Practical Enhancements to the Adaptive Signature Type of Design

• Activity Number: 330
• Type: Topic Contributed
• Date/Time: Tuesday, August 5, 2014 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Jonathan Denne*+ and Adarsh Joshi and Lei Shen and Peigang Li and Hollins Showalter and Eric Nantz
• Companies: Eli Lilly and Company and Gilead and Eli Lilly and Company and Eli Lilly and Company and Eli Lilly and Company and Eli Lilly and Company
• Keywords: biomarkers ; oncology ; two-stage ; adaptive ; randomization

Abstract

Because of the complexity of cancer biology, often the target pathway is not well understood at the time that the Phase III trials are initiated. Friedlin and Simon (2005) proposed a two-stage trial design for identifying a subgroup of interest in a learn stage, based on one or more baseline biomarkers, and then subsequently confirming it in a confirmation stage. We discuss some practical aspects of this type of design and describe an enhancement to this approach that can be built into the study randomization to increase the robustness of the evaluation, as well as statistical considerations in allocating patients to the learn stage versus the confirm stage.