Multi-Regional Trials

Abstract

The aims of a multi-regional trials are twofold: (a) to demonstrate efficacy for the entire study population across all involved regions; (b) to demonstrate consistency of results between regions. If part (b) is accomplished, i.e., if the assessment of consistent results between regions is successful, it is established that the drug effect is not sensitive to ethnic factors. Then, the global results obtained in part (a) can be transferred to the local regions. In this chapter, sample size calculation methods are given for two concepts commonly used for the assessment of consistency and for the case of two-group comparisons with normally distributed outcomes. Two approaches for the probability for establishing consistency are considered, namely the unconditional probability and the probability conditional on a statistically significant overall treatment effect.