title: Empirical shrinkage estimator for consistency assessment of treatment effects in multi-regional clinical trials.
abstract: Multi-regional clinical trials have been widely used for efficient global new drug developments. Both a fixed-effect model and a random-effect model can be used for trial design and data analysis of a multi-regional clinical trial. In this paper, we first compare these two models in terms of the required sample size, type I error rate control, and the interpretability of trial results. We then apply the empirical shrinkage estimation approach based on the random-effect model to two criteria of consistency assessment of treatment effects across regions. As demonstrated in our computations, compared with the sample estimator, the shrinkage estimator of the treatment effect of an individual region borrowing information from the other regions is much closer to the estimator of the overall treatment effect, has smaller variability, and therefore provides much higher probability for demonstrating consistency. We use a multinational trial example with time to event endpoint to illustrate the application of the method.
authors.affiliation: Biostatistics and Programming, Sanofi, 55 Corporate Drive, Bridgewater, NJ 08807, U.S.A. hui.quan@sanofi-aventis.com
authors.forename: Hui
authors.initials: H
authors.lastname: Quan
authors.forename: Mingyu
authors.initials: M
authors.lastname: Li
authors.forename: Weichung Joe
authors.initials: WJ
authors.lastname: Shih
authors.forename: Soo Peter
authors.initials: SP
authors.lastname: Ouyang
authors.forename: Joshua
authors.initials: J
authors.lastname: Chen
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Peng-Liang
authors.initials: PL
authors.lastname: Zhao
mesh_terms: D001499:Bayes Theorem; D056808:Biostatistics; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D003692:Delayed-Action Preparations; D055808:Drug Discovery; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D008790:Metoprolol / Q000008:administration & dosage; D015233:Models, Statistical; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D011336:Probability; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D018401:Sample Size; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D008790:Metoprolol