Information for people with thyroid disease

National Guideline Centre (UK)

Information for people with thyroid disease

Thyroid disease: assessment and management

Evidence review A

NICE Guideline, No. 145

Authors

National Guideline Centre (UK).

London: National Institute for Health and Care Excellence (NICE); 2019 Nov.

ISBN-13: 978-1-4731-3595-6

1. Information for people with thyroid disease

1.1. Review question: What information should people with thyroid disease, their family and carers receive?

1.2. Introduction

We asked the question: What information should people with thyroid disease, their family and carers receive? The NICE guideline on Patient Experience (CG138) has established that people receiving medical care (along with their carers and families) require information about their diagnosis, the course of their medical condition and their choices in regard to treatment. This is in order to control and minimise psychological stress, as well as to provide useful practical advice in managing their disease on a day to day basis and to issue important warnings.

The Thyroid Disease NICE Guideline Committee looked at findings from qualitative studies to see what sort of information and support people with thyroid diseases need. Many people need general information about where their thyroid is and what it does.

However, at present there is no standardised agreed practice for healthcare professionals and people with thyroid disease on who gives the person information, what information is given and when it is given. There are many good sources of information including the NHS Choices website and leaflets (both online and hard copy) from patient groups. Some of these are written by people with thyroid disease, working with endocrinologists and other experts.

1.3. Characteristics table

For full details see the review protocol in Appendix A:.

Table 1

Characteristics of review question.

1.4. Qualitative evidence

1.4.1. Included studies

Three qualitative studies were included in the review;²^, ³^, ⁶ these are summarised in Table 2 below. Key findings from these studies are summarised in Section 1.4.2 below. See also the study selection flow chart in Appendix C:, study evidence tables in Appendix D:, and excluded studies lists in Appendix G:.

1.4.2. Excluded studies

See the excluded studies list in Appendix H:.

1.4.3. Summary of qualitative studies included in the evidence review

Table 2

Summary of studies included in the review.

See Appendix D: for full evidence tables.

1.4.4. Qualitative evidence synthesis

1.4.4.1. Narrative summary of review findings

TSH targets & symptoms

Patients often appear to be unsure of the relationship of their symptoms to their thyroid disease. Blood tests that are within normal parameters are perceived to indicate a euthyroid state regardless of the presence of symptoms, and patients perceive that blood samples rather than symptom checks determine management. Some patients report feeling well regardless of whether their TSH levels are in range or not while others continue to feel unwell despite normal TSH results. As a result, patients report feeling that their symptoms cannot be managed or that symptoms are being ignored by clinicians or are assumed to be unrelated to their thyroid condition.

Explanation of quality assessment: minor methodological limitations; minor concerns about coherence; no concerns about relevance; minor concerns about adequacy. Overall assessment of confidence was moderate due to concerns about coherence and adequacy.

Non-specific nature of symptoms

People reported that due to the non-specific nature of thyroid symptoms their diagnoses were sometimes delayed or there was uncertainty regarding the cause of their symptoms and whether they could be directly related to hypothyroidism. The overlap between hypothyroidism symptoms and natural ageing also left some people questioning the veracity of their diagnosis and the need for treatment or led others to attribute symptoms such as tiredness and memory problems to ageing. GPs agreed on the non-specific nature of symptoms which overlap with numerous conditions and often results in a variety of symptoms experienced by patients being attributed to their thyroid.

Explanation of quality assessment: minor methodological limitations; very minor concerns about coherence; no concerns about relevance; minor concerns about adequacy. Overall assessment of confidence was moderate due to the concerns about adequacy.

Medication interactions

Health professionals reported that thyroid medication may interact with other medication, dietary and lifestyle factors including alcohol, coffee and smoking and this may influence its absorption. This potential interaction may explain an elevated TSH in cases where patients adhere to medication. Some patients reported receiving thyroid treatment promoting advice from their pharmacists such as timing of medication, avoiding food and other medication.

Importance of adherence

Health professionals reported good adherence to medication was important for optimal treatment and incorrect adherence was in their experience the main reason for inadequate thyroid control. Some patients felt they needed to take their levothyroxine to prevent the symptoms of hypothyroidism. The lack of information about medication including the reasons for potential alterations in dosage left some patients with doubts about the need for medication.

Explanation of quality assessment: minor methodological limitations; moderate concerns about coherence; no concerns about relevance; minor concerns about adequacy. Overall assessment of confidence was low due to the concerns about coherence.

Barriers to optimal thyroid replacement

People’s understanding of treatment and the perceived benefits of a change in dose are likely to influence the extent to which they adhere to it. A lack of an understanding may lead to incorrect adherence with some patients taking more medication than prescribed to alleviate symptoms of tiredness or to lose weight. Lack of consensual decision making between patients and their GPs when patients feel there is room for improvement of their treatment by the GP and overreliance on TSH within reference range as the sole measure of adequate hormone replacement are perceived barriers to optimising thyroid control.

