A Prospective Evaluation of Regional Effects in a Randomized Double-Blind Phase III Trial

• Activity Number: 350
• Type: Contributed
• Date/Time: Tuesday, August 5, 2014 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Xin Huang*+ and Lynn Navale
• Companies: Amgen and Amgen
• Keywords: regional analysis ; multiregional clinical trials ; intrinsic and extrinsic factors ; regional effects

Abstract

Large multiregional clinical trials may encounter unexpected regional difference in treatment effect. Lacking randomization balance within every region, the interpretation of these unexpected differences is challenging. Prospective evaluation of regional characteristics and blinded outcomes may facilitate some of the interpretation. We apply an adaptive strategy to a phase 3, randomized, double-blind trial (TRINOVA-1). A prospective supplementary study analysis plan is generated to document any pre-specified regional analysis which helps to reduce the risk of post hoc exaggerated emphases across many possible exploratory analyses and provide greater confidence in the validity of the conclusions. The results show that the approach may help the interpretation of unexpected regional difference due to different distribution of an intrinsic or extrinsic factor across regions.