Evidence review for sequencing modalities of RRT

National Guideline Centre (UK)

Evidence review for sequencing modalities of RRT

Renal replacement therapy and conservative management

Evidence review

NICE Guideline, No. 107

Authors

National Guideline Centre (UK).

London: National Institute for Health and Care Excellence (NICE); 2018 Oct.

ISBN-13: 978-1-4731-3107-1

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.

Table 1

PICO characteristics of review question.

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

Table 2

Summary of studies included in the evidence review.

See appendix D for full evidence tables.

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

Table 3

Clinical evidence summary: Peritoneal dialysis (PD) prior to transplant vs Haemodialysis (HD) prior to a transplant.

Table 4

Pre-emptive transplant for failing transplant vs Dialysis then transplant for failing transplant.

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

Table 5

Health economic evidence profile: sequencing of RRT.

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

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.”

References

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Appendices

Appendix A. Review protocols

Table 6. Review protocol: Sequences of modalities of RRT and conservative management

Table 7. Health economic review protocol

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 8. Database date parameters and filters used

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

Embase (Ovid) search terms

Cochrane Library (Wiley) search terms

B.2. Health Economics literature search strategy

Health economic evidence was identified by conducting a broad search relating to 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 9. Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

NHS EED and HTA (CRD) search terms

Appendix C. Clinical evidence selection

Figure 1. Flow chart of clinical study selection for the review of Sequencing for RRT modalities

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

Figure 2. Death after transplant (time to event) – follow-up 5y

Figure 3. Death after transplant (risk) – follow-up up to 5y

Figure 4. Graft failure (time to event) – follow-up 5y

Figure 5. Graft failure (risk) – follow-up up to 5y

E.2. Pre-emptive transplant for failing transplant vs Dialysis then transplant for failing transplant

Figure 6. Death after retransplant (time to event) – up to 10y

Figure 7. Graft failure (time to event) – up to 10y

Appendix I. Excluded studies

I.1. Excluded clinical studies

Table 12. Studies excluded from the clinical review

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 13. Studies excluded from the health economic review

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

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.

Bookshelf ID: NBK577489PMID: 35133740

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: Previously modality Age (<2, 2 to <18, 18 to <70, ≥70) DM vs no DM BAME vs non-BAME Unplanned starters vs planned starters
Interventions and Comparisons	Modalities 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 – including live donor or deceased, pre-emptive or reactive Conservative management 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)
Outcomes	Critical Patient, family/carer health-related quality of life (continuous) Mortality (dichotomous and time to event) Time to failure of RRT form (time to event) Important Hospitalisation (rates or continuous) Preferred place of death (dichotomous) Symptom scores and functional measures (continuous) Psychological distress and mental wellbeing (continuous) Cognitive impairment (dichotomous) Patient, family and carer experience of care (continuous) Growth (continuous) Malignancy (dichotomous) Adverse events Infections (dichotomous) Vascular access issues (dichotomous) Dialysis access issues (dichotomous) Acute transplant rejection episodes (dichotomous)
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: Age Health at baseline Co-morbidities Ethnicity

Table 2Summary of studies included in the evidence review

Study

Intervention and comparison

Population

Outcomes

Comments

CTS trial

Schwenger 2011³⁰

Dialysis prior to transplant

HD then transplant (n=45,651)

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

Dialysis prior to transplant

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

Post-transplant failure

Pre-emptive re-transplant (<7d between reported failure of transplant kidney and retransplant) (n=1,609)

