Design and Evaluation of Multiregional Trials with Heterogeneous Treatment Effect Across Regions

Abstract

To speed up drug development to allow faster access to medicines for patients globally, conducting multiregional trials incorporating subjects from many countries around the world under the same protocol may be desired. Several statistical methods have been proposed for the design and evaluation of multiregional trials. However, in most of the recent approaches for sample size determination in multiregional trials, a common treatment effect of the primary endpoint across regions is usually assumed. In practice, it might be expected that there is a difference in treatment effect due to regional difference (e.g., ethnic difference). In this article, a random effect model for heterogeneous treatment effect across regions is proposed for the design and evaluation of multiregional trials. We also address consideration of the determination of the number of subjects in a specific region to establish the consistency of treatment effects between the specific region and the entire group.

Key Words:

• Bridging study
• Ethnic effect
• Multiregional trials

ACKNOWLEDGMENTS

The work in this article contributed by Chi-Tian Chen and Chin-Fu Hsiao was supported by the grant WSC 100-2118-M-400-001 from the National Science Council, Taiwan. The views expressed in this article do not necessarily represent those of the U.S. Food and Drug Administration.