Availability of information

Health professionals perceive that patients research their condition online and get information from online forums. Thus professionals tend to provide a limited amount of information in verbal form and rarely use written information leaflets. Patients report receiving limited information, particularly about their symptoms and treatment and not being given information at the time of their diagnosis. Often due to time constraints, professionals report directing patients to online resources such as patient.co.uk. Patients report seeking information from informal sources to fully understand diagnostic decisions and treatment changes, such as the internet which they felt could be inaccurate and provoke anxiety leading them to put off researching.

Explanation of quality assessment: minor methodological limitations; very minor concerns about coherence; no concerns about relevance; no concerns about adequacy. Overall assessment of confidence was high.

Risks of over or under treatment

Health professionals perceive that patients lack awareness of the risks of over and under treatment. Indeed patients appeared to have poor knowledge of the consequences of poor treatment adherence or the risks associated with being out of the therapeutic treatment range. This may lead to incorrect adherence as patients have been reported by health professionals to take more than prescribed aiming to lose weight or to alleviate symptoms such as tiredness while the elderly tend to perceive increased doses as advantageous. Health professionals’ awareness of the cardiac complications and increased risk for fractures associated with overtreatment and their perception of patients’ lack of it prevents them from over treating patients, especially the elderly.

Explanation of quality assessment: minor methodological limitations, very minor concerns about coherence; no concerns about relevance; minor concerns about adequacy. Overall assessment of confidence was moderate due to the minor concerns about adequacy.

1.4.5. Qualitative evidence summary

Table 3

Summary of evidence.

1.5. Economic evidence

The committee agreed that health economic studies would not be relevant to this review question, and so health economic evidence relating to this question was not sought.

1.6. Evidence statements

1.6.1. Qualitative evidence statements

Three qualitative studies suggested the following about the information needs of people with thyroid disease, their family, carers or health professionals:
- Moderate quality evidence from 2 studies suggested that people need information about TSH targets and symptoms to alleviate their uncertainty about the relationship between their symptoms and their thyroid disease.
- Moderate quality evidence from 3 studies highlighted that it is important to have information on the non-specific nature of thyroid symptoms to prevent potential delays in diagnosis, help people understand their condition and the need for treatment and prevent them from attributing a number of symptoms on their thyroid.
- Moderate quality evidence from 2 studies highlighted that information about medication interactions should be given to patients, to prevent interacting dietary and lifestyle factors that may be influencing absorption from leading to suboptimal thyroid replacement in spite of medication adherence.
- Moderate quality evidence from 3 studies highlighted the importance of giving people information about the importance of good medication adherence to enable optimal treatment and eliminate potential doubt in regards to the need for medication.
- Low quality evidence from 3 studies highlighted the importance of informing people (health professionals) of barriers to optimal thyroid replacement such as patient’s understanding of treatment, overreliance on TSH levels and lack of consensual decision making to encourage information provision and facilitate adherence.
- High quality evidence from 3 studies highlighted the sources of information that patients require and their need for further information as the lack of sufficient verbal information provided by health professionals leads patients to online and potentially inaccurate resources in order to gain an understanding of their thyroid condition and its management.
- Moderate quality evidence from 3 studies highlighted the importance of providing people with information about the risks of over and under treatment, as patient’s lack of such awareness may often lead them to take more than prescribed to alleviate symptoms.

1.7. The committee’s discussion of the evidence

1.7.1. Interpreting the evidence

1.7.1.1. The quality of the evidence

The evidence quality ranged from high to low, the majority being of moderate quality due to mainly minor concerns about the coherence and adequacy of the findings. In particular, issues concerning the richness of data, depth of analysis and consistency of the findings across studies limited our confidence in the evidence. The findings were all applicable to the population and setting of this review. The studies were all conducted on a population with hypothyroidism or in health professionals supporting people with hypothyroidism. Participants of one study were older adults aged 80 and over. The committee were in agreement that the themes presented were consistent with their own experience with patient requests and with existing comments from stakeholders. Based on a combination of the evidence in the review, consensus and their clinical experience the committee agreed on the information that people with thyroid disease need.

1.7.1.2. Findings identified in the evidence synthesis and raised in committee discussion

General

Evidence from two studies suggested that people with thyroid disease need clarification on the relationship between TSH and their symptoms. The committee agreed that symptoms and thyroid function tests may not always be concordant, with people with thyroid disease, possibly experiencing or not experiencing symptoms in the presence of abnormal TSH. Within this framework, the committee thought it would be important to inform people that the goal of treatment is to have both well-being and TSH levels restored.

It was raised that discordance between thyroid function and the experience of symptoms is often a cause of under treatment such as when people are asymptomatic, they are less likely to engage with healthcare services. The committee emphasised that people should be made aware that treatment may be required even in the absence of symptoms due to the long term health consequences of untreated thyroid disease.

The committee raised that a considerable number of people with thyroid disease whose TSH is within reference range continue to feel unwell, noting that changes in treatment may be beneficial in terms of symptoms for those people. Hence it was agreed that information on the impact of treatment adjustments on symptom improvement in the presence of normal TFTs should be given.

