title: Unified additional requirement in consideration of regional approval for multiregional clinical trials.
abstract: To speed up the process of bringing a new drug to the market, more and more clinical trials are being conducted simultaneously in multiple regions. After demonstrating the overall drug's efficacy across regions, the regulatory and drug sponsor may also want to assess the drug's effect in specific region(s). Most of the recent approaches imposed a uniform criterion to assess the consistency of treatment effects between the interested region(s) and the entire study population regardless of the number of regions in multiregional clinical trials (MRCT). As a result, the needed sample size to achieve the desired probability of satisfying the regional requirement could be huge and implausible for the trial sponsors to implement. In this paper, we propose a unified additional requirement for regional approval by differing the parameters in the additional requirement depending on the number of planned regions. In particular, the values of the parameters are determined by a reasonable sample size increase with the desired probability satisfying the additional requirement. Considering the practicality of the global trial or sample size increase, we recommend specific values of the parameters for a different number of planned regions. We also introduce the assurance probability curve to evaluate the performance of different regional requirements.
authors.affiliation: a Takeda Pharmaceuticals, Cambridge, Massachusetts , USA.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Teng
authors.affiliation: b Division of Biometrics III, Center for Drug Evaluation and Research, US Food and Drug Administration , Silver Spring , Maryland , USA.
authors.forename: Yeh-Fong
authors.initials: YF
authors.lastname: Chen
authors.affiliation: c Department of Biostatistics, Boston University , Boston , Massachusetts , USA.|d Veristat, Southborough , Massachusetts , USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Chang
mesh_terms: D017277:Drug Approval / Q000379:methods / Q000706:statistics & numerical data*; D006801:Humans; D015337:Multicenter Studies as Topic / Q000379:methods / Q000706:statistics & numerical data*; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*; D018401:Sample Size; D016896:Treatment Outcome
keywords: Assurance probability curve; multiregional clinical trials; number of regions; regional requirement; sample size increase