 months (EQ-5D VAS, 0–100. high is good outcome, final values)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 48.3

The mean quality of life score in the intervention groups was

5.6 higher

(2.86 lower to 14.06 higher)

Quality of life at >3 months (EQ-5D VAS, 0–100, high is good outcome, final values)

(1 study)

18 months

⊕⊕⊝⊝

LOW¹

due to risk of bias

The mean quality of life score in the control groups was 51.9

The mean quality of life score in the intervention groups was

1.4 higher

(8.17 lower to 10.97 higher)

Physical function at ≤3 months (Final values, timed up and go, seconds, high is good outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean physical function score in the control groups was 9.99

The mean physical function score in the intervention groups was

0.62 lower

(1.40 lower to 0.16 higher)

Physical function at ≤3 months (FIQ physical function subscale, 0–100, final values, high is poor outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean physical function score in the control groups was 40

The mean physical function score in the intervention groups was

3 lower

(11.32 lower to 5.32 higher)

Physical function at >3 months (6 minute walking test, final values, metres, high is good outcome)

169

(3 studies)

12–24 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean physical function score in the control groups was 449.8

The mean physical function score in the intervention groups was

56.18 higher

(27.8 to 84.56 higher)

Physical function at >3 months (FIQ and SF-36 physical function subscales, 0–100, final values, high is poor outcome)

246

(3 studies)

16–24 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean physical function score in the control groups was 49.9

The mean physical function score in the intervention groups was

10.16 lower

(15.39 to 4.94 lower)

Physical function at >3 months (FIQ physical function subscale, 0–100, final values, high is poor outcome)

(1 study)

18 months

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean physical function score in the control groups was 39

The mean physical function score in the intervention groups was

3 lower

(16.14 lower to 10.14 higher)

Psychological distress at >3 months (Change scores and final values, beck depression inventory, 0–21, high is poor outcome)

123

(3 studies)

16–24 weeks

⊕⊕⊝⊝

LOW¹

due to risk of bias

The mean psychological distress score in the intervention groups was

3.36 lower

(6.16 to 0.56 lower)

Psychological distress at >3 months (Final values, VAS and FIQ depression scale, 0–10, high is poor outcome)

306

(4 studies)

12–24 weeks

⊕⊕⊝⊝

LOW¹

due to risk of bias

The mean psychological distress score in the control groups was 4.9

The mean psychological distress in the intervention groups was

0.39 lower

(1.05 lower to 0.28 higher)

Psychological distress at >3 months (Final values, VAS and FIQ anxiety scale, Beck anxiety inventory, final values, high is poor outcome)

320

(4 studies)

12–24 weeks

⊕⊕⊝⊝

LOW¹

due to risk of bias

The mean psychological distress score in the intervention groups was

0.28 standard deviations lower

(0.51 lower to 0.04 higher)

Psychological distress at >3 months (Change scores, STAI anxiety total scores, high is poor outcome)

(1 study)

23 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean psychological distress change score in the control groups was 4.8

The mean psychological distress score in the intervention groups was

9.7 lower

(23.6 lower to 4.2 higher)

Psychological distress at >3 months (final values, FIQ depression scale, 0–10, high is poor outcome)

(1 study)

18 months

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean psychological distress score in the control groups was 4.2

The mean psychological distress score in the intervention groups was

0.8 higher

(0.46 lower to 2.06 higher)

Psychological distress at >3 months (final values, FIQ anxiety scale, 0–10, high is poor outcome)

(1 study)

18 months

⊕⊕⊝⊝

LOW¹

due to risk of bias

The mean psychological distress score in the control groups was 4.8

The mean psychological distress score in the intervention groups was

0.2 higher

(1.06 lower to 1.46 higher)

Psychological distress at ≤3 months (Final values, BDI depression scale, high is poor outcome)

(1 study)

12 weeks

⊕⊕⊝⊝

LOW¹

due to risk of bias

The mean psychological distress score in the control groups was 30.14

The mean psychological distress score in the intervention groups was

12.77 lower

(14.65 to 10.88 lower)

Use of healthcare services at ≤3 months (Number of GP contacts)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean use of healthcare services in the control groups was 0.5

The mean use of healthcare services in the intervention groups was

1 higher

(0.11 lower to 2.11 higher)

Use of healthcare services at >3 months (Number of GP contacts)

(1 study)

18 months

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean use of healthcare services in the control groups was 0.7

The mean use of healthcare services in the intervention groups was

0.3 higher

(0.68 lower to 1.28 higher)

Use of healthcare services at ≤3 months (Number of medical specialist contacts)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean use of healthcare services in the control groups was

0.2

The mean use of healthcare services in the intervention groups was

0.1 higher

(0.18 lower to 0.38 higher)

Use of healthcare services at >3 months (Number of medical specialist contacts)

(1 study)

18 months

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean use of healthcare services in the control groups was

0.2

The mean use of healthcare services in the intervention groups was

0.2 higher

(0.08 lower to 0.48 higher)

Use of healthcare services at ≤3 months (Number of physiotherapist contacts)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean use of healthcare services in the control groups was

3.4

The mean use of healthcare services in the intervention groups was

3.1 lower

(4.49 to 1.17 lower)

Use of healthcare services at >3 months (Number of physiotherapist contacts)

(1 study)

18 months

⊕⊕⊝⊝

LOW¹

due to risk of bias

The mean use of healthcare services in the control groups was

4.8

The mean use of healthcare services in the intervention groups was

4.4 lower

(5.79 to 3.01 lower)

Sleep at >3 months (VAS sleep scale, PSQI, FIQ sleep subscale, final values, high is poor outcome)

414

(5 studies)

12–40 weeks

⊕⊝⊝⊝

VERY LOW¹^,³

due to risk of bias, inconsistency

The mean sleep score in the intervention groups was

0.16 standard deviations lower (0.43 lower to 0.1 higher)

Discontinuation

607

(9 studies)

8–24 weeks

⊕⊝⊝⊝

VERY LOW¹^,²^,³

due to risk of bias, inconsistency, imprecision

RD 0.11 (−0.04 to 0.27)

113 per 1000

110 more per 1000

(from 40 fewer to 270 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Downgraded for heterogeneity, unexplained by subgroup analysis

Table 35Clinical evidence summary: Strength training versus usual care

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Strength versus control (95% CI)
Pain reduction at ≤3 months (final values, VAS, high is poor outcome)	251 (3 studies) 6–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		The mean pain change in the control groups was 54.44	The mean pain score reduction in the intervention groups was 18.85 lower (34.50 to 3.21 lower)
Pain reduction at ≤3 months (change scores and final values, VAS, NRS, 0–100, high is poor outcome)	156 (3 studies) 6–8 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		-	The mean pain score reduction in the intervention groups was 15.76 lower (22.79 to 8.72 lower)
Pain reduction at >3 months (VAS, NRS, 0–100, final values and change scores, high is poor outcome)	449 (4 studies) 21–52 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		The mean pain change in the control groups was 32	The mean pain score reduction in the intervention groups was 16.06 lower (36.93 lower to 4.82 higher)
Quality of life at ≤3 months (SF-36 physical component summary, 0–100, change scores, high is good outcome)	42 (1 study) 8 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean change quality of life change score in the control groups was 2	The mean quality of life score at 8 in the intervention groups was 7.6 higher (0.25 lower to 15.45 higher)
Quality of life at ≤3 months (SF-36 mental component summary, 0–100, change scores, high is good outcome)	102 (2 studies) 8–16 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life change in the control groups was 8.37	The mean quality of life score at 8–16 in the intervention groups was 3.39 higher (2.43 lower to 9.21 higher)
Quality of life at ≤3 months (FIQ scale, 0–100, final values, high is poor outcome)	52 (2 studies) 8–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		The mean quality of life change in the control groups was 62.85	The mean quality of life in the intervention groups was 14.91 lower (45.78 lower to 15.96 higher)
Physical function at ≤3 months (Neck disability index, change scores and final values, 0–100, high is poor outcome)	146 (3 studies) 6–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		-	The mean physical function score in the intervention groups was 9.89 lower (23.15 lower to 3.37 higher)
Physical function at ≤3 months (final values, FIQ physical function subscale, Northwick Park Questionnaire, high is poor outcome)	151 (2 studies) 6–12 weeks	⊕⊕⊝⊝ VERY LOW¹ due to risk of bias		-	The mean physical function score in the intervention groups was 0 standard deviations higher (0.33 lower to 0.32 higher)
Physical function at ≤3 months (6 minute walking test, metres, final values, high is good outcome)	20 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 538.3m	The mean physical function score in the intervention groups was 8.4m lower (89.59 lower to 72.79 higher)
Physical function at >3 months months (final values, Northwick Park Questionnaire, Neck Disability Index, high is poor outcome)	163 (2 studies) 16–24 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, imprecision, inconsistency		-	The mean physical function score in the intervention groups was 0.23 standard deviations lower (0.68 lower to 1.14 higher)
Physical function at >3 months (change scores, SF-36 physical function subscale, HAQ, 0–100, high is poor outcome)	105 (3 studies) 16–21 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean physical function change score in control groups was −0.56	The mean physical function score in the intervention groups was 6.2 lower (10.41 to 2 lower)
Psychological distress at ≤3 months (Pain Catastrophising Scale, 0–100, high is poor outcome)	25 (1 study) 8 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress in the control group was +20	The mean psychological distress score in the intervention groups was 9 lower (19.70 lower to 1.70 higher)
Psychological distress at >3 months (BDI, 0–61, change scores, high is poor outcome)	21 (1 study) 21 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress change score in the control groups was +0.9	The mean psychological distress score in the intervention groups was 3.7 lower (6.37 to 1.03 lower)
Use of health care services at >3 months	179 (1 study) 52 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision	RR 0.68 (0.42 to 1.11)	333 per 1000	107 fewer per 1000 (from 193 fewer to 37 more)
Sleep at >3 months (VAS sleep, 0–100, change scores, high is poor outcome)	21 (1 study) 21 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean sleep change score in the control groups was −3	The mean sleep score at 21 in the intervention groups was 7 lower (20.9 lower to 6.9 higher)
Discontinuation at ≤3 months	133 (4 studies) 8–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	OR 2.27 (0.77 to 6.73)	65 per 1000	71 more per 1000 (from 14 fewer to 254 more)
Discontinuation at >3 months	252 (4 studies) 16–24 weeks	⊕⊕⊕⊝ MODERATE¹^,² due to risk of bias	RD 0.08 (−0.02 to 0.17	33 per 1000	33 fewer per 1000 (from 27 fewer to 34 fewer)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Downgraded for heterogeneity, unexplained by subgroup analysis

Table 36Clinical evidence summary Aerobic and strength versus usual care

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Aerobic and strength versus control (95% CI)
Pain at ≤3 months (VAS, 0–100, change scores, high is poor outcome)	129 (2 studies) 10–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		The mean pain change score in the control groups was 0.5	The mean pain score in the intervention groups was 2.45 lower (34.16 lower to 29.27 higher)
Pain at >3 months (VAS, FIQ pain subscale, 0–100, final values, high is poor outcome)	161 (3 studies) 18 weeks - 3 years	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean pain final values in the control groups was 56.83	The mean pain score in the intervention groups was 13.74 lower (22.11 to 5.37 lower)
Quality of life at ≤3 months (EQ-5D, −0.594 to 1, final values, high is poor outcome)	30 (1 study) 3 months	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life in the control groups was 0.334	The mean quality of life score in the intervention groups was 0.25 higher (0.05 to 0.45 higher)
Quality of life at ≤3 months (Fibromyalgia impact questionnaire, 0–100, final values, high is poor outcome)	54 (2 studies) 8 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 62.9	The mean quality of life score in the intervention groups was 3.42 lower (12.66 lower to 5.82 higher)
Quality of life at >3 months (Fibromyalgia impact questionnaire, 0–100, final values and change scores, high is poor outcome)	171 (4 studies) 16–52 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, imprecision, inconsistency		-	The mean quality of life score in the intervention groups was 9.05 lower (15.43 to 2.68 lower)
Quality of life at >3 months (EQ-5D, −0.594 to 1, final values, high is poor outcome)	30 (1 study) 8 months	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life in the control groups was 0.334	The mean quality of life score in the intervention groups was 0.19 higher (0.00 to 0.39 higher)
Quality of life at >3 months (SF-36 physical functioning subscale, 0–100, final values, high is good outcome)	42 (1 study) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 45.2	The mean quality of life score in the intervention groups was 11.6 higher (2.02 to 21.18 higher)
Quality of life at >3 months (SF-36 physical role subscale, 0–100, final values, high is good outcome)	42 (1 study) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 19.4	The mean quality of life score in the intervention groups was 1.9 higher (14.93 lower to 18.73 higher)
Quality of life at >3 months (SF-36 emotional role subscale, 0–100, final values, high is good outcome)	42 (1 study) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 52.1	The mean quality of life score in the intervention groups was 19 higher (6.96 lower to 44.96 higher)
Quality of life at >3 months (SF-36 vitality subscale, 0–100, final values, high is good outcome)	42 (1 study) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 28.6	The mean quality of life score in the intervention groups was 12.7 higher (2.73 to 22.67 higher)
Quality of life at >3 months (SF-36 mental health subscale, 0–100, final values, high is good outcome)	42 (1 study) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 44.2	The mean quality of life in the intervention groups was 15.8 higher (3.75 to 27.85 higher)
Quality of life at >3 months (SF-36 social role subscale, 0–100, final values, high is good outcome)	42 (1 study) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 52.2	The mean quality of life in the intervention groups was 11.7 higher (1.9 lower to 25.3 higher)
Quality of life at >3 months (SF-36 bodily pain subscale, 0–100, final values, high is good outcome)	42 (1 study) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 19.5	The mean quality of life in the intervention groups was 10.4 higher (0.16 lower to 20.96 higher)
Quality of life at >3 months (SF-36 general health subscale, 0–100, final values, high is good outcome)	42 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 33.5	The mean quality of life score in the intervention groups was 9.6 higher (2.82 to 16.38 higher)
Physical function at >3 months (seconds, quarter mile walk test, final values, high is poor outcome)	16 (1 study) 18 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 320.15	The mean physical function score in the intervention groups was 37.3 lower (63.19 to 11.41 lower)
Physical function at >3 months (metres, 6-minute walk test, final values, high is good outcome)	37 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 459.07	The mean physical function score in the intervention groups was 54.8 higher (0.54 lower to 110.14 higher)
Physical function at >3 months (FIQ physical function subscale, 0–10, final values, high is poor outcome)	30 (1 study) 32 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 3.7	The mean physical function score in the intervention groups was 1.3 lower (2.63 lower to 0.03 higher)
Physical function at ≤3 months (metres, 6-minute walk test, high is good outcome)	32 (1 study) 8 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 12.21	The mean physical function score in the intervention groups was 15.69 higher (33.37 lower to 64.75 higher)
Psychological distress at ≤3 months (BDI, 0–30, final values, high is poor outcome)	54 (2 studies) 8 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias, imprecision		The mean psychological distress score in the control groups was 21.03	The mean psychological distress score in the intervention groups was 1.44 lower (6.85 lower to 3.97 higher)
Psychological distress at ≤3 months (State anxiety inventory, 0–10, change scores, high is poor outcome)	58 (1 study) 8 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress change in the control groups was −0.4	The mean psychological distress score in the intervention groups was 0.1 higher (5.12 lower to 5.32 higher)
Psychological distress at ≤3 months (HADS anxiety, 0–21, high is poor outcome)	32 (1 study) 8 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias, imprecision		The mean psychological distress score in the control groups was 11.9	The mean psychological distress score in the intervention groups was 1.25 lower (3.77 lower to 1.27 higher)
Psychological distress at >3 months (CES-D, BDI, FIQ depression subscale, final values, high is poor outcome)	125 (4 studies) 18–32 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		-	The mean psychological distress score in the intervention groups was 0.45 standard deviations lower (0.81 to 0.09 lower)
Psychological distress at >3 months (State anxiety inventory, 20–80, final values and change scores, high is poor outcome)	83 (2 studies) 16–32 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		-	The mean psychological distress score in the intervention groups was 2.95 lower (9.75 lower to 3.85 higher)
Sleep at >3 months (Pittsburgh sleep quality index, high is poor outcome, change scores, 0–21)	58 (1 study) 16 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean sleep change in the control groups was +0.5	The mean sleep score in the intervention groups was 2.2 lower (3.39 to 1.01 lower)
Healthcare utilisation at >3 months	78 (1 study) 3 years	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 0.85 (0.49 to 1.47)	476 per 1000	71 fewer per 1000 (from 243 fewer to 224 more)
Discontinuation at ≤3 months	125 (4 studies) 8–12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision	RD 0 (−0.01 to 0.17)	17 per 1000	0 more per 1000 (from 10 fewer to 170 more)
Discontinuation at >3 months	230 (7 studies) 16–32 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RD 0.02 (−0.05 to 0.09)	49 per 1000	49 more per 1000 (from 43 fewer to 50 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Downgraded for heterogeneity, unexplained by subgroup analysis

Table 37Clinical evidence summary: Aerobic, strength and flexibility versus usual care

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95 % CI)

Anticipated absolute effects

Risk with Control

Risk difference with Aerobic, strength and flexibility versus control (95% CI)

Quality of life at ≤3 months (SF-36 mental component, 0–100, final values, high is good outcome)

(1 study)

12 weeks

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 32.9

The mean quality of life score in the intervention groups was

12.1 higher

(2.14 to 22.06 higher)

Quality of life at ≤3 months (SF-36 physical component, 0–100, final values, high is good outcome)

(1 study)

12 weeks

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 31.3

The mean quality of life score in the intervention groups was

5.1 higher

(3.18 lower to 13.38 higher)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 38Clinical evidence summary: Strength and flexibility versus usual care

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Strength and flexibility versus control (95% CI)
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	110 (2 studies) 2–12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 52.8	The mean pain score at 2–12 in the intervention groups was 11.71 lower (21.49 to 1.92 lower)
Pain at >3 months (VAS, SF-36 pain score, final values, 0–100, high is poor outcome)	144 (2 studies) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 50.45	The mean pain score in the intervention groups was 13.19 lower (20.33 to 6.05 lower)
Quality of life at ≤3 months (SF-36 mental component, 0–100, final values, high is poor outcome)	70 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 49.8	The mean quality of life score in the intervention groups was 0.6 lower (6.12 lower to 4.92 higher)
Quality of life at >3 months (SF-36 mental component, 0–100, final values, high is poor outcome)	144 (2 studies) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 45	The mean quality of life score in the intervention groups was 1.78 higher (1.35 lower to 4.91 higher)
Quality of life at ≤3 months (SF-36 physical component, 0–100, final values, high is poor outcome)	70 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 28.6	The mean quality of life score in the intervention groups was 1.7 higher (2.42 lower to 5.82 higher)
Quality of life at >3 months (SF-36 physical component, 0–100, final values, high is poor outcome)	144 (2 studies) 24 weeks	⊕⊕⊕⊝ LOW¹^,³ due to risk of bias, inconsistency		The mean quality of life score in the control groups was 37.3	The mean quality of life score in the intervention groups was 0.16 lower (3.87 lower to 3.56 higher)
Physical function at ≤3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)	70 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias, imprecision		The mean physical function score in the control groups was 39.1	The mean physical function score in the intervention groups was 5.5 lower (16.59 lower to 5.59 higher)
Physical function at >3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)	144 (2 studies) 24 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean physical function score in the control groups was 39.7	The mean physical function score in the intervention groups was 6.7 lower (12.3 to 1.1 lower)
Psychological distress at ≤3 months (ADS depression scale, 0–60, final values, high is poor outcome)	70 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 18.6	The mean psychological distress score in the intervention groups was 1.6 higher (2.59 lower to 5.79 higher)
Psychological distress at >3 months (ADS depression scale, 0–60, final values, high is poor outcome)	70 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 19.8	The mean psychological distress score in the intervention groups was 1.1 higher (3.41 lower to 5.61 higher)
Discontinuation at >3 months	157 (2 studies) 9–24 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	OR 0.88 (0.32 to 2.4)	117 per 1000	13 fewer per 1000 (from 76 fewer to 124 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Downgraded for heterogeneity, unexplained by subgroup analysis

Table 39Clinical evidence summary: Strength, proprioception and flexibility versus usual care

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Strength, proprioception and flexibility versus control (95% CI)
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	76 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 41.8	The mean pain score in the intervention groups was 16.6 lower (25.8 to 7.4 lower)
Pain at >3 months (VAS, 0–100, final values, high is poor outcome)	76 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 44.6	The mean pain score in the intervention groups was 11.5 lower (20.71 to 2.29 lower)
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)	76 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 42.9	The mean quality of life score in the intervention groups was 2.3 higher (0.13 lower to 4.73 higher)
Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)	76 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 42	The mean quality of life score in the intervention groups was 2 higher (1.48 lower to 5.48 higher)
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)	76 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 46.1	The mean quality of life score in the intervention groups was 1.6 higher (2.73 lower to 5.93 higher)
Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)	76 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 46.4	The mean quality of life score in the intervention groups was 0.5 higher (3.82 lower to 4.82 higher)
Psychological distress at ≤3 months (HADS: anxiety, 0–21, final values, high is poor outcome)	76 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 6.7	The mean psychological distress score in the intervention groups was 1.2 lower (2.68 lower to 0.28 higher)
Psychological distress at >3 months (HADS: anxiety, 0–21, final values, high is poor outcome)	76 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 6.7	The mean psychological distress score in the intervention groups was 1.2 lower (2.66 lower to 0.26 higher)
Psychological distress at ≤3 months (HADS: depression, 0–21, final values, high is poor outcome)	76 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 4.9	The mean psychological distress score in the intervention groups was 1.1 lower (2.4 lower to 0.2 higher)
Psychological distress at >3 months (HADS: depression, 0–21, final values, high is poor outcome)	76 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 5.4	The mean psychological distress score in the intervention groups was 1.3 lower (2.85 lower to 0.25 higher)
Physical function at ≤3 months (Neck disability index, 0–100, final values, high is poor outcome)	76 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 27.5	The mean physical function in the intervention groups was 4.8 lower (9.47 to 0.13 lower)
Physical function at >3 months (Neck disability index, 0–100, final values, high is poor outcome)	76 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 29.4	The mean physical function in the intervention groups was 4.3 lower (10.06 lower to 1.46 higher)
Discontinuation at ≤3 months	76 (1 study) 12 weeks	⊕⊕⊝⊝ LOW² due to imprecision	RR 1.37 (0.69 to 2.73)	256 per 1000	95 more per 1000 (from 79 fewer to 443 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 40Clinical evidence summary: Proprioception versus usual care

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Proprioception versus control (95% CI)
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	46 (1 study) 12 weeks	⊕⊕⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 5.63	The mean pain score in the intervention groups was 0.18 higher (1.09 lower to 1.45 higher)
Pain at >3 months (VAS, 0–10, final values, high is poor outcome)	46 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 6.36	The mean pain score in the intervention groups was 0.97 lower (2.47 lower to 0.53 higher)
Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)	46 (1 study) 12 weeks	⊕⊕⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 50.17	The mean quality of life score in the intervention groups was 1.88 lower (11.11 lower to 7.35 higher)
Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)	46 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 52.96	The mean quality of life score in the intervention groups was 3.59 lower (14.37 lower to 7.19 higher)
Physical function at ≤3 months (sit to stand test, final values, high is good outcome)	46 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 28.59	The mean physical function score in the intervention groups was 4.38 lower (14.37 lower to 7.19 higher)
Physical function at >3 months (sit to stand test, final values, high is good outcome)	46 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 25.77	The mean physical function score in the intervention groups was 0.86 lower (3.18 lower to 1.46 higher)
Psychological distress at ≤3 months (BDI, 0–61, final values, high is poor outcome)	46 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 13.95	The mean psychological distress score in the intervention groups was 4.74 lower (8.43 to 1.05 lower)
Psychological distress at >3 months (BDI, 0–61, final values, high is poor outcome)	46 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 14.86	The mean psychological distress score in the intervention groups was 4.86 lower (9.84 lower to 0.12 higher)
Discontinuation at >3 months	50 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision	RR 0.33 (0.04 to 2.99)	120 per 1000	80 fewer per 1000 (from 115 fewer to 239 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 41Clinical evidence summary: Mind-body exercise versus usual care

