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1. Sequencing for RRT modalities
1.1. Review question: What is the clinical and cost effectiveness of different sequences of modalities of renal replacement therapy and conservative management for people progressing or who have progressed through the later stages of CKD?
1.2. Introduction
This review is designed to determine the clinical and cost effectiveness of different sequences of renal replacement therapy, for example haemodialysis, haemodiafiltration or peritoneal dialysis prior to transplantation.
1.3. PICO table
For full details see the review protocol in appendix A.
1.4. Clinical evidence
1.4.1. Included studies
Three studies were included in the review;13, 30, 31 these are summarised in Table 2 below. Evidence from these studies is summarised in the clinical evidence summary below (Table 3).
A search was conducted for randomised trials and non-randomised studies comparing one modality over another for CKD, where a person received more than one modality of RRT sequentially. The papers identified were all non-randomised. Two papers looked at RRT treatment prior to transplantation, both comparing HD and PD. One looked at RRT treatment following a transplant that is failing, comparing pre-emptive retransplantation with non-pre-emptive retransplantation.
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
See appendix D for full evidence tables.
1.4.4. Quality assessment of clinical studies included in the evidence review
See appendix F for full GRADE tables.
1.5. Economic evidence
1.5.1. Included studies
1 health economic study with relevant comparisons has been included in this review: it compared switching from HD to PD and PD to HD with HD and PD alone7; See also the health economic study selection flow chart in appendix G.
No health economic studies were included that looked at transplant.
None of the included studies were in children.
Note that current UK RRT intervention costs are discussed in section 1.5.5.
1.5.2. Excluded studies
No health economic studies that were relevant to this question were excluded due to assessment of limited applicability or methodological limitations.
See also the health economic study selection flow chart in appendix G.
1.5.3. Summary of studies included in the economic evidence review
1.5.4. Unit costs
See Evidence report B: modalities of RRT for current unit costs of RRT.
1.6. Resource impact
No recommendations were made based on this review (Section 1.8).
1.7. Evidence statements
1.7.1. Clinical evidence statements
No evidence for quality of life, mortality, time to failure of RRT form, hospitalisation, preferred place of death, symptom scores and functional measures, psychological distress and mental wellbeing, cognitive impairment, experience of care, growth, malignancy, infections, vascular access issues, dialysis access issues, acute transplant rejection episodes.
Adults aged 18 to 70
Transplant after PD vs transplant after HD, NRS
No evidence for quality of life, hospitalisation, preferred place of death, symptom scores and functional measures, psychological distress and mental wellbeing, cognitive impairment, experience of care, growth, malignancy, infections, vascular access issues, dialysis access issues, acute transplant rejection episodes.
No clinical difference was found for mortality in time to event (1 study, very low quality) or relative risk (1 study very low quality) or graft failure in time to event (1 study, very low quality) or relative risk (1 study very low quality).
Pre-emptive transplant after transplant vs post-dialysis re-transplant after transplant
No evidence for quality of life, hospitalisation, preferred place of death, symptom scores and functional measures, psychological distress and mental wellbeing, cognitive impairment, experience of care, growth, malignancy, infections, vascular access issues, dialysis access issues, acute transplant rejection episodes.
There was a clinically important harm of pre-emptive transplant for graft failure (1 study, very low quality).
No clinical difference was found for mortality in time to event (1 study, very low quality) or graft failure in time to event (1 study, very low quality) or relative risk (1 study very low quality).
1.7.2. Health economic evidence statements
- One comparative cost analysis found that people who switched from HD to PD in the first year had lower costs at one year and three years than people who switched from PD to HD in the first year. This was assessed as partially applicable with potentially serious limitations.
1.8. The committee’s discussion of the evidence
1.9. Interpreting the evidence
1.9.1. The outcomes that matter most
The committee considered quality of life, mortality, and time to failure of RRT modalities to be critical outcomes and hospitalisation, preferred place of death, symptom scores and functional measures, psychological distress and mental wellbeing, cognitive impairment, experience of care, growth, malignancy, infections, vascular access issues, dialysis access issues and acute transplant rejection episodes to be important outcomes.
1.9.2. The quality of the evidence
No evidence was identified for children under the age of 18 or adults over the age of 70. No evidence was identified for the majority of possible sequences of treatment.
The only identified evidence was very low quality due to a combination of the non-randomised study design and other sources of risk of bias.
1.9.3. Benefits and harms
The comparison between transplanting after HD and transplanting after PD showed no clinically important difference for the two reported included outcomes (mortality and graft failure). The committee agreed that this was broadly consistent with their experience.
The comparison between pre-emptive transplant with a failing transplant and transplant after dialysis with a failing transplant showed no clinically important difference for mortality but a clinically important harm of pre-emptive transplant for graft failure. The committee noted that this somewhat contradicted the general benefits of pre-emptive first transplant. While the included study did adjust for the key confounders in the analysis, the committee agreed that there may still be residual confounding factors. There may be people in the pre-emptive group who, had they been given the time to require dialysis, may have accrued other reasons to make transplantation inappropriate. Overall the committee agreed that the evidence certainly did not support recommendations to aim for pre-emptive second transplants in people with failing transplants but it was not strong enough to warrant recommendations against pre-emptive second transplants.
