How similar are dialysis-dependent patients recruited to large, multicenter randomized clinical trials compared with the general dialysis-dependent population?
In this meta-analysis of 189 trials including 80 104 participants, trial participants were significantly younger, more likely to be male, and less likely to have diabetes or diabetic nephropathy than patients in the US national registry. Moreover, the mortality rate of dialysis-dependent patients recruited to large, multicenter randomized trials was substantially lower than that of registry patients, both overall and when only studies recruiting participants from the United States were considered.
These findings imply that caution should be exercised when generalizing results from clinical trials to the broader dialysis-dependent patient population.
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.
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.
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.
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.
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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Smyth B, Haber A, Trongtrakul K, et al. Representativeness of Randomized Clinical Trial Cohorts in End-stage Kidney Disease: A Meta-analysis. JAMA Intern Med. 2019;179(10):1316–1324. doi:https://doi.org/10.1001/jamainternmed.2019.1501
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