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

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 189 RCTs, enrolling 80 104 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  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.