title: Assessing consistent treatment effect in a multi-regional clinical trial: a systematic review.
abstract: A key issue in multi-regional clinical trials (MRCTs) is how to assess the consistency of treatment effect across regions, although there is no a priori reason to believe that the treatment effect should vary across the regions. In this article, we define the research question as an assessment of overall consistency across all regions for which all regions are considered equally important. This is different from the region/country-specific analyses (e.g. US vs Non-US), which are frequently requested by local regulatory agencies and usually performed for multiple agencies. We provide a systematic review of methods that may potentially be used for assessing consistency across regions, including commonly used quantitative/qualitative interaction tests, Japanese Pharmaceutical Medical Device Agency (PMDA) Methods 1 & 2, and those proposed for different purposes (e.g. bridging studies, meta-analysis, and vaccine lot consistency, among others). These methods are classified into three groups: global methods, multivariate quantitative methods, and multivariate qualitative methods. A case study is used to illustrate these methods. We also provide recommendations on how to choose appropriate methods and incorporate them in the study design.
authors.affiliation: Merck Research Labs, UG1CD-44, North Wales, PA, USA. joshua_chen@merck.com
authors.forename: Joshua
authors.initials: J
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Quan
authors.forename: Bruce
authors.initials: B
authors.lastname: Binkowitz
authors.forename: S Peter
authors.initials: SP
authors.lastname: Ouyang
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Shailendra
authors.initials: S
authors.lastname: Menjoge
authors.forename: Ekopimo
authors.initials: E
authors.lastname: Ibia
mesh_terms: D018849:Controlled Clinical Trials as Topic / Q000706:statistics & numerical data; D003625:Data Collection; D005843:Geography / Q000706:statistics & numerical data; D017408:Guidelines as Topic; D006801:Humans; D038622:Internationality; D015201:Meta-Analysis as Topic; D015337:Multicenter Studies as Topic / Q000379:methods / Q000706:statistics & numerical data; D015203:Reproducibility of Results; D012107:Research Design; D016896:Treatment Outcome