Design Issues in the NHLBI Randomized Trial of Genotype-Guided Dosing of Warfarin Therapy (COAG)

• Activity Number: 393
• Type: Invited
• Date/Time: Wednesday, August 5, 2009 : 8:30 AM to 10:20 AM
• Sponsor: Biometrics Section
• Author(s): Jonas H. Ellenberg*+ and Jungnam Joo and Nancy Geller and Yves Rosenberg and Stephen Kimmel and Benjamin French
• Companies: University of Pennsylvania and National Heart, Lung, and Blood Institute and National Heart, Lung, and Blood Institute and National Heart, Lung, and Blood Institute and University of Pennsylvania and University of Pennsylvania
• Keywords: Clinical Trial ; Targeted Therapy ; Design ; Genetics

Abstract

This paper describes some statistical considerations for the Clarification of Optimal Anticoagulation through Genetics (COAG) trial sponsored by the National Heart, Lung and Blood Institute (NHLBI). The COAG trial is a large, multicenter, double-blind, randomized trial to determine whether use of a genotype-guided dosing algorithm using clinical and genetic information to initiate Warfarin treatment will improve anticoagulation status when compared to a dosing algorithm using only clinical information. Several issues related to the design of the COAG trial are discussed, including: a subgroup analysis as a co-primary endpoint and optimal allocation of type I error by accounting for the correlation between the co-primary endpoints; and the sensitivity of the assumptions underlying power computations of an enriched versus an all-comer cohort with trial power investigated via simulations.