Summary:
Cardiovascular disease remains a leading cause of death, but stakeholders have recently raised concerns about the pace of innovation and investment in developing new therapeutics. Here, the authors characterized temporal trends in cardiovascular research and development over the past 2 decades and the likelihood of successful completion of pre-approval clinical trials. The authors also evaluated the reasons for discontinuation, novelty, and rates of trial results publication for cardiovascular therapies in late-stage development. Between 1990 and 2012, the number of new cardiovascular drugs entering clinical trials declined across all stages of development (p < 0.001 for linear trends). There was no evidence for a difference in probability of successful progression to the next stage of development between cardiovascular and noncardiovascular drugs. Small and medium-sized companies sponsored 43%, 38%, and 31% of new Phase 1, Phase 2, and Phase 3 trials, respectively. Roughly one-half of the drugs in Phase 3 trials were categorized as targeting a novel biological pathway. The number of cardiovascular trials sponsored by small and medium-sized companies and the number of novel drugs entering Phase 3 trials increased over time. Most drugs were discontinued in Phase 3 due to inadequate efficacy (44%) or safety issues (24%), but the Phase 3 trial results for only one-half of the discontinued drugs were published in peer-reviewed journals. These results shed light on important shifts in research and development activity and confirm the perceived challenges in cardiovascular translational research.
Key Words
Cardiovascular drug development; regulatory science; translational research.
Citation: Thomas J. Hwang, Julie C. Lauffenburger, Jessica M. Franklin, Aaron S. Kesselheim Temporal Trends And Factors Associated With Cardiovascular Drug Development, 1990 To2012 http://dx.doi.org/10.1016/j.jacbts.2016.03.012
Received: 25 March 2016, Accepted: 28 March 2016, Available online: 29 August 2016
Copyright: © 2016 The Authors. Published by Elseveier on behalf of the American college of Cardiology foundation. This is an open access article under the CC by-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Conclusions:
Over the past 2 decades, fewer investigational cardiovascular drugs have entered clinical trials across all stages of development, though recently, more therapies have targeted novel biological pathways and have been sponsored by small and medium-sized companies. Most cardiovascular drugs fail in Phase 3 clinical trials due to inadequate efficacy or safety concerns, but cardiovascular drugs do not appear to be more likely to fail than drugs for other diseases. Given the increasing burden of cardiovascular disease globally, the declining pipeline of new therapies is concerning. Policymakers should focus their efforts on supporting research aimed at improving gaps in the understanding of the pathophysiological bases for cardiovascular disorders, as well as facilitating translational efforts to develop new cardiovascular therapeutics.