It was emphasised that due to the underlying physiology of thyroid hormones it takes some time for changes in treatment to have an impact on thyroid function. Hence, the committee agreed that people with thyroid disease should be made aware of this to prevent potential frustration due to the persistence of symptoms despite treatment changes and to help people understand whether symptoms or their changes are truly thyroid related.

The committee highlighted the fact that people with thyroid disease as well as their carers often lack basic knowledge as to what the thyroid is and how it works and the committee agreed people need to be made aware of key issues including: the role and function of the thyroid gland, risks of over and under treatment, the exact medication taken, monitoring needs, information as to when to seek help and on the impact of thyroid disease and thyroid medication on fertility and pregnancy. It was noted that a lack of information coming from health professionals may often lead to misinformation with people with thyroid disease turning to potentially unreliable sources to get the information they need. Within this framework, it was highlighted that people could use direction towards legitimate and useful sources of information such as NHS choices to avoid misinformation.

Hypothyroidism

Evidence from three studies suggested that it is important to provide people information on medication interactions. The committee noted that thyroid medication interacts with other medication, nutrition supplements and tea or coffee and that for optimal thyroid replacement it should be taken in the morning or evening on an empty stomach. They agreed that people with hypothyroidism, should be made aware of drug interactions with levothyroxine and informed on when best to take it.

Evidence from three studies suggested people need information on thyroid medication and the importance of adherence as well as the risks of over and under treatment. Evidence from 3 studies also highlighted a lack of understanding of treatment as a barrier to optimal thyroid replacement and a lack of verbal information people with thyroid disease faced. Committee lay members agreed that people are sometimes not given enough verbal or written information on their thyroid condition and that they could use more information in the form of patient leaflets.

Thyrotoxicosis

No direct evidence on the information needs of people with thyrotoxicosis, thyroid enlargement, their families or carers was identified. However, the guideline committee agreed that the evidence highlighted certain key areas that people with thyroid disease require information on and highlighted the lack of verbal and written information currently given by health professionals.

In absence of evidence regarding the information needs of people with thyrotoxicosis, the committee agreed to make recommendations based on consensus for those people. It was agreed that it was important to provide people with thyrotoxicosis with written and verbal information on the different causes of their condition and the consequences of untreated thyrotoxicosis. It was raised that people with thyrotoxicosis may not receive full information on the advantages, disadvantages and uncertainties surrounding their treatment options. This is particularly critical for thyrotoxicosis where people must make decisions between distinct treatment modalities. The committee agreed that they should hence be given information on benefits and risks of all treatment modalities for example the side effects of antithyroid drugs, the specific implications of RAI, as well as information on radiation protection for carers and information on the implications and risks of surgery such as potential voice changes and hypoparathyroidism. The committee highlighted that it is particularly important to give people with thyrotoxicosis information on the risk and impact of thyroid eye disease (TED) although management of this was not a focus of the guideline.

Enlargement

The committee agreed it was important for people with thyroid enlargement to know the possible causes of their condition and that both goitre and nodules are common and rarely cancerous. They also felt it was important that although enlargement is rarely cancerous people are aware of red flag symptoms for malignancy or dangerous compression such as a hoarse voice and swallowing difficulties as well as their treatment options.

1.7.2. Cost effectiveness and resource use

Cost effectiveness evidence was not sought, as this was a qualitative review about information needs of people with thyroid disease.

The recommendations provide guidance regarding the type of information and support that should be provided to people with thyroid disease in line with the general principles of provision of information already established in the existing NICE Patient Experience Guideline and so were not considered likely to have a substantial resource impact over and above this. Where this level of information is not currently being provided there may be additional resource use for example if longer or more consultations are required or a written material needs to be produced. Better information may however also lead to downstream benefits for the patient and/or reductions in resource use, for example if it leads to medication being taken more appropriately.

References

1.: Davies L, Hendrickson CD, Hanson GS. Experience of us patients who self-identify as having an overdiagnosed thyroid cancer: A qualitative analysis. JAMA Otolaryngology--Head & Neck Surgery. 2017; 143(7):663–669 [PMC free article: PMC5824211] [PubMed: 28278335]

2.: Dew R, King K, Okosieme OE, Pearce S, Donovan G, Taylor P et al. Patients’ attitudes and perceptions towards treatment of hypothyroidism in general practice: an in-depth qualitative interview study. BJGP Open. 2017; 1 [PMC free article: PMC6169953] [PubMed: 30564669]

3.: Dew R, King K, Okosieme OE, Pearce SH, Donovan G, Taylor PN et al. Attitudes and perceptions of health professionals towards management of hypothyroidism in general practice: A qualitative interview study. BMJ Open. 2018; 8(2):e019970 [PMC free article: PMC5855452] [PubMed: 29467136]

4.: Hookham J, Collins EE, Truran P, Allahabadia A, Balasubramanian SP. Patient and clinician experience of definitive treatment options in Graves’ disease. Langenbeck’s Archives of Surgery. 2016; 401(7):1060

