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Original Investigation
June 1, 2020

Characteristics of Contemporary Randomized Clinical Trials and Their Association With the Trial Funding Source in Invasive Cardiovascular Interventions

Author Affiliations
  • 1Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York
  • 2Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
  • 3Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
  • 4IRCCS Neuromed, Pozzilli, Italy
  • 5Samuel J. Wood Library and C. V. Starr Biomedical Information Centre, Weill Cornell Medicine, New York, New York
  • 6Division of General Internal Medicine, Weill Cornell Medical College, New York, New York
  • 7Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
  • 8Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  • 9Department of Cardiovascular and Thoracic Sciences, Università Cattolica de Sacro Cuore, Roma, Italy
  • 10Department of Cardiovascular Surgery, Charite, Berlin, Germany
  • 11Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Berlin, Germany
  • 12German Center for Cardiovascular Research, Berlin, Germany
  • 13Department of Health Science and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland
  • 14Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California
JAMA Intern Med. 2020;180(7):993-1001. doi:10.1001/jamainternmed.2020.1670
Key Points

Questions  What are the characteristics, including design, outcomes, and reporting, of contemporary randomized clinical trials of invasive cardiovascular interventions, and what is their association with the funding source?

Findings  In this cross-sectional analysis of 216 trials of invasive cardiovascular interventions, most trials reported a statistically significant difference in the primary outcome favoring the experimental therapy and used reporting strategies that implied an advantage with nonsignificant differences in primary outcome (spin). Discrepancies between the registered and published primary outcomes were found in 38% of trials; a median of 5 patients experiencing a different outcome would have changed statistically significant results to nonsignificant; and commercially sponsored trials appeared to be associated with differences in trial design, results, and reporting.

Meaning  Findings of this study suggest that contemporary trials in invasive cardiovascular treatments may be small and fragile, have short follow-up, and have limited power to detect large treatment effects.

Abstract

Importance  Changes in evidence-based practice and guideline recommendations depend on high-quality randomized clinical trials (RCTs). Commercial device and pharmaceutical manufacturers are frequently involved in the funding, design, conduct, and reporting of trials, the implications of which have not been recently analyzed.

Objective  To evaluate the design, outcomes, and reporting of contemporary randomized clinical trials of invasive cardiovascular interventions and their association with the funding source.

Design, Setting, and Participants  This cross-sectional study analyzed published RCTs between January 1, 2008, to May 31, 2019. The trials included those involving coronary, vascular and structural interventional cardiology, and vascular and cardiac surgical procedures.

Main Outcomes and Measures  We assessed (1) trial characteristics, (2) finding of a statistically significant difference in the primary end point favoring the experimental intervention, (3) reporting of implied treatment advantage in trials without significant differences in primary end point, (4) existence of major discrepancies between registered and published primary outcomes, (5) number of patients whose outcomes would need to switch from a nonevent to an event to convert a significant difference in primary end point to nonsignificant, and (6) association with funding source.

Results  Of the 216 RCTs analyzed, 115 (53.2%) reported having commercial sponsorship. Most trials had 80% power to detect an estimated treatment effect of 30%, and 128 trials (59.3%) used composite primary end points. The median (interquartile range [IQR]) sample size was 502 (204-1702) patients, and the median (IQR) follow-up duration was 12 (1.0-14.4) months. Overall, 123 trials (57.0%) reported a statistically significant difference in the primary outcome favoring the experimental intervention; reporting strategies that implied an advantage were identified in 55 (65.5%) of 84 trials that reported nonsignificant differences. Commercial sponsorship was associated with a statistically significantly greater likelihood of favorable outcomes reporting (exponent of regression coefficient β, 2.80; 95% CI, 1.09-7.18; P = .03) and with the reporting of findings that are inconsistent with the trial results. Discrepancies between the registered and published primary outcomes were found in 82 trials (38.0%), without differences in trial sponsorship. A median (IQR) number of 5 (2.8-12.5) patients experiencing a different outcome would have change statistically significant results to nonsignificant. Commercial sponsorship was associated with a greater number of patients (exponent of regression coefficient β, 1.29; 95% CI, 1.00-1.66; P = .04).

Conclusions and Relevance  These results suggest that contemporary RCTs of invasive cardiovascular interventions are relatively small and fragile, have short follow-up, and have limited power to detect large treatment effects. Commercial support appeared to be associated with differences in trial design, results, and reporting.

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