Adaptive Designs for Confirmatory Clinical Trials with Subgroup Selection

Abstract

Growing interest in stratified medicine is leading to increasing importance of subgroup analyses in confirmatory clinical trials. Conventionally, confirmatory clinical trials either focus on a subgroup identified in advance or assess subgroup effects once the trial is completed. The focus of this article is methodology for adaptive clinical trials that both identify whether a treatment is particularly effective in a predefined subgroup, potentially enabling alteration of recruitment, and assess the effectiveness in the subgroup and/or whole population. Methods for such adaptive trials are described and compared, and the logistical and regulatory issues associated with such approaches are discussed.

Key Words:

• Adaptive signature design
• Stratified medicine
• Subgroup analysis
• Targeted therapy

ACKNOWLEDGMENTS

The authors are grateful to two anonymous referees for their helpful comments on an earlier draft of this article.