Type 2 diabetes mellitus development programs in the new regulatory environment with cardiovascular safety requirements

Abstract

Fred Yang,1 Murray Stewart,2 June Ye,2 David DeMets3 1AstraZeneca, Gaithersburg, MD, USA; 2GlaxoSmithKline, Upper Merion, PA, USA; 3Department of Biostatistics and Medical Informatics, University of Wisconsin–Madison, Madison, WI, USA Abstract: For type 2 diabetes mellitus treatment and clinical development, proper evaluation of cardiovascular risk has been required by regulatory agencies (eg, the US Food and Drug Administration) since cardiovascular safety is very important in this patient population. The US Food and Drug Administration issued general guidelines for cardiovascular safety evaluation that outlined the requirements considered adequate for cardiovascular safety evaluation. However, there are multiple options to obtain the data and fulfill these requirements. In this paper, we outline the potential pathways and challenges in various aspects of cardiovascular safety evaluation in type 2 diabetes clinical development, including study design, populations, and endpoints. Specifically, we discuss some challenges in statistical analysis which have implications for the design, implementation, and interpretation of these outcome studies. Keywords: T2DM, cardiovascular outcome, CV risk, noninferiority, superiority, major adverse cardiac event