5.: Hookham J, Truran P, Allahabadia A, Balasubramanian SP. Patients’ perceptions and views of surgery and radioiodine ablation in the definitive management of Graves’ disease. Postgraduate Medical Journal. 2017; 93(1099):266–270 [PubMed: 27651496]

6.: Ingoe LE, Hickey J, Pearce S, Rapley T, Razvi S, Wilkes S et al. Older patients’ experience of primary hypothyroidism: A qualitative study. Health Expectations. 2018; 21(3):628–635 [PMC free article: PMC5980608] [PubMed: 29464870]

7.: Lee B, Park JY, Shin HY, Park SH, Choi EB, Yoo J et al. What Do Korean Women Know and Want to Know about Thyroid Cancer? A Qualitative Study. Asian Pacific Journal of Cancer Prevention: Apjcp. 2016; 17(6):2901–7 [PubMed: 27356710]

8.: National Institute for Health and Care Excellence. Developing NICE guidelines: the manual [updated October 2018]. London. National Institute for Health and Care Excellence, 2014. Available from: http://www.nice.org.uk/article/PMG20/chapter/1%20Introduction%20and%20overview

9.: Razvi S, McMillan CV, Weaver JU. Instruments used in measuring symptoms, health status and quality of life in hypothyroidism: a systematic qualitative review. Clinical Endocrinology. 2005; 63(6):617–24 [PubMed: 16343094]

Appendices

Appendix A. Review protocols

Table 4. Table

Table 5. 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 2014, updated 2018 https://www.nice.org.uk/guidance/pmg20/resources/developing-nice-guidelines-the-manual-pdf-72286708700869

For more detailed information, please see the Methodology Review.

B.1. Clinical search literature search strategy

Searches for patient views were run in Medline (OVID), Embase (OVID), CINAHL, Current Nursing and Allied Health Literature (EBSCO) and PsycINFO (ProQuest). Search filters were applied to the search where appropriate.

Table 6. Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

CINAHL (EBSCO) search terms

PsycINFO (ProQuest) search terms

Appendix F. Health economic evidence tables

None

Appendix G. Health economic analysis

None

Appendix H. Excluded studies

H.1. Excluded qualitative studies

Table 7. Studies excluded from the qualitative review

H.2. Excluded health economic studies

None

FINAL

Qualitative evidence review underpinning recommendations 1.1.1 to 1.1.6 in the guideline

Developed by the National Guideline Centre, hosted by 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: NBK577215PMID: 35129919

Table 1Characteristics of review question

Objective	To identify the types of information that people with thyroid disease benefit from
Population and setting	People who have been diagnosed with thyroid disease, their family, carers or healthcare professionals Strata: people with thyroid disease, family, healthcare professionals, people with hypothyroidism, hyperthyroidism, thyroid enlargement
Context	Evidence reported in qualitative studies relating to the information needs of people with thyroid disease, their family or carers will be extracted. Suggested areas based on the committee experience include: Investigation Management Long-term follow-up Familial risk of thyroid disease Advice for women of child-bearing age Warning signs of thyroid eye disease (excluding management) Specific risks and benefits of treatment Uncertainty around adverse effects of treatment Information around the effects of radiation exposure Medication adherence and interactions
Review strategy	Synthesis of qualitative research. Results presented in narrative format. Quality of the evidence will be assessed by a GRADE CerQual approach for each review finding.

Table 2Summary of studies included in the review

Study

Design

Population

Research aim

Comments

Dew 2017²

Semi-structured face-to-face interviews and grounded theory analysis

Patients with overt hypothyroidism established on levothyroxine ≥12 months (n=27); n=15 with thyroid stimulating hormone (TSH) within reference range (0.4–4.0 mU/L)

To explore the experiences, attitudes and perceptions of patients with hypothyroidism towards their treatment, to explore the behavioural factors that may contribute to suboptimal treatment.

Hypothyroidism focused

Dew 2018³

Semi-structured interviews (majority face to face, on telephone) and grounded theory analysis

Health professionals from general practice and community pharmacies (n= 16), comprising 9 GPs, 4 pharmacists, 2 practice nurses and 1 nurse practitioner, recruited through the National Institute for Health Research (NIHR) Clinical Research Network

To investigate the attitudes and perceptions of health professionals towards management of hypothyroidism, to determine the clinical management and behavioural factors that may influence the adequacy of thyroid hormone replacement in patients with hypothyroidism.

Hypothyroidism focused

Ingoe 2018⁶

Semi-structured interviews, thematic and grounded theory analysis

Patients aged 80 and over with a diagnosis of primary hypothyroidism (n=18) who had agreed to randomisation on the SORTED 1a RCT (‘Accepters’, n=11) or from a group of patients who had declined the trial (‘Decliners’, n=7)

To explore the experience of hypothyroidism in older people and examine how this may influence their understanding and acceptance of diagnosis, treatment with Levothyroxine and the monitoring process.

Hypothyroidism focused

Interviews were conducted as part of a feasibility RCT examining the impact of reducing LT4 dose in patients aged 80 and over with an existing diagnosis of hypothyroidism, to explore barriers and facilitators to recruitment and retention of older patients in clinical trials;

Data saturation was based on the RCT objectives.

