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

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 79104 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