Differences in Patient Characteristics Affect Generalizability of Dialysis Clinical Trials

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Patients enrolled in major clinical trials of end stage kidney disease (ESKD) differ in key demographic and clinical characteristics, compared to the general population of dialysis patients, concludes a meta-analysis in JAMA Internal Medicine.

A systematic review identified 189 randomized clinical trials enrolling dialysis-dependent adults with ESKD. The studies, which enrolled at least 100 patients from 2 or more sites, included a total of 80,104 participants. Meta-analysis compared pre-specified characteristics of the RCT participants to patients in the US Renal Data System (USRDS) registry. Study characteristics associated with measures of generalizability were analyzed as well.

Patient age was the primary outcome: RCT participants were significantly younger than the USRDS patients, 58.9 versus 61.2 years. The clinical trial patients were also more likely to be male, 58.8% versus 55.7%, and less likely to have diabetes, 40.4% versus 44.2%. The RCT cohort was also much less likely to have diabetes as the cause of renal failure, 29.9% versus 44.2%, or hypertension as the cause of renal failure, 20.7% versus 29.0%. Based on 187 studies, mortality was 8.9 per 100 patient-years in the RCT cohort versus 18.6 per 100 patient-years in the USRDS cohort.

Most of the differences in patient characteristics were similar on analysis of studies recruiting from the United States, although diabetes was more common among RCT participants: 54.6% versus 44.2%. On analysis of study characteristics, mortality was lower in trials with commercial sponsorship or those published more recently.

Differing patient characteristics may affect the generalizability of clinical trial results. Previous studies have described differences in RCT cohorts versus the general population of patients undergoing kidney transplantation, but this issue has not been addressed in the ESKD population.

Dialysis patients enrolled in RCTs are younger, have differing patterns of comorbidity, and have lower mortality than the general population of ESKD patients. The researchers emphasize the need for caution in generalizing RCT results to older, frailer patients, and call for efforts to increase the generalizability of ESKD trials [Smyth B, et al. Representativeness of randomized clinical trial cohorts in end-stage kidney disease: A meta-analysis. JAMA Intern Med 2019; DOI: 10.1001/jamainternmed.2019.1501].