title: Establishing consistency across all regions in a multi-regional clinical trial.
abstract: In recent years, global collaboration has become a conventional strategy for new drug development. To accelerate the development process and shorten approval time, the design of multi-regional clinical trials (MRCTs) incorporates subjects from many countries/regions around the world under the same protocol. After showing the overall efficacy of a drug in a global trial, one can also simultaneously evaluate the possibility of applying the overall trial results to all regions and subsequently support drug registration in each region. However, most of the recent approaches developed for the design and evaluation of MRCTs focus on establishing criteria to examine whether the overall results from the MRCT can be applied to a specific region. In this paper, we use the consistency criterion of Method 1 from the Japanese Ministry of Health, Labour and Welfare (MHLW) guidance to assess whether the overall results from the MRCT can be applied to all regions. Sample size determination for the MRCT is also provided to take all the consistency criteria from each individual region into account. Numerical examples are given to illustrate applications of the proposed approach.
authors.affiliation: Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan, ROC.
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Tsou
authors.forename: H M
authors.initials: HM
authors.lastname: James Hung
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Chen
authors.forename: Wong-Shian
authors.initials: WS
authors.lastname: Huang
authors.forename: Wan-Jung
authors.initials: WJ
authors.lastname: Chang
authors.forename: Chin-Fu
authors.initials: CF
authors.lastname: Hsiao
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D017277:Drug Approval; D015195:Drug Design; D006801:Humans; D007391:International Cooperation; D007564:Japan; D015337:Multicenter Studies as Topic / Q000379:methods*; D012107:Research Design; D013997:Time Factors