MOST: Multi-Stage Optimal Sequential Trial Design for Phase II Clinical Trials with Biomarker Subgroups

• Activity Number: 85
• Type: Contributed
• Date/Time: Sunday, August 9, 2015 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Yong Zang*
• Companies: Florida Atlantic University
• Keywords: clinical trial ; phase II design ; molecularly targeted agent ; power and type I error ; sequential design

Abstract

Many molecularly targeted agents have been developed as new anticancer treatments. Although the primary goal of a phase II clinical trial for the molecularly targeted agent is to detect the possible treatment eeffect within the marker positive group, it is often present that we are also interested in exploring the uncertainty of the treatment benefit for the marker negative group. For this purpose, in this article, we propose two phase II sequential clinical trial designs to detect the eeffectiveness of the molecularly targeted agents for both the marker positive and marker negative groups by adopting the ordinal relationship between these two groups. The sequential designs test the marker positive group first and are followed by a possible sequential test for the marker negative group. If a molecularly targeted agent is rejected by the marker positive group, it is further rejected by the marker negative group and the trial is terminated to guarantee the individual ethics for the marker negative patients. We also propose a novel computing algorithm to find the optimal design parameters of the proposed sequential designs fast and eefficiently.