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. 2019 Oct 1;179(10):1316-1324.
doi: 10.1001/jamainternmed.2019.1501.

Representativeness of Randomized Clinical Trial Cohorts in End-stage Kidney Disease: A Meta-analysis

Brendan Smyth  1   2 , Anna Haber  3 , Konlawij Trongtrakul  4 , Carmel Hawley  5   6 , Vlado Perkovic  1 , Mark Woodward  1   7   8 , Meg Jardine  1   9
Affiliations

Representativeness of Randomized Clinical Trial Cohorts in End-stage Kidney Disease: A Meta-analysis

Brendan Smyth et al. JAMA Intern Med. .

Erratum in

Abstract

Importance: Systematic differences between patients included in randomized clinical trials (RCTs) and the general patient population may influence the generalizability of RCT findings. Comprehensive national registries of patients with end-stage kidney disease who are undergoing dialysis provide a unique opportunity to compare trial and real-world patient cohorts.

Objective: To determine if participants in large, multicenter dialysis trials were similar to the general population undergoing dialysis in terms of age, comorbidities, and mortality rate.

Data sources: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials were systematically searched on January 6, 2017, for studies published from January 1, 2007, to December 31, 2016. Data sources were published manuscripts, supplementary material, and trial registration information. Data on the general population undergoing dialysis were derived from the US Renal Data System (USRDS). Data were analyzed from March 17 to July 22, 2018.

Study selection: Randomized clinical trials enrolling only participants undergoing dialysis for end-stage kidney disease with 100 or more adult participants from 2 or more sites.

Data extraction and synthesis: Abstract screening and data extraction were performed independently by 2 researchers. Data were pooled using a random-effects model.

Main outcomes and measures: The primary outcome was difference in mean age between the RCT and USRDS populations. Secondary outcomes included differences in mortality rate and comorbidities.

Results: The search identified 186 RCTs, enrolling 79 104 participants. Compared with the 2011 USRDS population, RCT participants were younger (mean age, 58.9 years; 95% CI, 58.3-59.5 years vs 61.2 years; P < .001), more likely to be male (58.9%; 95% CI, 57.6%-60.1% vs 55.7%; P < .001), and have coronary artery disease (26.9%; 95% CI, 22.2%-31.7% vs 17.7%; P < .001) and less likely to have diabetes (40.2%; 95% CI, 36.7%-43.6% vs 44.2%; P = .03) or heart failure (19.6%; 95% CI, 15.1%-24.0% vs 29.8%; P < .001). The mortality rate per 100 patient-years during trial participation was less than half that of the USRDS population (8.9; 95% CI, 7.8-10.0 vs 18.6; P < .001). The differences in age, mortality, and coronary artery disease remained when studies recruiting only from the United States were considered. Diabetes was more common in RCT participants from the United States than in the registry population.

Conclusions and relevance: Participants in large, multicenter RCTs of patients with end-stage kidney disease undergoing dialysis are younger, have a different pattern of comorbidities, and have a lower mortality rate than the general population of patients undergoing dialysis. This finding has implications for the generalization of trial results to the broader patient population and for future trial design.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Smyth reported being supported by an Australian Government Research Training Program scholarship from the University of Sydney during the conduct of the study and receiving nonfinancial support from Roche International outside the submitted work. Dr Hawley reported receiving personal fees from GlaxoSmithKline, Johnson & Johnson, and Osuka; and grants from Baxter Healthcare, Fresenius Medical Care, PKD Australia, Queensland Health, and NHMRC Australia outside the submitted work. Dr Perkovic reported receiving personal fees from Bayer; grants from GlaxoSmithKline; other from Bristol-Myers Squibb Company; other from Eli Lilly; grants and other from Pfizer; personal fees from Servier; other from Boehringer Ingelheim; other from AstraZeneca; other from Novo Nordisk; other from Pharmalink; other from Relypsa; other from Baxter; other from Sanofi; other from Gilead; other from Novartis; other from Durect; other from Astellas; personal fees from Merck and Janssen; personal fees and other from Janssen; other from Tricida; other from Dimetrix; and other from AbbVie outside the submitted work. Dr Woodward reported receiving personal fees from Amgen and Kirin outside the submitted work. Dr Jardine reported receiving grants from Gambro, Amgen, Eli Lilly, and Merck; grants and other from Baxter; other from CSL; other from Akebia; other from Boehringer Ingelheim; other from Vifor; and other from Janssen outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Study Selection
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Comment in

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