Example-based illustrations of design, conduct, analysis and result interpretation of multi-regional clinical trials

• Published in: Contemporary clinical trials 2017-07, Vol.58, p.13-22
• Main Authors: Quan, Hui, Mao, Xuezhou, Tanaka, Yoko, Binkowitz, Bruce, Li, Gang, Chen, Josh, Zhang, Ji, Zhao, Peng-Liang, Ouyang, Soo Peter, Chang, Mark
• Format: Article
• Language: English
• Subjects: Between-region variability; Cardiovascular; Clinical Studies as Topic - methods; Clinical Studies as Topic - standards; Consistency of treatment effects; Continental Population Groups; Equivalence Trials as Topic; Fixed and random effects models; Hematology, Oncology and Palliative Medicine; Humans; Models, Statistical; Multicenter Studies as Topic - methods; Multicenter Studies as Topic - standards; Practice Patterns, Physicians; Randomized Controlled Trials as Topic - methods; Randomized Controlled Trials as Topic - standards; Reproducibility of Results; Residence Characteristics - statistics & numerical data; Sample size; Shrinkage estimate; Time Factors
• ISSN: 1551-7144; 1559-2030
• DOI: 10.1016/j.cct.2017.04.009

Abstract Extensive research has been conducted in the Multi-Regional Clinical Trial (MRCT) area. To effectively apply an appropriate approach to a MRCT, we need to synthesize and understand the features of different approaches. In this paper, examples are used to illustrate considerations regarding design, conduct, analysis and interpretation of result of MRCTs. We start with a brief discussion of region definitions and the scenarios where different regions have differing requirements for a MRCT. We then compare different designs and models as well as the corresponding interpretation of the results. We highlight the importance of paying special attention to trial monitoring and conduct to prevent potential issues associated with the final trial results. Besides evaluating the overall treatment effect for the entire MRCT, we also consider other key analyses including quantification of regional treatment effects within a MRCT, and assessment of consistency of these regional treatment effects.