Evaluating Cardiovascular Risk in Diabetes Clinical Trials: Lessons Learned from Saxagliptin

• Activity Number: 328
• Type: Topic Contributed
• Date/Time: Tuesday, August 3, 2010 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): J Mark Donovan*+
• Companies: Bristol-Myers Squibb
• Keywords: Multiplicity ; Meta-analysis ; diabetes ; cardiovascular risk

Abstract

We discuss a case study of an analysis of major cardiovascular (CV) events for a type 2 diabetes (T2D) drug program, presented at an FDA advisory committee meeting. The program included 8 controlled phase 2/3 trials, durations of 12-102 weeks at analysis. We used several meta-analytic techniques to assess whether there was an unacceptable increase in the CV risk associated with the drug. During FDA review of this drug, several changes took place in the regulatory landscape, including a separate advisory committee meeting discussing CV assessment for all T2D drug and biologic programs, and a new final Guidance was issued relating to CV assessment. We will discuss experiences with particular focus on how changes in the regulatory landscape affected the analysis. Examples include endpoint definition/identification of events, analyses of rare events, and handling of rescue medication.