Adaptive Clinical Trial Design and Simulation of a Phase II Migraine Headache Proof-of-Concept Study Using Adaptive Design Explorer

• Activity Number: 516
• Type: Contributed
• Date/Time: Wednesday, August 3, 2011 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Inna Perevozskaya*+ and Jihao Zhou and Pamela D. Garzone and Phil Stanley and John P. Huggins and Gilbert Y. Wong and Ronald G. Menton
• Companies: Pfizer Inc. and Pfizer Inc. and Pfizer Inc. and Pfizer Inc. and Pfizer Inc. and Pfizer Inc. and Pfizer Inc.
• Keywords: adaptive design ; experimental design ; clinical trial ; dose-response ; proof of concept ; migraine headache

Abstract

As advocated by the Critical Path Initiative, adaptive designs have received a great deal of attention. The recent FDA guidance on adaptive clinical trials seems to favor their use for early phase trials where scientific rigor is blended with certain regulatory flexibility. However, lack of adaptive trial design software poses a major challenge for their implementation in the industry. Here we report some of our recent experiences in building up adaptive designs and simulations for an early clinical study for a migraine headache compound using the software Adaptive Design Explorer. The primary efficacy endpoint for this study is the change from baseline in the frequency of migraine periods over 28 days. Several adaptive design types utilizing various dose-response models (e.g. logistic and Emax model functions, non-linear dynamic model (NDLM), etc.) are chosen and compared to select the best performing design. Number of interim analyses and other design parameters are optimized as well. The best performing designs are then compared to a traditional parallel group design in order to quantify the efficiency of adaptive designs.