Assessment of Regional Treatment Effect in a Multiregional Clinical Trial

The 11th question-and-answer document (Q&A) for ICH E5 (1998) was published in 2006. This Q&A describes points to consider for evaluating the possibility of bridging among regions by a multiregional trial. The primary objective of a multiregional bridging trial is to show the overall efficacy of a drug in all participating regions while also evaluating the possibility of applying the overall trial results to each region. To apply the overall results to a specific region, it suggested that the results in that region should be consistent with the overall results. The Japanese Ministry of Health, Labor, and Welfare (MHLW) published the “Basic Principles on Global Clinical Trials” guidance document (2007) and proposed two methods to support the bridging claims. Due to the limited sample sizes allocated to the region, the regular interaction test for treatment by region is not practical. On the other hand, the sample size requirement for the Japanese region as described in Uyama et al. (2005) and Uesaka (2009)...