ABSTRACT
The primary objective of multiregional clinical trial (MRCT) is to investigate the drug’s overall efficacy across regions while also assessing the drug’s performance in individual regions. In order to claim the study drug’s efficacy in
CONTENTS
10.1 Introduction .............................................................................................. 113 10.2 A Unified Consistency Requirement for Regional Approval ............ 114
10.2.1 Assumptions ............................................................................... 114 10.2.2 Consistency Requirements for Regional Approval ............... 115 10.2.3 Recommendation of Parameters (πi, αi) ................................... 116
10.3 Optimal Designs for MRCT .................................................................... 117 10.3.1 Two Optimal Sample Size Allocation Designs ...................... 117
10.3.1.1 MTSS Design .............................................................. 117 10.3.1.2 MU Design ................................................................. 118
10.3.2 Important Elements for Designing MRCT ............................. 119 10.3.3 MTSS Design for MRCT ............................................................ 120
10.3.3.1 MTSS Design When Postulated Treatment Effects Are Different ................................................. 120
10.3.3.2 MTSS Design When Desired Assurance Probabilities Are Different ....................................... 121
10.3.3.3 MTSS Design When Regional Requirements Are Different .............................................................. 121
10.3.3.4 MTSS Design When Some of Regions in an MRCT Are of Interest ................................................ 122
10.3.4 MU Design for MRCT ................................................................ 123 10.3.4.1 MU Design: The First Application .......................... 123 10.3.4.2 MU Design: The Second Application ..................... 123
10.3.5 Hypothetical Examples ............................................................. 124 10.4 Summary ................................................................................................... 127 References ............................................................................................................. 128
specific region(s), the local regulatory authority may require the sponsors to provide evidence of consistency in the treatment effect between the overall patient population and the local region. Based on the Japanese Ministry of Health, Labour and Welfare (MHLW [2007]) guidance, a number of consistency criteria have been proposed and the sample size planning for MRCT was also well discussed in Chen et al. (2012), Chen et al. (2010a), Huang et al. (2013), Hung et al. (2010), Luo et al. (2010), Ikeda and Bretz (2010), Kawai et al. (2008), Ko (2012), Quan et al. (2010a and b), Tsou et al. (2011), Tsou et al. (2012), and Uesaka (2009). In Section 10.2, we propose a unified consistency requirement that generalizes those proposed by Ko et al. (2010), Chen et al. (2012), and Tsong et al. (2012).