1.9.4. Cost effectiveness and resource use
One economic evaluation was included that compared costs in people who switched from HD to PD and PD to HD in the first year. Costs were lower in the group that switched from HD to PD however this was largely due to lower dialysis costs as PD costs were lower in this analysis. This study was judged partially applicable; in particular Canadian costs may not be applicable and the cost savings in dialysis costs with PD in this setting may not be seen in current UK practice based on current NHS reference costs.
No economic evidence was identified relating to other sequences.
1.9.5. Other factors the committee took into account
The committee discussed that if renal transplant is unsuitable or cannot be provided for the person with kidney disease in a timely fashion then the over-riding factor of choosing initial dialysis treatment and subsequent switches should be patient preference.”
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Appendices
Appendix A. Review protocols
Table 6Review protocol: Sequences of modalities of RRT and conservative management
Field | Content |
---|---|
Review question | What is the clinical and cost effectiveness of different sequences of modalities of renal replacement therapy and conservative management for people who are progressing or have progressed through to later stages of CKD? |
Type of review question | Intervention |
Objective of the review | Comparing the clinical and cost effectiveness of various modalities of RRT after failing previous modalities. |
Eligibility criteria – population / disease / condition / issue / domain |
People requiring RRT for CKD, who have received more than one modality of RRT sequentially, either because the earlier modality was considered to have failed, or because they received one modality while waiting for another (e.g. receiving dialysis prior to receiving a kidney transplant). Studies will be included where the majority meet one of these criteria. Studies will be downgraded for indirectness if >25% are RRT naïve. Definition of modality failure to be determined by studies. Stratified by:
|
Eligibility criteria – interventions |
Two RRT modalities received sequentially. RRT modalities are: Haemodialysis (HD) – including home or in centre, 3 days a week or more frequently, haemodialysis or haemodiafiltration Peritoneal dialysis (PD) – including CAPD, assisted PD or APD/CCPD Transplant (TPx) – including live donor or deceased, pre-emptive or reactive Conservative management |
Eligibility criteria – comparator(s) / control or reference (gold) standard |
Any modality or sub-modality vs any other, including where the comparison is between the first modality in a sequence (e.g. HD vs PD before transplantation), the second modality in a sequence (e.g. HD vs PD after transplantation) or between two sequences (e.g. HD then PD vs PD then HD) Studies comparing multiple sequences of RRT will also be included (for example HD then PD vs PD then HD) |
Outcomes and prioritisation |
Critical
When outcomes are reported at multiple timepoints, the later timepoints will be prioritised. Mortality and hospitalisation must be reported after at least 6 months of the intervention under investigation. All other outcomes must be reported after at least 1 month of the intervention under investigation. For the outcomes of quality of life, symptom scores/functional measures, psychological distress/mental wellbeing and experience of care – any validated measure will be accepted. Absolute MIDs of 30 per 1000 will be used for mortality and modality failure. Absolute MIDs of 100 per 1000 will be used for all other outcomes dichotomous outcomes. Where relative MIDs are required (if absolute effects are unavailable), 0.90 to 1.11 will be used for mortality and modality failure. The default relative MIDs of 0.8 to 1.25 will be used for all other dichotomous outcomes. Default continuous MIDs of 0.5x SD will be used for all continuous outcomes, except where published, validated MIDs exist. |
Eligibility criteria – study design | RCTs will be prioritised. If insufficient evidence is found for any specified comparisons non-randomised studies will be considered but only if outcomes are adjusted for the following key confounders:
|
Other inclusion exclusion criteria |
Any studies where the RRT is being delivered for acute kidney injury, not in the context of chronic kidney disease, will be excluded. Any studies where the RRT is being delivered in a level 2 or 3 care setting, will be excluded. |
Proposed sensitivity / subgroup analysis, or meta-regression |
People with a BMI ≥30 vs BMI <30 Aged ≥80 vs aged <80 T1DM vs T2DM Sub-modalities (for intermodality comparisons) Nocturnal vs diurnal HD |
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. |
Data management (software) |
|
Information sources – databases and dates |