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Mind-body exercises versus control (95% CI)
Pain at ≤3 months (VAS, Visual numeric scale, FIQ pain subscale, 0–100, final values and change scores, high is poor outcome)	393 (8 studies) 7–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		The mean pain score in the control groups was 50.3	The mean pain score in the intervention groups was 11.17 lower (17.32 to 5.02 lower)
Pain improvement at ≤3 months (30% improvement on NRS)	117 (1 study) 8 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias	RR 3.19 (1.56 to 6.52)	159 per 1000	348 more per 1000 (from 89 more to 878 more)
Pain improvement at >3 months (30% improvement on NRS)	117 (1 study) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision	RR 2.11 (1.06 to 4.21)	182 per 1000	202 more per 1000 (from 11 more to 584 more)
Pain at >3 months (VAS, SF-36 pain score, 0–100, final values, high is poor outcome) - Fibromyalgia	80 (1 study) 32 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean pain score in the control groups was 73	The mean pain score in the intervention groups was 26 lower (35.63 to 16.37 lower)
Pain at >3 months (VAS, SF-36 pain score, 0–100, final values, high is poor outcome) - Chronic neck pain	221 (3 studies) 24 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, imprecision		The mean pain score in the control groups was 48.5	The mean pain score in the intervention groups was 11.29 lower (174219.52 to 5.17 lower)
Quality of life at ≤3 months (WHOQOL-BREF, 0–5, final values, high is good outcome)	57 (1 study) 7 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, imprecision		The mean quality of life score in the control groups was 2.79	The mean quality of life score in the intervention groups was 0.58 higher (0.16 to 1 higher)
Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)	106 (3 studies) 8–14 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		The mean quality of life score in the control groups was 49.3	The mean quality of life score in the intervention groups was 1.55 lower (13.36 lower to 10.25 higher)
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)	220 (3 studies) 10–12 weeks	⊕⊕⊕⊝ MODERATE¹^,³ due to risk of bias		The mean quality of life score in the control groups was 37.3	The mean quality of life score in the intervention groups was 4.14 higher (2.15 to 6.12 higher)
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)	220 (3 studies) 10–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		The mean quality of life score in the control groups was 45.6	The mean quality of life score in the intervention groups was 2.33 higher (2.57 lower to 7.24 higher)
Quality of life at >3 months (SF-36 physical component, 0–100, final values, high is poor outcome)	221 (3 studies) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		The mean quality of life score in the control groups was 43.3	The mean quality of life score in the intervention groups was 1.64 lower (11.62 lower to 8.33 higher)
Quality of life at >3 months (SF-36 mental component, 0–100, final values, high is poor outcome)	221 (3 studies) 24 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, imprecision		The mean quality of life score in the control groups was 34.2	The mean quality of life score in the intervention groups was 0.69 higher (2.05 lower to 3.43 higher)
Quality of life at >3 months (SF-36, 0–100, functional capacity scale, final values, high is good outcome)	80 (1 study) 32 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean quality of life score in the control groups was 39.1	The mean quality of life score in the intervention groups was 17.2 higher (8.01 to 26.39 higher)
Quality of life at >3 months (SF-36, 0–100, physical aspects subscale, final values, high is good outcome)	80 (1 study) 32 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean quality of life score in the control groups was 13.8	The mean quality of life score in the intervention groups was 22.7 higher (9.73 to 35.67 higher)
Quality of life at >3 months (SF-36, 0–100, pain subscale, final values, high is good outcome)	80 (1 study) 32 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean quality of life score in the control groups was 29.1	The mean quality of life score in the intervention groups was 16.9 higher (9.19 to 24.61 higher)
Quality of life at >3 months (SF-36, 0–100, vitality subscale, final values, high is good outcome)	80 (1 study) 32 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean quality of life score in the control groups was 37.1	The mean quality of life score in the intervention groups was 10.5 higher (0.5 to 20.5 higher)
Quality of life at >3 months (SF-36, 0–100, general health subscale, final values, high is good outcome)	80 (1 study) 32 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean quality of life score in the control groups was 41.5	The mean quality of life score in the intervention groups was 3.4 higher (4.81 lower to 11.61 higher)
Quality of life at >3 months (SF-36, 0–100, social subscale, final values, high is good outcome)	80 (1 study) 32 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean quality of life score in the control groups was 51.3	The mean quality of life score in the intervention groups was 5.9 higher (5.61 lower to 17.41 higher)
Quality of life at >3 months (SF-36, 0–100, emotional subscale, final values, high is good outcome)	80 (1 study) 32 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean quality of life score in the control groups was 31.5	The mean quality of life score in the intervention groups was 20.4 higher (3.24 to 37.56 higher)
Quality of life at >3 months (SF-36, 0–100, mental health subscale, final values, high is good outcome)	80 (1 study) 32 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean quality of life score in the control groups was 46.2	The mean quality of life score in the intervention groups was 6.1 higher (3.42 lower to 15.62 higher)
Physical function at >3 months (Neck disability index, neck pain disability scale, final values, high is poor outcome)	363 (7 studies) 32 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		-	The mean physical function score in the intervention groups was 0.40 standard deviations lower (0.84 to 0.04 lower)
Physical function at >3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)	225 (3 studies) 32 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, imprecision		The mean physical function score in the control groups was 36.3	The mean physical function score in the intervention groups was 6.79 lower (10.57 to 3.01 lower)
Physical function at >3 months (6 minute walk test, metes, final values, high is good outcome)	80 (1 study) 32 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean physical function score in the control groups was 343	The mean physical function score in the intervention groups was 88 higher (51.42 to 124.58 higher)
Psychological distress at ≤3 months (HADS:D, Beck depression inventory, CES-D, ADS depression scale, final values, high is poor outcome)	306 (5 studies) 7–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		-	The mean psychological distress score in the intervention groups was 0.51 standard deviations lower (0.96 to 0.05 lower)
Psychological distress at ≤3 months (State trace anxiety inventory, final values, high is poor outcome) - Fibromyalgia	57 (1 study) 7 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, imprecision		The mean psychological distress score in the control groups was 51.7	The mean psychological distress score in the intervention groups was 9.91 lower (15.59 to 4.23 lower)
Psychological distress at ≤3 months (HADS:A, final values, high is poor outcome) - Chronic neck pain	77 (2 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, imprecision		The mean psychological distress score in the control groups was 6.7	The mean psychological distress score in the intervention groups was 0.2 lower (2 lower to 1.6 higher)
Psychological distress at >3 months (Beck depression inventory, HADS:D, final values, high is poor outcome)	223 (3 studies) 24–32 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		-	The mean psychological distress score in the intervention groups was 0.02 standard deviations lower (0.29 lower to 0.24 higher)
Psychological distress at >3 months (HADS:A, 0–21, final values, high is poor outcome)	77 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, imprecision		The mean psychological distress score in the control groups was 6.7	The mean psychological distress score in the intervention groups was 0.6 lower (2.38 lower to 1.18 higher)
Sleep at ≤3 months (VAS sleep outcome, pittsburgh sleep quality index, final values, high is poor outcome)	60 (2 studies) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, inconsistency, imprecision		-	The mean sleep score in the intervention groups was 0.43 standard deviations lower (1.58 lower to 0.72 higher)
Discontinuation at >3 months	784 (12 studies) 8–32 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, imprecision, inconsistency	RD 0.03 (−0.03 to 0.10)	77 per 1000	30 more per 1000 (from 30 fewer to 100 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded for heterogeneity, unexplained by subgroup analysis

3: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 42Clinical evidence summary: Flexibility versus usual care

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Flexibility versus control (95% CI)
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	28 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 64	The mean pain score in the intervention groups was 18 lower (37.89 lower to 1.89 higher)
Physical function at ≤3 months (FIQ physical function subscale, 0–30, final values, high is poor outcome)	28 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 10.5	The mean physical function score in the intervention groups was 1.5 lower (5.39 lower to 2.39 higher)
Discontinuation at ≤3 months	34 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	OR 8.41 (0.81 to 86.84)
Discontinuation at ≤3 months	34 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	OR 8.41 (0.81 to 86.84)	0 per 1000	180 more per 1000 (from 20 more to 370 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 43Clinical evidence summary: Aerobic exercise versus strength

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Aerobic exercise versus strength (95% CI)
Pain at ≤3 months (VAS, FIQ pain subscale, MDPI, 0–100, final values and change scores, high is poor outcome)	199 (4 studies) 3–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		-	The mean pain score in the intervention groups was 4.47 lower (20.48 lower to 11.54 higher)
Pain at >3 months (VAS, 0–100, change scores, high is poor outcome)	60 (1 study) 16 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean pain change score in the control groups was −27.7	The mean pain score in the intervention groups was 6.7 lower (16.22 lower to 2.82 higher)
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values and change scores, high is good outcome)	127 (3 studies) 8–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		-	The mean quality of life score in the intervention groups was 4.29 higher (8.4 lower to 16.98 higher)
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values and change scores, high is good outcome)	127 (3 studies) 8–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		-	The mean quality of life score in the intervention groups was 4.69 higher (6.6 lower to 15.97 higher)
Physical function at ≤3 months (Multidimensional fatigue inventory-20 reduced activity subscale, change scores, 0–20, high is poor outcome)	26 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean physical function change score in the control groups was −1.3	The mean physical function score in the intervention groups was 1 higher (1.18 lower to 3.18 higher)
Physical function at ≤3 months (6 minute walking test, metres, final values, high is good outcome)	75 (1 study) 12 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean physical function score in the control groups was 628.8	The mean physical function score at 12 weeks (6 minute walking test, metres, high is good outcome) in the intervention groups was 88.4 lower (114.7 to 62.1 lower)
Physical function at ≤3 months (Final values and change scores, SF-36 physical functioning subscale, 0–100, high is good outcome)	86 (2 studies) 8–16 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		-	The mean physical function score in the intervention groups was 1.85 higher (3.79 lower to 7.49 higher)
Psychological distress at ≤3 months (Hospital anxiety and depression anxiety score, 0–21, final values and change scores, high is poor outcome)	52 (2 studies) 8–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		-	The mean psychological distress score in the intervention groups was 0.93 lower (2.46 lower to 0.61 higher)
Psychological distress at ≤3 months (Final values and change scores, Hospital anxiety and depression scale, depression score, 0–21, high is poor outcome)	52 (2 studies) 8–12 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		-	The mean psychological distress score in the intervention groups was 0.04 higher (1.37 lower to 1.46 higher)
Psychological distress at ≤3 months (Final values, BDI, 0–60, high is poor outcome)	75 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean psychological distress score in the control groups was 9.9	The mean psychological distress score in the intervention groups was 12.7 higher (9.01 to 16.39 higher)
Sleep at ≤3 months (VAS Sleep scale, 0–100, final values, high is poor outcome)	26 (1 study) 8 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision		The mean psychological distress score in the control groups was 25.8	The mean sleep score in the intervention groups was 13.3 lower (31.93 lower to 5.33 higher)
Discontinuation at ≤3 months (due to other diagnoses, transportation problems)	196 (4 studies) 3–16 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, imprecision	RR 0.67 (0.32 to 1.4)	150 per 1000	49 fewer per 1000 (from 102 fewer to 60 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded for heterogeneity, unexplained by subgroup analysis

3: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 44Clinical evidence summary: Aerobic exercise versus flexibility

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Aerobic exercise versus flexibility (95% CI)
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	60 (1 study) 10 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 47	The mean pain score in the intervention groups was 3 higher (10.19 lower to 16.19 higher)
Pain at >3 months (VAS, 0–100, final values and change scores, high is poor outcome)	94 (2 studies) 20 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		-	The mean pain score in the intervention groups was 12.65 lower (22.45 to 2.84 lower)
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)	60 (1 study) 10 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 42.55	The mean quality of life score in the intervention groups was 2.82 higher (1.29 lower to 6.93 higher)
Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)	60 (1 study) 20 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 42.82	The mean quality of life score in the intervention groups was 2.55 higher (2.08 lower to 7.18 higher)
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)	60 (1 study) 10 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 39.87	The mean quality of life score in the intervention groups was 4.26 higher (1.69 lower to 10.21 higher)
Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)	60 (1 study) 20 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 40.09	The mean quality of life score in the intervention groups was 7.91 higher (2.43 to 13.39 higher)
Psychological distress at ≤3 months (BDI, 0–21, high is poor outcome)	60 (1 study) 10 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 13.56	The mean psychological distress score in the intervention groups was 0.44 higher (6.83 lower to 7.71 higher)
Psychological distress at >3 months (BDI, 0–21, final values, high is poor outcome)	60 (1 study) 20 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 12.15	The mean psychological distress score in the intervention groups was 0.74 lower (4.53 lower to 3.05 higher)
Psychological distress at ≤3 months (State trace anxiety inventory, 0–100, final values, high is poor outcome)	60 (1 study) 10 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 47.4	The mean psychological distress score in the intervention groups was 1.83 lower (6.33 lower to 2.67 higher)
Psychological distress at >3 months (State trace anxiety inventory, 0–100, final values, high is poor outcome)	60 (1 study) 20 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 45.04	The mean psychological distress score in the intervention groups was 4.83 lower (9.22 to 0.44 lower)
Discontinuation at >3 months	76 (1 study) 20 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 1.67 (0.67 to 4.13)	158 per 1000	106 more per 1000 (from 52 fewer to 495 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 45Clinical evidence summary: Aerobic exercise versus biomechanical exercise

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Control

Risk difference with Aerobic and strength versus aerobic (95% CI)

Pain at ≤3 months (VAS, 0–10, high score is poor outcome)

(1 study)

12 weeks

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean pain score in the control groups was

6.2

The mean pain score in the intervention groups was

0.6 lower

(1.79 lower to 0.59 higher)

Psychological distress at ≤3 months (Scale of Catastropic Thoughts on Pain, 0–5, high score is poor outcome)

(1 study)

12 weeks

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean pain score in the control groups was

2.5

The mean pain score in the intervention groups was

0.2 lower

(1.08 lower to 0.68 higher)

Quality of life at ≤3 months (SF36 role social subscale, 0–100, high score is good outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

64.2

The mean quality of life score in the intervention groups was

10.6 lower

(27.34 lower to 6.14 higher)

Quality of life at ≤3 months (SF36 general health status subscale, 0–100, high score is good outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

The mean quality of life score in the intervention groups was

2 lower

(15.89 lower to 11.89 higher)

Quality of life at ≤3 months (SF36 vitality subscale, 0–100, high score is good outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

43.8

The mean quality of life score in the intervention groups was

1.2 lower

(12.43 lower to 10.03 higher)

Quality of life at ≤3 months (SF36 functional capacity subscale, 0–100, high score is good outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

43.5

The mean quality of life score in the intervention groups was

9.6 lower

(21.76 lower to 2.56 higher)

Quality of life at ≤3 months (SF36 role physical subscale, 0–100, high score is good outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

36.2

The mean quality of score in the intervention groups was

14.3 lower

(35.85 lower to 7.25 higher)

Quality of life at ≤3 months (SF36 emotional aspects subscale, 0–100, high score is good outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

43.6

The mean quality of life score in the intervention groups was

9 lower

(34.66 lower to 16.66 higher)

Quality of life at ≤3 months (SF36 pain subscale, 0–100, high score is good outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

44.9

The mean quality of life score in the intervention groups was

7 lower

(18.72 lower to 4.72 higher)

Quality of life at ≤3 months (SF36 mental health subscale, 0–100, high score is good outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

65.9

The mean quality of life score in the intervention groups was

10.9 lower

(25.37 lower to 3.57 higher)

Sleep at ≤3 months (Pittsburgh Sleep Quality Index, 0–21, high score is poor outcome)

(1 study)

12 weeks

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean sleep score in the control groups was

9.9

The mean sleep score in the intervention groups was

0.4 lower

(2.64 lower to 1.84 higher)

Discontinuation at ≤3 months

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

RR 0.50 (0.10 to 2.44)

190 per 1000

95 fewer per 1000

(from 171 fewer to 274 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 46Clinical evidence summary: Aerobic and strength versus aerobic exercise

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Aerobic and strength versus aerobic (95% CI)
Quality of life at >3 months (FIQ, 0–100, change scores, high is poor outcome)	43 (1 study) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score change in the control groups was −8.8	The mean quality of life in the intervention groups was 0 higher (7.78 lower to 7.78 higher)
Psychological distress at >3 months (BDI, 0–61, change scores, high is poor outcome)	43 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress change in the control groups was −8.5	The mean psychological distress in the intervention groups was 2.1 higher (1.66 lower to 5.86 higher)
Discontinuation at >3 months	43 (1 study) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 1.05 (0.3 to 3.66)	182 per 1000	9 more per 1000 (from 127 fewer to 484 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 47Clinical evidence summary: Aerobic and strength versus flexibility

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Aerobic and strength versus flexibility (95% CI)
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	85 (1 study) 6 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 47	The mean pain score in the intervention groups was 4 lower (9.96 lower to 1.96 higher)
Pain at >3 months (VAS, 0–100, final values, high is poor outcome)	76 (1 study) 18 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 42	The mean pain score in the intervention groups was 8 lower (13.89 to 2.11 lower)
Quality of life at ≤3 months (NIH CPSI quality of life subscale, 0–12, final values, high is poor outcome)	85 (1 study) 6 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 6.9	The mean quality of life score in the intervention groups was 1.8 lower (2.69 to 0.91 lower)
Quality of life at >3 months (NIH CPSI quality of life subscale, 0–12, final values, high is poor outcome)	76 (1 study) 18 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 6.2	The mean quality of life score in the intervention groups was 1.8 lower (2.68 to 0.92 lower)
Psychological distress at ≤3 months (BDI, 0–21, final values, high is poor outcome)	85 (1 study) 6 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 9.3	The mean psychological distress score in the intervention groups was 0.5 higher (1.33 lower to 2.33 higher)
Psychological distress at >3 months (BDI, 0–21, final values, high is poor outcome)	76 (1 study) 18 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 7.8	The mean psychological distress score in the intervention groups was 0.5 higher (0.97 lower to 1.97 higher)
Discontinuation at ≤3 months	103 (1 study) 6 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 1.96 (0.72 to 5.34)	98 per 1000	94 more per 1000 (from 27 fewer to 425 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 48Clinical evidence summary: Aerobic and flexibility versus mind-body exercise

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Aerobic and flexibility versus mind-body (95% CI)
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, change scores, high is good outcome)	111 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean quality of life change in the control groups was +3.3	The mean quality of life score in the intervention groups was 1.5 lower (4.65 lower to 1.65 higher)
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, change scores, high is good outcome)	111 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life change in the control groups was +3.8	The mean quality of life score in the intervention groups was 3.2 lower (6.38 to 0.02 lower)
Quality of life at >3 months (SF-36 physical component summary score, 0–100, change scores, high is good outcome)	111 (1 study) 12 months	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean quality of life change in the control groups was +5.4	The mean quality of life score in the intervention groups was 2.8 lower (6.65 lower to 1.05 lower)
Quality of life at >3 months (SF-36 mental component summary score, 0–100, change scores, high is good outcome)	111 (1 study) 12 months	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean quality of life change in the control groups was +5.4	The mean quality of life score in the intervention groups was 2.4 lower (7.88 lower to 3.08 higher)
Physical function at ≤3 months (6 minute walking test change scores, metres, change scores, high is good outcome)	111 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean physical function change in the control groups was +7.4	The mean physical function score in the intervention groups was 1.9 higher (25.15 lower to 28.95 higher)
Physical function at >3 months (6 minute walking test change scores, metres, change scores, high is good outcome)	111 (1 study) 12 months	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean physical function change in the control groups was +30.2	The mean physical function score in the intervention groups was 22.2 lower (60.46 lower to 16.06 higher)
Psychological distress at ≤3 months (HADS: depression, 0–21, change scores, high is poor outcome)	111 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean psychological distress change in the control groups was −1.7	The mean psychological distress score in the intervention groups was 1.2 higher (0.68 lower to 3.08 higher)
Psychological distress at ≤3 months (HADS: anxiety, 0–21, change scores, high is poor outcome)	111 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress change in the control groups was −1.6	The mean psychological distress score in the intervention groups was 1.8 higher (0.4 to 3.2 higher)
Psychological distress at >3 months (HADS: anxiety, 0–21, change scores, high is poor outcome)	111 (1 study) 12 months	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress change in the control groups was −2.2	The mean psychological distress score in the intervention groups was 1.8 higher (0.12 lower to 3.48 higher)
Psychological distress at >3 months (HADS: depression, 0–21, change scores, high is poor outcome)	111 (1 study) 12 months	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean psychological distress change in the control groups was −2.2	The mean psychological distress score in the intervention groups was 1.6 higher (0.86 lower to 4.06 higher)
Sleep at ≤3 months (Pittsburgh sleep quality index, 0–21, change scores, high is poor outcome)	111 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean sleep change in the control groups was −1.6	The mean sleep score in the intervention groups was 0.7 higher (0.74 lower to 2.14 higher)
Sleep at >3 months (Pittsburgh sleep quality index, 0–21, change scores, high is poor outcome)	111 (1 study) 12 months	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean sleep change in the control groups was −2	The mean sleep score in the intervention groups was 0.8 higher (1.14 lower to 2.74 higher)
Discontinuation at ≤3 months	111 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 1.35 (0.71 to 2.57)	227 per 1000	79 more per 1000 (from 66 fewer to 356 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 49Clinical evidence summary: Aerobic exercise and flexibility versus aerobic exercise

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Control

Risk difference with Strength versus mind-body exercises (95% CI)

Pain perception at <3 months (Final score; VAS)

(1 study)

4 weeks

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean pain score in the control groups was

7.33

The mean pain perception score in the intervention groups was

0.65 lower

(0.86 to 0.44 lower)

Pain perception at >3 months (Final score; VAS)

(1 study)

12 weeks

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean pain score in the control groups was

6.74

The mean pain perception score in the intervention groups was

0.94 lower

(1.14 to 0.74 lower)

Quality of life at <3 months (final score; FIQ)

(1 study)

4 weeks

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean quality of life score in the control groups was

69.81

The mean quality of life score in the intervention groups was

5.49 lower

(7.46 to 3.52 lower)

Quality of life at >3 months (final score; FIQ)

(1 study)

12 weeks

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean quality of life score in the control groups was

66.1

The mean quality of life score in the intervention groups was

10.62 lower

(12.34 to 8.9 lower)

Sleep quality at <3 months (final score; Pittsburgh Sleep Quality Index)

(1 study)

4 weeks

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean sleep quality score in the control groups was

12.39

The mean sleep quality score in the intervention groups was

3.94 lower

(4.62 to 3.26 lower)

Sleep quality at >3 months (final score; Pittsburgh Sleep Quality Index)

(1 study)

12 weeks

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean sleep quality score in the control groups was

10.45

The mean sleep quality score in the intervention groups was

5.03 lower

(5.51 to 4.55 lower)

Discontinuation at >3 months

(1 study)

12 weeks

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

RD 0.00 (−0.06 to 0.06)

0 fewer per 1000

(from 6 fewer to 6 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 50Clinical evidence summary: Aerobic, strength, mind-body and proprioception versus flexibility

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with Control	Risk difference with Strength versus mind-body exercises (95% CI)
Quality of life at ≤3 months (FIQ total score, high is poor outcome)	21 (1 study) 7 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 46.44	The mean quality of life score in the intervention groups was 13.04 lower (21.92 to 4.16 lower)
Physical function at ≤3 months (number of steps, high is good outcome)	21 (1 study) 7 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 103.39	The mean physical function score in the intervention groups was 9.19 higher (11.24 lower to 29.62 higher)
Discontinuation at ≤3 months	35 (1 study) 7 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 0.66 (0.28 to 1.57)	474 per 1000	161 fewer per 1000 (from 341 fewer to 270 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 51Clinical evidence summary: Strength versus mind-body

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Control

Risk difference with Strength versus mind-body exercises (95% CI)

Pain (VAS, <3 months)

Scale from: 0 to 10.

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean pain in the control groups was

1.4

The mean pain in the intervention groups was

1.1 higher

(0.31 lower to 2.51 higher)

Quality of life (Nottingham health profile, <3 months)

Scale from: 0 to 600.

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life in the control groups was

89.8

The mean quality of life in the intervention groups was

56.1 higher

(13.21 lower to 125.41 higher)

Physical function (NDI, <3 months)

Scale from: 0 to 100.

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean physical function in the control groups was

8.2

The mean physical function in the intervention groups was

3.1 higher

(0.56 lower to 6.76 higher)

Psychological distress (BDI, <3 months)

Scale from: 0 to 63.

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean psychological distress in the control groups was

6.2

The mean psychological distress in the intervention groups was

3.3 higher

(1.24 lower to 7.84 higher)

Discontinuation at ≤3 months

122

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

RR 1.55 (0.68 to 3.52)

129 per 1000

71 more per 1000

(from 41 fewer to 325 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 52Clinical evidence summary: Strength versus biomechanical

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Control

Risk difference with Strength versus biomechanical exercises (95% CI)

Pain (VAS, <3 months)

Scale from: 0 to 10.

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean pain in the control groups was

1.7

The mean pain in the intervention groups was

0.8 higher

(0.52 lower to 2.12 higher)

Quality of life (Nottingham health profile, <3 months)

Scale from: 0 to 600.

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life in the control groups was

118.2

The mean quality of life in the intervention groups was

27.7 higher

(44.07 lower to 99.47 higher)

Physical function (NDI, <3 months)

Scale from: 0 to 100.

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean physical function in the control groups was

The mean physical function in the intervention groups was

1.3 higher

(2.29 lower to 4.89 higher)

Psychological distress (BDI, <3 months)

Scale from: 0 to 63.

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean psychological distress in the control groups was

8.5

The mean psychological distress in the intervention groups was

1.2 higher

(3.36 lower to 5.76 higher)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 53Clinical evidence summary: Strength versus flexibility

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Strength versus flexibility (95% CI)
Pain reduction at ≤3 months (VAS, 0–100, change scores and final values, high is poor outcome)	86 (2 studies) 12 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		-	The mean pain score reduction in the intervention groups was 8.09 lower (14.58 to 1.59 lower)
Quality of life at >3 months (SF-36 physical component, 0–100, final values, high is good outcome)	66 (1 study) 16 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 9.2	The mean quality of life score in the intervention groups was 1.5 higher (2.64 lower to 5.64 higher)
Quality of life at >3 months (SF-36 mental component, 0–100, final values, high is good outcome)	66 (1 study) 16 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 44.55	The mean quality of life score in the intervention groups was 5.39 lower (11.75 lower to 0.97 higher)
Physical function at ≤3 months (FIQ physical function subscale, 0–30, final values, high is poor outcome)	30 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 9.5	The mean physical function score in the intervention groups was 6 higher (2.34 to 9.66 higher)
Psychological distress at ≤3 months (BDI, 0–61, change scores, high is poor outcome)	56 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress change score in the control groups was −1.84	The mean psychological distress score in the intervention groups was 1.83 lower (3.99 lower to 0.33 higher)
Psychological distress at ≤3 months (BAI, 0–61, change scores, high is poor outcome)	56 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias, imprecision		The mean psychological distress change score in the control groups was +0.7	The mean psychological distress score in the intervention groups was 3.2 lower (6.42 lower to 0.02 higher)
Sleep at ≤3 months (FIQ sleep subscale, 0–10, change scores, high is poor outcome)	56 (1 study) 12 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean sleep change score in the control groups was −0.53	The mean sleep score in the intervention groups was 1.77 lower (2.62 to 0.92 lower)
Discontinuation at >3 months	157 (3 studies) 12–16 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 0.68 (0.36 to 1.28)
Discontinuation at >3 months	157 (3 studies) 12–16 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 0.68 (0.36 to 1.28)	214 per 1000	68 fewer per 1000 (from 137 fewer to 60 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 54Clinical evidence summary: Strength and flexibility versus flexibility

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Strength and flexibility versus flexibility (95% CI)
Quality of life at >3 months (SF-36 physical functioning subscale, 0–100, final values, high is good outcome)	86 (1 study) 12 months	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 92.4	The mean quality of life score in the intervention groups was 0.4 lower (4.92 lower to 4.12 higher)
Quality of life at >3 months (SF-36 role physical subscale, 0–100, final values, high is good outcome)	86 (1 study) 12 months	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 79.4	The mean quality of life score in the intervention groups was 1.1 lower (15.9 lower to 13.7 higher)
Quality of life at >3 months (SF-36 role emotional subscale, 0–100, final values, high is good outcome)	86 (1 study) 12 months	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 87	The mean quality of life score in the intervention groups was 2.1 higher (9.7 lower to 13.9 higher)
Quality of life at >3 months (SF-36 vitality subscale, 0–100, final values, high is good outcome)	86 (1 study) 12 months	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 63.4	The mean quality of life score in the intervention groups was 5.2 higher (2.96 lower to 13.36 higher)
Quality of life at >3 months (SF-36 emotional wellbeing subscale, 0–100, final values, high is good outcome)	86 (1 study) 12 months	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 75.9	The mean quality of life score in the intervention groups was 3.6 higher (3.43 lower to 10.63 higher)
Quality of life at >3 months (SF-36 social functioning subscale, 0–100, final values, high is good outcome)	86 (1 study) 12 months	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 88.7	The mean quality of life score in the intervention groups was 1.7 higher (5.28 lower to 8.68 higher)
Quality of life at >3 months (SF-36 bodily pain subscale, 0–100, final values, high is good outcome)	86 (1 study) 12 months	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 70.9	The mean quality of life score in the intervention groups was 1.7 lower (10.14 lower to 6.74 higher)
Quality of life at >3 months (SF-36 general health subscale, 0–100, final values, high is good outcome)	86 (1 study) 12 months	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 71.4	The mean quality of life score in the intervention groups was 0.7 higher (6.41 lower to 7.81 higher)
Discontinuation at >3 months	101 (1 study) 12 months	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 0.71 (0.27 to 1.84)	173 per 1000	50 fewer per 1000 (from 126 fewer to 145 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 55Clinical evidence summary: Strength and flexibility versus mind-body