Table 3Summary of evidence

Study design and sample size		Findings	Quality assessment
Number of studies contributing to the finding	Design	Findings	Criteria	Rating	Overall assessment of confidence
TSH targets & symptoms
2	Semi-structured interviews with thematic and grounded theory analysis (2 studies)	Normal blood tests in the presence of symptoms, feeling well regardless of TSH levels or unwell despite normal TSH results cause uncertainty in patients about the relationship between symptoms and thyroid disease.	Limitations	Minor limitations	MODERATE
			Coherence	Minor concerns about coherence
			Relevance	No concerns about relevance
			Adequacy	Minor concerns about adequacy
Non-specific symptoms
3	Semi-structured interviews with thematic and grounded theory analysis and semi-structured interviews with grounded theory analysis (3 studies)	The non-specific nature of thyroid symptoms meant that diagnosis was delayed for some people and left them questioning the veracity of the condition and the need for treatment, led them to attribute a number of symptoms on their thyroid or caused uncertainty about whether various symptoms they experienced could be directly related to their thyroid.	Limitations	Minor limitations	MODERATE
			Coherence	Very minor concerns about coherence
			Relevance	No concerns about relevance
			Adequacy	Minor concerns about adequacy
Medication interactions
2	Semi-structured interviews and grounded theory analysis (2 study)	The interactions of thyroid medication with other medication, comorbidities and dietary or lifestyle factors may explain suboptimal thyroid replacement despite medication compliance.	Limitations	Minor limitations	MODERATE
			Coherence	Very minor concerns about coherence
			Relevance	No concerns about relevance
			Adequacy	Minor concerns about adequacy
Importance of adherence
3	Semi-structured interviews with grounded theory analysis and semi-structured interviews with thematic and grounded theory analysis (3 studies)	Good adherence to medication is important for optimal treatment with patients reporting the need for treatment to prevent symptoms but a lack of information about medication may cast doubt about the need for it.	Limitations	Minor limitations	LOW
			Coherence	Moderate concerns about coherence
			Relevance	No concerns about relevance
			Adequacy	Minor concerns about adequacy
Barriers to optimal thyroid replacement
3	Semi-structured interviews with grounded theory analysis and semi-structured interviews with thematic and grounded theory analysis (3 studies)	Patients’ understanding of treatment may influence treatment adherence while lack of shared decision making between patients and GPs and overreliance on TSH levels as a measure of adequate thyroid replacement, present barriers to optimal treatment.	Limitations	Minor limitations	MODERATE
			Coherence	Moderate concerns about coherence
			Relevance	No concerns about relevance
			Adequacy	Minor concerns about adequacy
Availability of information
3	Semi-structured interviews with grounded theory analysis and semi-structured interviews with thematic and grounded theory analysis (3 studies)	A limited amount of verbal information is provided with patients often turning to online resources, which are often perceived as inaccurate, to understand their thyroid condition and its management.	Limitations	Minor limitations	HIGH
			Coherence	Very minor concerns about coherence
			Relevance	No concerns about relevance
			Adequacy	No concerns about adequacy
Risks of over or under treatment
3	Semi-structured interviews with grounded theory analysis and semi-structured interviews with thematic and grounded theory analysis (3 studies)	Health professionals but not patients appear to be aware of the risk of overtreatment which makes the former less likely to overtreat and the latter likely to occasionally take more than prescribed.	Limitations	Minor limitations	MODERATE
			Coherence	Minor concerns about coherence
			Relevance	No concerns about relevance
			Adequacy	Minor concerns about adequacy