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
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	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 LOW^a due to risk of bias	HR 1.1 (1.02 to 1.18)	No adjusted control rate available
Death after transplant (time to event)	57315 (1 study) 5 years	VERY LOW^a due to risk of bias	HR 1.1 (1.02 to 1.18)
Death after transplant (relative risk)	22776 (1 study) 0-5 years	VERY LOW^a due to risk of bias	RR 0.95 (0.85 to 1.06)	No adjusted control rate available
Death after transplant (relative risk)	22776 (1 study) 0-5 years	VERY LOW^a due to risk of bias	RR 0.95 (0.85 to 1.06)
Graft failure (time to event)	57315 (1 study) 5 years	VERY LOW^a due to risk of bias	HR 1.06 (1.01 to 1.12)	No adjusted control rate available
Graft failure (time to event)	57315 (1 study) 5 years	VERY LOW^a due to risk of bias	HR 1.06 (1.01 to 1.12)
Graft failure (relative risk)	22776 (1 study) 0-5 years	VERY LOW^a due to risk of bias	RR 1.05 (0.97 to 1.13)	No adjusted control rate available
Graft failure (relative risk)	22776 (1 study) 0-5 years	VERY LOW^a due to risk of bias	RR 1.05 (0.97 to 1.13)

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
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	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 LOW^a due to risk of bias	HR 1.02 (0.9 to 1.15)	No adjusted control rate available
Mortality (time to event) post-retransplant	11714 (1 study) 0-10 years	VERY LOW^a due to risk of bias	HR 1.02 (0.9 to 1.15)
Graft failure (time to event) - retransplant	11714 (1 study) 0-10 years	VERY LOW^a^,^b due to risk of bias, imprecision	HR 1.36 (1.21 to 1.53)	No adjusted control rate available
Graft failure (time to event) - retransplant	11714 (1 study) 0-10 years	VERY LOW^a^,^b due to risk of bias, imprecision	HR 1.36 (1.21 to 1.53)

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)

Cohort analysis with all cost models adjusted for age, sex, body mass index, race, comorbid conditions, cause of ESRD, and pre-dialysis care.
Comparative costing
Population: Adult patients who initiated long-term dialysis (PD or in-centre HD) for ESRD
Comparators:
- HD
- PD
- HD then switched to PD in first year
- PD then switched to HD in first year
Follow-up: 1 and 3 years

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

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.

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: Previously modality Age (<2, 2 to <18, 18 to <70, ≥70) DM vs no DM BAME vs non-BAME Unplanned starters vs planned starters
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 Patient, family/carer health-related quality of life (continuous) Mortality (dichotomous and time to event) Time to failure of RRT form (time to event) Important Hospitalisation (rates or continuous) Preferred place of death (dichotomous) Symptom scores and functional measures (continuous) Psychological distress and mental wellbeing (continuous) Cognitive impairment (dichotomous) Patient, family and carer experience of care (continuous) Growth (continuous) Malignancy (dichotomous) Adverse events Infections (dichotomous) Vascular access issues (dichotomous) Dialysis access issues (dichotomous) Acute transplant rejection episodes (dichotomous) Strategy: 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: Age Health at baseline Co-morbidities Ethnicity
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)	Pairwise meta-analyses were performed using Cochrane Review Manager (RevMan5). GRADEpro was used to assess the quality of evidence for each outcome. Endnote was used for bibliography, citations, sifting and reference management.
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.nice.org.uk/guidance/indevelopment/gid-ng10019
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.gradeworkinggroup.org/
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	Populations, interventions and comparators must be as specified in the individual review protocol above. Studies must be of a relevant 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 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	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 If a study is rated as both ‘Directly applicable’ and with ‘Minor limitations’ then it will be included in the guideline. If a study is rated as either ‘Not applicable’ or with ‘Very serious limitations’ then it will usually be excluded from the guideline. 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 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: 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 have been excluded before being assessed for applicability and methodological limitations. 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 have been 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 2001 or later but that depend on unit costs and resource data entirely or predominantly from before 2001 will be rated as ‘Not applicable’. Studies published before 2001 will have been excluded before being assessed for applicability and methodological limitations. Quality and relevance of effectiveness data used in the economic analysis: The more closely the clinical effectiveness data used in the economic analysis matches with the outcomes of the studies included in the clinical review the more useful the analysis will be for decision-making in the guideline. The following will be rated as ‘Very serious limitations’ and excluded: economic analyses undertaken as part of clinical studies that are excluded from the clinical review; economic models where relative treatment effects are based entirely on studies that are excluded from the clinical review; comparative costing analyses that only look at the cost of delivering dialysis (as current UK NHS reference costs are considered a more relevant estimate of this for the guideline); within-trial economic analyses based on non-randomised studies that do not meet the minimum adjustment criteria outlined in the main review protocol.

