title: General guidance on exploratory and confirmatory subgroup analysis in late-stage clinical trials.
abstract: This article focuses on a broad class of statistical and clinical considerations related to the assessment of treatment effects across patient subgroups in late-stage clinical trials. This article begins with a comprehensive review of clinical trial literature and regulatory guidelines to help define scientifically sound approaches to evaluating subgroup effects in clinical trials. All commonly used types of subgroup analysis are considered in the article, including different variations of prospectively defined and post-hoc subgroup investigations. In the context of confirmatory subgroup analysis, key design and analysis options are presented, which includes conventional and innovative trial designs that support multi-population tailoring approaches. A detailed summary of exploratory subgroup analysis (with the purpose of either consistency assessment or subgroup identification) is also provided. The article promotes a more disciplined approach to post-hoc subgroup identification and formulates key principles that support reliable evaluation of subgroup effects in this setting.
authors.affiliation: a Center for Statistics in Drug Development, Quintiles , Overland Park , Kansas , USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Dmitrienko
authors.affiliation: b Clinical Statistics, Bayer HealthCare , Berlin , Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Muysers
authors.affiliation: c Clinical Statistics , Bayer HealthCare , Wuppertal , Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Fritsch
authors.affiliation: a Center for Statistics in Drug Development, Quintiles , Overland Park , Kansas , USA.
authors.forename: Ilya
authors.initials: I
authors.lastname: Lipkovich
mesh_terms: D015415:Biomarkers; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D006801:Humans; D012107:Research Design
chemical_list: D015415:Biomarkers
keywords: Biomarker evaluation; enrichment designs; regulatory guidance; subgroup analysis; subgroup identification