Mario Gaudino1, Irbaz Hameed1, Mohamed Rahouma1, Faiza M Khan1, Derrick Y Tam2, Giuseppe Biondi-Zoccai3,4, Michelle Demetres5, Mary E Charlson6, Marc Ruel7, Filippo Crea8,9, Volkmar Falk10,11,12,13, Leonard N Girardi1, Stephen Fremes2, Joanna Chikwe14. 1. Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York. 2. Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. 3. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy. 4. IRCCS Neuromed, Pozzilli, Italy. 5. Samuel J. Wood Library and C. V. Starr Biomedical Information Centre, Weill Cornell Medicine, New York, New York. 6. Division of General Internal Medicine, Weill Cornell Medical College, New York, New York. 7. Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. 8. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 9. Department of Cardiovascular and Thoracic Sciences, Università Cattolica de Sacro Cuore, Roma, Italy. 10. Department of Cardiovascular Surgery, Charite, Berlin, Germany. 11. Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Berlin, Germany. 12. German Center for Cardiovascular Research, Berlin, Germany. 13. Department of Health Science and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland. 14. Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.
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.
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.
Authors: Mario Gaudino; Irbaz Hameed; Giuseppe Biondi-Zoccai; Derrick Y Tam; Stephen Gerry; Mohamed Rahouma; Faiza M Khan; Dominick J Angiolillo; Umberto Benedetto; David P Taggart; Leonard N Girardi; Filippo Crea; Marc Ruel; Stephen E Fremes Journal: Circ Cardiovasc Qual Outcomes Date: 2019-12-11
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