Sensitivity Analyses Adjusting for Early Discontinuation of Study Medication in the RE-LY Trial: An Open-Label, Randomized, Active-Controlled, Time-to-Event Noninferiority Trial

• Activity Number: 501
• Type: Topic Contributed
• Date/Time: Wednesday, August 4, 2010 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Xiuyu Cong*+ and Qiqi Deng and Susan Q. Wang
• Companies: Boehringer Ingelheim Pharmaceuticals, Inc. and Boehringer Ingelheim Pharmaceuticals, Inc. and Boehringer Ingelheim Pharmaceuticals, Inc.
• Keywords: adjust for early discontinuation ; time-to-event ; non-inferiority clinical trial

Abstract

RE-LY was designed as a non-inferiority trial to compare the effect of dabigatran etexilate versus warfarin for the prevention of stroke and systemic embolism events in patients with non-valvular atrial fibrillation (AF). The primary analysis followed the conventional intent-to-treat (ITT) approach. However, it was noticed that patients randomized to the dabigatran groups had higher rate of early discontinuation of study medication and higher rate of taking non-study anticoagulant medication after discontinuation than those in the warfarin group. Several sensitivity analyses have been conducted to adjust for such early discontinuation. This talk will present the application of two statistical methods: 1) the inverse probability of censoring weighted (IPCW) Cox proportional model; 2) Cox proportional model including time to early discontinuation as a time-dependent covariate.