Multiplicity considerations in subgroup analysis.

This paper deals with the general topic of subgroup analysis in late-stage clinical trials with emphasis on multiplicity considerations. The discussion begins with multiplicity issues arising in the context of exploratory subgroup analysis, including principled approaches to subgroup search that are applied as part of subgroup exploration exercises as well as in adaptive biomarker-driven designs. Key considerations in confirmatory subgroup analysis based on one or more pre-specified patient populations are reviewed, including a survey of multiplicity adjustment methods recommended in multi-population phase III clinical trials. Guidelines for interpretation of significant findings in several patient populations are introduced to facilitate the decision-making process and achieve consistent labeling across development programs.