title: Designing Issues in Confirmatory Adaptive Population Enrichment Trials.
abstract: Adaptive population enrichment designs enable the data-driven selection of one or more pre-specified subpopulations in an interim analysis, and the confirmatory proof of efficacy in the selected subset at the end of the trial. Sample size reassessment and other adaptive design changes can be performed as well. Strong control of the experimentwise Type I error rate is guaranteed by use of the combination testing principle together with the closed testing argument. In this paper the general methodology and designing issues when planning such a design are reviewed. It is shown how to derive overall confidence intervals and p-values. Criteria for assessing the operating characteristics of these designs are given, and the application is illustrated by examples.
authors.affiliation: a Aptiv Solutions , Reston , Virginia , USA.
authors.forename: Gernot
authors.initials: G
authors.lastname: Wassmer
authors.forename: Vlad
authors.initials: V
authors.lastname: Dragalin
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data*; D006801:Humans; D012107:Research Design / Q000706:statistics & numerical data*; D018401:Sample Size
keywords: Adaptive design; Clinical trials; Group sequential tests; Population enrichment; Subgroup selection