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.

Gaudino, M. F. L., Hameed, I., Rahouma, M., Khan, F. M., Tam, D. Y., Biondi-Zoccai, G., Demetres, M., Charlson, M. E., Ruel, M., Crea, F., Falk, V., Girardi, L. N., Fremes, S., Chikwe, J., Characteristics of Contemporary Randomized Clinical Trials and Their Association with the Trial Funding Source in Invasive Cardiovascular Interventions, <<JAMA INTERNAL MEDICINE>>, 2020; 180 (7): 993-1001. [doi:10.1001/jamainternmed.2020.1670] [http://hdl.handle.net/10807/166642]

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

Gaudino, Mario Fulvio Luigi;Crea, Filippo;
2020

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.
2020
Inglese
Gaudino, M. F. L., Hameed, I., Rahouma, M., Khan, F. M., Tam, D. Y., Biondi-Zoccai, G., Demetres, M., Charlson, M. E., Ruel, M., Crea, F., Falk, V., Girardi, L. N., Fremes, S., Chikwe, J., Characteristics of Contemporary Randomized Clinical Trials and Their Association with the Trial Funding Source in Invasive Cardiovascular Interventions, <<JAMA INTERNAL MEDICINE>>, 2020; 180 (7): 993-1001. [doi:10.1001/jamainternmed.2020.1670] [http://hdl.handle.net/10807/166642]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/166642
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