Recently published findings suggest that participants in randomized clinical trials have significantly different characteristics, comorbidities and outcomes than patients with ESKD in the general population.
“The single or pooled results from randomized clinical trials (RCTs) are considered the highest level of evidence for treatment efficacy in modern medicine,” Brendan Smyth, MBBS, of the George Institute for Global Health and University of New South Wales in Australia, and colleagues wrote. “For the results of an RCT to be generalizable to a specific patient population, the study cohort and population of interest must be sufficiently similar in clinically relevant characteristics so that the intervention effect from the RCT can be reasonably expected to be replicated in the population of interest. Although RCTs in kidney transplant recipients have been shown to enroll younger participants than the general population in the United States of patients who have received kidney transplants (suggesting important limitations to generalizability), to our knowledge, this question has not been addressed in the dialysis population.”
To compare trial participants with real-world patients, researchers analyzed data from 189 RCTs (80,104 total participants) along with general population data from the US Renal Data System.
Researchers found that, compared with the 2011 USRDS population, participants in RCTs were younger (mean age, 58.9 years vs. 61.2), more likely to be male (58.8% vs. 55.7%) and more likely to have coronary artery disease (26.7% vs. 17.7%).
RCT participants were also less likely to have diabetes (40.4% vs. 44.2%) or heart failure (19.9% vs. 29.8%).
Participants in randomized clinical trials have significantly different characteristics, comorbidities and outcomes than patients with ESKD in the general population.
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Finally, researchers observed that the mortality rate for trial participants was less than half that of the USRDS population (8.9 vs. 18.6).
“Although some of the differences observed between the RCT and registry cohorts were small, when considered collectively these differences may imply that the magnitude of treatment effects assumed from the evidence base may not be realized when those interventions are applied to a more representative cohort of patients,” the researchers wrote. “This finding emphasizes the importance of clinicians and policymakers carefully considering the generalizability of particular RCT results to their own distinct populations. It also supplies a clear rationale for increasing the effort to produce pragmatic RCTs. Such trials, for example the TiME (Time to Reduce Mortality in ESRD) trial of longer hemodialysis sessions, are characterized by an effort to maximize generalizability by the minimization of inclusion and exclusion criteria, the use of routinely collected data and an emphasis on real-world practice.”
In a related editorial, Joseph S. Ross, MD, MHS, of Yale University School of Medicine, and Ken Covinsky, MD, of the University of California, San Francisco, wrote: “Not only do Smyth et al show that RCT participants were significantly younger, more likely to be male, and less likely to have diabetes or diabetic neuropathy when compared with the patients undergoing dialysis in the United States Renal Data System registry, but they show that their mortality risk is less than half than that of the registry patients. This finding has particular importance because patients undergoing dialysis often underestimate their disease prognosis, both because of uncertainty as well as optimism. ... Randomized clinical trials should include older patients and those with serious comorbid illness if we want evidence that can be used to inform decision making for all our patients.” – by Melissa J. Webb
Disclosures: Smyth reports support from an Australian Government Research Training Program scholarship from the University of Sydney, as well as nonfinancial support from Roche International. Please see the study for all other authors’ relevant financial disclosures.