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Strength and flexibility versus mind-body (95% CI)
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	117 (2 studies) 9–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		The mean pain score in the control groups was 42.2	The mean pain score in the intervention groups was 10.4 lower (23.66 lower to 2.85 higher)
Pain at >3 months (VAS, 0–100, final values, high is poor outcome)	140 (2 studies) 24 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean pain score in the control groups was 39.9	The mean pain score in the intervention groups was 0.78 lower (8.05 lower to 6.49 higher)
Quality of life at ≤3 months (SF-36 mental component, 0–100, final values, high is good outcome)	117 (2 studies) 9–12 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 46.95	The mean quality of life score in the intervention groups was 2.88 higher (0.8 lower to 6.55 higher)
Quality of life at >3 months (SF-36 mental component, 0–100, final values, high is good outcome)	140 (2 studies) 24 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 45.45	The mean quality of life score in the intervention groups was 1.05 higher (2.28 lower to 4.38 higher)
Quality of life at ≤3 months (SF-36 physical component, 0–100, final values, high is good outcome)	117 (2 studies) 9–12 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 37.3	The mean quality of life score in the intervention groups was 1.04 higher (1.9 lower to 3.99 higher)
Quality of life at >3 months (SF-36 physical component, 0–100, final values, high is good outcome)	140 (2 studies) 24 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, imprecision		The mean quality of life score in the control groups was 39.2	The mean quality of life score in the intervention groups was 2.21 lower (4.81 lower to 0.38 higher)
Physical function at ≤3 months (Neck disability index, neck pain disability scale, final values, high is poor outcome)	117 (2 studies) 9–12 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, imprecision		-	The mean physical function score in the intervention groups was 0.22 standard deviations lower (0.59 lower to 0.14 higher)
Physical function at >3 months (Neck pain disability scale, final values, high is poor outcome)	140 (2 studies) 24 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean physical function score in the control groups was 19.9	The mean physical function score in the intervention groups was 0.22 higher (5.02 lower to 5.46 higher)
Psychological distress at ≤3 months (Depression scale ADS, 0–60, final values, high is poor outcome)	66 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, imprecision		The mean psychological distress score in the control groups was 19.7	The mean psychological distress score in the intervention groups was 0.5 higher (3.66 lower to 4.66 higher)
Psychological distress at >3 months (Depression scale ADS, 0–60, final values, high is poor outcome)	66 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,³ due to risk of bias, The mean quality of life score in the control groups was imprecision		The mean psychological distress score in the control groups was 22.7	The mean psychological distress score in the intervention groups was 1.8 lower (6.07 lower to 2.47 higher)
Discontinuation at >3 months	209 (3 studies) 9–24 weeks	⊕⊝⊝⊝ VERY LOW¹^,³ due to risk of bias, imprecision	OR 0.87 (0.35 to 2.14)	103 per 1000	12 fewer per 1000 (from 64 fewer to 94 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded for heterogeneity, unexplained by subgroup analysis

3: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 56Clinical evidence summary: Strength, flexibility and proprioception versus mind-body

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Strength, flexibility and proprioception versus mind-body (95% CI)
Pain reduction at ≤3 months (VAS, 0–100, final values, high is poor outcome)	75 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 32.4	The mean pain score in the intervention groups was 7.2 lower (16.72 lower to 2.32 higher)
Pain reduction at >3 months (VAS, 0–100, final values, high is poor outcome)	75 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 35	The mean pain score reduction in the intervention groups was 1.9 lower (12.99 lower to 9.19 higher)
Quality of life at ≤3 months (SF-36 physical component summary score, final values, 0–100, high is good outcome)	75 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 47.3	The mean quality of life score in the intervention groups was 2.1 lower (5.48 lower to 1.28 higher)
Quality of life at >3 months (SF-36 physical component summary score, final values, 0–100, high is good outcome)	75 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 46.5	The mean quality of life score in the intervention groups was 2.5 lower (6.22 lower to 1.22 higher)
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)	75 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 46.8	The mean quality of life score in the intervention groups was 0.9 higher (3.77 lower to 5.57 higher)
Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)	75 (1 study) 24 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 47	The mean quality of life score in the intervention groups was 0.1 lower (4.96 lower to 4.76 higher)
Physical function at ≤3 months (Neck disability index, 0–100, final values, high is poor outcome)	75 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 21.5	The mean physical function score in the intervention groups was 1.2 higher (3.7 lower to 6.1 higher)
Physical function at >3 months (Neck disability index, 0–100, final values, high is poor outcome)	75 (1 study) 24 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean physical function score in the control groups was 24.3	The mean physical function score in the intervention groups was 0.8 higher (5.31 lower to 6.91 higher)
Psychological distress at ≤3 months (HADS: anxiety, 0–21, final values, high is poor outcome)	75 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 6.5	The mean psychological distress score in the intervention groups was 1 lower (2.8 lower to 0.8 higher)
Psychological distress at >3 months (HADS: anxiety, 0–21, final values, high is poor outcome)	75 (1 study) 24 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 6.1	The mean psychological distress score in the intervention groups was 0.6 lower (2.34 lower to 1.14 higher)
Psychological distress at ≤3 months (HADS: depression, 0–21, final values, high is poor outcome)	75 (1 study) 12 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean psychological distress score in the control groups was 3.9	The mean psychological distress score in the intervention groups was 0.1 lower (1.52 lower to 1.32 higher)
Psychological distress at >3 months (HADS: depression, 0–21, final values, high is poor outcome)	75 (1 study) 24 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean psychological distress score in the control groups was 4.1	The mean psychological distress score in the intervention groups was 0 higher (1.51 lower to 1.51 higher)
Discontinuation at ≤3 months	75 (1 study) 12 weeks	⊕⊕⊕⊕ HIGH	RR 4.45 (1.38 to 14.35)	79 per 1000	273 more per 1000 (from 30 more to 1000 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 57Clinical evidence summary: Strength versus proprioception

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95 % CI)

Anticipated absolute effects

Risk with Control

Risk difference with Strength versus proprioception (95% CI)

Physical function at ≤3 months (Neck disability index, 0–50, final values, high is poor outcome)

(1 study)

8 weeks

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean physical function score in the control groups was 4.14

The mean physical function score in the intervention groups was

0.32 higher

(1.47 lower to 2.11 higher)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

Table 58Clinical evidence summary: Mind-body versus flexibility

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Mind-body versus flexibility (95% CI)
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	55 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 69	The mean pain score in the intervention groups was 2 higher (9.65 lower to 13.65 higher)
Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)	49 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 77.6	The mean quality of life score in the intervention groups was 22.9 lower (33.4 to 12.4 lower)
Psychological distress at ≤3 months (BDI, 0–61, final values, high is poor outcome)	81 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 17.8	The mean psychological distress score in the intervention groups was 0.5 higher (3.55 lower to 4.55 higher)
Sleep at ≤3 months (Pittsburgh sleep quality index, 0–21, final values, high is poor outcome)	81 (1 study) 12 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean sleep score in the control groups was 13.7	The mean sleep score in the intervention groups was 0 higher (1.92 lower to 1.92 higher)
Discontinuation at ≤3 months	62 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 1.83 (0.83 to 4.02)	Moderate
Discontinuation at ≤3 months	62 (1 study) 12 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 1.83 (0.83 to 4.02)	219 per 1000	182 more per 1000 (from 37 fewer to 661 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 59Clinical evidence summary: Mind-body versus biomechanical

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Control

Risk difference with Mind-body versus biomechanical (95% CI)

Pain (VAS, <3 months)

Scale from: 0 to 10.

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean pain in the control groups was

1.7

The mean pain in the intervention groups was

0.3 lower

(1.51 lower to 0.91 higher)

Quality of life (Nottingham health profile, <3 months)

Scale from: 0 to 600.

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life in the control groups was

118.2

The mean quality of life in the intervention groups was

28.4 lower

(84.68 lower to 27.88 higher)

Physical function (NDI, <3 months)

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean physical function in the control groups was

The mean physical function in the intervention groups was

1.8 lower

(4.86 lower to 1.26 higher)

Psychological distress (Depression, BDI, <3 months) Scale from: 0 to 63.

(1 study)

6 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean psychological distress in the control groups was

8.5

The mean psychological distress in the intervention groups was

2.1 lower

(6.11 lower to 1.91 higher)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 60Clinical evidence summary: Flexibility and proprioception versus flexibility

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95 % CI)	Risk with Control	Risk difference with Flexibility and proprioception versus flexibility (95% CI)
Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)	57 (1 study) 6 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 65.55	The mean quality of life score in the intervention groups was 12.7 lower (21.27 to 4.13 lower)
Psychological distress at ≤3 months (BDI, 0–63, final values, high is poor outcome)	57 (1 study) 6 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean psychological distress score in the control groups was 13.79	The mean psychological distress score in the intervention groups was 3.88 higher (0.46 lower to 8.22 higher)
Discontinuation at ≤3 months	68 (1 study) 6 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 1.65 (0.53 to 5.12)	Moderate
Discontinuation at ≤3 months	68 (1 study) 6 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 1.65 (0.53 to 5.12)	121 per 1000	79 more per 1000 (from 57 fewer to 499 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 61Clinical evidence summary: Flexibility and relaxation versus aerobic exercise

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with Control	Risk difference with Flexibility and relaxation versus aerobic (95% CI)
Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)	133 (1 study) 12 months	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 55.6	The mean quality of life score in the intervention groups was 0.4 higher (4.64 lower to 5.44 higher)
Discontinuation at ≤3 months	136 (1 study) 12 months	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 0.97 (0.47 to 2.01)
Discontinuation at ≤3 months	136 (1 study) 12 months	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 0.97 (0.47 to 2.01)	30 per 1000	10 fewer per 1000 (from 130 fewer to 120 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 62Clinical evidence summary: Exercise versus psychological therapies

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with

Risk difference with Exercise versus psychological therapies (95% CI)

Pain at ≤3 months (VAS, FIQ pain scale, 0–100, high is poor outcome, final values and change scores) - Fibromyalgia

251

(4 studies)

8–12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²^,³

due to risk of bias, inconsistency, imprecision

The mean pain score in the control groups was

31.35

The mean pain score in the intervention groups was

1.61 lower

(15.09 lower to 11.87 higher)

Pain at >3 months (VAS, NRS, 0–100, high is poor outcome, final values)

468

(4 studies)

12–52 weeks

⊕⊝⊝⊝

VERY LOW¹^,²^,³

due to risk of bias, inconsistency, imprecision

The mean pain score in the control groups was 50.35

The mean pain score in the intervention groups was

7.19 lower

(13.98 to 0.41 lower)

Quality of life at ≤3 months (FIQ, 0–100, high is poor outcome, final values and change scores)

292

(4 studies)

6–12 weeks

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean quality of life score in the intervention groups was

6.7 lower

(10.88 to 2.52 lower)

Quality of life at >3 months (EQ-5D, high is good outcome, final values)

152

(1 study)

9 months

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was 0.754

The mean quality of life score in the intervention groups was

0.05 lower

(0.12 lower to 0.02 higher)

Quality of life at >3 months (SF36 social aspects subscale, 0–100, high score is good outcome

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

63.9

The mean quality of life score outcome in the intervention groups was

3.4 higher

(9.27 lower to 16.07 higher)

Quality of life at >3 months (SF36 general health status aspects subscale, 0–100, high score is good outcome

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

44.6

The mean quality of life score in the intervention groups was

2.6 higher

(8.08 lower to 13.28 higher)

Quality of life at >3 months (SF36 funcitonal capacity aspects subscale, 0–100, high score is good outcome

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score outcome in the control groups was

The mean quality of life score in the intervention groups was

13.1 higher

(2.72 to 23.48 higher)

Quality of life at >3 months (SF36 limitations due to physical aspects subscale, 0–100, high score is good outcome

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

38.1

The mean quality of score in the intervention groups was

17.2 higher

(2.83 lower to 37.23 higher)

Quality of life at >3 months (SF36 limitations due to emotional aspects subscale, 0–100, high score is good outcome

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

37.5

The mean quality of life score in the intervention groups was

11.9 higher

(8.74 lower to 32.54 higher)

Quality of life at >3 months (SF36 pain subscale, 0–100, high score is good outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

29.9

The mean quality of life score in the intervention groups was

5 higher

(5.39 lower to 15.39 higher)

Quality of life at >3 months (SF36 mental health subscale, 0–100, high score is good outcome)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean quality of life score in the control groups was

58.6

The mean quality of life score in the intervention groups was

0.9 higher

(11.04 lower to 12.84 higher)

Physical function at ≤3 months (FIQ physical function subscale, 0–10, high is poor outcome, change scores)

(1 study)

12 weeks

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean physical function change in the control groups was −0.5

The mean physical function score in the intervention groups was

0.7 lower

(2.75 lower to 1.35 higher)

Physical function at ≤3 months (6 minute walk test, metres, high is good outcome, final values)

139

(2 studies)

12 weeks

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean physical function score in the control groups was 429.4

The mean physical function score in the intervention groups was

26.42 higher

(0.85 lower to 53.69 higher)

Physical function at >3 months (6 minute walking test, metres, high is good outcome, final values)

165

(2 studies)

12–5 weeks

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean physical function score in the control groups was 474.5

The mean physical function score in the intervention groups was

49.05 higher

(25.45 to 72.65 higher)

Psychological distress at ≤3 months (CES-D, 0–100, high is poor outcome, final values)

(1 study)

12 weeks

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean psychological distress score in the control groups was 67

The mean psychological distress score in the intervention groups was

10.3 lower

(20.07 to 0.53 lower)

Psychological distress at >3 months (Hospital anxiety and depression scale, depression subscale, 0–21, high is poor outcome, change scores)

104

(1 study)

15 weeks

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean psychological distress change in the control groups was +0.3

The mean psychological distress score in the intervention groups was

1 lower

(2.25 lower to 0.25 higher)

Psychological distress at >3 months (Hospital anxiety and depression scale, anxiety subscale, 0–21, high is poor outcome, change scores)

105

(1 study)

15 weeks

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean psychological distress change in the control groups was +0.5

The mean psychological distress score in the intervention groups was

0.8 lower

(2.01 lower to 0.41 higher)

Sleep at >3 months (the sleep scale, 0–30, final values, high is poor outcome)

190

(1 study)

9 months

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean sleep in the control groups was 12.4

The mean sleep score in the intervention groups was

0.3 higher

(1.22 lower to 1.82 higher)

Sleep at >3 months (Pittsburgh sleep quality index, 0–21, high is poor outcome, change scores)

105

(1 study)

15 weeks

⊕⊕⊝⊝

LOW¹

due to risk of bias, imprecision

The mean sleep change in the control groups was +0.5

The mean sleep score in the intervention groups was

1.1 lower

(2.32 lower to 0.12 higher)

Discontinuation at >3 months (due to increased pain, personal reasons, lost to follow up)

1062

(10 studies)

8–52 weeks

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

RD −0.03 (−0.07 to 0.02)

172 per 1000

30 fewer per 1000

(from 70 fewer to 20 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 63Clinical evidence summary: Manual therapy and exercise versus manual therapy

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with Control	Risk difference with Manual therapy and exercise versus manual therapy (95% CI)
Pain at ≤3 months (NRS, high is poor outcome, final values, 0–10, final values)	101 (1 study) 11 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 3.7	The mean pain score in the intervention groups was 0.8 lower (1.66 lower to 0.06 higher)
Pain at >3 months (NRS, high is poor outcome, final values, 0–10, final values)	101 (1 study) 52 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias, imprecision		The mean pain score in the control groups was 3.9	The mean pain score in the intervention groups was 0.5 lower (1.42 lower to 0.42 higher)
Physical function at ≤3 months (Neck disability index, high is poor outcome, final values, 0–50, final values)	101 (1 study) 11 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias, imprecision		The mean physical function score in the control groups was 18.7	The mean physical function score in the intervention groups was 5.1 lower (9.65 to 0.55 lower)
Physical function at >3 months (Neck disability index, high is poor outcome, final values, 0–50)	101 (1 study) 24 months	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 20.5	The mean physical function score in the intervention groups was 4.9 lower (9.85 lower to 0.05 higher)
Discontinuation at ≤3 months	127 (1 study) 11 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 0.91 (0.47 to 1.79)
Discontinuation at ≤3 months	127 (1 study) 11 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 0.91 (0.47 to 1.79)	222 per 1000	20 fewer per 1000 (from 118 fewer to 175 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 64Clinical evidence summary: Manual therapy and exercise versus exercise

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with Control	Risk difference with Manual therapy and exercise versus exercise (95% CI)
Pain at ≤3 months (VAS, NRS, high is poor outcome, final values, 0–100, final values)	542 (6 studies) 4–12 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, imprecision, inconsistency		The mean pain score in the control groups was 30.9	The mean pain score in the intervention groups was 6.34 lower (13.82 lower to 1.13 higher)
Pain at >3 months (NRS, VAS, high is poor outcome, final values, 0–100)	394 (3 studies) 52 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean pain score in the control groups was 32	The mean pain score in the intervention groups was 0.95 higher (3.51 lower to 5.4 higher)
Quality of life at >3 months (Fibromyalgia impact questionnaire, 0–100, final values, high is poor outcome)	21 (1 study) 16 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean quality of life score in the control groups was 46.9	The mean quality of life score in the intervention groups was 1 lower (13.87 lower to 11.87 higher)
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)	180 (1 study) 12 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 50.1	The mean quality of life score in the intervention groups was 0.6 higher (1.34 lower to 2.54 higher)
Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)	180 (1 study) 52 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 49.8	The mean quality of life score in the intervention groups was 0.2 higher (1.79 lower to 2.19 higher)
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)	180 (1 study) 12 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 54.6	The mean quality of life score in the intervention groups was 0.7 lower (3.55 lower to 2.15 higher)
Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)	180 (1 study) 52 weeks	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean quality of life score in the control groups was 54.8	The mean quality of life score in the intervention groups was 1.8 lower (4.34 lower to 0.74 higher)
Physical function at >3 months (Neck disability index, functional performance scale, final values, high is poor outcome, 0–100)	477 (5 studies) 11–16 weeks	⊕⊝⊝⊝ VERY LOW¹^,²^,³ due to risk of bias, inconsistency, imprecision		-	The mean physical function score in the intervention groups was 0.29 standard deviations lower (0.62 lower to 0.04 higher)
Physical function at >3 months (Neck disability index, high is poor outcome, final values, 0–100)	394 (3 studies) 24 months	⊕⊕⊕⊝ MODERATE¹ due to risk of bias		The mean physical function score in the control groups was 16.7	The mean physical function score in the intervention groups was 0.17 lower (2.6 lower to 2.25 higher)
Physical function at ≤3 months (Neck disability index, high is poor outcome, 0–100)	86 (2 studies) 4–10 weeks	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean physical function score in the control groups was 18.68	The mean physical function score in the intervention groups was 8.14 lower (9.92 to 6.35 lower)
Discontinuation	542 (6 studies) 6–16 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RD 0 (−0.05 to 0.06)	127 per 1000	0 fewer per 1000 (from 50 fewer to 60 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

3: Downgraded for heterogeneity, unexplained by subgroup analysis

Table 65Clinical evidence summary: Exercise versus manual therapy

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with Control	Risk difference with Exercise versus manual therapy (95% CI)
Pain at ≤3 months (NRS, high is poor outcome, final values, 0–10)	101 (1 study) 11 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 3.7	The mean pain score in the intervention groups was 1.3 lower (2.11 to 0.49 lower)
Pain at >3 months (NRS, high is poor outcome, final values, 0–10)	101 (1 study) 52 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean pain score in the control groups was 3.9	The mean pain score in the intervention groups was 0.5 lower (1.42 lower to 0.42 higher)
Physical function at ≤3 months (Neck disability index, high is poor outcome, final values, 0–50)	94 (1 study) 11 weeks	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 18.7	The mean physical function score in the intervention groups was 5.9 lower (10.6 to 1.2 lower)
Physical function at >3 months (Neck disability index, high is poor outcome, final values, 0–50)	94 (1 study) 24 months	⊕⊕⊝⊝ LOW¹^,² due to risk of bias, imprecision		The mean physical function score in the control groups was 20.5	The mean physical function score in the intervention groups was 3.9 lower (9.14 lower to 1.34 higher)
Discontinuation at ≤3 months	127 (1 study) 11 weeks	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 1.34 (0.74 to 2.43)	222 per 1000	75 more per 1000 (from 58 fewer to 317 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 66Health economic evidence profile: Aerobic exercise therapy vs. psychological therapy or usual care

Study	Applicability	Limitations	Other comments	Incremental cost	Incremental QALYs	Cost effectiveness	Uncertainty
Beasley, 2015²⁸ [UK]	Directly applicable^(a)	Potentially serious limitations^(b)	Within-trial analysis (same paper) Cost-utility analysis (QALYs) Population: > 25 years and over with chronic widespread pain according to the definition in the American College of Rheumatology (ACR) 1990 criteria for fibromyalgia, for which they have consulted their general practitioner in the previous year. 6 month interventions Follow-up: 30 months (24 months post treatment) Comparators: Treatment as usual. Telephone-delivered cognitive behaviour therapy (TCBT): initial assessment (45–60 mins) followed by 7 weekly sessions (30–45 mins each), 1 session at three months, and 1 session at 6 months after randomisation. Exercise therapy: leisure-facility-and-gym-based exercise program consistent with American College of Sport Medicine guidelines for improving cardiorespiratory fitness. (only partly supervised with monthly instructor led appointments and people otherwise used the gym)	Complete case analysis:			Used non-parametric bootstrapping.
				(3-1): £1,924	(3-1): 0.025	ICER: £76,960 per QALY gained
				(3-2) £1,350	(3-2): −0.072	Dominated
				Multiple imputation analysis:
				(3-1): £1,256	(3-1): 0.071	ICER: £17,690 per QALY gained
				(3-2): £702	(3-2): −0.069	Dominated

: Abbreviations: ICER: incremental cost-effectiveness ratio; QALY: quality-adjusted life years; RCT: randomised controlled trial

(a): UK NHS study, used EQ-5D. Participation in study based on self-reported symptoms and recruited through primary care, may not necessarily be representative of general population with chronic widespread pain caused by fibromyalgia.

(b): Treatment as usual not defined, usual care provided by GP was not restricted and may not be the same across all participants in that group. Within-study analysis which may not reflect full body of evidence. The imputed results are also quite different to the complete case data results, leading to a change in conclusion on cost effectiveness. It is hard to know which results should be used without knowing the details of the imputations and the nature of the missing data.

Table 67Health economic evidence profile: Aquatic based aerobic exercise + usual care versus usual care

Study

Applicability

Limitations

Other comments

Incremental cost

Incremental QALYs

Cost effectiveness

Uncertainty

Gusi 2008¹¹⁶(Spain)

Partially applicable^(a)

Potentially serious limitations^(b)

Within trial analysis²⁵²^,²⁵³
Cost-utility analysis (QALYs)
Population: women with Fibromyalgia.
8 month intervention.
Follow-up: 8 months

Comparing:

Exercise + usual care: Exercise programme in a waist high pool of warm water (33°C). A qualified exercise leader instructed and trained the group three times a week for 1 h per session over a period of 8 months.
Treatment as usual

£475^(c)

0.131 QALYs

£3,630 per QALY gained

Probability exercise cost effective: Determined by reading off the graph based on the ‘2005 adjusted investment ceiling set at €34,729/QALY): approx. 97%

Various sensitivity analyses tested such as varying the number of people per group (participation), the salaries of the staff. And testing worst and best case scenarios based on participation, salaries, and extremes of confidence interval for QALY difference. Only the worst case scenario led to the intervention not being cost effective based on the threshold published in the Spanish literature.

: Abbreviations: ICER= incremental cost-effectiveness ratio; QALY= quality-adjusted life years; RCT= randomised controlled trial FM = Fibromyalgia.

(a): Uses EQ-5D. Non-UK study.

(b): Only based on one study. Date and costs may not reflect current NHS context. Costs of staff look very low compared to UK costs which will affect the ICER. Recruitment of participants was through local FM association, perhaps not representative of wider population with FM.

(c): 2005 Spanish Euros converted to UK pounds.²⁰⁸ Cost components incorporated: Programme cost (based on staff costs, renting the pool, management costs of the programme like insurance). Health care costs (consultations, drug process).

Table 68Base case results (discounted)

Base case	Analysis	Incremental cost	Incremental QALYs	Cost per QALY gained	Probability cost effective at £20k
Lifetime	Probabilistic	£380	0.04	£9,121	86%
Lifetime	Deterministic	£380	0.031	£12,327	NA
No extrapolation beyond last trial observation (36 weeks)	Probabilistic	£380	0.03	£12,683	93%
No extrapolation beyond last trial observation (36 weeks)	Deterministic	£380	0.030	£12,739	NA

: Abbreviations: QALYs: quality adjusted life years, £20k: £20,000.

Table 69Health economic review protocol

Review question	All questions – health economic evidence
Objectives	To identify health economic studies relevant to any of the review questions.
Search criteria	Populations, interventions and comparators must be as specified in the clinical review protocol above. Studies must be of a relevant health economic study design (cost–utility analysis, cost-effectiveness analysis, cost–benefit analysis, cost–consequences analysis, comparative cost analysis). Studies must not be a letter, editorial or commentary, or a review of health economic evaluations. (Recent reviews will be ordered although not reviewed. The bibliographies will be checked for relevant studies, which will then be ordered.) Unpublished reports will not be considered unless submitted as part of a call for evidence. Studies must be in English.
Search strategy	A health economic study search will be undertaken using population-specific terms and a health economic study filter – see appendix B below.
Review strategy	Studies not meeting any of the search criteria above will be excluded. Studies published before 2002. Abstract-only studies and studies from non-OECD countries or the USA will also be excluded. Each remaining study will be assessed for applicability and methodological limitations using the NICE economic evaluation checklist which can be found in appendix H of Developing NICE guidelines: the manual (2014).²⁰¹ Inclusion and exclusion criteria If a study is rated as both ‘Directly applicable’ and with ‘Minor limitations’ then it will be included in the guideline. A health economic evidence table will be completed and it will be included in the health economic evidence profile. If a study is rated as either ‘Not applicable’ or with ‘Very serious limitations’ then it will usually be excluded from the guideline. If it is excluded then a health economic evidence table will not be completed and it will not be included in the health economic evidence profile. If a study is rated as ‘Partially applicable’, with ‘Potentially serious limitations’ or both then there is discretion over whether it should be included. Where there is discretion The health economist will make a decision based on the relative applicability and quality of the available evidence for that question, in discussion with the guideline committee if required. The ultimate aim is to include health economic studies that are helpful for decision-making in the context of the guideline and the current NHS setting. If several studies are considered of sufficiently high applicability and methodological quality that they could all be included, then the health economist, in discussion with the committee if required, may decide to include only the most applicable studies and to selectively exclude the remaining studies. All studies excluded on the basis of applicability or methodological limitations will be listed with explanation in the excluded health economic studies appendix below. The health economist will be guided by the following hierarchies. Setting: UK NHS (most applicable). OECD countries with predominantly public health insurance systems (for example, France, Germany, Sweden). OECD countries with predominantly private health insurance systems (for example, Switzerland). Studies set in non-OECD countries or in the USA will be excluded before being assessed for applicability and methodological limitations. Health economic study type: Cost–utility analysis (most applicable). Other type of full economic evaluation (cost–benefit analysis, cost-effectiveness analysis, cost–consequences analysis). Comparative cost analysis. Non-comparative cost analyses including cost-of-illness studies will be excluded before being assessed for applicability and methodological limitations. Year of analysis: The more recent the study, the more applicable it will be. Studies published in 2002 or later but that depend on unit costs and resource data entirely or predominantly from before 2002 will be rated as ‘Not applicable’. Studies published before 2002 will be excluded before being assessed for applicability and methodological limitations. Quality and relevance of effectiveness data used in the health economic analysis: The more closely the clinical effectiveness data used in the health economic analysis match with the outcomes of the studies included in the clinical review the more useful the analysis will be for decision-making in the guideline.

