Impact of FDA-Required Cardiovascular Outcome Trials on Type 2 Diabetes Clinical Study Initiation From 2008 to 2017

Background: Since 2008, the US Food and Drug Administration (FDA) has required that drug manufacturers conduct postmarket cardiovascular outcomes trials (CVOTs) for approved type 2 diabetes mellitus (T2DM) drugs. The utility and impact of these studies in determining atherosclerotic cardiovascular risk was reviewed during an FDA Advisory Committee Meeting held on October 24, 2018. Drug manufacturers and patient advocates at this meeting contended that the FDA-required CVOT studies discouraged private sector investment into developing novel T2DM drugs. Here, we explore these contentions by reviewing private sector investment in T2DM drug development from 2000 through 2008, followed by a deductive analysis of how associated events-including the implementation of the CVOT requirement-may have precipitated any observed changes. Methods: We collected and analyzed industry-sponsored interventional trials for T2DM initiated between January 1, 2000, and December 31, 2017, and compared observed trends with those seen across all trials, specific diseases, and against patent filings of novel antidiabetic agents. Results: The analysis shows a marked decline in initiated T2DM clinical trials from 2008 through 2017. Possible influencing factors, including the 2008 financial crisis and a slow in the discovery of novel antidiabetic agents may have contributed, but could not fully account for this decline in T2DM studies. Conclusions: These observations are consistent with the statements made by industry representatives and patient advocates at the 2018 Advisory Committee meeting. As the FDA reconsiders postmarket requirements for T2DM products, these observations underscore the importance of considering more efficient postmarket study structures to assess cardiovascular safety beyond mandatory CVOTs.