Clinical search databases to be used: Medline, Embase, Cochrane Library Date: All years Health economics search databases to be used: Medline, Embase, NHSEED, HTA Date: Medline, Embase from 2014 NHSEED, HTA – all years Language: Restrict to English only Supplementary search techniques: backward citation searching Key papers: Not known |
Identify if an update | Not an update |
Author contacts |
https://www |
Highlight if amendment to previous protocol | Not an amendment |
Search strategy – for one database | For details please see appendix B |
Data collection process – forms / duplicate | A standardised evidence table format will be used, and published as appendices of the evidence report. |
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). |
Methods for assessing bias at outcome / study level |
Standard study checklists were 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 |
Criteria for quantitative synthesis | For details please see section 6.4 of Developing NICE guidelines: the manual. |
Methods for quantitative analysis – combining studies and exploring (in)consistency | For details please see the separate Methods report for this guideline. |
Meta-bias assessment – publication bias, selective reporting bias | For details please see section 6.2 of Developing NICE guidelines: the manual. |
Confidence in cumulative evidence | For details please see sections 6.4 and 9.1 of Developing NICE guidelines: the manual. |
Rationale / context – what is known | For details please see the introduction to the evidence review. |
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 Jan Dudley 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. |
Sources of funding / support | NGC is funded by NICE and hosted by the Royal College of Physicians. |
Name of sponsor | NGC is funded by NICE and hosted by the Royal College of Physicians. |
Roles of sponsor | NICE funds NGC to develop guidelines for those working in the NHS, public health and social care in England. |
PROSPERO registration number | Not registered |
Table 7Health economic review protocol
Review question | All questions – health economic evidence |
---|---|
Objectives | To identify economic studies relevant to any of the review questions. |
Search criteria |
|
Search strategy | An economic study search will be undertaken using population-specific terms and an economic study filter – see Appendix B.2 Health economics literature search strategy. |
Review strategy |
Studies not meeting any of the search criteria above will be excluded. Studies published before 2001, 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 G of the 2012 NICE guidelines manual.22 Each included study is summarised in an economic evidence profile and an evidence table. Any excluded studies are detailed in the excluded studies table with the reason for exclusion in Appendix I. Inclusion and exclusion criteria
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 Committee if required. The ultimate aim is to include 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. For example, if a high quality study from a UK perspective is available a similar study from another country’s perspective may be excluded. The health economist will be guided by the following hierarchies. Setting:
|
Appendix B. Literature search strategies
B.1. Clinical search literature search strategy
The literature searches for this review are detailed below and complied with the methodology outlined in Developing NICE guidelines: the manual 2014, updated 2017 https://www.nice.org.uk/guidance/pmg20/resources/developing-nice-guidelines-the-manual-pdf-72286708700869
For more detailed information, please see the Methodology Review.
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 8Database date parameters and filters used
Database | Dates searched | Search filter used |
---|---|---|
Medline (OVID) | 1946 – 11 December 2017 |
Exclusions Randomised controlled trials Systematic review studies Observational studies |
Embase (OVID) | 1974 – 11 December 2017 |
Exclusions Randomised controlled trials Systematic review studies Observational studies |
The Cochrane Library (Wiley) |
Cochrane Reviews to 2017 Issue 12 of12 CENTRAL to 2017 Issue 11 of12 DARE, and NHSEED to 2015 Issue 2 of 4 HTA to 2016 Issue 4 of 4 | None |
- Line 81 (Medline) and line 75 (Embase) were added to the search strategy to reduce the number of items retrieved for observational studies as the overall results from the search were very large.This was checked to ensure that relevant studies were not excluded.
Medline (Ovid) search terms
1. | exp Renal Replacement Therapy/ |
2. | ((renal or kidney) adj2 replace*).ti,ab. |
3. | (hemodiafilt* or haemodiafilt* or (biofilt* adj1 acetate-free)).ti,ab. |
4. | (hemodialys* or haemodialys*).ti,ab. |
5. | ((kidney* or renal) adj3 (transplant* or graft*)).ti,ab. |
6. | capd.ti,ab. |
7. | dialys*.ti,ab. |
8. | (artificial adj1 kidney*).ti,ab. |
9. | or/1-8 |
10. | limit 9 to English language |
11. | letter/ |
12. | editorial/ |
13. | news/ |
14. | exp historical article/ |
15. | Anecdotes as Topic/ |
16. | comment/ |
17. | case report/ |