Database

Dates searched

Search filter used

Medline (OVID)

1946 – 20 May 2020

Exclusions

Randomised controlled trials

Systematic review studies

Embase (OVID)

1974 – 20 May 2020

Exclusions

Randomised controlled trials

Systematic review studies

The Cochrane Library (Wiley)

Cochrane Reviews to 2020 Issue 5 of 12

CENTRAL to 2020 Issue 5 of 12

None

Medline (Ovid) search terms

1.	Chronic pain/
2.	((chronic or persist* or idiopathic or atypical or a-typical) adj4 pain).ti,ab.
3.	exp Complex Regional Pain Syndromes/
4.	(complex regional pain syndrome* or CRPS or causalgia).ti,ab.
5.	((reflex or sympathetic) adj2 dystroph*).ti,ab.
6.	fibromyalgia/
7.	(fibromyalgia* or fibrositis or myofascial pain syndrome).ti,ab.
8.	vulvodynia/
9.	(vulvodynia or vestibulodynia or dyspareunia or vulvar vestibulitis or vulvitis).ti,ab.
10.	interstitial cystitis/
11.	(interstitial adj2 cystitis).ti,ab.
12.	algodystrophy/
13.	(algodystroph* or sudek or sudeck*).ti,ab.
14.	exp myofascial pain syndromes/
15.	cystitis, interstitial/
16.	(loin pain adj (haematuria or hematuria) adj syndrome*).ti,ab.
17.	(LPHS or prostatodynia or CPPS or atypic* odontalgia or a-typic* odontalgia or burning mouth syndrome* or phantom tooth pain or neuropathic orofacial pain or “myofascial pain” or MPS).ti,ab.
18.	((pelvic or pelvis) adj pain syndrome*).ti,ab.
19.	((non-cardiac or noncardiac) adj3 chest adj3 pain).ti,ab.
20.	(temporomandibular adj3 joint adj3 pain).ti,ab.
21.	((prostate or vulv* or bladder or perineal) adj3 pain).ti,ab.
22.	(functional pain syndrome* or non-cancer pain or noncancer pain).ti,ab.
23.	((pelvic or pelvis or abdominal) adj3 pain adj3 (unknown or un-known or idiopathic or atypic* or a-typic*)).ti,ab.
24.	or/1–23
25.	letter/
26.	editorial/
27.	news/
28.	exp historical article/
29.	Anecdotes as Topic/
30.	comment/
31.	case report/
32.	(letter or comment*).ti.
33.	or/25–32
34.	randomized controlled trial/ or random*.ti,ab.
35.	33 not 34
36.	animals/ not humans/
37.	exp Animals, Laboratory/
38.	exp Animal Experimentation/
39.	exp Models, Animal/
40.	exp Rodentia/
41.	(rat or rats or mouse or mice).ti.
42.	or/35–41
43.	24 not 42
44.	limit 43 to English language
45.	exp exercise/
46.	exp exercise therapy/
47.	exp Exercise Movement Techniques/
48.	exp “physical education and training”/
49.	(pilates or yoga or feldenkrais or swim* or walk* or run* or jog* or treadmill* or tread mill*).ti,ab.
50.	(stretch* adj3 (active* or passive* or relax* or static* or dynamic* or gentl* or ballistic* or force* or isometric or technique* or exercis* or therap*)).ti,ab.
51.	(aerobic* adj (exercise* or train* or therap*)).ti,ab.
52.	((corrective* or biomechanic* or propiocet* or balance or flexib) adj2 (exercise or train* or therap*)).ti,ab.
53.	((biomechanic* or mckenzie) adj (method* or course*)).ti,ab.
54.	((strength* or stabil* or program* or train* or therap* or technique* or treat) adj3 exercise).ti,ab.
55.	(physical adj (fitness or conditioning or education or training or mobility or activit$ or exertion or effort)).ti,ab.
56.	danc*.ti,ab.
57.	(fitness* adj3 (program* or train* or therap*)).ti,ab.
58.	(tai ji or tai chi or taichi or taiji or taijiquan).ti,ab.
59.	(qigong or ch’i k#ng or ch’i g#ng or chi k#ng or chi g#ng or qi k#ng or qi g#ng).ti,ab.
60.	core stability.ti,ab.
61.	exp hydrotherapy/
62.	((water* or bath* or pool or pools or shower* or underwater* or spa or spas or aqua) adj2 (exercise or train* or therap* or treat*)).ti,ab.
63.	(hydrotherap* or hydro-therap*).ti,ab.
64.	(graded motor imagery or GMI or mirror therapy).ti,ab.
65.	or/45–64
66.	44 and 65
67.	randomized controlled trial.pt.
68.	controlled clinical trial.pt.
69.	randomi#ed.ti,ab.
70.	placebo.ab.
71.	randomly.ti,ab.
72.	Clinical Trials as topic.sh.
73.	trial.ti.
74.	or/67–73
75.	Meta-Analysis/
76.	exp Meta-Analysis as Topic/
77.	(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.
78.	((systematic* or evidence) adj3 (review or overview*)).ti,ab.
79.	(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.
80.	(search strategy or search criteria or systematic search or study selection or data extraction).ab.
81.	(search* adj4 literature).ab.
82.	(medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or cinahl or science citation index or bids or cancerlit).ab.
83.	cochrane.jw.
84.	((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.
85.	or/75–84
86.	66 and (74 or 85)

Embase (Ovid) search terms

1.	Chronic pain/
2.	((chronic or persist* or idiopathic or atypical or a-typical) adj4 pain).ti,ab.
3.	exp Complex regional pain syndrome/
4.	(complex regional pain syndrome* or CRPS or causalgia).ti,ab.
5.	((reflex or sympathetic) adj2 dystroph*).ti,ab.
6.	fibromyalgia/
7.	(fibromyalgia* or fibrositis or myofascial pain syndrome).ti,ab.
8.	vulvodynia/
9.	(vulvodynia or vestibulodynia or dyspareunia or vulvar vestibulitis or vulvitis).ti,ab.
10.	interstitial cystitis/
11.	(interstitial adj2 cystitis).ti,ab.
12.	algodystrophy/
13.	(algodystroph* or sudek or sudeck*).ti,ab.
14.	myofascial pain/
15.	noncardiac chest pain/
16.	cystalgia/
17.	Pelvis pain syndrome/
18.	(loin pain adj (haematuria or hematuria) adj syndrome*).ti,ab.
19.	(LPHS or prostatodynia or CPPS or atypic* odontalgia or a-typic* odontalgia or burning mouth syndrome* or phantom tooth pain or neuropathic orofacial pain or “myofascial pain” or MPS).ti,ab.
20.	((pelvic or pelvis) adj pain syndrome*).ti,ab.
21.	((non-cardiac or noncardiac) adj3 chest adj3 pain).ti,ab.
22.	(temporomandibular adj3 joint adj3 pain).ti,ab.
23.	((prostate or vulv* or bladder or perineal) adj3 pain).ti,ab.
24.	(functional pain syndrome* or non-cancer pain or noncancer pain).ti,ab.
25.	((pelvic or pelvis or abdominal) adj3 pain adj3 (unknown or un-known or idiopathic or atypic* or a-typic*)).ti,ab.
26.	or/1–25
27.	letter.pt. or letter/
28.	note.pt.
29.	editorial.pt.
30.	case report/ or case study/
31.	(letter or comment*).ti.
32.	or/27–31
33.	randomized controlled trial/ or random*.ti,ab.
34.	32 not 33
35.	animal/ not human/
36.	nonhuman/
37.	exp Animal Experiment/
38.	exp Experimental Animal/
39.	animal model/
40.	exp Rodent/
41.	(rat or rats or mouse or mice).ti.
42.	or/34–41
43.	26 not 42
44.	exp exercise/
45.	exp kinesiotherapy/
46.	exp physical education/
47.	(pilates or yoga or feldenkrais or swim* or walk* or run* or jog* or treadmill* or tread mill*).ti,ab.
48.	(stretch* adj3 (active* or passive* or relax* or static* or dynamic* or gentl* or ballistic* or force* or isometric or technique* or exercis* or therap*)).ti,ab.
49.	(aerobic* adj (exercise* or train* or therap*)).ti,ab.
50.	((corrective* or biomechanic* or propiocet* or balance or flexib) adj2 (exercise or train* or therap*)).ti,ab.
51.	((biomechanic* or mckenzie) adj (method* or course*)).ti,ab.
52.	((strength* or stabil* or program* or train* or therap* or technique* or treat) adj3 exercise).ti,ab.
53.	(physical adj (fitness or conditioning or education or training or mobility or activit$ or exertion or effort)).ti,ab.
54.	danc*.ti,ab.
55.	(fitness* adj3 (program* or train* or therap*)).ti,ab.
56.	(tai ji or tai chi or taichi or taiji or taijiquan).ti,ab.
57.	(qigong or ch’i k#ng or ch’i g#ng or chi k#ng or chi g#ng or qi k#ng or qi g#ng).ti,ab.
58.	core stability.ti,ab.
59.	exp hydrotherapy/
60.	((water* or bath* or pool or pools or shower* or underwater* or spa or spas or aqua) adj2 (exercise or train* or therap* or treat*)).ti,ab.
61.	(hydrotherap* or hydro-therap*).ti,ab.
62.	(graded motor imagery or GMI or mirror therapy).ti,ab.
63.	or/44–62
64.	43 and 63
65.	limit 64 to English language
66.	randomized controlled trial.pt.
67.	controlled clinical trial.pt.
68.	randomi#ed.ti,ab.
69.	placebo.ab.
70.	randomly.ti,ab.
71.	Clinical Trials as topic.sh.
72.	trial.ti.
73.	or/66–72
74.	Meta-Analysis/
75.	exp Meta-Analysis as Topic/
76.	(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.
77.	((systematic* or evidence) adj3 (review or overview*)).ti,ab.
78.	(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.
79.	(search strategy or search criteria or systematic search or study selection or data extraction).ab.
80.	(search* adj4 literature).ab.
81.	(medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or cinahl or science citation index or bids or cancerlit).ab.
82.	cochrane.jw.
83.	((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.
84.	or/74–83
85.	65 and (73 or 84)

Cochrane Library (Wiley) search terms

#1.	MeSH descriptor: [Chronic Pain] explode all trees
#2.	((chronic or persist* or idiopathic or atypical or a-typical) near/4 pain):ti,ab
#3.	MeSH descriptor: [Complex Regional Pain Syndromes] explode all trees
#4.	(complex regional pain syndrome* or CRPS or causalgia):ti,ab
#5.	((reflex or sympathetic) near/2 dystroph*):ti,ab
#6.	MeSH descriptor: [Fibromyalgia] explode all trees
#7.	(fibromyalgia* or fibrositis or myofascial pain syndrome):ti,ab
#8.	MeSH descriptor: [Vulvodynia] explode all trees
#9.	(vulvodynia or vestibulodynia or dyspareunia or vulvar vestibulitis or vulvitis):ti,ab
#10.	MeSH descriptor: [Cystitis, Interstitial] explode all trees
#11.	(interstitial near/2 cystitis):ti,ab
#12.	MeSH descriptor: [Reflex Sympathetic Dystrophy] explode all trees
#13.	(algodystroph* or sudek or sudeck*):ti,ab
#14.	MeSH descriptor: [Myofascial Pain Syndromes] explode all trees
#15.	(loinpain near (haematuria or hematuria) near syndrome*):ti,ab
#16.	(LPHS or prostatodynia or CPPS or atypic* odontalgia or a-typic* odontalgia or burning mouth syndrome* or phantom tooth pain or neuropathic orofacial pain or “myofascial pain” or MPS):ti,ab
#17.	((pelvic or pelvis) near pain syndrome*):ti,ab
#18.	((non-cardiac or noncardiac) near/3 chest near/3 pain):ti,ab
#19.	(temporomandibular near/3 joint near/3 pain):ti,ab
#20.	((prostate or vulv* or bladder or perineal) near/3 pain):ti,ab
#21.	(functional pain syndrome* or non-cancer pain or noncancer pain):ti,ab
#22.	((pelvic or pelvis or abdominal) near/3 pain near/3 (unknown or un-known or idiopathic or atypic* or a-typic*)):ti,ab
#23.	(or #1–#22)
#24.	MeSH descriptor: [Exercise] explode all trees
#25.	MeSH descriptor: [Exercise Therapy] explode all trees
#26.	MeSH descriptor: [Exercise Movement Techniques] explode all trees
#27.	MeSH descriptor: [Physical Education and Training] explode all trees
#28.	(pilates or yoga or feldenkrais or swim* or walk* or run* or jog* or treadmill* or tread mill*):ti,ab
#29.	(stretch* near/3 (active* or passive* or relax* or static* or dynamic* or gentl* or ballistic* or force* or isometric or technique* or exercis* or therap*)):ti,ab
#30.	(aerobic* near (exercise* or train* or therap*)):ti,ab
#31.	((corrective* or biomechanic* or propiocet* or balance or flexib) near/2 (exercise or train* or therap*)):ti,ab
#32.	((biomechanic* or mckenzie) near (method* or course*)):ti,ab
#33.	((strength* or stabil* or program* or train* or therap* or technique* or treat) near/3 exercise):ti,ab
#34.	(physical near (fitness or conditioning or education or training or mobility or activit$ or exertion or effort)):ti,ab
#35.	danc*:ti,ab
#36.	(fitness* near/3 (program* or train* or therap*)):ti,ab
#37.	(tai ji or tai chi or taichi or taiji or taijiquan):ti,ab
#38.	(qigong or ch’i k?ng or ch’i g?ng or chi k?ng or chi g?ng or qi k?ng or qi g?ng):ti,ab
#39.	core stability:ti,ab
#40.	MeSH descriptor: [Hydrotherapy] explode all trees
#41.	((water* or bath* or pool or pools or shower* or underwater* or spa or spas or aqua) near/2 (exercise or train* or therap* or treat*)):ti,ab
#42.	(hydrotherap* or hydro-therap*):ti,ab
#43.	(graded motor imagery or GMI or mirror therapy):ti,ab
#44.	(or #24–#43)
#45.	#23 and #44

Table 70Database date parameters and filters used

Database

Dates searched

Search filter used

Medline

2014 – 30 September 2019

Exclusions

Health economics studies

Health economics modelling studies

Embase

2014 – 30 September 2019

Exclusions

Health economics studies

Health economics modelling studies

Centre for Research and Dissemination (CRD)

HTA - Inception – 30 September 2019

NHSEED - Inception to March 2015

None

Medline search terms

1.	chronic pain/ or pain, intractable/
2.	((persist* or intract* or chronic or longstanding or long standing or longterm or long term or refractory or prolong* or long last* or sustain* or linger* or syndrome) adj3 pain).ti,ab.
3.	((chronic or persist* or idiopathic or atypical or a-typical) adj4 pain).ti,ab.
4.	exp Complex Regional Pain Syndromes/
5.	(complex regional pain syndrome* or CRPS or causalgia).ti,ab.
6.	fibromyalgia/
7.	((reflex or sympathetic) adj2 dystroph*).ti,ab.
8.	vulvodynia/
9.	(vulvodynia or vestibulodynia or dyspareunia or vulvar vestibulitis or vulvitis).ti,ab.
10.	interstitial cystitis/
11.	(interstitial adj2 cystitis).ti,ab.
12.	algodystrophy/
13.	(algodystroph* or sudek or sudeck*).ti,ab.
14.	exp myofascial pain syndromes/
15.	cystitis, interstitial/
16.	(loin pain adj (haematuria or hematuria) adj syndrome*).ti,ab.
17.	(LPHS or prostatodynia or CPPS or atypic* odontalgia or a-typic* odontalgia or burning mouth syndrome* or phantom tooth pain or neuropathic orofacial pain or “myofascial pain” or MPS).ti,ab.
18.	((pelvic or pelvis) adj pain syndrome*).ti,ab.
19.	((non-cardiac or noncardiac) adj3 chest adj3 pain).ti,ab.
20.	(temporomandibular adj3 joint adj3 pain).ti,ab.
21.	((prostate or vulv* or bladder or perineal) adj3 pain).ti,ab.
22.	(functional pain syndrome* or non-cancer pain or noncancer pain).ti,ab.
23.	((pelvic or pelvis or abdominal) adj3 pain adj3 (unknown or un-known or idiopathic or atypic* or a-typic*)).ti,ab.
24.	(fibromyalgia* or fibrositis or myofascial pain syndrome).ti,ab.
25.	or/1–24
26.	letter/
27.	editorial/
28.	news/
29.	exp historical article/
30.	Anecdotes as Topic/
31.	comment/
32.	case report/
33.	(letter or comment*).ti.
34.	or/26–33
35.	randomized controlled trial/ or random*.ti,ab.
36.	34 not 35
37.	animals/ not humans/
38.	exp Animals, Laboratory/
39.	exp Animal Experimentation/
40.	exp Models, Animal/
41.	exp Rodentia/
42.	(rat or rats or mouse or mice).ti.
43.	or/36–42
44.	25 not 43
45.	Economics/
46.	Value of life/
47.	exp “Costs and Cost Analysis”/
48.	exp Economics, Hospital/
49.	exp Economics, Medical/
50.	Economics, Nursing/
51.	Economics, Pharmaceutical/
52.	exp “Fees and Charges”/
53.	exp Budgets/
54.	budget*.ti,ab.
55.	cost*.ti.
56.	(economic* or pharmaco?economic*).ti.
57.	(price* or pricing*).ti,ab.
58.	(cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.
59.	(financ* or fee or fees).ti,ab.
60.	(value adj2 (money or monetary)).ti,ab.
61.	or/45–60
62.	exp models, economic/
63.	*Models, Theoretical/
64.	*Models, Organizational/
65.	markov chains/
66.	monte carlo method/
67.	exp Decision Theory/
68.	(markov* or monte carlo).ti,ab.
69.	econom* model*.ti,ab.
70.	(decision* adj2 (tree* or analy* or model*)).ti,ab.
71.	or/62–70
72.	44 and (61 or 71)

Embase (Ovid) search terms

1.	chronic pain/ or pain, intractable/
2.	((persist* or intract* or chronic or longstanding or long standing or longterm or long term or refractory or prolong* or long last* or sustain* or linger* or syndrome) adj3 pain).ti,ab.
3.	((chronic or persist* or idiopathic or atypical or a-typical) adj4 pain).ti,ab.
4.	exp Complex regional pain syndrome/
5.	(complex regional pain syndrome* or CRPS or causalgia).ti,ab.
6.	((reflex or sympathetic) adj2 dystroph*).ti,ab.
7.	fibromyalgia/
8.	(fibromyalgia* or fibrositis or myofascial pain syndrome).ti,ab.
9.	vulvodynia/
10.	(vulvodynia or vestibulodynia or dyspareunia or vulvar vestibulitis or vulvitis).ti,ab.
11.	interstitial cystitis/
12.	(interstitial adj2 cystitis).ti,ab.
13.	algodystrophy/
14.	(algodystroph* or sudek or sudeck*).ti,ab.
15.	myofascial pain/
16.	noncardiac chest pain/
17.	cystalgia/
18.	Pelvis pain syndrome/
19.	(loin pain adj (haematuria or hematuria) adj syndrome*).ti,ab.
20.	(LPHS or prostatodynia or CPPS or atypic* odontalgia or a-typic* odontalgia or burning mouth syndrome* or phantom tooth pain or neuropathic orofacial pain or “myofascial pain” or MPS).ti,ab.
21.	((pelvic or pelvis) adj pain syndrome*).ti,ab.
22.	((non-cardiac or noncardiac) adj3 chest adj3 pain).ti,ab.
23.	(temporomandibular adj3 joint adj3 pain).ti,ab.
24.	((prostate or vulv* or bladder or perineal) adj3 pain).ti,ab.
25.	(functional pain syndrome* or non-cancer pain or noncancer pain).ti,ab.
26.	((pelvic or pelvis or abdominal) adj3 pain adj3 (unknown or un-known or idiopathic or atypic* or a-typic*)).ti,ab.
27.	or/1–26
28.	letter.pt. or letter/
29.	note.pt.
30.	editorial.pt.
31.	case report/ or case study/
32.	(letter or comment*).ti.
33.	or/28–32
34.	randomized controlled trial/ or random*.ti,ab.
35.	33 not 34
36.	animal/ not human/
37.	nonhuman/
38.	exp Animal Experiment/
39.	exp Experimental Animal/
40.	animal model/
41.	exp Rodent/
42.	(rat or rats or mouse or mice).ti.
43.	or/35–42
44.	27 not 43
45.	health economics/
46.	exp economic evaluation/
47.	exp health care cost/
48.	exp fee/
49.	budget/
50.	funding/
51.	budget*.ti,ab.
52.	cost*.ti.
53.	(economic* or pharmaco?economic*).ti.
54.	(price* or pricing*).ti,ab.
55.	(cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.
56.	(financ* or fee or fees).ti,ab.
57.	(value adj2 (money or monetary)).ti,ab.
58.	or/45–57
59.	statistical model/
60.	exp economic aspect/
61.	59 and 60
62.	*theoretical model/
63.	*nonbiological model/
64.	stochastic model/
65.	decision theory/
66.	decision tree/
67.	monte carlo method/
68.	(markov* or monte carlo).ti,ab.
69.	econom* model*.ti,ab.
70.	(decision* adj2 (tree* or analy* or model*)).ti,ab.
71.	or/61–70
72.	44 and (58 or 71)

NHS EED and HTA (CRD) search terms

#1.	MeSH DESCRIPTOR Chronic Pain EXPLODE ALL TREES
#2.	(((persist* or intract* or chronic or longstanding or long standing or longterm or long term or refractory or prolong* or long last* or sustain* or linger* or syndrome) adj3 pain))
#3.	(((chronic or persist* or idiopathic or atypical or a-typical) adj4 pain))
#4.	MeSH DESCRIPTOR Complex Regional Pain Syndromes EXPLODE ALL TREES
#5.	((complex regional pain syndrome* or CRPS or causalgia))
#6.	MeSH DESCRIPTOR Fibromyalgia EXPLODE ALL TREES
#7.	(((reflex or sympathetic) adj2 dystroph*))
#8.	MeSH DESCRIPTOR Vulvodynia EXPLODE ALL TREES
#9.	((vulvodynia or vestibulodynia or dyspareunia or vulvar vestibulitis or vulvitis))
#10.	MeSH DESCRIPTOR Cystitis, Interstitial EXPLODE ALL TREES
#11.	((interstitial adj2 cystitis))
#12.	MeSH DESCRIPTOR Reflex Sympathetic Dystrophy EXPLODE ALL TREES
#13.	((algodystroph* or sudek or sudeck*))
#14.	MeSH DESCRIPTOR Myofascial Pain Syndromes EXPLODE ALL TREES
#15.	((loin pain adj (haematuria or hematuria) adj syndrome*))
#16.	((LPHS or prostatodynia or CPPS or atypic* odontalgia or a-typic* odontalgia or burning mouth syndrome* or phantom tooth pain or neuropathic orofacial pain or “myofascial pain” or MPS))
#17.	(((pelvic or pelvis) adj pain syndrome*))
#18.	(((non-cardiac or noncardiac) adj3 chest adj3 pain))
#19.	((temporomandibular adj3 joint adj3 pain))
#20.	(((prostate or vulv* or bladder or perineal) adj3 pain))
#21.	((functional pain syndrome* or non-cancer pain or noncancer pain))
#22.	(((pelvic or pelvis or abdominal) adj3 pain adj3 (unknown or un-known or idiopathic or atypic* or a-typic*)))
#23.	((fibromyalgia* or fibrositis or myofascial pain syndrome))
#24.	(#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23)

Figure 1Flow chart of clinical study selection for the review of exercise

Figure 2Pain at ≤3 months (VAS, final values, 0–100, high is poor outcome)

Figure 3Pain at >3 months (VAS, FIQ pain subscale, final values, 0–100, high is poor outcome)

Figure 4Pain at >3 months (FIQ pain subscale, final values, 0–100, high is poor outcome)

Note: 18 month timepoint not meta-analysed with 12–24 week data.

Figure 5Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)

Figure 6Quality of life at >3 months (SF-36 functional capacity subscale, 0–100, final values, high is good outcome)

Figure 7Quality of life at >3 months (SF-36 physical appearance subscale, 0–100, final values, high is good outcome)

Figure 8Quality of life at >3 months (SF-36 pain subscale, 0–100, final values, high is good outcome)

Figure 9Quality of life at >3 months (SF-36 vitality subscale, 0–100, final values, high is good outcome)

Figure 10Quality of life at >3 months (SF-36 social aspects subscale, 0–100, final values, high is good outcome)

Figure 11Quality of life at >3 months (SF-36 emotional aspects subscale, 0–100, final values, high is good outcome)

Figure 12Quality of life at >3 months (SF-36 mental health subscale, 0–100, final values, high is good outcome)

Figure 13Quality of life at ≤3 months (EQ-5D, −0.594–1, final values, high is good outcome)

Figure 14Quality of life at >3 months (EQ-5D, −0.594–1, final values, high is good outcome)

Figure 15Quality of life at ≤3 months (EQ-5D-VAS, 0–100, final values, high is good outcome)

Figure 16Quality of life at >3 months (EQ-5D-VAS, 0–100, final values, high is good outcome)

Figure 17Physical function at ≤3 months (Timed up and go, seconds, high is good outcome)

Figure 18Physical function at ≤3 months (FIQ physical function subscale, 0–100, final values, high is poor outcome)

Figure 19Physical function at >3 months (6 minute walking test, final values, metres)

Figure 20Physical function at >3 months (FIQ and SF-36 physical function subscales, 0–100, final values, high is poor outcome)

Figure 21Physical function at >3 months (FIQ physical function subscale, 0–100, final values, high is poor outcome)

Note: 18 month timepoint not meta-analysed with 16–24 week data.

Figure 22Psychological distress at >3 months (Final values and change scores, BDI, 0–61, high is poor outcome)

Figure 23Psychological distress at >3 months (Final values, VAS and FIQ depression scale, 0–10, high is poor outcome)

Figure 24Psychological distress at >3 months (Final values, VAS and FIQ anxiety scales, BAI, high is poor outcome)

Figure 25Psychological distress at >3 months (Change scores, STAI anxiety total scores, 0–21, high is poor outcome)

Figure 26Psychological distress at >3 months (Final values, FIQ depression scale, 0–10, high is poor outcome)

Note: 18 month timepoint not meta-analysed with 12–24 week data.

Figure 27Psychological distress at >3 months (Final values, FIQ anxiety scale, 0–10, high is poor outcome)

Note: 18 month timepoint not meta-analysed with 12–24 week data.

Figure 28Psychological distress at ≤3 months (Final values, BDI dpression scale, high is poor outcome)

Figure 29Use of healthcare services at 12 weeks (Number of GP contacts)

Figure 30Use of healthcare services at 18 months (Number of GP contacts)

Figure 31Use of healthcare services at 12 weeks (Number of medical specialist contacts)

Figure 32Use of healthcare services at 18 months (Number of medical specialist contacts)

Figure 33Use of healthcare services at 12 weeks (Number of physiotherapist contacts)

Figure 34Use of healthcare services at 18 months (Number of physiotherapist contacts)

Figure 35Sleep at >3 months (VAS sleep scale, PSQI, FIQ sleep subscale, final values, high is poor outcome)

Figure 36Discontinuation at >3 months

Heterogeneity not explained by subgroup analysis.

Figure 37Pain reduction at ≤3 months (final values, VAS, high is poor outcome)

Heterogeneity not explained by subgroup analysis.

Figure 38Pain reduction at ≤3 months (change scores and final values, VAS, NRS, 0–100, high is poor outcome)

Figure 39Pain reduction at >3 months (VAS, NRS, 0–100, final values and change scores, high is poor outcome)

Heterogeneity not explained by subgroup analysis.

Figure 40Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, change scores, high is good outcome)

Figure 41Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, change scores, high is good outcome)

Figure 42Quality of life at ≤3 months (FIQ, 0–100,final values, high is poor outcome)

Heterogeneity not explained by subgroup analysis.

Figure 43Physical function at ≤3 months (Neck disability index, change scores and final values, 0–100, high is poor outcome)

Heterogeneity not explained by subgroup analysis.