Table 4

ID	Field	Content
I	Review question	What information should people with thyroid disease, their family and carers receive?
II	Type of review question	Qualitative A review of health economic evidence related to the same review question was conducted in parallel with this review. For details see the health economic review protocol for this NICE guideline.
III	Objective of the review	To identify the types of information that people with thyroid disease benefit from
IV	Eligibility criteria – population / disease / condition / issue / domain	Studies will be included if they seek the viewpoint of people who have been diagnosed with thyroid disease, their family, carers or healthcare professionals
V	Eligibility criteria – intervention(s) / exposure(s) / prognostic factor(s)	Not applicable
VI	Eligibility criteria – comparator(s) / control or reference (gold) standard	Not applicable
VII	Outcomes and prioritisation	Evidence reported in qualitative studies relating to the information needs of people with thyroid disease, their family or carers will be extracted. Themes identified in the evidence will be used to compile the overall qualitative evidence synthesis, however suggested areas based on the committee experience include: Investigation Management Long term follow-up Familial risk of thyroid disease Advice for women of child-bearing age Warning signs of thyroid eye disease (excluding management) Specific risks and benefits of treatment Uncertainty around adverse effects of treatment Information around the effects of radiation exposure Medication adherence and interactions
VIII	Eligibility criteria – study design	Qualitative interview and focus group studies (including studies using grounded theory, phenomenology or other appropriate qualitative approaches); quantitative data from questionnaires will only be considered if insufficient qualitative evidence is identified
IX	Other inclusion exclusion criteria	Qualitative studies will be added to the review until themes within the analysis became saturated; i.e. studies will only be included if they contribute towards the development and richness of existing themes or to the development of new themes
X	Proposed sensitivity / subgroup analysis, or meta-regression	Stratifications People with thyroid disease vs family vs healthcare professionals People with hypothyroidism, hyperthyroidism, thyroid enlargement
XI	Selection process – duplicate screening / selection / analysis	A sample of at least 10% of the abstract lists were double-sifted by a senior research fellow and discrepancies rectified, with committee input where consensus could not be reached, for more information please see the separate Methods report for this guideline.
XII	Data management (software)	Endnote was used for bibliography, citations, sifting and reference management
XIII	Information sources – databases and dates	Medline, Embase, CINAHL, PsycINFO
XIV	Identify if an update	Not an update
XV	Author contacts	https://www.nice.org.uk/guidance/indevelopment/gid-ng10074
XVI	Highlight if amendment to previous protocol	Not an amendment
XVII	Search strategy – for one database	For details please see Appendix B:
XVIII	Data collection process – forms / duplicate	A standardised evidence table format will be used, and published as Appendix D: of the evidence report.
XIX	Data items – define all variables to be collected	For details please see evidence tables in Appendix D: (clinical evidence tables) or H (health economic evidence tables).
XX	Methods for assessing bias at outcome / study level	The Critical Appraisal Skills Programme (CASP) Qualitative checklist was used to critically appraise individual studies. For details please see section 6.2 of Developing NICE guidelines: the manual The risk of bias across all available evidence was evaluated for each outcome using an adaptation of the ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE) toolbox’ developed by the international GRADE working group http://www.gradeworkinggroup.org/
XXI	Criteria for quantitative synthesis	For details please see section 6.4 of Developing NICE guidelines: the manual.
XXII	Methods for quantitative analysis – combining studies and exploring (in)consistency	For details please see the separate Methods report for this guideline.
XXIII	Meta-bias assessment – publication bias, selective reporting bias	For details please see section 6.2 of Developing NICE guidelines: the manual.
XXIV	Confidence in cumulative evidence	For details please see sections 6.4 and 9.1 of Developing NICE guidelines: the manual.
XXV	Rationale / context – what is known	For details please see the introduction to the evidence review.
XXVI	Describe contributions of authors and guarantor	A multidisciplinary committee developed the evidence review. The committee was convened by the National Guideline Centre (NGC) and chaired by Sarah Fisher in line with section 3 of Developing NICE guidelines: the manual. Staff from NGC undertook systematic literature searches, appraised the evidence, conducted meta-analysis and cost-effectiveness analysis where appropriate, and drafted the evidence review in collaboration with the committee. For details please see Developing NICE guidelines: the manual.
XXVII	Sources of funding / support	NGC is funded by NICE and hosted by the Royal College of Physicians.
XXVIII	Name of sponsor	NGC is funded by NICE and hosted by the Royal College of Physicians.
XXIX	Roles of sponsor	NICE funds NGC to develop guidelines for those working in the NHS, public health and social care in England.
XXX	PROSPERO registration number	Not registered

Table 5Health 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 2003, 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).⁸ 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 2003 or later but that depend on unit costs and resource data entirely or predominantly from before 2003 will be rated as ‘Not applicable’. Studies published before 2003 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.

Table 6Database date parameters and filters used

Database	Dates searched	Search filter used
Medline (OVID)	1946 – 07 January 2019	Exclusions Qualitative studies
Embase (OVID)	1974 – 07 January 2019	Exclusions Qualitative studies
CINAHL, Current Nursing and Allied Health Literature (EBSCO)	Inception – 07 January 2019	Qualitative studies
PsycINFO (ProQuest)	Inception – 07 January 2019	Qualitative studies

Medline (Ovid) search terms

1.	exp thyroid diseases/
2.	hyperthyroid*.ti,ab.
3.	hypothyroid*.ti,ab.
4.	thyrotoxicosis.ti,ab.
5.	(thyroid adj3 (swell* or dysfunction* or enlarg* or nodule* or node* or disease* or condition* or disorder*)).ti,ab.
6.	or/1–5
7.	letter/
8.	editorial/
9.	news/
10.	exp historical article/
11.	Anecdotes as Topic/
12.	comment/
13.	case report/
14.	(letter or comment*).ti.
15.	or/7–14
16.	randomized controlled trial/ or random*.ti,ab.
17.	15 not 16
18.	animals/ not humans/
19.	exp Animals, Laboratory/
20.	exp Animal Experimentation/
21.	exp Models, Animal/
22.	exp Rodentia/
23.	(rat or rats or mouse or mice).ti.
24.	or/17–23
25.	6 not 24
26.	limit 25 to English language
27.	“patient acceptance of health care”/ or exp patient satisfaction/ or consumer health information/ or needs assessment/
28.	Patient Education as Topic/ or exp patients/ or exp family/ or caregivers/ or patient preference/
29.	((information* or advice or advising or advised or support) adj3 (patient or need* or requirement* or assess* or seek* or access* or disseminat*)).ti,ab.
30.	(information* adj2 support*).ti,ab.
31.	((client* or patient* or user* or carer* or consumer* or customer* or parent* or famil* or spouse) adj2 (attitud or priorit* or perception* or preferen* or expectation* or choice* or perspective* or view* or satisfact* or inform* or experience or experiences or opinion* or preference* or focus group*)).ti,ab.
32.	or/27–31
33.	Qualitative research/ or Narration/ or exp Interviews as Topic/ or exp “Surveys and Questionnaires”/ or Health care surveys/
34.	(qualitative or interview* or focus group* or theme* or questionnaire* or survey*).ti,ab.
35.	(metasynthes* or meta-synthes* or metasummar* or meta-summar* or metastud* or meta-stud* or metathem* or meta-them* or ethno* or emic or etic or phenomenolog* or grounded theory or constant compar* or (thematic* adj3 analys) or theoretical sampl or purposive sampl* or hermeneutic* or heidegger* or husserl* or colaizzi* or van kaam* or van manen* or giorgi* or glaser* or strauss* or ricoeur* or spiegelberg* or merleau*).ti,ab.
36.	or/33–35
37.	26 and 32 and 36