18. | (letter or comment*).ti. |
19. | or/11-18 |
20. | randomized controlled trial/ or random*.ti,ab. |
21. | 19 not 20 |
22. | animals/ not humans/ |
23. | Animals, Laboratory/ |
24. | exp animal experiment/ |
25. | exp animal model/ |
26. | exp Rodentia/ |
27. | (rat or rats or mouse or mice).ti. |
28. | or/21-27 |
29. | 10 not 28 |
30. | randomized controlled trial.pt. |
31. | controlled clinical trial.pt. |
32. | randomi#ed.ti,ab. |
33. | placebo.ab. |
34. | drug therapy.fs. |
35. | randomly.ti,ab. |
36. | trial.ab. |
37. | groups.ab. |
38. | or/30-37 |
39. | Clinical Trials as topic.sh. |
40. | trial.ti. |
41. | or/30-33,35,39-40 |
42. | Meta-Analysis/ |
43. | Meta-Analysis as Topic/ |
44. | (meta analy* or metanaly* or metaanaly* or meta regression).ti,ab. |
45. | ((systematic* or evidence*) adj3 (review* or overview*)).ti,ab. |
46. | (reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab. |
47. | (search strategy or search criteria or systematic search or study selection or data extraction).ab. |
48. | (search* adj4 literature).ab. |
49. | (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. |
50. | cochrane.jw. |
51. | ((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab. |
52. | or/42-51 |
53. | 29 and (41 or 52) |
54. | exp Renal Replacement Therapy/ |
55. | ((renal or kidney*) adj2 replace*).ti,ab. |
56. | (hemodiafilt* or haemodiafilt* or haemofilt* or hemofilt*).ti,ab. |
57. | (hemodialys* or haemodialys*).ti,ab. |
58. | ((kidney* or renal or pre-empt* or preempt*) adj3 (transplant* or graft*)).ti,ab. |
59. | (capd or apd or ccpd or dialys*).ti,ab. |
60. | or/54-59 |
61. | letter/ |
62. | editorial/ |
63. | news/ |
64. | exp historical article/ |
65. | Anecdotes as Topic/ |
66. | comment/ |
67. | case report/ |
68. | (letter or comment*).ti. |
69. | or/61-68 |
70. | randomized controlled trial/ or random*.ti,ab. |
71. | 147 not 148 |
72. | animals/ not humans/ |
73. | Animals, Laboratory/ |
74. | exp Animal Experimentation/ |
75. | exp Models, Animal/ |
76. | exp Rodentia/ |
77. | (rat or rats or mouse or mice).ti. |
78. | or/72-77 |
79. | 60 not 78 |
80. | limit 79 to English language |
81. | (mycophenolic acid or azathioprine or sirolimus or everolimus or tacrolimus or cyclosporin* or steroid or calcineurin inhibitor or anaemi* or anemi* or vitamin d or immunosuppres*).ti.1 |
82. | 80 not 81 |
83. | Epidemiologic studies/ |
84. | Observational study/ |
85. | exp Cohort studies/ |
86. | (cohort adj (study or studies or analys* or data)).ti,ab. |
87. | ((follow up or observational or uncontrolled or non randomi#ed or epidemiologic*) adj (study or studies or data)).ti,ab. |
88. | ((longitudinal or retrospective or prospective or cross sectional) and (study or studies or review or analys* or cohort* or data)).ti,ab. |
89. | Controlled Before-After Studies/ |
90. | Historically Controlled Study/ |
91. | Interrupted Time Series Analysis/ |
92. | (before adj2 after adj2 (study or studies or data)).ti,ab. |
93. | or/83-92 |
94. | Registries/ |
95. | Management Audit/ or Clinical Audit/ or Nursing Audit/ or Medical Audit/ |
96. | (registry or registries).ti,ab. |
97. | (audit or audits or auditor or auditors or auditing or auditable).ti,ab. |
98. | or/94-97 |
99. | 93 or 98 |
100. | 82 and 99 |
101. | 100 not 53 |
102. | 53 or 101 |
Embase (Ovid) search terms
1. | exp *renal replacement therapy/ |
2. | ((renal or kidney) adj2 replace*).ti,ab. |
3. | (hemodiafilt* or haemodiafilt* or (biofilt* adj1 acetate-free)).ti,ab. |
4. | (hemodialys* or haemodialys*).ti,ab. |
5. | ((kidney* or renal) adj3 (transplant* or graft*)).ti,ab. |
6. | capd.ti,ab. |
7. | dialys*.ti,ab. |
8. | (artificial adj1 kidney*).ti,ab. |
9. | or/1-8 |
10. | limit 9 to English language |
11. | letter.pt. or letter/ |
12. | note.pt. |
13. | editorial.pt. |
14. | case report/ or case study/ |
15. | (letter or comment*).ti. |
16. | or/11-15 |
17. | randomized controlled trial/ or random*.ti,ab. |
18. | 16 not 17 |
19. | animal/ not human/ |
20. | nonhuman/ |
21. | exp Animal Experiment/ |
22. | exp Experimental Animal/ |
23. | animal model/ |
24. | exp Rodent/ |
25. | (rat or rats or mouse or mice).ti. |
26. | or/18-25 |
27. | 10 not 26 |
28. | random*.ti,ab. |
29. | factorial*.ti,ab. |
30. | (crossover* or cross over*).ti,ab. |
31. | ((doubl* or singl*) adj blind*).ti,ab. |
32. | (assign* or allocat* or volunteer* or placebo*).ti,ab. |
33. | crossover procedure/ |
34. | single blind procedure/ |
35. | randomized controlled trial/ |
36. | double blind procedure/ |
37. | or/28-36 |
38. | systematic review/ |
39. | meta-analysis/ |
40. | (meta analy* or metanaly* or metaanaly* or meta regression).ti,ab. |
41. | ((systematic or evidence) adj3 (review* or overview*)).ti,ab. |
42. | (reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab. |
43. | (search strategy or search criteria or systematic search or study selection or data extraction).ab. |
44. | (search* adj4 literature).ab. |
45. | (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. |