Figure 44Physical function at ≤3 months (final values, FIQ physical function subscale, Northwick pain questionnaire, high is poor outcome)

Heterogeneity not explained by subgroup analysis.

Figure 45Physical function at ≤3 months (6 minute walking test, final values, metres)

Figure 46Physical function at >3 months (final values, Northwick Park questionnaire, Neck disability index, high is poor outcome)

Figure 47Physical function at >3 months (change scores, SF-36 physical function subscale, HAQ, 0–100, high is poor outcome)

Figure 48Psychological distress at ≤3 months (final scores, pain catastrophising scale, 0–100, high is poor outcome)

Figure 49Psychological distress at >3 months (BDI, 0–61, change scores, high is poor outcome)

Figure 50Use of healthcare services at >3 months

Figure 51Sleep at >3 months (VAS sleep scale, 0–100, change scores, high is poor outcome)

Figure 52Discontinuation at ≤3 months

Figure 53Discontinuation at >3 months

Figure 54Pain at ≤3 months (VAS, 0–100, change scores, high is poor outcome)

Heterogeneity not explained by subgroup analysis.

Figure 55Pain at >3 months (VAS, FIQ pain subscale 0–100, final values, high is poor outcome)

Figure 56Quality of life at ≤3 months (EQ-5D, −0.594 to 1, final values, high is good outcome)

Figure 57Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)

Figure 58Quality of life at >3 months (FIQ, 0–100, final values and change scores, high is poor outcome

Heterogeneity not explained by subgroup analysis.

Figure 59Quality of life at ≤3 months (EQ-5D, −0.594 to 1, final values, high is good outcome)

Figure 60Quality of life at >3 months (SF-36 physical functioning subscale, 0–100, final values, high is good outcome)

Figure 61Quality of life at >3 months (SF-36 physical role subscale, 0–100, final values, high is good outcome)

Figure 62Quality of life at >3 months (SF-36 emotional role subscale, 0–100, final values, high is good outcome)

Figure 63Quality of life at >3 months (SF-36 vitality subscale, 0–100, final values, high is good outcome)

Figure 64Quality of life at >3 months (SF-36 mental health subscale, 0–100, final values, high is good outcome)

Figure 65Quality of life at >3 months (SF-36 social role subscale, 0–100, final values, high is good outcome)

Figure 66Quality of life at >3 months (SF-36 bodily pain subscale, 0–100, final values, high is good outcome)

Figure 67Quality of life at >3 months (SF-36 general health subscale, 0–100, final values, high is good outcome)

Figure 68Physical function at >3 months (quarter mile walk test, seconds, final values, high is poor outcome`)

Figure 69Physical function at >3 months (6 minute walk test, final values, metres)

Figure 70Physical function at ≤3 months (6 minute walk test, final values, metres)

Figure 71Physical function at >3 months (FIQ physical function subscale, 0–10, final values, high is poor outcome)

Figure 72Psychological distress at ≤3 months (BDI, 0–30, final values, high is poor outcome)

Figure 73Psychological distress at ≤3 months (State anxiety inventory, 0–100, change scores, high is poor outcome)

Figure 74Psychological distress at ≤3 months (HADS anxiety, 0–21, high is poor outcome)

Figure 75Psychological distress at >3 months (CES-D, BDI, FIQ depression subscale, final values, high is poor outcome)

Figure 76Psychological distress at >3 months (State anxiety inventory, 20–80, final values and change scores, high is poor outcome)

Figure 77Sleep at >3 months (Pittsburgh sleep quality index, 0–21, change scores, high is poor outcome)

Figure 78Health care utilisation at >3 months

Figure 79Discontinuation at ≤3 months

Figure 80Discontinuation at >3 months

Figure 81Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 82Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 83Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)

Figure 84Pain at >3 months (VAS, SF-36 pain score, 0–100, final values, high is poor outcome)

Figure 85Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 86Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 87Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 88Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 89Physical function at ≤3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)

Figure 90Physical function at >3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)

Figure 91Psychological distress at ≤3 months (ADS depression scale, 0–60, final values, high is poor outcome)

Figure 92Psychological distress at >3 months (ADS depression scale, 0–60, final values, high is poor outcome)

Figure 93Discontinuation at >3 months

Figure 94Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)

Figure 95Pain at >3 months (VAS, 0–100, final values, high is poor outcome)

Figure 96Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 97Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 98Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 99Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 100Psychological distress at ≤3 months (HADS anxiety, 0–21, final values, high is poor outcome)

Figure 101Psychological distress at >3 months (HADS anxiety, 0–21, final values, high is poor outcome)

Figure 102Psychological distress at ≤3 months (HADS depression, 0–21, final values, high is poor outcome)

Figure 103Psychological distress at >3 months (HADS depression, 0–21, final values, high is poor outcome)

Figure 104Physical function at ≤3 months (Neck disability index, 0–100, final values, high is poor outcome)

Figure 105Physical function at >3 months (Neck disability index, 0–100, final values, high is poor outcome)

Figure 106Discontinuation at ≤3 months

Figure 107Pain at ≤3 months (VAS, 0–10, final values, high is poor outcome)

Figure 108Pain at >3 months (VAS, 0–10, final values, high is poor outcome)

Figure 109Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)

Figure 110Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)

Figure 111Physical function at ≤3 months (Sit to stand test, final values, high is good outcome)

Figure 112Physical function at >3 months (Sit to stand test, final values, high is good outcome)

Figure 113Psychological distress at ≤3 months (BDI, 0–61, final values, high is poor outcome)

Figure 114Psychological distress at >3 months (BDI, 0–61, final values, high is poor outcome)

Figure 115Discontinuation at >3 months

Figure 116Pain at ≤3 months (VAS, FIQ pain subscale, 0–100, final values and change scores, high is poor outcome)

Figure 117Pain improvement at <3 months (30% improvement on NRS)

Figure 118Pain improvement at >3 months (30% improvement on NRS)

Figure 119Pain at >3 months (VAS, SF-36 pain score, final values, 0–100, high is poor outcome)

NB: Heterogeneity explained by subgroup analysis

Figure 120Quality of life at ≤3 months (WHOQOL-BREF, 0–5, final values, high is good outcome)

Figure 121Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)

Figure 122Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 123Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Heterogeneity not explained by subgroup analysis

Figure 124Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Heterogeneity not explained by subgroup analysis

Figure 125Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 126Quality of life at >3 months (SF-36 functional capacity subscale, 0–100, final values, high is good outcome)

Figure 127Quality of life at >3 months (SF-36 physical subscale, 0–100, final values, high is good outcome)

Figure 128Quality of life at >3 months (SF-36 pain subscale, 0–100, final values, high is good outcome)

Figure 129Quality of life at >3 months (SF-36 vitality subscale, 0–100, final values, high is good outcome)

Figure 130Quality of life at >3 months (SF-36 general health subscale, 0–100, final values, high is good outcome)

Figure 131Quality of life at >3 months (SF-36 social subscale, 0–100, final values, high is good outcome)

Figure 132Quality of life at >3 months (SF-36 emotional subscale, 0–100, final values, high is good outcome)

Figure 133Quality of life at >3 months (SF-36 mental health subscale, 0–100, final values, high is good outcome)

Figure 134Physical function at >3 months (Neck pain disability scale, NDI, final values, high is poor outcome)

Heterogeneity not explained by subgroup analysis.

Figure 135Physical function at >3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)

Figure 136Physical function at >3 months (6 minute walk test, metres, final values, high is good outcome)

Figure 137Psychological distress at ≤3 months (HADS:D, BDI, CES-D, ADS depression, final values, high is poor outcome)

Heterogeneity not explained by subgroup analysis.

Figure 138Psychological distress at ≤3 months (HADS:A 0–61, STAI 0–21, final values, high is poor outcome)

Figure 139Psychological distress at >3 months (BDI, HADS:D, final values, high is poor outcome)

Figure 140Psychological distress at >3 months (HADS:A, 0–21, final values, high is poor outcome)

Figure 141Sleep at ≤3 months (VAS sleep outcome, Pittsburgh sleep quality index, final values, high is poor outcome)

Figure 142Discontinuation at >3 months

Heterogeneity not explained by subgroup analysis

Figure 143Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)

Figure 144Physical function at ≤3 months (FIQ physical function subscale, 0–30, final values, high is poor outcome)

Figure 145Discontinuation at ≤3 months

Figure 146Pain at ≤3 months (VAS, FIQ pain subscale, MDPI, 0–100, final values and change scores, high is poor outcome)

Heterogeneity not explained by subgroup analysis

Figure 147Pain at >3 months (VAS, 0–100, change scores, high is poor outcome)

Figure 148Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values and change scores, high is good outcome)

Heterogeneity not explained by subgroup analysis.

Figure 149Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values and change scores, high is good outcome)

Heterogeneity not explained by subgroup analysis.

Figure 150Physical function at ≤3 months (multidimensional fatigue inventory reduced activity subscale, change scores, 0–20, high is poor outcome)

Figure 151Physical function at ≤3 months (6 minute walking test, final values, metres)

Figure 152Physical function at >3 months (final values and change scores, SF-36 physical functioning subscale, 0–100, high is poor outcome)

Figure 153Psychological distress at ≤3 months (HADS: anxiety, 0–21, final values and change scores, high is poor outcome)

Figure 154Psychological distress at ≤3 months (HADS: depression, 0–21, final values and change scores, high is poor outcome)

Figure 155Psychological distress at ≤3 months (BDI, 0–60, final values, high is poor outcome)

Figure 156Sleep at ≤3 months (VAS sleep scale, 0–100, final values, high is poor outcome)

Figure 157Discontinuation at >3 months

Figure 158Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)

Figure 159Pain at >3 months (VAS, 0–100, final values and change scores, high is poor outcome)

Figure 160Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 161Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 162Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 163Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 164Psychological distress at ≤3 months (BDI, 0–21, final values, high is poor outcome)

Figure 165Psychological distress at >3 months (BDI, 0–21, final values, high is poor outcome)

Figure 166Psychological distress at ≤3 months (STAI anxiety, 0–100, final values, high is poor outcome)

Figure 167Psychological distress at >3 months (STAI anxiety, 0–100, final values, high is poor outcome)

Figure 168Discontinuation at >3 months

Figure 169Pain at ≤3 months (VAS, 0–10, high score is poor outcome)

Figure 170Quality of life at ≤3 months (SF36, 0–100, high score is good outcome)

Figure 171Psychological distress at ≤3 months (Scale of Catastropic Thoughts on Pain, 0–5, high score is poor outcome)

Figure 172Sleep at ≤3 months (Pittsburgh Sleep Quality Index, 0–21, high score is poor outcome)

Figure 173Discontinuation at ≤3 months

Figure 174Quality of life at >3 months (FIQ, 0–100, change scores, high is poor outcome)

Figure 175Psychological distress at >3 months (BDI, 0–61, change scores, high is poor outcome)

Figure 176Discontinuation at >3 months

Figure 177Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)

Figure 178Pain at >3 months (VAS, 0–100, final values, high is poor outcome)

Figure 179Quality of life at ≤3 months (NIS CPSI quality of life subscale 0–12, final values, high is poor outcome)

Figure 180Quality of life at >3 months (NIS CPSI quality of life subscale 0–12, final values, high is poor outcome)

Figure 181Psychological distress at ≤3 months (BDI, 0–21, final values, high is poor outcome)

Figure 182Psychological distress at >3 months (BDI, 0–21, final values, high is poor outcome)

Figure 183Discontinuation at ≤3 months

Figure 184Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, change scores, high is good outcome)

Figure 185Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, change scores, high is good outcome)

Figure 186Quality of life at >3 months (SF-36 physical component summary score, 0–100, change scores, high is good outcome)

Figure 187Quality of life at >3 months (SF-36 mental component summary score, 0–100, change scores, high is good outcome)

Figure 188Physical function at ≤3 months (6 minute walking test, change scores, metres)

Figure 189Physical function at >3 months (6 minute walking test, change scores, metres)

Figure 190Psychological distress at ≤3 months (HADS depression, 0–21, change scores, high is poor outcome)

Figure 191Psychological distress at ≤3 months (HADS anxiety, 0–21, change scores, high is poor outcome)

Figure 192Psychological distress at >3 months (HADS anxiety, 0–21, change scores high is poor outcome)

Figure 193Psychological distress at >3 months (HADS depression, 0–21, change scores, high is poor outcome)

Figure 194Sleep at ≤3 months (Pittsburgh sleep quality index, 0–21, change scores, high is poor outcome)

Figure 195Sleep at >3 months (Pittsburgh sleep quality index, 0–21, change scores, high is poor outcome)

Figure 196Discontinuation at ≤3 months

Figure 197Pain at 4 weeks (VAS, 0–100, high is poor outcome)

Figure 198Pain at 12 weeks (VAS, 0–100, high is poor outcome)

Figure 199Quality of life at 4 weeks (FIQ, 0–100, high is poor outcome)

Figure 200Quality of life at 12 weeks (FIQ, 0–100, high is poor outcome)

Figure 201Sleep quality at 4 weeks (final score; Pittsburgh Sleep Quality Index)

Figure 202Sleep quality at 12 weeks (final score; Pittsburgh Sleep Quality Index)

Figure 203Discontinuation at 12 weeks

Figure 204Quality of life at ≤3 months (FIQ total score, high is poor outcome)

Figure 205Physical function at ≤3 months (number of steps, high is good outcome)

Figure 206Discontinuation at ≤3 months

Figure 207Pain at ≤3 months (VAS, 0–10, final values, high is poor outcome)

Figure 208Quality of life at ≤3 months (Nottingham Health Profile, 0–600, final values, high is poor outcome)

Figure 209Physical function at ≤3 months (Neck Disability Index, 0–100, final values, high is poor outcome)

Figure 210Psychological distress at ≤3 months (Beck Depression Inventory, 0–63, final values, high is poor outcome)

Figure 211Discontinuation at <3 months

Figure 212Pain at ≤3 months (VAS, 0–10, final values, high is poor outcome)

Figure 213Quality of life at ≤3 months (Nottingham Health Profile, 0–600, final values, high is poor outcome)

Figure 214Physical function at ≤3 months (Neck Disability Index, 0–100, final values, high is poor outcome)

Figure 215Psychological distress at ≤3 months (Beck Depression Inventory, 0–63, final values, high is poor outcome)

Figure 216Pain at ≤3 months (VAS, 0–100, change scores and final values, high is poor outcome)

Figure 217Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 218Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 219Physical function at ≤3 months (FIQ physical function subscale, 0–30, final values, high is poor outcome)

Figure 220Psychological distress at ≤3 months (BDI, 0–61, change scores, high is poor outcome)

Figure 221Psychological distress at ≤3 months (BAI, 0–61, change scores, high is poor outcome)

Figure 222Sleep at ≤3 months (FIQ sleep subscale, 0–10, change scores, high is poor outcome)

Figure 223Discontinuation at >3 months

Figure 224Quality of life at >3 months (SF-36 physical functioning subscale, 0–100, final values, high is good outcome)

Figure 225Quality of life at >3 months (SF-36 physical role subscale, 0–100, final values, high is good outcome)

Figure 226Quality of life at >3 months (SF-36 emotional subscale, 0–100, final values, high is good outcome)

Figure 227Quality of life at >3 months (SF-36 vitality subscale, 0–100, final values, high is good outcome)

Figure 228Quality of life at >3 months (SF-36 emotional wellbeing subscale, 0–100, final values, high is good outcome)

Figure 229Quality of life at >3 months (SF-36 social functioning subscale, 0–100, final values, high is good outcome)

Figure 230Quality of life at >3 months (SF-36 bodily pain subscale, 0–100, final values, high is good outcome)

Figure 231Quality of life at >3 months (SF-36 general health subscale, 0–100, final values, high is good outcome)

Figure 232Discontinuation at >3 months

Figure 233Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)

Figure 234Pain at >3 months (VAS, 0–100, final values, high is poor outcome)

Figure 235Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 236Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 237Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 238Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 239Physical function at ≤3 months (Neck disability index, neck pain disability scale, final values, high is poor outcome)

Figure 240Physical function at >3 months (Neck disability index, neck pain disability scale, final values, high is poor outcome)

Figure 241Psychological distress at ≤3 months (ADS depression scale, 0–60, final values, high is poor outcome)

Figure 242Psychological distress at >3 months (ADS depression scale, 0–60, final values, high is poor outcome)

Figure 243Discontinuation at >3 months

Figure 244Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)

Figure 245Pain at >3 months (VAS, 0–100, final values, high is poor outcome)

Figure 246Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 247Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 248Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 249Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 250Physical function at ≤3 months (Neck disability index, 0–100, final values, high is poor outcome)

Figure 251Physical function at >3 months (Neck disability index, 0–100, final values, high is poor outcome)

Figure 252Psychological distress at ≤3 months (HADS anxiety, 0–21, final values, high is poor outcome)

Figure 253Psychological distress at >3 months (HADS anxiety, 0–21, final values, high is poor outcome)

Figure 254Psychological distress at ≤3 months (HADS depression, 0–21, final values, high is poor outcome)

Figure 255Psychological distress at >3 months (HADS depression, 0–21, final values, high is poor outcome)

Figure 256Discontinuation at ≤3 months

Figure 257Physical function at ≤3 months (Neck disability index, 0–50, final values, high is poor outcome)

Figure 258Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)

Figure 259Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)

Figure 260Psychological distress at ≤3 months (BDI, 0–61, final values, high is poor outcome)

Figure 261Sleep at ≤3 months (Pittsburgh sleep quality index, 0–21, final values, high is poor outcome)

Figure 262Discontinuation at ≤3 months

Figure 263Pain at ≤3 months (VAS, 0–10, high is poor outcome)

Figure 264Quality of life ≤3 months (Nottingham Health Profile, 0–600, high is poor outcome)

Figure 265Physical function ≤3 months (Neck Disability Index, 0–100, high is poor outcome)

Figure 266Psychological distress ≤3 months (Beck Depression Inventory, 0–63, high is poor outcome)

Figure 267Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome

Figure 268Psychological distress at ≤3 months (BDI, 0–63, final values, high is poor outcome)

Figure 269Discontinuation at ≤3 months

Figure 270Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)

Figure 271Discontinuation at ≤3 months

Figure 272Pain at ≤3 months (VAS, NRS, 0–100, final values, high is poor outcome)

NB: Heterogeneity not explained by subgroup analysis

Figure 273Pain at >3 months (VAS, NRS, 0–100, final values, high is poor outcome)

NB: Heterogeneity not explained by subgroup analysis

Figure 274Quality of life at ≤3 months (FIQ, 0–100, final values and change scores, high is poor outcome)

Figure 275Quality of life at >3 months (EQ-5D, −0.594–1, high is good outcome, final values)

Figure 276Quality of life at ≤3 months (SF36, 0–100, high score is good outcome

Figure 277Physical function at ≤3 months (FIQ physical function subscale, 0–10, high is poor outcome, change scores)

Figure 278Physical function at ≤3 months (6 minute walking test, metres, high is good outcome, final values)

Figure 279Physical function at >3 months (6 minute walking test, final values, metres)

Figure 280Psychological distress at ≤3 months (CES-D, 0–100, final values, high is poor outcome)

Figure 281Psychological distress at >3 months (HADS depression, 0–21, change scores, high is poor outcome)

Figure 282Psychological distress at >3 months (HADS anxiety, 0–21, change scores, high is poor outcome)

Figure 283Sleep at >3 months (the sleep scale, 0–20, final values, high is poor outcome)

Figure 284Sleep at >3 months (pittsburgh sleep quality index, 0–100, change scores, high is poor outcome)

Figure 285Discontinuation at >3 months

Figure 286Pain at ≤3 months (NRS, high is poor outcome, 0–10, final values)

Figure 287Pain at >3 months (NRS, high is poor outcome, 0–10, final values)

Figure 288Physical function at ≤3 months (Neck disability index, high is poor outcome, final values, 0–50)

Figure 289Physical function at >3 months (Neck disability index, high is poor outcome, final values, 0–50)

Figure 290Discontinuation at ≤3 months

Figure 291Pain at <3 months (VAS, NRS, high is poor outcome, final values, 0–100)

Heterogeneity not explained by subgroup analysis.

Figure 292Pain at >3 months (NRS, VAS, 0–100, final values, high is poor outcome)

Figure 293Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)

Figure 294Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 295Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)

Figure 296Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 297Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)

Figure 298Physical function at >3 months (neck disability index, functional performance scale, final values, high is poor outcome)

Heterogeneity not explained by subgroup analysis.

Figure 299Physical function at >3 months (neck disability index, high is poor outcome, final values, 0–100)

Figure 300Physical function at ≤3 months (Neck disability index, high is poor outcome, 0–100)

Figure 301Discontinuation at >3 months

Figure 302Pain at ≤3 months (NRS, 0–10, final values, high is poor outcome)

Figure 303Pain at >3 months (NRS, 0–10, final values, high is poor outcome)

Figure 304Physical function at ≤3 months (Neck disability index, 0–50, final values, high is poor outcome)

Figure 305Physical function at >3 months (Neck disability index, 0–50, final values, high is poor outcome)

Figure 306Discontinuation at ≤3 months

Table 71Clinical evidence profile: Aerobic versus usual care

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Aerobic exercise	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	20	20	-	MD 21.5 lower (30.38 to 12.62 lower)	⊕⊕⊕◯ MODERATE	CRITICAL
Pain at >3 months (VAS, FIQ pain subscale, 0–100, final values, high is poor outcome)
9	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	300	228	-	MD 6.97 lower (10.77 to 3.17 lower)	⊕⊕◯◯ LOW	CRITICAL
Pain at >3 months (FIQ pain subscale, 0–100, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	47	48	-	MD 1 lower (10.34 lower to 8.34 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)
5	randomised trials	very serious¹	serious²	no serious indirectness	serious²	none	228	144	-	MD 7.89 lower (13.23 to 2.55 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 functional capacity subscale, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	27	27	-	MD 12.5 higher (3.85 to 21.15 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 physical appearance subscale, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	27	27	-	MD 16 higher (2.68 lower to 34.68 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 pain subscale, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	27	27	-	MD 7.5 higher (8.62 lower to 23.62 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 vitality subscale, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	27	27	-	MD 7.7 higher (2.49 lower to 17.89 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 social aspects subscale, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	27	27	-	MD 8.9 higher (3.16 lower to 20.96 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 emotional aspects subscale, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	27	27	-	MD 9.7 higher (10.7 lower to 30.1 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 mental health subscale, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	27	27	-	MD 3.4 higher (7.46 lower to 14.26 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (EQ-5D, −0.594–1, high is good outcome, final values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	47	48	-	MD 0.03 higher (0.15 lower to 0.09 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (EQ-5D, −0.594–1, high is good outcome, final values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	128	131	-	MD 0.06 higher (0.01 lower to 0.13 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (EQ-5D VAS, 0–100. high is good outcome, final values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	47	48	-	MD 5.6 higher (2.86 lower to 14.06 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (EQ-5D VAS, 0–100, high is good outcome, final values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	47	48	-	MD 1.4 higher (8.17 lower to 10.97 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at 12 weeks (Final values, timed up and go, seconds, high is good outcome) (Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	40	20	-	MD 0.62 lower (1.40 lower to 0.16 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at ≤3 months (FIQ physical function subscale, 0–100, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	47	48	-	MD 3 lower (11.32 lower to 5.32 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at >3 months (6 minute walking test, final values, metres, high is good outcome)
3	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	91	78	-	MD 56.18 higher (27.8 to 84.56 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at >3 months (FIQ and SF-36 physical function subscales, 0–100, final values, high is poor outcome)
3	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	159	87	-	MD 10.16 lower (15.39 to 4.94 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at >3 months (FIQ physical function subscale, 0–100, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	47	48	-	MD 3 lower (16.14 lower to 10.14 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at >3 months (Change scores and final values, beck depression inventory, 0–21, high is poor outcome)
3	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	60	63	-	MD 3.36 lower (6.16 to 0.56 lower)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (Final values, VAS and FIQ depression scale, 0–10, high is poor outcome)
4	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	190	116	-	MD 0.39 lower (1.05 lower to 0.28 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (Final values, VAS and FIQ anxiety scale, Beck anxiety inventory, final values, high is poor outcome)
4	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	197	123	-	SMD 0.28 lower (0.51 lower to 0.04 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at >3 months (Change scores, STAI anxiety total scores, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	27	23	-	MD 9.7 lower (23.6 lower to 4.2 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at >3 months (final values, FIQ depression scale, 0–10, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	47	48	-	MD 0.8 higher (0.46 lower to 2.06 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at >3 months (final values, FIQ anxiety scale, 0–10, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	47	48	-	MD 0.2 higher (1.06 lower to 1.46 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at 12 weeks (Final values, BDI dpression scale, high is poor outcome) (Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	40	20	-	MD 12.77 lower (14.65 to 10.88 lower)	⊕⊕◯◯ LOW	CRITICAL
Use of healthcare services ≤3 months (Number of GP contacts)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	47	48	-	MD 1 higher (0.11 lower to 2.11 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Use of healthcare services >3 months (Number of GP contacts)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	47	48	-	MD 0.3 higher (0.68 lower to 1.28 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Use of healthcare services ≤3 months (Number of medical specialist contacts)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	47	48	-	MD 0.1 higher (0.18 lower to 0.38 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Use of healthcare services >3 months (Number of medical specialist contacts)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	47	48	-	MD 0.2 higher (0.08 lower to 0.48 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Use of healthcare services at ≤3 months (Number of physiotherapist contacts)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	47	48	-	MD 3.1 lower (4.49 to 1.17 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Use of healthcare services at >3 months (Number of physiotherapist contacts)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	47	48	-	MD 4.4 lower (5.79 to 3.01 lower)	⊕⊕◯◯ LOW	CRITICAL
Sleep at >3 months (VAS sleep scale, PSQI, FIQ sleep subscale, final values, high is poor outcome)
5	randomised trials	very serious¹	serious³	no serious indirectness	no serious imprecision²	none	209	205	-	SMD 0.16 lower (0.43 lower to 0.1 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Discontinuation at >3 months
9	randomised trials	serious¹	very serious²	no serious indirectness	serious³	none	70/316 (22.2%)	33/291 (11.3%)	RD 0.11 (−0.04 to 0.27)	110 more per 1000 (from 40 fewer to 270 more)	⊕◯◯◯ VERY LOW	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Downgraded for heterogeneity, unexplained by subgroup analysis.

