title: Weighted evidence approach of bridging study.
abstract: The ICH E5 Guidance facilitates the registration of medicine among ICH regions by recommending a framework for evaluating the impact of ethnic factors upon a medicine's effect. It further describes the use of bridging studies, when necessary, to allow extrapolation of foreign clinical data to a new region. Bridging studies are performed in a new region for medicines already approved in the original region. The conventional noninferiority criterion requires the treatment effect (adjusted for placebo) attained in the new region preserves a prespecified proportion of the treatment effect attained in the original region. Such a bridging criterion, however, is often impractical. Hsiao et al. (2007) proposed a Bayesian approach that borrows the strength of the original trial to establish the treatment effect in the bridging region through using a weighted prior distribution. The weight, however, is often difficult to prespecify. In this presentation, we consider the overall treatment effect by combining the weighted effects attained in the original and bridging regions. The maximum weight allowed to be placed on the estimate of bridging region in order to show a significant overall treatment effect represents the strength of the treatment effect in the bridging region. Regional approval will be evaluated either by comparing the weight estimate with the prespecified limit or by benefit-risk evaluation of the medicine. Sample size requirements for the approaches are derived. The simulation results of type I error rate and power for the proposed methods are given. An example illustrates the application of the proposed procedures.
authors.affiliation: Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. tsouhh@nhri.org.tw
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Tsou
authors.forename: Yi
authors.initials: Y
authors.lastname: Tsong
authors.forename: Jung-Tzu
authors.initials: JT
authors.lastname: Liu
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Dong
authors.forename: Yute
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000465:Algorithms; D002986:Clinical Trials as Topic / Q000379:methods / Q000706:statistics & numerical data; D003198:Computer Simulation; D016001:Confidence Intervals; D003625:Data Collection; D003627:Data Interpretation, Statistical; D005006:Ethnicity; D017408:Guidelines as Topic; 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; D012107:Research Design; D018401:Sample Size; D016896:Treatment Outcome