The level of pragmatism in CV-related randomized clinical trials (RCTs) has only increased moderately over the past two decades, according to work published in JAMA Cardiology Sept. 1.
Pragmatic trials, as they’re described by first author Nariman Sepehrvand, MD, and colleagues, are studies designed to produce results relevant to the population in which they’ll be applied. They enroll participants representative of the intervention’s target population and simplify trial-related procedures in an effort to better inform decision-makers like politicians, clinicians and administrators.
“They carry the potential to address some of the limitations of RCTs such as the lack of external validity, high cost and lengthy processes, often by streamlining the trial design and implementation,” Sepehrvand and co-authors wrote. “However, there is a paucity of data on how the landscape of CV RCTs have changed over the past few decades in terms of their placement on the pragmatic-explanatory continuum.”
Sepehrvand et al. included all cardiovascular-related RCTs published in JAMA, the Lancet, the New England Journal of Medicine, Circulation, the European Heart Journal and the Journal of the American College of Cardiology in 2000, 2005, 2010 and 2015 in their analysis. RCTs were assessed by two independent adjudicators, both with extensive experience in RCTs and cardiology.
The authors measured pragmatism using the Pragmatic Explanatory Continuum Index Summary (PRECIS)-2 tool, which considers factors like trial design, setting, recruitment, organization and analysis to score RCTs on a five-point ordinal scale ranging from “very pragmatic” to “very explanatory.” Of 616 RCTs published in the 15-year period, the mean PRECIS-2 score was 3.26.
The level of pragmatism in cardiovascular RCTs increased over time, from 3.07 in 2000 to 3.46 in 2015. The hike was most evident in trial design domains of eligibility, setting, intervention delivery and primary endpoint, and more pragmatic trials were more likely to have larger sample sizes, more sites, longer follow-ups and mortality as a primary endpoint.
Sepehrvand and colleagues also pointed out that PRECIS-2 scores were higher for neutral trials than those with positive results and in phase III and IV trials compared with phase I and II studies.
“This finding deserves careful thought,” Fatima Rodriguez, MD, MPH, and colleagues wrote in a related editorial, noting the goal of PRECIS is not to strive for the highest score but rather to evaluate the best design for the question addressed by the trial. The editorialists also made note of Sepehrvand et al.’s finding that there were no differences in PRECIS-2 scores by funding source (industry vs. government), suggesting major regulatory bodies like the National Institutes of Health might not be investing enough in “stimulating the transformation in this field.”
“Clearly, new methods are needed to accelerate the efficient generation of evidence using the RCT design,” Rodriguez and co-authors said. “The concept of pragmatic clinical trials is hardly new, yet as Sepehrvand et al. show, more work is needed to break from traditional trial design.
“As they point out, it would be advisable for clinical trialists to self-rate the degree of pragmatism of their proposed trial using a tool like PRECIS-2, and when appropriate for the study question, they should make every effort to increase the degree of pragmatism.”