Abstract 17159: A Changing Landscape: Contemporary Characteristics of Major Cardiovascular Superiority Trials
Background: Superiority clinical trials hold promises of impactful interventions for the future of evidence-based medicine but require extensive resources and may place study patients at risk. Advances made through cardiovascular (CV) trials in past decades have drastically improved patient outcomes, but little is known about the modern landscape of CV superiority trials and how it has evolved over time.
Methods: We performed a comprehensive search in PubMed using keywords and MeSH terms to identify all superiority CV trials with a primary clinical endpoint from January 1, 2006 to December 31, 2011 in the New England Journal of Medicine (NEJM), JAMA, and the Lancet. We used chi-square and Cochran-Armitage Trend tests to assess for statistical significance.
Results: We identified 188 trials (108 drug trials, 20 device trials and 60 others). Overall, 69 trials (36.7%) had positive results, demonstrating superiority of the new intervention for the primary endpoint, while 119 trials (63.3%) showed negative results, including 16 trials (8.5% of total) in which the intervention group performed significantly worse. Temporally, the proportion of negative trials increased from 44.4% in 2006 to 76.7% in 2011 (p for trend=0.02, Figure). Median sample size for positive trials and negative trials were 1800 patients (IQR 575, 5762.5) and 2331 patients (IQR 1222, 5745), respectively. There was a significant association between journal and study results (NEJM 34.3% positive, JAMA 23.8% positive, Lancet 56.1% positive; p=.007).
Conclusions: The majority of CV trials in the contemporary, high-impact literature are drug trials, enroll large study populations, and produce negative results, with a trend towards higher proportions of negative trials in recent years. This may suggest a need to assess the role and clinical significance of negative trials in practice, as well as closely weigh the likelihood of risks and benefits in the development of future trials.
- © 2013 by American Heart Association, Inc.