46. | cochrane.jw. |
47. | ((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab. |
48. | or/38-47 |
49. | 27 and (37 or 48) |
50. | *renal replacement therapy/ |
51. | ((renal or kidney*) adj2 replace*).ti,ab. |
52. | (hemodiafilt* or haemodiafilt* or haemofilt* or hemofilt*).ti,ab. |
53. | (hemodialys* or haemodialys*).ti,ab. |
54. | ((kidney* or renal or pre-empt* or preempt*) adj3 (transplant* or graft*)).ti,ab. |
55. | (capd or apd or ccpd or dialys*).ti,ab. |
56. | or/50-55 |
57. | letter.pt. or letter/ |
58. | note.pt. |
59. | editorial.pt. |
60. | case report/ or case study/ |
61. | (letter or comment*).ti. |
62. | or/57-61 |
63. | randomized controlled trial/ or random*.ti,ab. |
64. | 62 not 63 |
65. | animal/ not human/ |
66. | nonhuman/ |
67. | exp Animal Experiment/ |
68. | exp Experimental Animal/ |
69. | animal model/ |
70. | exp Rodent/ |
71. | (rat or rats or mouse or mice).ti. |
72. | or/64-71 |
73. | 56 not 72 |
74. | limit 73 to English language |
75. | (mycophenolic acid or azathioprine or sirolimus or everolimus or tacrolimus or cyclosporin* or steroid or calcineurin inhibitor or anaemi* or anemi* or vitamin d or immunosuppres*).ti.1 |
76. | 74 not 75 |
77. | Clinical study/ |
78. | Observational study/ |
79. | family study/ |
80. | longitudinal study/ |
81. | retrospective study/ |
82. | prospective study/ |
83. | cohort analysis/ |
84. | follow-up/ |
85. | cohort*.ti,ab. |
86. | 84 and 85 |
87. | (cohort adj (study or studies or analys* or data)).ti,ab. |
88. | ((follow up or observational or uncontrolled or non randomi#ed or epidemiologic*) adj (study or studies or data)).ti,ab. |
89. | ((longitudinal or retrospective or prospective or cross sectional) and (study or studies or review or analys* or cohort* or data)).ti,ab. |
90. | (before adj2 after adj2 (study or studies or data)).ti,ab. |
91. | or/77-83,86-90 |
92. | register/ |
93. | medical audit/ |
94. | (registry or registries).ti,ab. |
95. | (audit or audits or auditor or auditors or auditing or auditable).ti,ab. |
96. | or/92-95 |
97. | 91 or 96 |
98. | 76 and 97 |
99. | 98 not 49 |
100. | 49 or 99 |
Cochrane Library (Wiley) search terms
#1. | MeSH descriptor: [Renal Replacement Therapy] explode all trees |
#2. | ((renal or kidney*) near/2 replace*):ti,ab |
#3. | (hemodiafilt* or haemodiafilt* or haemofilt* or hemofilt*):ti,ab |
#4. | (hemodialys* or haemodialys*):ti,ab |
#5. | ((kidney* or renal or pre-empt* or preempt*) near/3 (transplant* or graft*)):ti,ab |
#6. | (capd or apd or ccpd or dialys*):ti,ab |
#7. | (biofilt* near/1 acetate-free):ti,ab |
#8. | (artificial near/1 kidney*):ti,ab |
#9. | (or #1-#8) |
B.2. Health Economics literature search strategy
Health economic evidence was identified by conducting a broad search relating to renal replacement therapy 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.
Table 9Database date parameters and filters used
Database | Dates searched | Search filter used |
---|---|---|
Medline & Embase | 2014 – 11 December 2017 |
Exclusions Health economics studies |
Centre for Research and Dissemination (CRD) | HTA & NHS EED- Inception – 11 December 2017 | None |
Medline (Ovid) search terms
1. | exp Renal Replacement Therapy/ |
2. | ((renal or kidney) adj2 replace*).ti,ab. |
3. | (hemodiafilt* or haemodiafilt* or (biofilt* adj1 acetate-free)).ti,ab. |
4. | (hemodialys* or haemodialys*).ti,ab. |
5. | ((kidney* or renal) adj3 (transplant* or graft*)).ti,ab. |
6. | capd.ti,ab. |
7. | dialys*.ti,ab. |
8. | (artificial adj1 kidney*).ti,ab. |
9. | or/1-8 |
10. | limit 9 to English language |
11. | letter/ |
12. | editorial/ |
13. | news/ |
14. | exp historical article/ |
15. | Anecdotes as Topic/ |
16. | comment/ |
17. | case report/ |
18. | (letter or comment*).ti. |
19. | or/11-18 |
20. | randomized controlled trial/ or random*.ti,ab. |
21. | 19 not 20 |
22. | animals/ not humans/ |
23. | Animals, Laboratory/ |
24. | exp animal experiment/ |
25. | exp animal model/ |
26. | exp Rodentia/ |
27. | (rat or rats or mouse or mice).ti. |
28. | or/21-27 |
29. | 10 not 28 |
30. | Economics/ |
31. | Value of life/ |
32. | exp “Costs and Cost Analysis”/ |
33. | exp Economics, Hospital/ |
34. | exp Economics, Medical/ |
35. | Economics, Nursing/ |
36. | Economics, Pharmaceutical/ |
37. | exp “Fees and Charges”/ |
38. | exp Budgets/ |
39. | budget*.ti,ab. |
40. | cost*.ti. |
41. | (economic* or pharmaco?economic*).ti. |
42. | (price* or pricing*).ti,ab. |
43. | (cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab. |
44. | (financ* or fee or fees).ti,ab. |
45. | (value adj2 (money or monetary)).ti,ab. |
46. | or/30-45 |
47. | 29 and 46 |
Embase (Ovid) search terms
1. | exp renal replacement therapy/ |
2. | ((renal or kidney) adj2 replace*).ti,ab. |
3. | (hemodiafilt* or haemodiafilt* or (biofilt* adj1 acetate-free)).ti,ab. |
4. | (hemodialys* or haemodialys*).ti,ab. |
5. | ((kidney* or renal) adj3 (transplant* or graft*)).ti,ab. |
6. | capd.ti,ab. |
7. | dialys*.ti,ab. |
8. | (artificial adj1 kidney*).ti,ab. |
