Assessing Benefit and Consistency of Treatment Effect Under a Discrete Random Effects Model in Multiregional Clinical Trials

The traditionally uniform treatment effect assumption may be inappropriate in an multiregional clinical trial (MRCT) because of the impact on the drug effect due to regional differences. Lan and and Pinheiro (2012) proposed a discrete random effects model (DREM) to account the treatment effects heterogeneity among regions. However, the benefit of the overall drug effect and the consistency of the treatment effect in each region are two major issues in MRCTs. In this article, the power of benefit is derived under DREM and the overall sample size determination in an MRCT. Comparison of DREM and traditional continuous random effects model (CREM) is also illustrated here. In order to assess the treatment benefit and consistency simultaneously under DREM, we consider the concept of the Method 2 in “Basic Principles on Global Clinical Trials” guidance to construct the probability function of benefit and consistency. We also optimize the sample size allocation to reach maximum power for the benefit and consistency.