Embase (Ovid) search terms

1.	exp thyroid diseases/
2.	hyperthyroid*.ti,ab.
3.	hypothyroid*.ti,ab.
4.	thyrotoxicosis.ti,ab.
5.	(thyroid adj3 (swell* or dysfunction* or enlarg* or nodule* or node* or disease* or condition* or disorder*)).ti,ab.
6.	or/1–5
7.	letter.pt. or letter/
8.	note.pt.
9.	editorial.pt.
10.	case report/ or case study/
11.	(letter or comment*).ti.
12.	or/7–11
13.	randomized controlled trial/ or random*.ti,ab.
14.	12 not 13
15.	animal/ not human/
16.	nonhuman/
17.	exp Animal Experiment/
18.	exp Experimental Animal/
19.	animal model/
20.	exp Rodent/
21.	(rat or rats or mouse or mice).ti.
22.	or/14–21
23.	6 not 22
24.	limit 23 to English language
25.	patient attitude/ or patient preference/ or patient satisfaction/ or consumer attitude/ or needs assessment/
26.	patient information/ or consumer health information/ or patients/ or family/ or caregivers/
27.	((information* or advice or advising or advised or support) adj3 (patient or need* or requirement* or assess* or seek* or access* or disseminat*)).ti,ab.
28.	(information* adj2 support*).ti,ab.
29.	((client* or patient* or user* or carer* or consumer* or customer* or parent* or famil* or spouse) adj2 (attitud or priorit* or perception* or preferen* or expectation* or choice* or perspective* or view* or satisfact* or inform* or experience or experiences or opinion* or preference* or focus group*)).ti,ab.
30.	patient education/
31.	or/25–30
32.	health survey/ or exp questionnaire/ or exp interview/ or qualitative research/ or narrative/
33.	(qualitative or interview* or focus group* or theme* or questionnaire* or survey*).ti,ab.
34.	(metasynthes* or meta-synthes* or metasummar* or meta-summar* or metastud* or meta-stud* or metathem* or meta-them* or ethno* or emic or etic or phenomenolog* or grounded theory or constant compar* or (thematic* adj3 analys) or theoretical sampl or purposive sampl* or hermeneutic* or heidegger* or husserl* or colaizzi* or van kaam* or van manen* or giorgi* or glaser* or strauss* or ricoeur* or spiegelberg* or merleau*).ti,ab.
35.	or/32–34
36.	24 and 31 and 35

CINAHL (EBSCO) search terms

S1.	(MH “Thyroid Diseases+”)
S2.	hyperthyroid*
S3.	hypothyroid*
S4.	thyrotoxicosis
S5.	(thyroid n3 (swell* or dysfunction* or enlarg* or nodule* or node* or disease* or condition* or disorder*))
S6.	s1 or s2 or s3 or s4 or s5
S7.	(MH “Consumer Satisfaction+”) OR (MH “Patient Education”) OR (MH “Health Education”)
S8.	((information* or advice or advising or advised or support) n3 (patient or need* or requirement* or assess* or seek* or access* or disseminat*))
S9.	(information* n2 support*)
S10.	((client* or patient* or user* or carer* or consumer* or customer) n2 (attitud or priorit* or perception* or preferen* or expectation* or choice* or perspective* or view* or satisfact* or inform* or experience or experiences or opinion*))
S11.	S7 OR S8 OR S9 OR S10
S12.	(MH “Qualitative Studies+”)
S13.	(MH “Qualitative Validity+”)
S14.	(MH “Interviews+”) OR (MH “Focus Groups”) OR (MH “Surveys”) OR (MH “Questionnaires+”)
S15.	(qualitative or interview* or focus group* or theme* or questionnaire* or survey*)
S16.	(metasynthes* or meta-synthes* or metasummar* or meta-summar* or metastud* or meta-stud* or metathem* or meta-them* or ethno* or emic or etic or phenomenolog* or grounded theory or constant compar* or (thematic* n3 analys) or theoretical sampl or purposive sampl* or hermeneutic* or heidegger* or husserl* or colaizzi* or van kaam* or van manen* or giorgi* or glaser* or strauss* or ricoeur* or spiegelberg* or merleau*)
S17.	S12 OR S13 OR S14 OR S15 OR S16
S18.	S6 AND S11 AND S17
	Limit to English language

