New York-Presbyterian and Weill Cornell Medicine clinical investigators discovered that in randomized clinical trials, commercial sponsorship influences how studies are designed and results are reported in ways that often benefit the study’s sponsor. What does this mean? The biopharmaceutical industry needs to consider improving study design, reporting, and guidelines to avoid bias in these trials, suggest the New York-based clinical investigators.
The study focuses on coronary, vascular and structural interventional cardiology, as well as vascular and cardiac surgeries because of the enormous burden cardiovascular diseases places on public health. The stakes are big: it accounts for about 800,000 deaths annually and 6% of total dollars spent on healthcare. Hence, a rigorous approach is required for evaluating new interventions for heart disease reports the study authors. The study was published recently in Jama Internal Medicine.
Clinical Trials are Heavily Influential in Cardiovascular World
Sponsor-financed randomized, controlled trials heavily influence the medical community in the cardiovascular field. And for good reason, as Dr. Mario Gaudino, a professor in cardiothoracic surgery and director of translational and clinical research in cardiothoracic surgery at Weill Cornell Medicine, as well as a cardiovascular surgeon at New York-Presbyterian/Weill Cornell Medical Center, reports, “In medicine in general, but in particular cardiovascular medicine, we see randomized clinical trials as the best form of evidence.” Dr. Guadino continued, “Our practice is very influenced by the results of randomized clinical trials. If those trials are not properly performed and reported, there’s a risk that we use the wrong strategy and don’t treat patients in the best possible way.”
The New York-based investigators analyzed data from 216 randomized clinical trials published between 2008 and mid-2019 that involved invasive cardiovascular treatments. Among the factors they assessed using a variety of quantitative measures: the trial characteristics (including design, outcomes and reporting) and whether or not the study was funded by a commercial sponsor.
What they found was surprising: relatively few trials, on average less than 20 per year, had been conducted, and the majority of those studies were small and industry sponsored. Most of these trials had limited power to detect large treatment effects and followed patients for a limited period of time. The industry-sponsored trials were less likely to look at the most clinically important outcomes and more likely to focus on outcomes that are not very relevant for patients. Industry-sponsored trials were more likely to find results that favor the industry product. Moreover, in case of industry sponsored trials, no differences between groups was found, and researchers found evidence of interpretation bias favoring the sponsor.
The Fragility Index
The Fragility Index represents the number of patients whose status would need to change from a nonevent to an event that is required to convert a statistically significant outcome to a non-significant result. The smaller the Fragility Index, the more fragile the trial’s outcome.
In this study, the investigators used the Fragility Index to assess the strength of trial results. Again, lower values indicate less robust results and in this case the investigators found that overall Fragility Index to be quite low. They did find commercially sponsored trials to be more robust and less fragile.
Clinical Trial Design Improvements
Dr. Gaudino shared the team’s concerns, commenting, “We need to do a better job designing trials that are important for patients—in the end, the call of clinical research is to provide information that’s relevant to the patient; it isn’t to sell a device.” He declared that the role of sponsors needs to be more clearly defined. Although clinical sponsors are incredibly important in support of research, their role must be clearly defined, regulated and include a level of transparency that at times isn’t sufficient today. Conflicts of interest must be declared.
Call to Action: TrialSite News was developed to not only track research sites and investigators—their wins and challenges—but also identify and embrace their important findings. The results of this study should be understood by those organizations involved with cardiovascular-focused medicine for the implications of studies not necessarily designed with the patient in mind.
For other investigators see the source.