Table 72Clinical evidence profile: Strength versus usual care

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Strength	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain reduction at ≤3 months (final values, VAS, high is poor outcome)
3	randomised trials	very serious¹	very serious²	no serious indirectness	serious³	none	150	101	-	MD −18.85 (34.50 to 3.21 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Pain reduction at ≤3 months (change scores and final values, VAS, NRS, 0–100, high is poor outcome)
3	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	88	68	-	MD 15.76 lower (22.79 to 8.72 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Pain reduction at >3 months (VAS, NRS, 0–100, final values and change scores, high is poor outcome)
4	randomised trials	very serious¹	serious³	no serious indirectness	serious²	none	230	219	-	MD 16.06 lower (36.93 lower to 4.82 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (SF-36 physical component summary, 0–100, change scores, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	22	20	-	MD 7.6 higher (0.25 lower to 15.45 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (SF-36 mental component summary, 0–100, change scores, high is good outcome)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	52	50	-	MD 3.39 higher (2.43 lower to 9.21 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (FIQ scale, 0–100, final values, high is poor outcome)
2	randomised trials	very serious¹	serious³	no serious indirectness	very serious²	none	28	24	-	MD 14.91 lower (45.78 lower to 15.96 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at ≤3 months (Neck disability index, change scores and final values, 0–100, high is poor outcome)
3	randomised trials	serious¹	very serious²	no serious indirectness	very serious³	none	83	63	-	MD 9.89 lower (23.15 lower to 3.37 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at ≤3 months (final values, FIQ physical function subscale, Northwick Park Questionnaire, high is poor outcome)
2	randomised trials	very serious¹	Serious³	no serious indirectness	no serious imprecision	none	75	76	-	SMD 0.23 lower (0.68 lower to 1.14 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at ≤3 months (6 minute walking test, metres, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	8	12	-	MD 8.4 lower (89.59 lower to 72.79 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at >3 months (final values, Northwick Park Questionnaire, Neck Disability Index, high is poor outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	84	79	-	SMD 0.32 lower (0.64 lower to 0.00 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (change scores, SF-36 physical function subscale, HAQ, 0–100, high is poor outcome)
3	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	52	53	-	MD 6.2 lower (10.41 to 2 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at ≤3 months (pain catastrophising scale, 0–100, final scores, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	13	12		MD 9.00 lower (19.70 lower to 1.70 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at >3 months (BDI, 0–61, change scores, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	11	10	-	MD 3.7 lower (6.37 to 1.03 lower)	⊕⊕◯◯ LOW	CRITICAL
Use of health care services at >3 months
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	27/119 (22.7%)	20/60 (33.3%)	RR 0.68 (0.42 to 1.11)	107 fewer per 1000 (from 193 fewer to 37 more)	⊕⊕◯◯ LOW	IMPORTANT
Sleep at >3 months (VAS sleep, 0–100, change scores, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	11	10	-	MD 7 lower (20.9 lower to 6.9 higher)	⊕⊕◯◯ LOW	IMPORTANT
Discontinuation at ≤3 months
4	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	11/70 (15.7%)	6.5%	Peto OR 2.27 (0.77 to 6.73)	71 more per 1000 (from 14 fewer to 254 more)	⊕◯◯◯ VERY LOW	IMPORTANT
Discontinuation at >3 months
4	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision²	none	26/121 (21.5%)	3.3%	RD 0.08 (−0.02 to 0.17	33 fewer per 1000 (from 27 fewer to 34 fewer)	⊕⊕⊕◯ MODERATE	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Downgraded for heterogeneity, unexplained by subgroup analysis

Table 73Clinical evidence profile: Aerobic and strength versus usual care

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Aerobic and strength	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain reduction at ≤3 months (VAS, 0–100, change scores, high is poor outcome)
2	randomised trials	serious¹	very serious³	no serious indirectness	very serious²	none	85	44	-	MD 2.45 lower (34.16 lower to 29.27 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Pain at >3 months (VAS, FIQ pain subscale, 0–100, final values, high is poor outcome)
3	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	103	58	-	MD 13.74 lower (22.11 to 5.37 lower)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (EQ-5D, −0.594 to 1, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	15	15	-	MD 0.25 higher (0.05 to 0.45 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (Fibromyalgia impact questionnaire, 0–100, final values, high is poor outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	25	-	MD 3.42 lower (12.66 lower to 5.82 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (Fibromyalgia impact questionnaire, 0–100, final values and change scores, high is poor outcome)
4	randomised trials	very serious¹	Serious³	no serious indirectness	serious²	none	90	81	-	MD 9.05 lower (15.43 to 2.68 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (EQ-5D, −0.594 to 1, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	15	15	-	MD 0.19 higher (0.00 to 0.39 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 physical functioning subscale, 0–100, final values, high is good outcome)
1	randomised trials	Very serious¹	no serious inconsistency	no serious indirectness	serious²	none	21	21	-	MD 11.6 higher (2.02 to 21.18 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 physical role subscale, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	serious²	no serious imprecision	none	21	21	-	MD 1.9 higher (14.93 lower to 18.73 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 emotional role subscale, 0–100, final values, high is good outcome)
1	randomised trials	Very serious¹	no serious inconsistency	no serious indirectness	serious²	none	21	21	-	MD 19 higher (6.96 lower to 44.96 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 vitality subscale, 0–100, final values, high is good outcome)
1	randomised trials	Very serious¹	no serious inconsistency	no serious indirectness	serious²	none	21	21	-	MD 12.7 higher (2.73 to 22.67 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 mental health subscale, 0–100, final values, high is good outcome)
1	randomised trials	Very serious¹	no serious inconsistency	no serious indirectness	serious²	none	21	21	-	MD 15.8 higher (3.75 to 27.85 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 24 weeks (SF-36 social role subscale, 0–100, final values, high is good outcome)
1	randomised trials	Very serious¹	no serious inconsistency	no serious indirectness	serious²	none	21	21	-	MD 11.7 higher (1.9 lower to 25.3 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 bodily pain subscale, 0–100, final values, high is good outcome)
1	randomised trials	Very serious¹	no serious inconsistency	no serious indirectness	serious²	none	21	21	-	MD 10.4 higher (0.16 lower to 20.96 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 general health subscale, 0–100,final values, high is good outcome)
1	randomised trials	Very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	21	21	-	MD 9.6 higher (2.82 to 16.38 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (seconds, quarter mile walk test, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	8	8	-	MD 37.3 lower (63.19 to 11.41 lower)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (metres, 6-minute walk test, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	19	-	MD 54.8 higher (0.54 lower to 110.14 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (FIQ physical function subscale, final values, 0–10, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	15	15	-	MD 1.3 lower (2.63 lower to 0.03 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at 8 weeks (metres, 6-minute walk test, high is good outcome) (Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	16	16	-	MD 15.69 higher (33.37 lower to 64.75 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress ≤3 months (BDI, 0–30, final values, high is poor outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	25	-	MD 1.44 lower (6.85 lower to 3.97 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress ≤3 months (State anxiety inventory, 0–10, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	34	24	-	MD 0.1 higher (5.12 lower to 5.32 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at 8 weeks (HADS, 0–21, high is poor outcome) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	16	16	-	MD 1.25 lower (3.77 lower to 1.27 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (CES-D, BDI, FIQ depression subscale, final values, high is poor outcome)
4	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	62	63	-	SMD 0.45 lower (0.81 to 0.09 lower)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (State anxiety inventory, 20–80, final values, high is poor outcome)
2	randomised trials	very serious¹	serious³	no serious indirectness	serious²	none	44	39	-	MD 2.95 lower (9.75 lower to 3.85 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Sleep at >3 months (Pittsburg sleep quality index, high is poor outcome, final values, 0–21)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	34	24	-	MD 2.2 lower (3.39 to 1.01 lower)	⊕⊕◯◯ LOW	CRITICAL
Healthcare utilisation at >3 months (follow-up 3 years)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	23/57 (40.4%)	10/21 (47.6%)	RR 0.85 (0.49 to 1.47)	71 fewer per 1000 (from 243 fewer to 224 more)	⊕◯◯◯ VERY LOW	CRITICAL
Discontinuation at ≤3 months
4	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	7/65 (10.8%)	1/60 (1.7%)	RD 0 (−0.01 to 0.17)	0 fewer per 1000 (from 10 fewer to 170 more)	⊕⊕◯◯ LOW	IMPORTANT
Discontinuation at >3 months
7	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	20/170 (11.8%)	4.9%	RD 0.05 (−0.03 to 0.12)	47 fewer per 1000 (from 43 fewer to 50 fewer)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Downgraded for heterogeneity, unexplained by subgroup analysis

Table 74Clinical evidence profile: Aerobic, strength and flexibility versus usual care

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Aerobic, strength and flexibility	Control	Relative (95% CI)	Absolute	Quality	Importance
Quality of life at ≤3 months (SF-36 mental component, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	12	13	-	MD 12.1 higher (2.14 to 22.06 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (SF-36 physical component, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	12	13	-	MD 5.1 higher (3.18 lower to 13.38 higher)	⊕⊕◯◯ LOW	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 75Clinical evidence profile: Strength and flexibility versus usual care

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Strength and flexibility	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	55	55	-	MD 11.71 lower (21.49 to 1.92 lower)	⊕⊕◯◯ LOW	CRITICAL
Pain at >3 months (VAS, SF-36 pain score, final values, 0–100, high is poor outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	70	74	-	MD 13.19 lower (20.33 to 6.05 lower)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (SF-36 mental component, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	35	35	-	MD 0.6 lower (6.12 lower to 4.92 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 mental component, 0–100, final values, high is poor outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	70	74	-	MD 1.78 higher (1.35 lower to 4.91 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (SF-36 physical component, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	35	35	-	MD 1.7 higher (2.42 lower to 5.82 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 physical component, 0–100, final values, high is poor outcome)
2	randomised trials	serious¹	Serious³	no serious indirectness	no serious imprecision	none	70	74	-	MD 0.16 lower (3.87 lower to 3.56 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at ≤3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious¹	none	35	35	-	MD 5.5 lower (16.59 lower to 5.59 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	70	74	-	MD 6.7 lower (12.3 to 1.1 lower)	⊕⊕⊕◯ MODERATE	CRITICAL
Psychological distress at ≤3 months (ADS depression scale, 0–60, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	35	35	-	MD 1.6 higher (2.59 lower to 5.79 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (ADS depression scale, 0–60, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	35	35	-	MD 1.1 higher (3.41 lower to 5.61 higher)	⊕⊕◯◯ LOW	CRITICAL
Discontinuation at >3 months
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	8/78 (10.3%)	11.7%	OR 0.88 (0.32 to 2.4)	13 fewer per 1000 (from 76 fewer to 124 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Downgraded due to heterogeneity, unexplained by subgroup analysis

Table 76Clinical evidence profile: Strength, proprioception and flexibility versus usual care

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Strength, proprioception and flexibility	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 16.6 lower (25.8 to 7.4 lower)	⊕⊕◯◯ LOW	CRITICAL
Pain at >3 months (VAS, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 11.5 lower (20.71 to 2.29 lower)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 2.3 higher (0.13 lower to 4.73 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 2 higher (1.48 lower to 5.48 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 1.6 higher (2.73 lower to 5.93 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 0.5 higher (3.82 lower to 4.82 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (HADS: anxiety, 0–21, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 1.2 lower (2.68 lower to 0.28 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (HADS: anxiety, 0–21, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 1.2 lower (2.66 lower to 0.26 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (HADS: depression, 0–21, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 1.1 lower (2.4 lower to 0.2 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (HADS: depression, 0–21, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 1.3 lower (2.85 lower to 0.25 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at ≤3 months (Neck disability index, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 4.8 lower (9.47 to 0.13 lower)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (Neck disability index, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	39	-	MD 4.3 lower (10.06 lower to 1.46 higher)	⊕⊕◯◯ LOW	CRITICAL
Discontinuation at ≤3 months
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	very serious²	none	13/37 (35.1%)	25.6%	RR 1.37 (0.69 to 2.73)	95 more per 1000 (from 79 fewer to 443 more)	⊕⊕◯◯ LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 77Clinical evidence profile: Proprioception versus usual care

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Proprioception	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	24	22	-	MD 0.18 higher (1.09 lower to 1.45 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Pain at >3 months (VAS, 0–10, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	24	22	-	MD 0.97 lower (2.47 lower to 0.53 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	24	22	-	MD 1.88 lower (11.11 lower to 7.35 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	24	22	-	MD 3.59 lower (14.37 lower to 7.19 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at ≤3 months (sit to stand test, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	24	24	-	MD 4.38 lower (6.82 to 1.94 lower)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (sit to stand test, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	24	22	-	MD 0.86 lower (3.18 lower to 1.46 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (BDI, 0–61, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	24	22	-	MD 4.74 lower (8.43 to 1.05 lower)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (BDI, 0–61, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	24	22	-	MD 4.86 lower (9.84 lower to 0.12 higher)	⊕⊕◯◯ LOW	CRITICAL
Discontinuation at >3 months
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	1/25 (4%)	3/25 (12%)	RR 0.33 (0.04 to 2.99)	80 fewer per 1000 (from 115 fewer to 239 more)	⊕⊕◯◯ LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 78Clinical evidence profile: Mind-body versus usual care

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Mind-body exercises	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, Visual numeric scale, FIQ pain subscale, 0–100, final values and change scores, high is poor outcome)
8	randomised trials	very serious¹	serious²	no serious indirectness	serious³	none	193	200	-	MD 11.17 lower (1717.3285 to 5.02 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Pain improvement at ≤3 months (30% improvement on NRS)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	37/73 (50.7%)	15.9%	RR 3.19 (1.56 to 6.52)	348 more per 1000 (from 89 more to 878 more)	⊕⊕◯◯ LOW	CRITICAL
Pain improvement at >3 months (30% improvement on NRS)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	28/73 (38.4%)	8/44 (18.2%)	RR 2.11 (1.06 to 4.21)	202 more per 1000 (from 11 more to 584 more)	⊕◯◯◯ VERY LOW	CRITICAL
Pain at >3 months (VAS, SF-36 pain score, 0–100, final values, high is poor outcome) - Fibromyalgia
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	40	40	-	MD 26 lower (35.63 to 16.37 lower)	⊕⊕◯◯ LOW	CRITICAL
Pain at >3 months (VAS, SF-36 pain score, 0–100, final values, high is poor outcome) - Chronic neck pain
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	108	113	-	MD 11.29 lower (174219.52 to 5.17 lower)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (WHOQOL-BREF, 0–5, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	29	28	-	MD 0.58 higher (0.16 to 1 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)
3	randomised trials	very serious¹	serious²	no serious indirectness	very serious³	none	52	54	-	MD 1.55 lower (13.36 lower to 10.25 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)
3	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision³	none	107	113	-	MD 4.14 higher (2.15 to 6.12 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)
3	randomised trials	serious¹	serious²	no serious indirectness	serious³	none	107	113	-	MD 2.33 higher (2.57 lower to 7.24 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 physical component, 0–100, final values, high is poor outcome)
3	randomised trials	serious¹	serious²	no serious indirectness	very serious³	none	108	113	-	MD 1.64 lower (11.62 lower to 8.33 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 mental component, 0–100, final values, high is poor outcome)
3	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	108	113	-	MD 0.69 higher (2.05 lower to 3.43 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36, 0–100, functional capacity scale, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	40	40	-	MD 17.2 higher (8.01 to 26.39 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36, 0–100, physical aspects subscale, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	40	40	-	MD 22.7 higher (9.73 to 35.67 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36, 0–100, pain subscale, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	40	40	-	MD 16.9 higher (9.19 to 24.61 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36, 0–100, vitality subscale, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	40	40	-	MD 10.5 higher (0.5 to 20.5 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36, 0–100, general health subscale, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	40	40	-	MD 3.4 higher (4.81 lower to 11.61 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36, 0–100, social subscale, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	40	40	-	MD 5.9 higher (5.61 lower to 17.41 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36, 0–100, emotional subscale, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	50	40	-	MD 20.4 higher (4.14 to 36.66 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36, 0–100, mental health subscale, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	40	40	-	MD 6.1 higher (3.42 lower to 15.62 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at ≤3 months (Neck disability index, neck pain disability scale, final values, high is poor outcome)
7	randomised trials	very serious¹	serious²	no serious indirectness	serious³	none	171	192	-	SMD 0.40 lower (0.84 to 0.04 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at >3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)
3	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	112	113	-	MD 6.79 lower (10.57 to 3.01 lower)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (6 minute walk test, metes, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	40	40	-	MD 88 higher (51.42 to 124.58 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (HADS:D, Beck depression inventory, CES-D, ADS depression scale, final values, high is poor outcome)
5	randomised trials	very serious¹	serious²	no serious indirectness	serious³	none	148	158	-	SMD 0.51 lower (0.96 to 0.05 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at ≤3 months (State trace anxiety inventory, final values, high is poor outcome) - Fibromyalgia
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	29	28	-	MD 9.91 lower (15.59 to 4.23 lower)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (HADS:A, final values, high is poor outcome) - Chronic neck pain
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	38	39	-	MD 0.2 lower (2 lower to 1.6 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (Beck depression inventory, HADS:D, final values, high is poor outcome)
3	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	109	114	-	MD 0.02 lower (0.29 lower to 0.24 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Psychological distress at >3 months (HADS:A, 0–21, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	38	39	-	MD 0.6 lower (2.38 lower to 1.18 higher)	⊕⊕◯◯ LOW	CRITICAL
Sleep at ≤3 months (VAS sleep outcome, pittsburgh sleep quality index, final values, high is poor outcome)
2	randomised trials	serious¹	serious²	no serious indirectness	serious²	none	29	31	-	SMD 0.43 lower (1.58 lower to 0.72 higher)	⊕◯◯◯ VERY LOW	IMPORTANT
Discontinuation at >3 months
12	randomised trials	very serious¹	serious²	no serious indirectness	serious³	none	65/389 (16.7%)	7.7%	RD 0.03 (−0.03 to 0.10)	40 more per 1000 (from 30 fewer to 100 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded for heterogeneity, unexplained by subgroup analysis

3: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 79Clinical evidence profile: Flexibility versus usual care

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Flexibility	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	16	12	-	MD 18 lower (37.89 lower to 1.89 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at ≤3 months (FIQ physical function subscale, 0–30, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	14	14	-	MD 1.5 lower (5.39 lower to 2.39 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Discontinuation at ≤3 months
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	3/17 (17.6%)	0/17 (0%)	Peto OR 8.41 (0.81 to 86.84)	-	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 80Clinical evidence profile: Aerobic versus strength

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Aerobic exercise	Strength	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, FIQ pain subscale, MDPI, 0–100, final values and change scores, high is poor outcome)
4	randomised trials	serious¹	serious²	no serious indirectness	serious³	none	113	86	-	MD 4.47 lower (20.48 lower to 11.54 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Pain at >3 months (VAS, 0–100, change scores, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	30	30	-	MD 6.7 lower (16.22 lower to 2.82 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values and change scores, high is good outcome)
3	randomised trials	very serious¹	serious²	no serious indirectness	serious³	none	77	50	-	MD 4.29 higher (8.4 lower to 16.98 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values and change scores, high is good outcome)
3	randomised trials	very serious¹	serious²	no serious indirectness	serious³	none	77	50	-	MD 4.69 higher (6.6 lower to 15.97 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at ≤3 months (Multidimensional fatigue inventory-20 reduced activity subscale, change scores, 0–20, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious³	none	14	12	-	MD 1 higher (1.18 lower to 3.18 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at ≤3 months (6 minute walking test, metres, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	50	25	-	MD 88.4 lower (114.7 to 62.1 lower)	⊕⊕⊕◯ MODERATE	CRITICAL
Physical function at ≤3 months (Final values and change scores, SF-36 physical functioning subscale, 0–100, high is good outcome)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	43	43	-	MD 1.85 higher (3.79 lower to 7.49 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (Hospital anxiety and depression anxiety score, 0–21, final values and change scores, high is poor outcome)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	27	25	-	MD 0.93 lower (2.46 lower to 0.61 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at ≤3 months (Final values and change scores, Hospital anxiety and depression scale, depression score, 0–21, high is poor outcome)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	27	25	-	MD 0.04 higher (1.37 lower to 1.46 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (Final values, BDI, 0–60, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious³	none	50	25	-	MD 12.7 higher (9.01 to 16.39 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Sleep at ≤3 months (VAS Sleep scale, 0–100, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	13	13	-	MD 13.3 lower (31.93 lower to 5.33 higher)	⊕◯◯◯ VERY LOW	IMPORTANT
Discontinuation at ≤3 months (due to other diagnoses, transportation problems)
4	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	10/98 (10.2%)	15%	RR 0.67 (0.32 to 1.4)	49 fewer per 1000 (from 102 fewer to 60 more)	⊕⊕◯◯ LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded for heterogeneity, unexplained by subgroup analysis

3: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 81Clinical evidence profile: Aerobic versus flexibility

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Aerobic exercise	Flexibility	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	28	-	MD 3 higher (10.19 lower to 16.19 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Pain at >3 months (VAS, 0–100, final values and change scores, high is poor outcome)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	50	44	-	MD 12.65 lower (22.45 to 2.84 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	28	-	MD 2.82 higher (1.29 lower to 6.93 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	28	-	MD 2.55 higher (2.08 lower to 7.18 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	28	-	MD 4.26 higher (1.69 lower to 10.21 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	28	-	MD 7.91 higher (2.43 to 13.39 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at ≤3 months (BDI, 0–21, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	32	28	-	MD 0.44 higher (6.83 lower to 7.71 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at >3 months (BDI, 0–21, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	28	-	MD 0.74 lower (4.53 lower to 3.05 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at ≤3 months (State trace anxiety inventory, 0–100, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	28	-	MD 1.83 lower (6.33 lower to 2.67 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at >3 months (State trace anxiety inventory, 0–100, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	32	28	-	MD 4.83 lower (9.22 to 0.44 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Discontinuation at >3 months
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	10/38 (26.3%)	15.8%	RR 1.67 (0.67 to 4.13)	106 more per 1000 (from 52 fewer to 495 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 82Clinical evidence profile: Aerobic exercise versus biomechanical exercise

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Aerobic exercise versus biomechanical	Control	Relative (95% CI)	Absolute	Quality	Importance
Quality of life at 12 weeks (SF36 role social subscale, 0–100, high score is good outcome) (Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	21	21	-	MD 10.6 lower (27.34 lower to 6.14 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 general health status subscale, 0–100, high score is good outcome) (Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	21	21	-	MD 2 lower (15.89 lower to 11.89 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 vitality subscale, 0–100, high score is good outcome) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	21	21	-	MD 1.2 lower (12.43 lower to 10.03 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 functional capacity subscale, 0–100, high score is good outcome) (Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	21	21	-	MD 9.6 lower (21.76 lower to 2.56 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 role physical subscale, 0–100, high score is good outcome) (Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	21	21	-	MD 14.3 lower (35.85 lower to 7.25 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 emotional aspects subscale, 0–100, high score is good outcome) (Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	21	21	-	MD 9 lower (34.66 lower to 16.66 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 pain subscale, 0–100, high score is good outcome) (Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	21	21	-	MD 7 lower (18.72 lower to 4.72 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 mental health subscale, 0–100, high score is good outcome) (Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	21	21	-	MD 10.9 lower (25.37 lower to 3.57 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Sleep at 12 weeks (Pittsburgh Sleep Quality Index, 0–21, high score is poor outcome) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	21	21	-	MD 0.4 lower (2.64 lower to 1.84 higher)	⊕⊕◯◯ LOW	CRITICAL
Pain at 12 weeks (VAS, 0–10, high score is poor outcome) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	21	21	-	MD 0.6 lower (1.79 lower to 0.59 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at 12 weeks (Scale of Catastropic Thoughts on Pain, 0–5, high score is poor outcome) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious¹	none	21	21	-	MD 0.2 lower (1.08 lower to 0.68 higher)	⊕⊕◯◯ LOW	CRITICAL
Discontinuation at 12 weeks
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	2/21 (9.5%)	4/21 (19%)	RR 0.50 (0.10 to 2.44)	95 fewer per 1000 (from 171 fewer to 274 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 83Clinical evidence profile: Aerobic and strength versus aerobic

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Aerobic and strength	Aerobic	Relative (95% CI)	Absolute	Quality	Importance
Quality of life at >3 months (FIQ, 0–100, change scores, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	21	22	-	MD 0 higher (7.78 lower to 7.78 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at >3 months (BDI, 0–61, change scores, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	21	22	-	MD 2.1 higher (1.66 lower to 5.86 higher)	⊕⊕◯◯ LOW	CRITICAL
Discontinuation at >3 months
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	4/21 (19%)	18.2%	RR 1.05 (0.3 to 3.66)	9 more per 1000 (from 127 fewer to 484 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 84Clinical evidence profile: Aerobic and strength versus flexibility

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Aerobic and strength	Flexibility	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	41	44	-	MD 4 lower (9.96 lower to 1.96 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Pain at >3 months (VAS, 0–100, final values, high is poor outcome
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	36	40	-	MD 8 lower (13.89 to 2.11 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (NIH CPSI quality of life subscale, 0–12, final values, high is poor outcome
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	41	44	-	MD 1.8 lower (2.69 to 0.91 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (NIH CPSI quality of life subscale, 0–12, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	36	40	-	MD 1.8 lower (2.68 to 0.92 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at ≤3 months (BDI, 0–21, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	41	44	-	MD 0.5 higher (1.33 lower to 2.33 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at >3 months (BDI, 0–21, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	36	40	-	MD 0.5 higher (0.97 lower to 1.97 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Discontinuation at ≤3 months
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	10/52 (19.2%)	9.8%	RR 1.96 (0.72 to 5.34)	94 more per 1000 (from 27 fewer to 425 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 85Clinical evidence profile: Aerobic and flexibility versus mind-body

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Aerobic and flexibility	Mind-body	Relative (95% CI)	Absolute	Quality	Importance
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, change scores, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	36	75	-	MD 1.5 lower (4.65 lower to 1.65 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, change scores, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	36	75	-	MD 3.2 lower (6.38 to 0.02 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 physical component summary score, 0–100, change scores, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	36	75	-	MD 2.8 lower (6.65 lower to 1.05 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 mental component summary score, 0–100, change scores, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	36	75	-	MD 2.4 lower (7.88 lower to 3.08 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at ≤3 months (6 minute walking test change scores, metres, change scores, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	36	75	-	MD 1.9 higher (25.15 lower to 28.95 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (6 minute walking test change scores, metres, change scores, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	36	75	-	MD 22.2 lower (60.46 lower to 16.06 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (HADS: depression, 0–21, change scores, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	36	75	-	MD 1.2 higher (0.68 lower to 3.08 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (HADS: anxiety, 0–21, change scores, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	36	75	-	MD 1.8 higher (0.4 to 3.2 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at >3 months (HADS: anxiety, 0–21, change scores, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	36	75	-	MD 1.8 higher (0.12 to 3.48 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at >3 months (HADS: depression, 0–21, change scores, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	36	75	-	MD 1.6 higher (0.86 lower to 4.06 higher)	⊕⊕◯◯ LOW	CRITICAL
Sleep at ≤3 months (Pittsburgh sleep quality index, 0–21, change scores, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	36	75	-	MD 0.7 higher (0.74 lower to 2.14 higher)	⊕⊕◯◯ LOW	IMPORTANT
Sleep at >3 months (Pittsburgh sleep quality index, 0–21, change scores, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	36	75	-	MD 0.8 higher (1.14 lower to 2.74 higher)	⊕⊕◯◯ LOW	IMPORTANT
Discontinuation at ≤3 months
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	11/36 (30.6%)	22.7%	RR 1.35 (0.71 to 2.57)	79 more per 1000 (from 66 fewer to 356 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 86Clinical evidence profile: Aerobic exercise and flexibility versus aerobic exercise

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Aerobic and flexibility versus aerobic	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain perception at ≤3 months (Final score; VAS) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	32	32	-	MD 0.65 lower (0.86 to 0.44 lower)	⊕⊕⊕◯ MODERATE	CRITICAL
Pain perception at >3 months (Final score; VAS) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	32	32	-	MD 0.94 lower (1.14 to 0.74 lower)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at ≤3 months (final score; FIQ) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	32	32	-	MD 5.49 lower (7.46 to 3.52 lower)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at >3 months (final score; FIQ) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	32	32	-	MD 10.62 lower (12.34 to 8.9 lower)	⊕⊕⊕◯ MODERATE	CRITICAL
Sleep quality at ≤3 months (final score; Pittsburgh Sleep Quality Index) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	32	32	-	MD 3.94 lower (4.62 to 3.26 lower)	⊕⊕⊕◯ MODERATE	IMPORTANT
Sleep quality at >3 months (final score; Pittsburgh Sleep Quality Index) (Copy) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	32	32	-	MD 5.03 lower (5.51 to 4.55 lower)	⊕⊕⊕◯ MODERATE	IMPORTANT
Discontinuation at >3 months
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	0/32 (0%)	0/32 (0%)	RD 0 (−0.06 to 0.06_	-	⊕⊕⊕◯ MODERATE	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

Table 87Clinical evidence profile: Aerobic, strength, mind-body and proprioception versus flexibility

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Aerobic, strength, mind-body and propioception versus flexibility	Control	Relative (95% CI)	Absolute	Quality	Importance
Quality of life at 7 weeks (FIQ total score, high is poor outcome) (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	11	10	-	MD 13.04 lower (21.92 to 4.16 lower)	⊕⊕◯◯ LOW	CRITICAL
Physical function at 7 weeks (number of steps, high is good outcome) (Better indicated by higher values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	11	10	-	MD 9.19 higher (11.24 lower to 29.62 higher)	⊕⊕◯◯ LOW	CRITICAL
Discontinuation at 7 weeks
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	5/16 (31.3%)	9/19 (47.4%)	RR 0.66 (0.28 to 1.57)	161 fewer per 1000 (from 341 fewer to 270 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 88Clinical evidence profile: Strength versus mind-body

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Strength versus mind-body	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain (VAS, <3 months) (follow-up 6 weeks; range of scores: 0–10; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	18	-	MD 1.1 higher (0.31 lower to 2.51 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life (Nottingham health profile, <3 months) (range of scores: 0–600; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	18	-	MD 56.1 higher (13.21 lower to 125.41 higher)	⊕◯◯◯ VERY LOW
Physical function (NDI, <3 months) (follow-up 6 weeks; range of scores: 0–100; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	18	-	MD 3.1 higher (0.56 lower to 6.76 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress (BDI, <3 months) (follow-up 6 weeks; range of scores: 0–63; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	18	-	MD 3.3 higher (1.24 lower to 7.84 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Discontinuation at ≤3 months
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	12/60 (20%)	12.9%	RR 1.55 (0.68 to 3.52)	71 more per 1000 (from 41 fewer to 325 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 89Clinical evidence profile: Strength versus biomechanical

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Strength versus biomechanical	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain (VAS, <3 months) (follow-up 6 weeks; range of scores: 0–10; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	20	-	MD 0.8 higher (0.52 lower to 2.12 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life (Nottingham health profile, <3 months) (follow-up 6 weeks; range of scores: 0–600; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	20	-	MD 27.7 higher (44.07 lower to 99.47 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function (NDI, <3 months) (follow-up 6 weeks; range of scores: 0–100; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	20	-	MD 1.3 higher (2.29 lower to 4.89 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress (BDI, <3 months) (follow-up 6 weeks; range of scores: 0–63; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	20	-	MD 1.2 higher (3.36 lower to 5.76 higher)	⊕◯◯◯ VERY LOW	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 90Clinical evidence profile: Strength versus flexibility

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Strength	Flexibility	Relative (95% CI)	Absolute	Quality	Importance
Pain reduction at ≤3 months (VAS, 0–100, change scores and final values, high is poor outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	44	42	-	MD 8.09 lower (14.58 to 1.59 lower)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at >3 months (SF-36 physical component, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	35	31	-	MD 1.5 higher (2.64 lower to 5.64 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 mental component, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	35	31	-	MD 5.39 lower (11.75 lower to 0.97 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at ≤3 months (FIQ physical function subscale, 0–30, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	16	14	-	MD 6 higher (2.34 to 9.66 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (BDI, 0–61, change scores, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	28	28	-	MD 1.83 lower (3.99 lower to 0.33 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (BAI, 0–61, change scores, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious¹	none	28	28	-	MD 3.2 lower (6.42 lower to 0.02 higher)	⊕⊕◯◯ LOW	CRITICAL
Sleep at ≤3 months (FIQ sleep subscale, 0–10, change scores, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	28	28	-	MD 1.77 lower (2.62 to 0.92 lower)	⊕⊕⊕◯ MODERATE	IMPORTANT
Discontinuation at >3 months
3	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	13/81 (16%)	18/76 (23.7%)	RR 0.68 (0.36 to 1.28)	76 fewer per 1000 (from 152 fewer to 66 more)	⊕◯◯◯ VERY LOW	IMPORTANT
3	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none			RR 0.68 (0.36 to 1.28)		⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 91Clinical evidence profile: Strength and flexibility versus flexibility

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Strength and flexibility	Flexibility	Relative (95% CI)	Absolute	Quality	Importance
Quality of life at >3 months (SF-36 physical functioning subscale, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	43	43	-	MD 0.4 lower (4.92 lower to 4.12 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 role physical subscale, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	43	43	-	MD 1.1 lower (15.9 lower to 13.7 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at >3 months (SF-36 role emotional subscale, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	43	43	-	MD 2.1 higher (9.7 lower to 13.9 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at >3 months (SF-36 energy subscale, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	43	43	-	MD 5.2 higher (2.96 lower to 13.36 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 emotional wellbeing subscale, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	43	43	-	MD 3.6 higher (3.43 lower to 10.63 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 social functioning subscale, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	43	43	-	MD 1.7 higher (5.28 lower to 8.68 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at 12 months (SF-36 bodily pain subscale, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	43	43	-	MD 1.7 lower (10.14 lower to 6.74 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 general health subscale, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	43	43	-	MD 0.7 higher (6.41 lower to 7.81 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Discontinuation at >3 months
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	6/49 (12.2%)	17.3%	RR 0.71 (0.27 to 1.84)	50 fewer per 1000 (from 126 fewer to 145 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 92Clinical evidence profile: Strength and flexibility versus mind-body

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Strength and flexibility	Mind-body	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, 0–100, high is poor outcome)
2	randomised trials	serious¹	serious²	no serious indirectness	serious³	none	60	57	-	MD 10.4 lower (23.66 lower to 2.85 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Pain at >3 months (VAS, 0–100, high is poor outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	70	70	-	MD 0.78 lower (8.05 lower to 6.49 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at ≤3 months (SF-36 mental component, 0–100, high is good outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	60	57	-	MD 2.88 higher (0.8 lower to 6.55 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at >3 months (SF-36 mental component, 0–100, high is good outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	70	70	-	MD 1.05 higher (2.28 lower to 4.38 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at 9–12 weeks (SF-36 physical component, 0–100, high is good outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	60	57	-	MD 1.04 higher (1.9 lower to 3.99 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at >3 months (SF-36 physical component, 0–100, high is good outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	70	70	-	MD 2.21 lower (4.81 lower to 0.38 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at ≤3 months (Neck disability index, neck pain disability scale, high is poor outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	60	57	-	SMD 0.22 lower (0.59 lower to 0.14 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (Neck pain disability scale, high is poor outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	70	70	-	MD 0.22 higher (5.02 lower to 5.46 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Psychological distress at 12 weeks (Depression scale ADS, 0–60, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	35	31	-	MD 0.5 higher (3.66 lower to 4.66 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (Depression scale ADS, 0–60, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious³	none	35	31	-	MD 1.8 lower (6.07 lower to 2.47 higher)	⊕⊕◯◯ LOW	CRITICAL
Discontinuation at >3 months
3	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious³	none	10/106 (9.4%)	10.3%	OR 0.87 (0.35 to 2.14)	12 fewer per 1000 (from 64 fewer to 94 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded for heterogeneity, unexplained by subgroup analysis

3: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 93Clinical evidence profile: Strength, flexibility and proprioception versus mind-body

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Strength, flexibility and proprioception	mind-body	Relative (95% CI)	Absolute	Quality	Importance
Pain reduction at ≤3 months (VAS, 0–100, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	38	-	MD 7.2 lower (16.72 lower to 2.32 higher)	⊕⊕◯◯ LOW	CRITICAL
Pain reduction at >3 months (VAS, 0–100, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	38	-	MD 1.9 lower (12.99 lower to 9.19 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	38	-	MD 2.1 lower (5.48 lower to 1.28 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at >3 months (SF-36 physical component summary score, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	38	-	MD 2.5 lower (6.22 lower to 1.22 higher)	⊕⊕◯◯ LOW	CRITICAL
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	37	38	-	MD 0.9 higher (3.77 lower to 5.57 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at >3 months (SF-36 mental component summary score, 0–100, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	37	38	-	MD 0.1 lower (4.96 lower to 4.76 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at ≤3 months (Neck disability index, 0–100, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	38	-	MD 1.2 higher (3.7 lower to 6.1 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (Neck disability index, 0–100, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	37	38	-	MD 0.8 higher (5.31 lower to 6.91 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Psychological distress at ≤3 months (HADS: anxiety, 0–21, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	38	-	MD 1 lower (2.8 lower to 0.8 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (HADS: anxiety, 0–21, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	37	38	-	MD 0.6 lower (2.34 lower to 1.14 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (HADS: depression, 0–21, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	37	38	-	MD 0.1 lower (1.52 lower to 1.32 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Psychological distress at >3 months (HADS: depression, 0–21, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	37	38	-	MD 0 higher (1.51 lower to 1.51 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Discontinuation at ≤3 months
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none	13/37 (35.1%)	7.9%	RR 4.45 (1.38 to 14.35)	273 more per 1000 (from 30 more to 1000 more)	⊕⊕⊕⊕ HIGH	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 94Clinical evidence profile: Strength versus proprioception

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Strength

Proprioception

Relative (95% CI)

Absolute

Physical function ≤3 months (Neck disability index, 0–50, high is poor outcome)

randomised trials

serious¹

no serious inconsistency

no serious indirectness

no serious imprecision

none

MD 0.32 higher (1.47 lower to 2.11 higher)

⊕⊕⊕◯

MODERATE

CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

Table 95Clinical evidence profile: Mind-body versus flexibility

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Mind-body	Flexibility	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, 0–100, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	29	26	-	MD 2 higher (9.65 lower to 13.65 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (FIQ, 0–100, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	25	24	-	MD 22.9 lower (33.4 to 12.4 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at ≤3 months (BDI, 0–61, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	42	39	-	MD 0.5 higher (3.55 lower to 4.55 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Sleep at ≤3 months (Pittsburgh sleep quality index, 0–21, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	42	39	-	MD 0 higher (1.92 lower to 1.92 higher)	⊕⊕◯◯ LOW	IMPORTANT
Discontinuation at ≤3 months
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	12/30 (40%)	21.9%	RR 1.83 (0.83 to 4.02)	182 more per 1000 (from 37 fewer to 661 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 96Clinical evidence profile: Mind-body versus biomechanical

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Mindbody versus biomechanical	Control	Relative (95% CI)	Absolute	Quality	Importance
Pain (VAS, <3 months) (follow-up 6 weeks; range of scores: 0–10; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	18	20	-	MD 0.3 lower (1.51 lower to 0.91 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life (Nottingham health profile, <3 months) (follow-up 6 weeks; range of scores: 0–600; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	20	-	MD 28.4 lower (84.68 lower to 27.88 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function (NDI, <3 months) (follow-up 6 weeks; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	20	-	MD 1.8 lower (4.86 lower to 1.26 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress (Depression, BDI, <3 months) (follow-up 6 weeks; range of scores: 0–63; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	18	20	-	MD 2.1 lower (6.11 lower to 1.91 higher)	⊕◯◯◯ VERY LOW	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 97Clinical evidence profile: Flexibility and proprioception versus flexibility

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Flexibility and proprioception	Flexibility	Relative (95% CI)	Absolute	Quality	Importance
Quality of life at ≤3 months (FIQ, 0–100, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	28	29	-	MD 12.7 lower (21.27 to 4.13 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Psychological distress at ≤3 months (BDI, 0–63, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	28	29	-	MD 3.88 higher (0.46 lower to 8.22 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Discontinuation at ≤3 months
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	7/35 (20%)	12.1%	RR 1.65 (0.53 to 5.12)	79 more per 1000 (from 57 fewer to 499 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 98Clinical evidence profile: Flexibility and relaxation versus aerobic

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Flexibility and relaxation	Aerobic	Relative (95% CI)	Absolute	Quality	Importance
Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	65	68	-	MD 0.4 higher (4.64 lower to 5.44 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Discontinuation at ≤3 months
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	12/69	12/67	RR 0.97 (0.47 to 2.01)	10 fewer per 1000 (from 130 fewer to 120 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 99Clinical evidence profile: Exercise versus psychological therapies

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Exercise	Psychological therapies	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, FIQ pain scale, 0–100, high is poor outcome)
4	randomised trials	serious¹	very serious²	no serious indirectness	very serious³	none	131	120	-	MD 1.61 lower (15.09 lower to 11.87 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Pain at >3 months (VAS, NRS, 0–100, high is poor outcome)
4	randomised trials	serious¹	serious²	no serious indirectness	serious³	none	121	110	-	MD 7.19 lower (13.98 to 0.41 lower)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (FIQ, 0–100, high is poor outcome)
4	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	151	141	-	MD 6.7 lower (10.88 to 2.52 lower)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at >3 months (EQ-5D, high is good outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	81	71	-	MD 0.05 lower (0.12 lower to 0.02 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 social aspects subscale, 0–100, high score is good outcome (Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	30	30	-	MD 3.4 higher (9.27 lower to 16.07 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 general health status aspects subscale, 0–100, high score is good outcome (Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	30	30	-	MD 2.6 higher (8.08 lower to 13.28 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 funcitonal capacity aspects subscale, 0–100, high score is good outcome (Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	30	-	MD 13.1 higher (2.72 to 23.48 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 limitations due to physical aspects subscale, 0–100, high score is good outcome (Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	30	30	-	MD 17.2 higher (2.83 lower to 37.23 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 limitations due to emotional aspects subscale, 0–100, high score is good outcome (Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	30	30	-	MD 11.9 higher (8.74 lower to 32.54 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 pain subscale, 0–100, high score is good outcome) (Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	30	30	-	MD 5 higher (5.39 lower to 15.39 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at 12 weeks (SF36 mental health subscale, 0–100, high score is good outcome) (Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	30	30	-	MD 0.9 higher (11.04 lower to 12.84 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at ≤3 months (FIQ physical function subscale, 0–10, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	51	47	-	MD 0.7 lower (2.75 lower to 1.35 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at ≤3 months (6 minute walk test, metres, high is good outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	76	63	-	MD 26.42 higher (0.85 lower to 53.69 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (6 minute walking test, metres, high is good outcome)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	86	79	-	MD 49.05 higher (25.45 to 72.65 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at ≤3 months (CES-D, 0–100, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	34	28	-	MD 10.3 lower (20.07 to 0.53 lower)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (Hospital anxiety and depression scale, depression subscale, 0–21, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	56	48	-	MD 1 lower (2.25 lower to 0.25 higher)	⊕⊕◯◯ LOW	CRITICAL
Psychological distress at >3 months (Hospital anxiety and depression scale, anxiety subscale, 0–21, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	56	49	-	MD 0.8 lower (2.01 lower to 0.41 higher)	⊕⊕◯◯ LOW	CRITICAL
Sleep at >3 months (the sleep scale, 0–30, final values, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	99	91	-	MD 0.3 higher (1.22 lower to 1.82 higher)	⊕⊕⊕◯ MODERATE	IMPORTANT
Sleep at >3 months (Pittsburgh sleep quality index, 0–21, high is poor outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	56	49	-	MD 1.1 lower (2.32 lower to 0.12 higher)	⊕⊕◯◯ LOW	IMPORTANT
Discontinuation at >3 months (due to increased pain, personal reasons, lost to follow up)
10	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	78/540 (14.4%)	90/522 (17.2%)	RD −0.03 (−0.07 to 0.02)	30 fewer per 1000 (from 70 fewer to 20 more)	⊕⊕◯◯ LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 100Clinical evidence profile: Manual therapy and exercise versus manual therapy

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Manual therapy and exercise	Manual therapy	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (NRS, high is poor outcome, final values, 0–10)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	51	50	-	MD 0.8 lower (1.66 lower to 0.06 higher)	⊕⊕◯◯ LOW	CRITICAL
Pain at >3 months (NRS, high is poor outcome, final values, 0–10)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	51	50	-	MD 0.5 lower (1.42 lower to 0.42 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at ≤3 months (Neck disability index, high is poor outcome, final values, 0–50)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	51	50	-	MD 5.1 lower (9.65 to 0.55 lower)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (Neck disability index, high is poor outcome, final values, 0–50)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	51	50	-	MD 4.9 lower (9.85 lower to 0.05 higher)	⊕⊕◯◯ LOW	CRITICAL
Discontinuation at ≤3 months
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	13/64 (20.3%)	14/63 (22.2%)	RR 0.91 (0.47 to 1.79)	20 fewer per 1000 (from 118 fewer to 176 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 101Clinical evidence profile: Manual therapy and exercise versus exercise

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Manual therapy and exercise	Exercise	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (VAS, NRS, high is poor outcome, final values, 0–100)
6	randomised trials	serious¹	very serious²	no serious indirectness	serious³	none	265	277	-	MD 6.34 lower (13.82 lower to 1.13)	⊕◯◯◯ VERY LOW	CRITICAL
Pain at >3 months (NRS, VAS, high is poor outcome, final values, 0–100)
3	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	198	196	-	MD 0.95 higher (3.51 lower to 5.4 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at >3 months (Fibromyalgia impact questionnaire, 0–100, final values, high is poor outcome)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	10	11	-	MD 1 lower (13.87 lower to 11.87 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Quality of life at ≤3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	91	89	-	MD 0.6 higher (1.34 lower to 2.54 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at >3 months (SF-36 physical component summary score, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	91	89	-	MD 0.2 higher (1.79 lower to 2.19 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at ≤3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	91	89	-	MD 0.7 lower (3.55 lower to 2.15 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Quality of life at >3 months (SF-36 mental component summary score, 0–100, final values, high is good outcome)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	91	89	-	MD 1.8 lower (4.34 lower to 0.74 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Physical function at >3 months (Neck disability index, functional performance scale, final values, high is poor outcome, 0–100)
5	randomised trials	serious¹	serious³	no serious indirectness	serious²	none	239	238	-	SMD 0.29 lower (0.62 lower to 0.04 higher)	⊕◯◯◯ VERY LOW	CRITICAL
Physical function at >3 months (Neck disability index, high is poor outcome, final values, 0–100)
3	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	198	196	-	MD 0.17 lower (2.6 lower to 2.25 higher)	⊕⊕⊕◯ MODERATE	CRITICAL
Physical function at 4–10 weeks (Neck disability index, high is poor outcome, 0–100) (Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	36	50	-	MD 8.14 lower (9.92 to 6.35 lower)	⊕⊕◯◯ LOW	CRITICAL
Discontinuation at ≤3 months
6	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious¹	none	36/275 (13.1%)	34/267 (12.7%)	RD 0 (−0.05 to 0.06)	0 fewer per 1000 (from 50 fewer to 60 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

3: Downgraded for heterogeneity, unexplained by subgroup analysis

Table 102Clinical evidence profile: Exercise versus manual therapy

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Exercise	Manual therapy	Relative (95% CI)	Absolute	Quality	Importance
Pain at ≤3 months (NRS, high is poor outcome, final values, 0–10)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	51	50	-	MD 1.3 lower (2.11 to 0.49 lower)	⊕⊕◯◯ LOW	CRITICAL
Pain at >3 months (NRS, high is poor outcome, final values, 0–10)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	51	50	-	MD 0.5 lower (1.42 lower to 0.42 higher)	⊕⊕◯◯ LOW	CRITICAL
Physical function at ≤3 months (Neck disability index, high is poor outcome, final values, 0–50)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	44	50	-	MD 5.9 lower (10.6 to 1.2 lower)	⊕⊕◯◯ LOW	CRITICAL
Physical function at >3 months (Neck disability index, high is poor outcome, final values, 0–50)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	44	50	-	MD 3.9 lower (9.14 lower to 1.34 higher)	⊕⊕◯◯ LOW	CRITICAL
Discontinuation at ≤3 months
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	19/64 (29.7%)	22.2%	RR 1.34 (0.74 to 2.43)	75 more per 1000 (from 58 fewer to 317 more)	⊕◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias, or by 2 increments if the majority of the evidence was at very high risk of bias

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Figure 307Flow chart of health economic study selection for the guideline

* Non-relevant population, intervention, comparison, design or setting; non-English language

Table 103Studies excluded from the clinical review

Study	Exclusion reason
Acosta-Gallego, 2018²	Incorrect comparison (land versus pool based exercises)
Actrn, 2018³	Clinical trial registry
Adamse 2018⁴	Systematic review with different PICO
Alentorn-Geli, 2008⁷	Whole body vibration
Alentorn-Geli, 2009⁶	No useable outcomes
Allende, 2018⁸	No useable outcomes
Amanollahi 2013¹¹	Not in English
Amris 2014¹³	Incorrect intervention: pain management programme
Andersen 2008¹⁴	No useable outcomes
Andrade 2017¹⁶	No useable outcomes
Andrade 2018¹⁵	Systematic review, incorrect study design: non-randomised
Anonymous 2019⁷⁶	Incorrect comparison: both groups received TENS and hot packs in addition to interventions
Arami 2012¹⁸	Not in English
Arcos-Carmona 2011¹⁹	Not in English
Arimi 2017¹²	Systematic review with different PICO
Asenlof 2005²⁰	Incorrect intervention: pain management programme
Asenlof 2009²¹	Incorrect intervention: psychological
Assis 2006²²	Incorrect comparison: aerobic comparison
Assuncao Junior 2018²⁴	Incorrect study design: no comparator
Astin 2003²⁵	Incorrect comparison: exercise and meditation versus education
Bai 2015²⁶	Systematic review, incorrect population
Beltran-Alacreu 2015²⁹	Incorrect interventions: pain management programme
Bertozzi 2013³¹	Systematic review with different PICO
Bidonde 2019³²	Cochrane review published after review finalised; references checked
Bjersing 2017³⁵	Subgroup analysis, not relevant
Bland 2010³⁶	Abstract
Bobos 2016³⁷	Incorrect comparison: different strength training protocols
Bowering 2013⁴⁰	Systematic review with different PICO
Brage 2015⁴¹	Incorrect comparison: education
Bravo 2019⁴²	Incorrect intervention: body awareness therapy
Buckelew 1998⁴⁴	No useable outcomes
Burckhardt 1992⁴⁵	Abstract
Burckhardt 1994⁴⁶	No useable outcomes: no variation data
Busch 2007⁴⁷	Cochrane review, incorrect comparison
Busch 2008⁴⁸	Systematic review with different PICO
Cantarero-Villanueva 2012⁵¹	Incorrect population
Carbonell-Baeza 2012⁵²	Protocol
Cerrillo-Urbina 2015⁵⁶	Systematic review with different PICO
Champagne 2018⁵⁷	Abstract
Chan 2012⁵⁸	Systematic review with different PICO
Cho 2016⁶⁰	Incorrect comparison: lymphatic drainage
Chung 2018⁶¹	Incorrect comparison: different neck exercises
Collado-Mateo 2017⁶²	Incorrect intervention: virtual reality
Cramer 2013⁶⁴	Non-comparative follow up data
Cramer 2017⁶³	Systematic review with different PICO
Cramer 2017⁶⁶	Cochrane review, incorrect population: breast cancer pain
de Araujo Cazotti 2018⁶⁸	Incorrect comparison: pharmacological
Demir-Gocmen 2013⁷⁰	Incorrect comparison: supervised versus home exercises
Dobkin 2005⁷¹	Incorrect study design: no comparator
Dunleavy 2016⁷²	Incorrect study design (not randomised)
Duray, 2018⁷³	Incorrect comparison (not relevant)
Duruturk 2015⁷⁴	No useable outcomes
Dusunceli 2006⁷⁵	Incorrect comparison: TENS
Ekici 2008⁷⁷	Not in English
Emilson 2017⁷⁹	Incorrect comparison: pain management, follow-up study
Ernberg 2016⁸²	Incorrect comparison: healthy controls
Evcik 2008⁸⁷	Incorrect comparison: land versus water based, same exercises
Falla 2006⁸⁸	Incorrect comparison: different strength training protocols
Falla 2007⁸⁹	Incorrect comparison: different neck exercise protocols
Fernandes 2016⁹¹	Incorrect comparison: swimming versus walking
Field 2003⁹²	Incorrect comparison: exercise and manual therapy versus relaxation
Fontaine 2007⁹⁵	Incorrect intervention (exercise and psychological therapy)
Fontaine 2011⁹³	No comparator
Galindez-ibarbengoetxea 2018⁹⁶	Unclear intervention time
Garcia-Hermoso 2015⁹⁸	Systematic review with different PICO
Geneen 2017¹⁰²	Cochrane review, incorrect population: chronic non-cancer pain
Ghaderi 2017¹⁰³	Incorrect comparison: neck stabilisation exercises versus neck strengthening, both interventions offer exercises to strengthen neck muscles
Ghodrati 2020¹⁰⁴	Incorrect comparison: manual therapy vs. manual therapy + exercise
Giannotti 2014¹⁰⁵	Incorrect interventions: physical and psychological elements, pain management programme
Gowans 1999¹¹¹	Not guideline condition. Not review population. No extractable data. Wrong study type: results are not extractable
Gowans 2004¹¹²	No comparator
Gowans 2007¹⁰⁹	Systematic review with different PICO
Gross 2015¹¹⁴	Cochrane review, incorrect population, different outcomes: with some overlap
GunendiZ 2008¹¹⁵	Incorrect interventions: exercise combined with TENS and thermotherapy
Gutierrez-Espinoza 2019¹¹⁷	Incorrect intervention: targeted at improving range of movement in the glenohumeral joint only and doesn’t fall into any protocol categories of general exercise
Hakkinen 2002¹²⁰	No relevant outcomes
Hammond 2006¹²¹	Incorrect comparison: relaxation versus exercise and education
Har 2000¹²²	Not available
Hoeger Bement 2011¹²³	Incorrect comparison (not relevant)
Humphreys 2002¹²⁶	Incorrect comparison: healthy controls
Iaroshevskyi, 2019¹²⁷	Incorrect study design
Ide 2008¹²⁸	Incorrect interventions: breathing exercises
Im 2013¹²⁹	Incorrect intervention, incorrect comparison: whirlpool therapy versus warm gel packs
Isomeri 1992¹³⁰	Abstract
Isomeri 1993¹³¹	No useable outcomes
Jensen 2001¹³³ (Bergstrom 2012³⁰)	Incorrect population (low back pain)
Jentoft, 2001¹³⁴	Incorrect interventions: pool based versus land based, same exercise protocol
Jones 2011¹³⁵	Summary article
Jordan 1998¹³⁷	No useable outcomes
Jull 2009¹³⁸	Incorrect comparison: psychological therapies
Kalamir¹³⁹	No relevant outcomes
Kaleth 2013¹⁴⁰	No useable outcomes
Kay 1992¹⁴¹	No useable outcomes
Keel, 1998¹⁴³	Incorrect intervention: pain management programme
Kelley 2010¹⁴⁴	Systematic review with different PICO
Khan 2014¹⁴⁶	Incorrect comparison (both groups are different types of strength exercises)
Khan, 2018¹⁴⁵	Incorrect comparison (not relevant)
Kim 2019¹⁵⁰	Cochrane review published after review finalised; references checked
Kim 2016¹⁴⁸	Incorrect comparison: different neck exercise protocols
Kim 2016¹⁴⁹	Incorrect comparison: manual therapy versus ultrasound
Kim 2016¹⁵¹	Systematic review with different PICO
Lagueux 2014¹⁵⁴	Conference abstract
Langhorst 2009¹⁵⁶	Systematic review, incorrect interventions: hydrotherapy, no exercise
Langhorst 2013¹⁵⁵	Systematic review with different PICO
Latorre 2013¹⁵⁸	Incorrect study design (not randomised)
Lauche 2017¹⁶¹	No useable outcomes
Law 2009¹⁶²	Incorrect study design: not randomised
Letafatkar 2020¹⁶⁴	Unclear population: inclusion citeria stated >3 months pain duration, but 50% had symptoms 6–12 weeks duration
Lima 2013¹⁶⁵	Systematic reviewwith different PICO
Lopez-de-Uralde-Villanueva 2020¹⁶⁷	Incorrect comparison: manual therapy vs. manual therapy + education vs. manual therapy + education + exercise
Lopez-Pousa 2015¹⁶⁸	Incorrect comparison: walking in a young vs. mature forest
Lopez-Rodriguez 2012¹⁶⁹	Not in English
López-Rodríguez 2013¹⁷⁰	Not in English
Lorena 2015¹⁷¹	Not in English
Mannerkorpi 2000¹⁷⁷	Incorrect interventions: pain management programme
Mannerkorpi 2002¹⁷³	No comparator
Mannerkorpi 2009¹⁷⁶	Incorrect interventions: pain management programme
Mannerkorpi 2010¹⁷⁵	Incorrect comparison: different walking protocols
Martin-Martinez¹⁷⁸	Incorrect interventions (virtual reality)
Matsutani 2007¹⁸⁰	Incorrect intervention: laser therapy
McDowell 2017¹⁸⁴	Systematic review with different PICO
McVeigh 2008¹⁸⁵	Systematic review, incorrect interventions: hydrotherapy, no exercise
Meiworm 1999¹⁸⁷	Not in English
Meiworm 2000¹⁸⁶	Incorrect study design: not randomised
Mendez-Rebolledo 2017¹⁸⁸	Systematic review with different PICO
Mesquita 2014¹⁹⁰	Abstract
Meyer, 2000¹⁹¹	No useable outcomes
Miles 2014¹⁹³	Not available
Molinari 2018¹⁹⁴	Incorrect intervention: behavioural
Moseley 2004¹⁹⁶	No relevant outcomes
Moseley 2006¹⁹⁵	Incorrect population: phantom limb pain
Mosely 2005¹⁹⁷	Incorrect comparison
Moustafa 2015¹⁹⁸	Incorrect interventions: cervical manipulation, incorrect comparison
Nct, 2018²⁰²	Clinical trial registry
Nct, 2018²⁰³	Clinical trial registry
Nickel 2005²⁰⁵	Incorrect comparison: pharmacological
Norregaard, 1997²⁰⁷	No useable outcomes
Ote Karaca 2017²⁰⁹	Incorrect population: low back pain
Perez-De la Cruz 2015²¹¹	Not in English
Peters 2002²¹²	Incorrect population
Petersen 2015²¹³	Incorrect comparison, incorrect interventions: manual therapy with different neck exercises
Phattharasupharerk 2019²¹⁴	Incorrect population: low back pain
Pico-Espinosa 2020²¹⁵	Incorrect population: subacute and persistent pain included and results not reported separately
Pike 2015²¹⁶	Conference abstract
Plumbe 2016²¹⁷	Cochrane review: incorrect interventions, incorrect comparison: manipulation versus inactive control
Rajalaxmi, 2018²¹⁸	Unclear methods, no usable outcomes
Ramel 2009²¹⁹	Meta-analysis with different PICO
Ramsay 2000²²⁰	Incorrect comparison: different types of aerobic exercise
Redondo 2004²²¹	Incorrect intervention: pain management programme
Reynolds 2020²²³	Incorrect comparison: manual therapy + exercise vs. other manual therapy + exercise
Ris 2016²²⁵	Incorrect comparison: pain management programme with and without training
Rivas Neira 2017²²⁶	Protocol
Rolving 2014²²⁷	No useable outcomes: unclear values
Ryan 2002²²⁸	Not available
Saadat, 2019²²⁹	Incorrect intervention (combination)
Salo 2010²³¹	No useable outcomes
Sarmento 2020²³⁶	Incorrect comparator: sham Qigong
Sawynok 2013²³⁷	No useable outcomes
Saxena 2017²³⁸	Incorrect comparison: exercise versus medication
Segura-Jimenez 2013²⁴⁰	No comparator, incorrect study design: not randomised
Skillgate 2015²⁴⁴	Protocol
Skillgate 2020²⁴⁵	Incorrect population: subacute and persistent pain included and results not reported separately
Song 2012²⁴⁶	Conference abstract
Taggart 2003²⁴⁸	No comparator
Taimela 2000²⁴⁹	No useable outcomes
Thompson 2016²⁵¹	Incorrect comparison: exercises and psychological intervention versus exercises alone
Tomas-Carus 2007²⁵⁵	Not in English
Valencia 2009²⁵⁸	Incorrect comparison: different types of stretching
Valkeinen 2005²⁶¹	No relevant outcomes
van 2014²⁶²	Cochrane review, incorrect population: medically unexplained symptoms
van Koulil 2011²⁶⁵	Incorrect interventions: rehabilitation programme
Verstappen 1997²⁶⁶	No relevant outcomes
Villafaina 2019²⁶⁹	Incorrect interventions (virtual reality)
Villafaina 2019²⁶⁸	Incorrect interventions (virtual reality)
Vitorino 2006²⁷⁰	Incorrect comparison: same exercises on land versus water
Vonk 2009²⁷²	Incorrect interventions: graded exercise therapy with psychological therapy
Wang 2010²⁷⁵	Incorrect interventions (psychological combination)
Wiklund 2018²⁷⁷	Incorrect population: chronic pain
Yang 2005²⁸⁰	Incorrect population: general chronic pain, no useable outcomes
Ylinen 2004²⁸³	Not in English
Ylinen 2005²⁸²	No relevant outcomes
Ylinen 2006²⁸⁶	No comparator
Zamuner 2015²⁸⁷	Incorrect comparison: healthy controls
Zijlstra 2005²⁸⁸	Incorrect study design. Intervention included flying to and staying in a luxurious hotel: with spa treatments, exercise therapy, relaxation
Zonneveld 2012²⁸⁹	Incorrect population: multiple conditions causing unexplained physical symptoms

