Biomarker-Defined Subgroup Selection Adaptive Design for Phase III Confirmatory Trial

• Activity Number: 322 - Data-Driven Patient Management in the Era of Precision Medicine - from Discovery, Diagnostics, to Therapeutics
• Type: Invited
• Date/Time: Tuesday, July 31, 2018 : 10:30 AM to 12:20 PM
• Sponsor: Council of Chapters
• Author(s): Rui Tang* and Xiaoye Ma and Hui Yang
• Companies: Shire and University of Minnesota and Amgen Inc.
• Keywords: Adaptive Designs; biomarker ; Bayesian Predictive Power; oncology; personalized medicine ; clinical trials

Abstract

In the era of precision medicine, biomarkers play an important role in personalized medicine to determine strategies for drug evaluation and treatment selection. Adaptive enrichment designs have been proposed with interim decision rules to select a biomarker-defined subpopulation to optimize study performance. In this session, I will discuss the statistical challenge of application of biomarker subgroup selection in trial design perspective and how to optimize design to support the clinical trial to maximize the overall probability of success. With a group-sequential design as a reference, the performance of several proposed adaptive designs are evaluated and compared under various scenarios (e.g., sample size, study power, enrichment effects) where type-I-error rates are well controlled through closed testing procedures and where subpopulation selections are based upon the predictive probability of trial success. The suitable designs will be discussed and compared through simulation illustration. A paper of our work has been recently published in the journal of Statistics in Biosciences.