9. | or/1-8 |
10. | limit 9 to English language |
11. | letter.pt. or letter/ |
12. | note.pt. |
13. | editorial.pt. |
14. | case report/ or case study/ |
15. | (letter or comment*).ti. |
16. | or/11-15 |
17. | randomized controlled trial/ or random*.ti,ab. |
18. | 16 not 17 |
19. | animal/ not human/ |
20. | nonhuman/ |
21. | exp Animal Experiment/ |
22. | exp Experimental Animal/ |
23. | animal model/ |
24. | exp Rodent/ |
25. | (rat or rats or mouse or mice).ti. |
26. | or/18-25 |
27. | 10 not 26 |
28. | *health economics/ |
29. | exp *economic evaluation/ |
30. | exp *health care cost/ |
31. | exp *fee/ |
32. | budget/ |
33. | funding/ |
34. | budget*.ti,ab. |
35. | cost*.ti. |
36. | (economic* or pharmaco?economic*).ti. |
37. | (price* or pricing*).ti,ab. |
38. | (cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab. |
39. | (financ* or fee or fees).ti,ab. |
40. | (value adj2 (money or monetary)).ti,ab. |
41. | or/28-40 |
42. | 27 and 41 |
NHS EED and HTA (CRD) search terms
#1. | MeSH DESCRIPTOR Renal Replacement Therapy EXPLODE ALL TREES |
#2. | (((renal or kidney) adj2 replace*)) |
#3. | ((hemodiafilt* or haemodiafilt* or (biofilt* adj1 acetate-free))) |
#4. | ((hemodialys* or haemodialys*)) |
#5. | (((kidney* or renal) adj3 (transplant* or graft*))) |
#6. | (capd) |
#7. | (dialys*) |
#8. | ((artificial adj1 kidney*)) |
#9. | #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 |
Appendix C. Clinical evidence selection
Appendix D. Clinical evidence tables
Download PDF (224K)
Appendix E. Forest plots
E.1. Peritoneal dialysis (PD) prior to transplant vs Haemodialysis (HD) prior to a transplant
Appendix F. GRADE tables
Table 10Peritoneal dialysis (PD) prior to transplant vs Haemodialysis (HD) prior to a transplant
Quality assessment | No of patients |
Effect PD vs HD | Quality | Importance | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
No of studies | Design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | Peritoneal dialysis (PD) prior to transplant | Haemodialysis (HD) prior to a transplant | Relative (95% CI) | Absolute | ||
Death after transplant (time to event) (follow-up 0-5 years) | ||||||||||||
1 | observational studies | very serious1 | no serious inconsistency | no serious indirectness | no serious imprecision | none | 11,664 | 45,651 | HR 1.1 (1.02 to 1.18) | - | VERY LOW | CRITICAL |
Death after transplant (relative risk) (follow-up 0-5 years) | ||||||||||||
1 | observational studies | very serious1 | no serious inconsistency | no serious indirectness | no serious imprecision | none | 5,621 | 17,155 | RR 0.95 (0.85 to 1.06) | - | VERY LOW | CRITICAL |
Graft failure (time to event) (follow-up 0-5 years) | ||||||||||||
1 | observational studies | very serious1 | no serious inconsistency | no serious indirectness | no serious imprecision | none | 11,664 | 45,651 | HR 1.06 (1.01 to 1.12) | - | VERY LOW | CRITICAL |
Graft failure (relative risk) (follow-up 0-5 years) | ||||||||||||
1 | observational studies | very serious1 | no serious inconsistency | no serious indirectness | no serious imprecision | none | 5,621 | 17,155 | RR 1.05 (0.97 to 1.13) | - | VERY LOW | CRITICAL |
Table 11Clinical evidence profile: Pre-emptive transplant for failing transplant vs Dialysis then transplant for failing transplant
Quality assessment | No of patients |
Effect PreT vs Non-PreT | Quality | Importance | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
No of studies | Design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | Pre-emptive transplant for failing transplant | Dialysis then transplant for failing transplant | Relative (95% CI) | Absolute | ||
Mortality (time to event) post-retransplant (follow-up 0-10 years) | ||||||||||||
1 | observational studies | very serious1 | no serious inconsistency | no serious indirectness | no serious imprecision | none | 1,609 | 10,105 | HR 1.02 (0.9 to 1.15) | - | VERY LOW | CRITICAL |
Graft failure (time to event) - retransplant (follow-up 0-10 years) | ||||||||||||
1 | observational studies | very serious1 | no serious inconsistency | no serious indirectness | serious2 | none | 1,609 | 10,105 | HR 1.36 (1.21 to 1.53) | - | VERY LOW | CRITICAL |
Appendix G. Health economic evidence selection
Figure 8Flow chart of economic study selection for the guideline
A = starting RRT
B = modality of RRT, subgroups and CM
C = sequencing
D = planning for RRT
E = When to assess
F = what to assess
G = Indicators for switching or stopping RRT
I = diet and fluids
J = frequency of review
L = decision support interventions
M = coordinating care
Note: Reviews H and K do not have an economic component
* Non-relevant population, intervention, comparison, design or setting; non-English language
Appendix H. Health economic evidence tables
Download PDF (228K)
Appendix I. Excluded studies
I.1. Excluded clinical studies
Table 12Studies excluded from the clinical review
Study | Exclusion reason |
---|---|
Albrechtsen 19871 | Wrong comparison |
Ardalan 20112 | NRS without adequate adjustment |
Binaut 19973 | NRS without adequate adjustment |
Bray 20064 | Wrong intervention |
Cecka 19955 | NRS without adequate adjustment |
Chertow 19966 | Wrong comparison |
Cosio 19988 | Inappropriate comparison |
De Jonge 20069 | NRS without adequate adjustment |
Donnelly 198510 | NRS without adequate adjustment |
Doxiadis 199811 | Incorrect interventions |
Freier 197612 | NRS without adequate adjustment |
Griveas 200514 | NRS without adequate adjustment |
Iles-Smith 199915 | Wrong comparison |
Jimenez 200816 | NRS without adequate adjustment |
Johnston 201317 | NRS without adequate adjustment |
Koc 201218 | NRS without adequate adjustment |
Kostro 201619 | NRS without adequate adjustment |
Lorent 201620 | NRS without adequate adjustment |
Nadeau-Fredette 201521 | Wrong comparison |
Odor-Morales 198723 | NRS without adequate adjustment |
Opelz 199224 | Incorrect interventions |
Persijn 198426 | Wrong intervention |
Resende 200927 | NRS without adequate adjustment |
Rigo 201128 | NRS without adequate adjustment |
Schold 200629 | Inappropriate comparison |
Traynor 201132 | NRS without adequate adjustment |
Van den Berg-Loonen 200833 | Wrong comparison |
West 199234 | Inappropriate comparison |
Zhou 199135 | Descriptive study |
I.2. Excluded health economic studies
Studies that meet the review protocol population and interventions and economic study design criteria but have not been included in the review based on applicability and/or methodological quality are summarised below with reasons for exclusion.
Table 13Studies excluded from the health economic review
Reference | Reason for exclusion |
---|---|
None. |
Appendix J. Research recommendations
J.1. HD/HDF before PD vs PD before HD/HDF
Research question: What is the clinical and cost effectiveness of haemodialysis/haemodiafiltration before PD versus PD before haemodialysis/haemodiafiltration?
Why this is important:
In general this guideline concluded that the decision to use HD/HDF or PD was one guided by patient choice. However some people believe that the order of treatments may have an effect on overall efficacy, no high quality evidence was found in this area. If evidence was available this would allow people to make a more informed choice between HD/HDF and PD at the first point in the treatment pathway.
Criteria for selecting high-priority research recommendations
PICO question |
Population: people in the later stages of CKD who are not receiving a pre-emptive transplant Intervention(s): HD/HDF (at least 90 days) before PD Comparison: PD (at least 90 days) before HD/HDF Outcome(s): quality of life, mortality, time to failure of RRT modality, resource use/hospitalisation, symptom scores/functional measures, experience of care, adverse events (infections, access issues) |
---|---|
Importance to patients or the population | Improved evidence in this area could allow people to make a more informed choice with the long term consequences of choosing to start on either HD/HDF or PD |
Relevance to NICE guidance | If one particularly strategy was found to be more clinically and cost effective than the other, this could feed into recommendations on which strategy may be optimal |
Relevance to the NHS | If one strategy was more cost effective than the other, and supported by sufficient clinical benefit or lack of harm, recommendations promoting this strategy could be cost saving |
National priorities | Not applicable |
Current evidence base | There were no RCTs or non-randomised studies available in this area |
Equality | Not applicable |
Study design | Ideally this would be an RCT but given the likely long timeframe required for follow-up, non-randomised cohort studies with adequate adjustment for key confounders (including age, ethnicity, co-existing conditions and some estimate of baseline health (e.g. quality of life)) may be more feasible and appropriate |
Feasibility | As above |
Other comments | Not applicable |
Importance |
|
Tables
Table 1PICO characteristics of review question
Population |
People requiring RRT for CKD, who have received more than one modality of RRT sequentially, either because the earlier modality was considered to have failed, or because they received one modality while waiting for another (e.g. receiving dialysis prior to receiving a kidney transplant). Studies will be included where the majority meet one of these criteria. Studies will be downgraded for indirectness if >25% are RRT naïve. Definition of modality failure to be determined by studies. Stratified by:
|
---|---|
Interventions and Comparisons | Modalities
|
Outcomes | Critical
|
Study design | RCTs will be prioritised. If insufficient evidence is found for any specified comparisons non-randomised studies will be considered but only if outcomes are adjusted for the following key confounders:
|
Table 2Summary of studies included in the evidence review
Study | Intervention and comparison | Population | Outcomes | Comments |
---|---|---|---|---|
CTS trial Schwenger 201130 |
