Optimal Designs for Multiregional Clinical Trials with Regional Consistency Requirement

• Activity Number: 372
• Type: Contributed
• Date/Time: Tuesday, August 11, 2015 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Zhaoyang Teng* and Mark Chang
• Companies: Takeda Pharmaceutical International Co. and AMAG Pharmaceuticals
• Keywords: Multi-Regional Clinical Trials ; Optimal Designs ; Consistency Requirement ; Sample Size Allocaiton

Abstract

In multi-regional clinical trials (MRCT), the evidence of consistency in treatment effects between the local region and the entire trial is usually required for regional approval in addition to the global efficacy. Most of the developed designs for MRCT only considered applying the consistency requirement for a specific region, and the sample size proportion to this region was determined, but not to others. By allocating most samples in one particular region may leave insufficient samples to the others to guarantee certain probability of success. Thus, in order to guarantee certain probability of success for all regions of interest, the total sample size increase is sometimes ineluctable. However, different sample size allocations will lead to different total sample size increases. In this paper, we propose two optimal designs for MRCT which provide more effective sample size allocation to ensure certain overall power and probability of regional success for all regions of interest with minimal total sample size requirement. We also introduce the important factors which should be considered in designing MRCT and analyze how each factor affects sample size planning of MRCT.