PsycINFO (ProQuest) search terms

(MAINSUBJECT.EXACT.EXPLODE(“Thyroid Disorders”) OR TI,AB(HYPERTHYROID* OR HYPOTHYROID* OR THYROTOXICOSIS) OR TI,AB(THYROID NEAR/3 (SWELL* OR DYSFUNCTION* OR ENLARG* OR NODULE* OR NODE* OR DISEASE* OR CONDITION* OR DISORDER*))) AND (SU.EXACT(“Client Education”) OR SU.EXACT.EXPLODE(“Client Attitudes”) OR TI,AB((information* OR advice OR advising OR advised OR support*) NEAR/3 (patient* OR need* OR requirement* OR assess* OR seek* OR access* OR disseminat*)) OR TI,AB(information* NEAR/2 support*) OR TI,AB((client* OR patient* OR user* OR carer* OR consumer* OR customer*) NEAR/2 (attitud* OR priorit* OR perception* OR preferen* OR expectation* OR choice* OR perspective* OR view* OR satisfact* OR inform* OR experience OR experiences OR opinion*))) AND ((su.exact.explode(“qualitative research”) or su.exact(“narratives”) or su.exact.explode(“questionnaires”) or su.exact.explode(“interviews”) or su.exact.explode(“health care services”) or ti,ab(qualitative or interview* or focus group* or theme* or questionnaire* or survey*) or ti,ab(metasynthes* or meta-synthes* or metasummar* or meta-summar* or metastud* or meta-stud* or metathem* or meta-them* or ethno* or emic or etic or phenomenolog* or grounded theory or constant compar* or (thematic* near/3 analys*) or theoretical-sampl* or purposive-sampl* or hermeneutic* or heidegger* or husserl* or colaizzi* or van kaam* or van manen* or giorgi* or glaser* or strauss* or ricoeur* or spiegelberg* or merleau*)))

Limit to English language

Figure 1Flow chart of qualitative study selection for the review of information

Figure 2Flow chart of health economic study selection for the guideline

* Non-relevant population, intervention, comparison, design or setting; non-English language

TFT; thyroid function test, FNA; fine-needle aspiration, US; ultrasound, RAI; radioactive iodine, ATDs; antithyroid drugs, Mang; management, SCH; Subclinical hypothyroidism, SCT; Subclinical thyrotoxicosis.

Table 7Studies excluded from the qualitative review

Reference	Reason for exclusion
Davies 2017¹	Inappropriate population
Hookham 2016⁴	Abstract only
Hookham 2017⁵	Inappropriate study design
Lee 2016⁷	Inappropriate population
Razvi 2005⁹	Inappropriate study design

Information for people with thyroid disease

Authors

1. Information for people with thyroid disease

1.1. Review question: What information should people with thyroid disease, their family and carers receive?

1.2. Introduction

1.3. Characteristics table

Table 1

1.4. Qualitative evidence

1.4.1. Included studies

1.4.2. Excluded studies

1.4.3. Summary of qualitative studies included in the evidence review

Table 2

1.4.4. Qualitative evidence synthesis

1.4.4.1. Narrative summary of review findings

TSH targets & symptoms

Non-specific nature of symptoms

Medication interactions

Importance of adherence

Barriers to optimal thyroid replacement

Availability of information

Risks of over or under treatment

1.4.5. Qualitative evidence summary

Table 3

1.5. Economic evidence

1.6. Evidence statements

1.6.1. Qualitative evidence statements

1.7. The committee’s discussion of the evidence

1.7.1. Interpreting the evidence

1.7.1.1. The quality of the evidence

1.7.1.2. Findings identified in the evidence synthesis and raised in committee discussion

General

Hypothyroidism

Thyrotoxicosis

Enlargement

1.7.2. Cost effectiveness and resource use

References

Appendices

Appendix A. Review protocols

Appendix B. Literature search strategies

B.1. Clinical search literature search strategy

Appendix C. Qualitative evidence selection

Appendix D. Qualitative evidence tables

Appendix E. Health economic evidence selection

Appendix F. Health economic evidence tables

Appendix G. Health economic analysis

Appendix H. Excluded studies

H.1. Excluded qualitative studies

H.2. Excluded health economic studies

Table 1Characteristics of review question

Table 2Summary of studies included in the review

Table 3Summary of evidence

Table 4

Table 5Health economic review protocol

Table 6Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

CINAHL (EBSCO) search terms

PsycINFO (ProQuest) search terms

Figure 1Flow chart of qualitative study selection for the review of information

Figure 2Flow chart of health economic study selection for the guideline

Table 7Studies excluded from the qualitative review