PD then transplant (n=11,664) |
Recipient of a first kidney transplant, deceased-donor Aged 18 or over. Mean age 50y Gender (M:F) 65:35 92% Caucasian |
Mortality (post-transplant) Failure RRT modality (transplant) |
Collaborative Transplant Study trial is multicentre registry with participating centres in Europe, N. America, Australia and New Zealand (85% from Europe) Data 1998-2007 Duration: 5 years post-transplant (outcome censored at five years for model) |
Snyder 200231 |
HD then transplant (n=17,155) PD then transplant (n=5,621) |
Recipient of dialysis and subsequent first kidney transplant Aged 18 or over, median age ~44y Gender (M:F) 53:47 ~50% Caucasian, ~30% African American |
Mortality (post-transplant) Failure RRT modality (transplant) |
Database connected to U.S. Medicare Data 1995-2000 Duration: Up to 5 years post-dialysis (transplant could take place from 90 days after dialysis) |
USRDS (retransplant) Goldfarb-rumyantzev 200613 |
Non-pre-emptive re-transplant (n=10,105) |
People who received retransplants (both kidney and kidney-pancreas) regardless of number of previous transplants Any age, mean ~39y Gender (M:F) 59:41 ~78% White, 18% African American |
Mortality (post-retransplant) Failure RRT modality (retransplant) |
United States Renal Data Service (USRDS) and United Network for Organ Sharing (UNOS) used throughout USA Data 1990-1999 Duration: Up to 10 years post-transplant |
Table 3Clinical evidence summary: Peritoneal dialysis (PD) prior to transplant vs Haemodialysis (HD) prior to a transplant
Outcomes | No of Participants (studies) Follow up | Quality of the evidence (GRADE) | Relative effect (95% CI) | Anticipated absolute effects | |
---|---|---|---|---|---|
Risk with Haemodialysis (HD) prior to a transplant | Risk difference with Peritoneal dialysis (PD) prior to transplant (95% CI) | ||||
Death after transplant (time to event) |
57315 (1 study) 5 years |
VERY LOWa due to risk of bias |
HR 1.1 (1.02 to 1.18) | No adjusted control rate available | |
Death after transplant (relative risk) |
22776 (1 study) 0-5 years |
VERY LOWa due to risk of bias |
RR 0.95 (0.85 to 1.06) | No adjusted control rate available | |
Graft failure (time to event) |
57315 (1 study) 5 years |
VERY LOWa due to risk of bias |
HR 1.06 (1.01 to 1.12) | No adjusted control rate available | |
Graft failure (relative risk) |
22776 (1 study) 0-5 years |
VERY LOWa due to risk of bias |
RR 1.05 (0.97 to 1.13) | No adjusted control rate available | |
- a
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 4Pre-emptive transplant for failing transplant vs Dialysis then transplant for failing transplant
Outcomes | No of Participants (studies) Follow up | Quality of the evidence (GRADE) | Relative effect (95% CI) | Anticipated absolute effects | |
---|---|---|---|---|---|
Risk with Non-pre-emptive | Risk difference with Pre-emptive transplant for failing transplant (95% CI) | ||||
Mortality (time to event) post-retransplant |
11714 (1 study) 0-10 years |
VERY LOWa due to risk of bias |
HR 1.02 (0.9 to 1.15) | No adjusted control rate available | |
Graft failure (time to event) - retransplant |
11714 (1 study) 0-10 years |
due to risk of bias, imprecision |
HR 1.36 (1.21 to 1.53) | No adjusted control rate available | |
- a
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
- b
Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs
Table 5Health economic evidence profile: sequencing of RRT
Study | Applicability | Limitations | Other comments | Incremental cost | Incremental effects | Cost effectiveness | Uncertainty |
---|---|---|---|---|---|---|---|
Chui 20137 (Canada) | Partially applicable(a) | Potentially serious limitations(b) |
|
Vs HD 1 year PD: −£31,097 HD>PD: −£14,478 PD>HD: −£6,493 Vs HD 3 years PD: −£66,404 HD>PD: −£34,820 PD>HD: −£1,522 | n/a | n/a |
95% CI - 1 year incremental cost vs HD: PD: −£34,064 to −£28,130 HD > PD: −£18,692 to −£10,264 PD >HD: −£12,845 to −£140 95% CI - 3 years incremental cost vs HD: PD: −£45,117 to −£24,523 HD > PD: −£74,672 to −£58,136 PD >HD: −£16,008 to £12,964 |
Abbreviations: CI = confidence interval; HD = haemodialysis; ICER: incremental cost-effectiveness ratio; PD = peritoneal dialysis; QALY: quality-adjusted life years; RCT: randomised controlled trial
- (a)
2010 Canadian costs based on resource use from 1999-2006 may not reflect current NHS context. Discounting not applied. Health outcomes not incorporated.
- (b)
Within-trial analysis (cohort) so does not reflect the full body of evidence in this area (note: no parallel clinical study, costs only). It is unclear whether any transport costs are included.
- (c)
Cost components incorporated: dialysis costs, inpatient costs, medication costs, and physician fees.
Final
Intervention evidence review
These evidence reviews were developed by the National Guideline Centre
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/or their carer or guardian.
Local commissioners and/or 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.