Table 104Studies excluded from the health economic review

Reference

Reason for exclusion

McBeth 2012¹⁸¹

This study was assessed as partially applicable with potentially serious limitations.

However, other available evidence was of greater applicability and methodological quality and therefore this study was selectively excluded. This is the same study as the included economic evaluation but has shorter follow up period.

Van Eijk-Hustings 2016²⁶³

This study was assessed as partially applicable with potentially serious limitations. It has methodological limitations as it is a cost comparison study, based on an RCT included in the clinical review but also using additional data as it takes a period from diagnosis to after the interventions (which includes before the interventions) and compares costs across the interventions. So slightly odd methodology.

Van Eijk-Hustings 2013²⁶⁴

This study was assessed as partially applicable with potentially serious limitations.

However, other available evidence was of greater applicability as this was a cost consequences analysis.

Table 105MIDs for continuous outcomes: Aerobic exercise versus usual care

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	9.05
Pain at >3 months (VAS, FIQ pain subscale, 0–100, final values, high is poor outcome)	10.8
Pain at >3 months (FIQ pain subscale, 0–100, high is poor outcome)	10.4
Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)	7.05
Quality of life at ≤3 months (EQ-5D VAS, 0–100. high is good outcome, final values)	10.05
Quality of life at >3 months (EQ-5D VAS, 0–100, high is good outcome, final values)	11.43
Physical function at ≤3 months (timed up and go, seconds, final values, high is good outcome)	0.76
Physical function at ≤3 months (FIQ physical function subscale, 0–100, final values, high is poor outcome)	10.39
Physical function at >3 months (6 minute walking test, final values, metres, high is good outcome)	44.25
Physical function at >3 months (FIQ and SF-36 physical function subscales, 0–100, final values, high is poor outcome)	9.75
Physical function at >3 months (FIQ physical function subscale, 0–100, final values, high is poor outcome)	10.39
Psychological distress at >3 months (Change scores and final values, beck depression inventory, 0–21, high is poor outcome)	4.3
Psychological distress at >3 months (Final values, VAS and FIQ depression scale, 0–10, high is poor outcome)	1.35
Psychological distress at >3 months (Final values, VAS and FIQ anxiety scale, Beck anxiety inventory, final values, high is poor outcome)	0.5 (SMD)
Psychological distress at >3 months (Change scores, STAI anxiety total scores, high is poor outcome)	12.5
Psychological distress at >3 months (final values, FIQ depression scale, 0–10, high is poor outcome)	1.39
Psychological distress at >3 months (final values, FIQ anxiety scale, 0–10, high is poor outcome)	1.39
Psychological distress at ≤3 months (final values, BDI depression scale, high is poor outcome)	1.51
Use of healthcare services at ≤3 months (Number of GP contacts)	1.39
Use of healthcare services at >3 months (Number of GP contacts)	1.04
Use of healthcare services at ≤3 months (Number of medical specialist contacts)	0.35
Use of healthcare services at >3 months (Number of medical specialist contacts)	0.35
Use of healthcare services at ≤3 months (Number of physiotherapist contacts)	2.43
Use of healthcare services at >3 months (Number of physiotherapist contacts)	2.43
Sleep at >3 months (VAS sleep scale, PSQI, FIQ sleep subscale, final values, high is poor outcome)	0.5 (SMD)

Table 106MIDs for continuous outcomes: Strength training versus usual care

Outcomes	MID
Pain reduction at ≤3 months (final values, VAS, NRS, high is poor outcome)	10.75
Pain reduction at ≤3 months (change scores and final values, VAS, NRS, 0–100, high is poor outcome)	10.5
Pain reduction at >3 months (VAS, NRS, 0–100, final values and change scores, high is poor outcome)	12.25
Quality of life at ≤3 months (FIQ scale, 0–100, final values, high is poor outcome)	5.3
Physical function at ≤3 months (Neck disability index, change scores and final values, 0–100, high is poor outcome)	2.57
Physical function at ≤3 months (final values, FIQ physical function subscale, Northwick Park Questionnaire, high is poor outcome)	0.5 (SMD)
Physical function at ≤3 months (6 minute walking test, metres, final values, high is good outcome)	49.25
Physical function at >3 months months (final values, Northwick Park Questionnaire, Neck Disability Index, high is poor outcome)	0.5 (SMD)
Physical function at >3 months (change scores, SF-36 physical function subscale, HAQ, 0–100, high is poor outcome)	5.27
Psychological distress at ≤3 months (final values, pain catastrophising scale, high is poor outcome)	7
Psychological distress at >3 months (BDI, 0–61, change scores, high is poor outcome)	1.55
Sleep at >3 months (VAS sleep, 0–100, change scores, high is poor outcome)	8.72

Table 107MIDs for continuous outcomes: Aerobic and strength versus usual care

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, change scores, high is poor outcome)	7.5
Pain at >3 months (VAS, FIQ pain subscale, 0–100, final values, high is poor outcome)	4
Quality of life at ≤3 months (Fibromyalgia impact questionnaire, 0–100, final values, high is poor outcome)	8.82
Quality of life at >3 months (Fibromyalgia impact questionnaire, 0–100, final values and change scores, high is poor outcome)	6.89
Physical function at >3 months (seconds, quarter mile walk test, final values, high is poor outcome)	13.21
Physical function at >3 months (metres, 6-minute walk test, final values, high is good outcome)	34.77
Physical function at >3 months (FIQ physical function subscale, 0–10, final values, high is poor outcome)	1
Physical function at ≤3 months (metres, 6-minute walk test, high is good outcome)	38.15
Psychological distress at ≤3 months (BDI, 0–30, final values, high is poor outcome)	5.32
Psychological distress at ≤3 months (State anxiety inventory, 0–10, change scores, high is poor outcome)	5.25
Psychological distress at ≤3 months (HADS anxiety, 0–21, high is poor outcome)	1.85
Psychological distress at >3 months (CES-D, BDI, FIQ depression subscale, final values, high is poor outcome)	0.5 (SMD)
Psychological distress at >3 months (State anxiety inventory, 20–80, final values and change scores, high is poor outcome)	2.26
Sleep at >3 months (Pittsburgh sleep quality index, high is poor outcome, change scores, 0–21)	1.06

Table 108MIDs for continuous outcomes: Strength and flexibility versus usual care

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	12.58
Pain at >3 months (VAS, SF-36 pain score, final values, 0–100, high is poor outcome)	11.43
Physical function at ≤3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)	10.85
Physical function at >3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)	9.28
Psychological distress at ≤3 months (ADS depression scale, 0–60, final values, high is poor outcome)	4
Psychological distress at >3 months (ADS depression scale, 0–60, final values, high is poor outcome)	4.5

Table 109MIDs for continuous outcomes: Strength, proprioception and flexibility versus usual care

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	11.25
Pain at >3 months (VAS, 0–100, final values, high is poor outcome)	10
Psychological distress at ≤3 months (HADS: anxiety, 0–21, final values, high is poor outcome)	1.7
Psychological distress at >3 months (HADS: anxiety, 0–21, final values, high is poor outcome)	1.7
Psychological distress at ≤3 months (HADS: depression, 0–21, final values, high is poor outcome)	1.7
Psychological distress at >3 months (HADS: depression, 0–21, final values, high is poor outcome)	2
Physical function at ≤3 months (Neck disability index, 0–100, final values, high is poor outcome)	5.7
Physical function at >3 months (Neck disability index, 0–100, final values, high is poor outcome)	6.35

Table 110MIDs for continuous outcomes: Proprioception versus usual care

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	0.81
Pain at >3 months (VAS, 0–10, final values, high is poor outcome)	1.17
Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)	5.98
Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)	8.46
Physical function at ≤3 months (sit to stand test, final values, high is good outcome)	2.28
Physical function at >3 months (sit to stand test, final values, high is good outcome)	2.41
Psychological distress at ≤3 months (BDI, 0–61, final values, high is poor outcome)	2.9
Psychological distress at >3 months (BDI, 0–61, final values, high is poor outcome)	4.73

Table 111MIDs for continuous outcomes: Mind-body exercise versus usual care

Outcomes	MID
Pain at ≤3 months (VAS, Visual numeric scale, FIQ pain subscale, 0–100, final values and change scores, high is poor outcome)	11.13
Pain at >3 months (VAS, SF-36 pain score, 0–100, final values, high is poor outcome) - Fibromyalgia	8.5
Pain at >3 months (VAS, SF-36 pain score, 0–100, final values, high is poor outcome) - Chronic neck pain	10.12
Quality of life at ≤3 months (WHOQOL-BREF, 0–5, final values, high is good outcome)	0.46
Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)	8.5
Physical function at ≤3 months (Neck disability index, neck pain disability scale, final values, high is poor outcome)	0.5 (SMD)
Physical function at >3 months (Neck pain disability scale, 0–100, final values, high is poor outcome)	6.85
Physical function at >3 months (6 minute walk test, metes, final values, high is good outcome)	38.95
Psychological distress at ≤3 months (HADS:D, Beck depression inventory, CES-D, ADS depression scale, final values, high is poor outcome)	0.5 (SMD)
Psychological distress at ≤3 months (State trace anxiety inventory, final values, high is poor outcome) - Fibromyalgia	5.42
Psychological distress at ≤3 months (HADS:A, final values, high is poor outcome) - Chronic neck pain	1.6
Psychological distress at >3 months (Beck depression inventory, HADS:D, final values, high is poor outcome)	0.5 (SMD)
Psychological distress at >3 months (HADS:A, 0–21, final values, high is poor outcome)	1.7
Sleep at ≤3 months (VAS sleep outcome, pittsburgh sleep quality index, final values, high is poor outcome)	0.5 (SMD)

Table 112MIDs for continuous outcomes: Flexibility versus usual care

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	13.5
Physical function at ≤3 months (FIQ physical function subscale, 0–30, final values, high is poor outcome)	2.65

Table 113MIDs for continuous outcomes: Aerobic exercise versus strength

Outcomes	MID
Pain at ≤3 months (VAS, FIQ pain subscale, MDPI, 0–100, final values and change scores, high is poor outcome)	6.48
Pain at >3 months (VAS, 0–100, change scores, high is poor outcome)	9.75
Physical function at ≤3 months (Multidimensional fatigue inventory-20 reduced activity subscale, change scores, 0–20, high is poor outcome)	1.05
Physical function at ≤3 months (6 minute walking test, metres, final values, high is good outcome)	27.75
Psychological distress at ≤3 months (Hospital anxiety and depression anxiety score, 0–21, final values and change scores, high is poor outcome)	1.53
Psychological distress at ≤3 months (Final values and change scores, Hospital anxiety and depression scale, depression score, 0–21, high is poor outcome)	1.35
Psychological distress at ≤3 months (Final values, BDI, 0–60, high is poor outcome)	3.1
Sleep at ≤3 months (VAS Sleep scale, 0–100, final values, high is poor outcome)	14.85

Table 114MIDs for continuous outcomes: Aerobic exercise versus flexibility

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	12.5
Pain at >3 months (VAS, 0–100, final values and change scores, high is poor outcome)	10.7
Psychological distress at ≤3 months (BDI, 0–21, high is poor outcome)	5.13
Psychological distress at >3 months (BDI, 0–21, final values, high is poor outcome)	4.2
Psychological distress at ≤3 months (State trace anxiety inventory, 0–100, final values, high is poor outcome)	4.31
Psychological distress at >3 months (State trace anxiety inventory, 0–100, final values, high is poor outcome)	4.17

Table 115MIDs for continuous outcomes: Aerobic exercise versus biomechanical exercise

Outcomes	MID
Pain at ≤3 months (VAS, 0–10, high score is poor outcome)	0.7
Psychological distress at ≤3 months (Scale of Catastrophic Thoughts on Pain, 0–5, high score is poor outcome)	0.7
Sleep at ≤3 months (Pittsburgh Sleep Quality Index, 0–21, high score is poor outcome)	1.85

Table 116MIDs for continuous outcomes: Aerobic and strength versus aerobic exercise

Outcomes	MID
Quality of life at >3 months (FIQ, 0–100, change scores, high is poor outcome)	7
Psychological distress at >3 months (BDI, 0–61, change scores, high is poor outcome)	4

Table 117MIDs for continuous outcomes: Aerobic and strength versus flexibility

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	7
Pain at >3 months (VAS, 0–100, final values, high is poor outcome)	6
Quality of life at ≤3 months (NIH CPSI quality of life subscale, 0–12, final values, high is poor outcome)	1.05
Quality of life at >3 months (NIH CPSI quality of life subscale, 0–12, final values, high is poor outcome)	1.05
Psychological distress at ≤3 months (BDI, 0–21, final values, high is poor outcome)	2.15
Psychological distress at >3 months (BDI, 0–21, final values, high is poor outcome)	1.5

Table 118MIDs for continuous outcomes: Aerobic and flexibility versus mind-body exercise

Outcomes	MID
Physical function at ≤3 months (6 minute walking test change scores, metres, change scores, high is good outcome)	49.05
Physical function at >3 months (6 minute walking test change scores, metres, change scores, high is good outcome)	70.14
Psychological distress at ≤3 months (HADS: depression, 0–21, change scores, high is poor outcome)	3.76
Psychological distress at ≤3 months (HADS: anxiety, 0–21, change scores, high is poor outcome)	2.54
Psychological distress at >3 months (HADS: anxiety, 0–21, change scores, high is poor outcome)	3.04
Psychological distress at >3 months (HADS: depression, 0–21, change scores, high is poor outcome)	4.97
Sleep at ≤3 months (Pittsburgh sleep quality index, 0–21, change scores, high is poor outcome)	2.65
Sleep at >3 months (Pittsburgh sleep quality index, 0–21, change scores, high is poor outcome)	3.54

Table 119MIDS for continuous outcomes: Aerobic exercise and flexibility versus aerobic exercise

Outcomes	MID
Pain perception at <3 months (Final score; VAS 0–10; high is poor outcome)	0.19
Pain perception at >3 months (Final score; VAS, 0–10; high is poor outcome)	0.21
Quality of life at <3 months (final score; FIQ, 0–100, high is poor outcome)	2.04
Quality of life at >3 months (final score; FIQ, 0–100, high is poor outcome)	2.11
Sleep quality at <3 months (final score; Pittsburgh Sleep Quality Index, 0–21, high is poor outcome)	0.73
Sleep quality at >3 months (final score; Pittsburgh Sleep Quality Index, 0–21, high is poor outcome)	0.5

Table 120MIDs for continuous outcomes: Aerobic, strength, mind-body and proprioception versus flexibility

Outcomes	MID
Quality of life at ≤3 months (FIQ total score, 0–100, high is poor outcome)	6.51
Physical function at ≤3 months (number of steps, high is good outcome)	15.44

Table 121MIDs for continuous outcomes: Strength versus mind-body

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	0.45
Quality of life at ≤3 months (NHP, 0–600, final values, high is poor outcome)	59.05
Physical function at ≤3 months (Neck disability index, 0–100, final values, high is poor outcome)	2.65
Psychological distress at ≤3 months (BDI, 0–61, final values, high is poor outcome)	3.1

Table 122MIDs for continuous outcomes: Mind-body versus biomechanical

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	0.65
Quality of life at ≤3 months (NHP, 0–600, final values, high is poor outcome)	48.95
Physical function at ≤3 months (Neck disability index, 0–100, final values, high is poor outcome)	3.3
Psychological distress at ≤3 months (BDI, 0–61, final values, high is poor outcome)	3.8

Table 123MIDs for continuous outcomes: Strength versus flexibility

Outcomes	MID
Pain reduction at ≤3 months (VAS, 0–100, change scores and final values, high is poor outcome)	9.78
Physical function at ≤3 months (FIQ physical function subscale, 0–30, final values, high is poor outcome)	2.6
Psychological distress at ≤3 months (BDI, 0–61, change scores, high is poor outcome)	2.02
Psychological distress at ≤3 months (BAI, 0–61, change scores, high is poor outcome)	3.23
Sleep at ≤3 months (FIQ sleep subscale, 0–10, change scores, high is poor outcome)	0.81

Table 124MIDs for continuous outcomes: Strength and flexibility versus mind-body

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	13.8
Pain at >3 months (VAS, 0–100, final values, high is poor outcome)	12.55
Physical function at ≤3 months (Neck disability index, neck pain disability scale, final values, high is poor outcome)	0.5 (SMD)
Physical function at >3 months (Neck pain disability scale, final values, high is poor outcome)	9.04
Psychological distress at ≤3 months (Depression scale ADS, 0–60, final values, high is poor outcome)	3.7
Psychological distress at >3 months (Depression scale ADS, 0–60, final values, high is poor outcome)	3.7

Table 125MIDs for continuous outcomes: Strength, flexibility and proprioception versus mind-body

Outcomes	MID
Pain reduction at ≤3 months (VAS, 0–100, final values, high is poor outcome)	11.75
Pain reduction at >3 months (VAS, 0–100, final values, high is poor outcome)	13.85
Physical function at ≤3 months (Neck disability index, 0–100, final values, high is poor outcome)	6.1
Physical function at >3 months (Neck disability index, 0–100, final values, high is poor outcome)	7.05
Psychological distress at ≤3 months (HADS: anxiety, 0–21, final values, high is poor outcome)	2.35
Psychological distress at >3 months (HADS: anxiety, 0–21, final values, high is poor outcome)	2.25
Psychological distress at ≤3 months (HADS: depression, 0–21, final values, high is poor outcome)	1.9
Psychological distress at >3 months (HADS: depression, 0–21, final values, high is poor outcome)	1.9

Table 126MIDs for continuous outcomes: Strength versus proprioception

Outcomes	MID
Physical function at ≤3 months (Neck disability index, 0–50, final values, high is poor outcome)	1.31

Table 127MIDs for continuous outcomes: Mind-body versus flexibility

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	11
Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)	11.1
Psychological distress at ≤3 months (BDI, 0–61, final values, high is poor outcome)	4.35
Sleep at ≤3 months (Pittsburgh sleep quality index, 0–21, final values, high is poor outcome)	2.2

Table 128MIDs for continuous outcomes: Mind-body versus biomechanical

Outcomes	MID
Pain at ≤3 months (VAS, 0–100, final values, high is poor outcome)	0.65
Quality of life at ≤3 months (NHP, 0–600, final values, high is poor outcome)	48.95
Physical function at ≤3 months (Neck disability index, 0–100, final values, high is poor outcome)	3.3
Psychological distress at ≤3 months (BDI, 0–61, final values, high is poor outcome)	3.8

Table 129MIDs for continuous outcomes: Flexibility and proprioception versus flexibility

Outcomes	MID
Quality of life at ≤3 months (FIQ, 0–100, final values, high is poor outcome)	8.85
Psychological distress at ≤3 months (BDI, 0–63, final values, high is poor outcome)	3.59

Table 130MIDs for continuous outcomes: Flexibility and relaxation versus aerobic exercise

Outcomes	MID
Quality of life at >3 months (FIQ, 0–100, final values, high is poor outcome)	7.9

Table 131MIDs for continuous outcomes: Exercise versus psychological therapies

Outcomes	MID
Pain at ≤3 months (VAS, FIQ pain scale, 0–100, high is poor outcome, final values and change scores) - Fibromyalgia	10.61
Pain at >3 months (VAS, NRS, 0–100, high is poor outcome, final values)	9.75
Quality of life at ≤3 months (FIQ, 0–100, high is poor outcome, final values and change scores)	8.35
Physical function at ≤3 months (FIQ physical function subscale, 0–10, high is poor outcome, change scores)	0.17
Physical function at ≤3 months (6 minute walk test, metres, high is good outcome, final values)	35.95
Physical function at >3 months (6 minute walking test, metres, high is good outcome, final values)	39
Psychological distress at ≤3 months (CES-D, 0–100, high is poor outcome, final values)	9.3
Psychological distress at >3 months (Hospital anxiety and depression scale, depression subscale, 0–21, high is poor outcome, change scores)	1.4
Psychological distress at >3 months (Hospital anxiety and depression scale, anxiety subscale, 0–21, high is poor outcome, change scores)	1.35
Sleep at >3 months (the sleep scale, 0–30, final values, high is poor outcome)	2.85
Sleep at >3 months (Pittsburgh sleep quality index, 0–21, high is poor outcome, change scores)	1.5

Table 132MIDs for continuous outcomes: Manual therapy and exercise versus manual therapy

Outcomes	MID
Pain at ≤3 months (NRS, high is poor outcome, final values, 0–10, final values)	1.15
Pain at >3 months (NRS, high is poor outcome, final values, 0–10, final values)	1.15
Physical function at ≤3 months (Neck disability index, high is poor outcome, final values, 0–50, final values)	6.5
Physical function at >3 months (Neck disability index, high is poor outcome, final values, 0–50)	6.75

Table 133MIDs for continuous outcomes: Manual therapy and exercise versus exercise

Outcomes	MID
Pain at ≤3 months (VAS, NRS, high is poor outcome, final values, 0–100, final values)	4.25
Pain at >3 months (NRS, VAS, high is poor outcome, final values, 0–100)	11.35
Quality of life at >3 months (Fibromyalgia impact questionnaire, 0–100, final values, high is poor outcome)	7.95
Physical function at >3 months (Neck disability index, functional performance scale, final values, high is poor outcome, 0–100)	0.5 (SMD)
Physical function at >3 months (Neck disability index, high is poor outcome, final values, 0–100)	6.2
Physical function at ≤3 months (Neck disability index, high is poor outcome, 0–100)	8.14

Table 134MIDs for continuous outcomes: Exercise versus manual therapy

Outcomes	MID
Pain at ≤3 months (NRS, high is poor outcome, final values, 0–10)	1.15
Pain at >3 months (NRS, high is poor outcome, final values, 0–10)	1.15
Physical function at ≤3 months (Neck disability index, high is poor outcome, final values, 0–50)	6.5
Physical function at >3 months (Neck disability index, high is poor outcome, final values, 0–50)	6.75