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

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)

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

Figure 1Flow chart of clinical study selection for the review of Sequencing for RRT modalities

Figure 2Death after transplant (time to event) – follow-up 5y

Figure 3Death after transplant (risk) – follow-up up to 5y

Figure 4Graft failure (time to event) – follow-up 5y

Figure 5Graft failure (risk) – follow-up up to 5y

Figure 6Death after retransplant (time to event) – up to 10y

Figure 7Graft failure (time to event) – up to 10y

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	Quality	Importance
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	Quality	Importance
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

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

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

Table 13Studies excluded from the health economic review

Reference	Reason for exclusion
None.

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	Medium: the research is relevant to the recommendations in the guideline, but the research recommendations are not key to future updates.

Evidence review for sequencing modalities of RRT

Authors

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

1.3. PICO table

Table 1

1.4. Clinical evidence

1.4.1. Included studies

1.4.2. Excluded studies

1.4.3. Summary of clinical studies included in the evidence review

Table 2

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

Table 3

Table 4

1.5. Economic evidence

1.5.1. Included studies

1.5.2. Excluded studies

1.5.3. Summary of studies included in the economic evidence review

Table 5

1.5.4. Unit costs

1.6. Resource impact

1.7. Evidence statements

1.7.1. Clinical evidence statements

Adults aged 18 to 70

Transplant after PD vs transplant after HD, NRS

Pre-emptive transplant after transplant vs post-dialysis re-transplant after transplant

1.7.2. Health economic evidence statements

1.8. The committee’s discussion of the evidence

1.9. Interpreting the evidence

1.9.1. The outcomes that matter most

1.9.2. The quality of the evidence

1.9.3. Benefits and harms

1.9.4. Cost effectiveness and resource use

1.9.5. Other factors the committee took into account

References

Appendices

Appendix A. Review protocols

Appendix B. Literature search strategies

B.1. Clinical search literature search strategy

B.2. Health Economics literature search strategy

Appendix C. Clinical evidence selection

Appendix D. Clinical evidence tables

Appendix E. Forest plots

E.1. Peritoneal dialysis (PD) prior to transplant vs Haemodialysis (HD) prior to a transplant

E.2. Pre-emptive transplant for failing transplant vs Dialysis then transplant for failing transplant

Appendix F. GRADE tables

Appendix G. Health economic evidence selection

Appendix H. Health economic evidence tables

Appendix I. Excluded studies

I.1. Excluded clinical studies

I.2. Excluded health economic studies

Appendix J. Research recommendations

J.1. HD/HDF before PD vs PD before HD/HDF

Table 1PICO characteristics of review question

Table 2Summary of studies included in the evidence review

Table 3Clinical evidence summary: Peritoneal dialysis (PD) prior to transplant vs Haemodialysis (HD) prior to a transplant

Table 4Pre-emptive transplant for failing transplant vs Dialysis then transplant for failing transplant

Table 5Health economic evidence profile: sequencing of RRT

Table 6Review protocol: Sequences of modalities of RRT and conservative management

Table 7Health economic review protocol

Table 8Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

Cochrane Library (Wiley) search terms

Table 9Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

NHS EED and HTA (CRD) search terms

Figure 1Flow chart of clinical study selection for the review of Sequencing for RRT modalities

Figure 2Death after transplant (time to event) – follow-up 5y

Figure 3Death after transplant (risk) – follow-up up to 5y

Figure 4Graft failure (time to event) – follow-up 5y

Figure 5Graft failure (risk) – follow-up up to 5y

Figure 6Death after retransplant (time to event) – up to 10y

Figure 7Graft failure (time to event) – up to 10y

Table 10Peritoneal dialysis (PD) prior to transplant vs Haemodialysis (HD) prior to a transplant

Table 11Clinical evidence profile: Pre-emptive transplant for failing transplant vs Dialysis then transplant for failing transplant

Figure 8Flow chart of economic study selection for the guideline

Table 12Studies excluded from the clinical review