title: Ethnic sensitive or molecular sensitive beyond all regions being equal in multiregional clinical trials.
abstract: For decades, clinical trials have been the primary mechanism for medical products to enter the marketplace. Over more than a decade, globalization of medical product development via a multiregional clinical trial (MRCT) approach has generated greater enthusiasm because of tangible benefits in terms of cost and time for drug development. There are, however, many challenges including and not limited to design issues, statistical analysis methods, interpretation of extreme region performance, and in-process quality assurance issues. This article presents a number of examples to exemplify regional variability expected versus precision of treatment effect estimates that are generally impacted by the type of primary efficacy endpoint evaluated. We explore region-driven intrinsic and extrinsic ethnic factors for potential explanation of regional heterogeneity caused by differences in medical practice and / or disease etiology. Bayesian credible interval may be considered as a viable approach to assess the robustness of region-specific treatment effect. Ethnic-sensitive or molecular-sensitive region-driven designs may be explored to prospectively address the potential regional heterogeneity versus the potential predictiveness of causal genetic variants or molecular target biomarkers on treatment effect.
authors.affiliation: Office of Biostatistics, OTS/CDER, Food and Drug Adminstration, Silver Spring, Maryland 20993-0002, USA. suejane.wang@fda.hhs.gov
authors.forename: Sue-Jane
authors.initials: SJ
authors.lastname: Wang
authors.forename: H M
authors.initials: HM
authors.lastname: James Hung
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D015415:Biomarkers; D002986:Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D004358:Drug Therapy / Q000379:methods; D023381:Endpoint Determination; D005006:Ethnicity; D014644:Genetic Variation; D006801:Humans; D015337:Multicenter Studies as Topic / Q000379:methods*; D010597:Pharmacogenetics; D015203:Reproducibility of Results; D012107:Research Design
chemical_list: D015415:Biomarkers