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Original Investigation
September 1, 2019

Trends in the Explanatory or Pragmatic Nature of Cardiovascular Clinical Trials Over 2 Decades

Author Affiliations
  • 1Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada
  • 2Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
  • 3Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada
  • 4Department of Medicine, University of Calgary, Calgary, Alberta, Canada
  • 5Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
JAMA Cardiol. Published online September 1, 2019. doi:10.1001/jamacardio.2019.3604
Key Points

Question  How pragmatic or explanatory are cardiovascular randomized clinical trials?

Findings  In this study of 616 cardiovascular randomized clinical trials, the level of pragmatism assessed by the Pragmatic Explanatory Continuum Index Summary–2 score increased moderately from 2000 to 2015. The increase occurred mainly in the eligibility, setting, and flexibility of intervention delivery, and primary end point domains of the trial design.

Meaning  Knowing more about current trials will help researchers in the design and delivery of cardiovascular trials that are required for broader application of the studied interventions.

Abstract

Importance  Pragmatic trials test interventions using designs that produce results that may be more applicable to the population in which the intervention will be eventually applied.

Objective  To investigate how pragmatic or explanatory cardiovascular (CV) randomized clinical trials (RCT) are, and if this has changed over time.

Data Source  Six major medical and CV journals, including New England Journal of Medicine, Lancet, JAMA, Circulation, European Heart Journal, and Journal of the American College of Cardiology.

Study Selection  All CV-related RCTs published during 2000, 2005, 2010, and 2015 were identified and included.

Data Extraction and Synthesis  Included RCTs were assessed by 2 independent adjudicators with expertise in RCT and CV medicine.

Main Outcomes and Measures  The outcome measure was the level of pragmatism evaluated using the Pragmatic Explanatory Continuum Index Summary (PRECIS)–2 tool, which uses a 5-point ordinal scale (ranging from very pragmatic to very explanatory) across 9 domains of trial design, including eligibility, recruitment, setting, organization, intervention delivery, intervention adherence, follow-up, primary outcome, and analysis.

Results  Of 616 RCTs, the mean (SD) PRECIS-2 score was 3.26 (0.70). The level of pragmatism increased over time from a mean (SD) score of 3.07 (0.74) in 2000 to 3.46 (0.67) in 2015 (P < .001 for trend; Cohen d relative effect size, 0.56). The increase occurred mainly in the domains of eligibility, setting, intervention delivery, and primary end point. PRECIS-2 score was higher for neutral trials than those with positive results (P < .001) and in phase III/IV trials compared with phase I/II trials (P < .001) but similar between different sources of funding (public, industry, or both; P = .38). More pragmatic trials had more sites, larger sample sizes, longer follow-ups, and mortality as the primary end point.

Conclusions and Relevance  The level of pragmatism increased moderately over 2 decades of CV trials. Understanding the domains of current and future clinical trials will aid in the design and delivery of CV trials with broader application.

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