title: Consideration of regional difference in design and analysis of multi-regional trials.
abstract: Clinical trial strategy, particularly in developing pharmaceutical products, has recently expanded to a global level in the sense that multiple geographical regions participate in the trial simultaneously under the same study protocol. The possible benefits of this strategy are obvious, at least from the cost and efficiency considerations. The challenges with this strategy are many, ranging from trial or data quality assurance to statistical methods for design and analysis of such trials. In many regulatory submissions, the presence of regional differences in the estimated treatment effect, whether they are different only in magnitude or in direction, often presents great difficulty in interpretation of the global trial results, particularly for the acceptability by the local regulatory authorities. This article presents a number of useful statistical analysis tools for exploration of regional differences and a method that may be worth consideration in designing a multi-regional clinical trial.
authors.affiliation: Division of Biometrics I, OB/CDER/FDA, Silver Spring, MD 20993-0002, USA. hsienming.hung@fda.hhs.gov
authors.forename: H M James
authors.initials: HM
authors.lastname: Hung
authors.forename: Sue-Jane
authors.initials: SJ
authors.lastname: Wang
authors.forename: Robert T
authors.initials: RT
authors.lastname: O'Neill
mesh_terms: D017277:Drug Approval / Q000706:statistics & numerical data; D005163:Factor Analysis, Statistical; D005843:Geography; D017408:Guidelines as Topic; D006801:Humans; D038622:Internationality; D015337:Multicenter Studies as Topic / Q000191:economics / Q000592:standards / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic; D017062:Small-Area Analysis