Considerations for Design and Data Analysis of Adaptive Superiority/Noninferiority Cardiovascular Trials

• Activity Number: 663
• Type: Topic Contributed
• Date/Time: Thursday, August 5, 2010 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Hui Quan*+ and Mingyu Li and Peng-Liang Zhao and Meehyung Cho and Ji Zhang and Yujun Wu
• Companies: sanofi-aventis and Celgene Corporation and sanofi-aventis and sanofi-aventis and Sanofi-Aventis and Sanofi-Aventis
• Keywords: diluted treatment effect ; ITT analysis ; treatment emerging analysis ; conditional power ; meta-analysis ; exposure adjusted event rate

Abstract

The FDA guidance for evaluating CV risk in new therapies to treat type 2 diabetes recommends to conduct appropriate data analysis to rule out CV safety concern. CV trials for chronic conditions are usually large scale/long term trials and can be designed as adaptive superiority/non-inferiority trials. In these trials, treatment effect may not manifest immediately after patients take study medication and there will be a dilution in treatment effect after discontinuation. These factors should be taken into account for planning of study sample size and timeline. In this paper, we derive closed form formulas for the number of events and total exposure as functions of many other parameters. We then outline some considerations for the design of an adaptive superiority/non-inferiority CV trial based on ideas of other authors. We also use an example to illustrate the application of the methods.