Two-Stage Approach to Evaluate Cardiovascular Risk of New Anti-Diabetic Therapies

• Activity Number: 368
• Type: Contributed
• Date/Time: Tuesday, August 11, 2015 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Raymond Lam* and Shailaja Suryawanshi
• Companies: Merck and Merck
• Keywords: Two Stages ; CV Risk ; Meta Analysis ; Group Sequential Design ; T2DM

Abstract

Regulatory agencies including the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and Health Canada have recommended that prior to filing for marketing approval of new antihyperglycemic agents developed to treat Type 2 Diabetes Mellitus (T2DM), Sponsors should demonstrate that the therapy will not result in an unacceptable increase in cardiovascular (CV) risk. The FDA proposes a 2-stage approach for this evaluation. The goal of Stage 1 is to rule out a CV risk increase of 80%, compared to a control group, based on a composite endpoint of major cardiovascular adverse events to support approval for marketing. The goal of Stage 2 is to rule out a risk increase of 30% as a post-approval marketing requirement. Methods for the 2-stage approach including group sequential designs, alpha spending allocation, and a meta-analytic approach for executing this strategy will be discussed.