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?
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.
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.
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.
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.
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.
Identify all potential conflicts of interest that might be relevant to your comment.
Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.
Err on the side of full disclosure.
If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.
Not all submitted comments are published. Please see our commenting policy for details.
Gaudino M, Hameed I, Rahouma M, et al. Characteristics of Contemporary Randomized Clinical Trials and Their Association With the Trial Funding Source in Invasive Cardiovascular Interventions. JAMA Intern Med. 2020;180(7):993–1001. doi:10.1001/jamainternmed.2020.1670
Customize your JAMA Network experience by selecting one or more topics from the list below.
Create a personal account or sign in to: