The Use of Adaptive Designs in Antiviral Drug Development

• Activity Number: 324
• Type: Contributed
• Date/Time: Tuesday, August 11, 2015 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Fraser Smith* and Karen Qi
• Companies: FDA/CDER/OTS/OB/DBIV and FDA/CDER/OTS/OB/DBIV
• Keywords: adaptive designs ; antiviral drug development ; conditional power ; sample size re-estimation ; HIV ; clinical trials

Abstract

Adaptive Designs have been used in phase II trials to select an optimal dose and dosage regimen, primary efficacy endpoint and targeted subgroups for further evaluation based on a comparison of the short-term antiviral activity, safety and tolerability. Adaptive designs are typically used for increasing the sample size after performing an interim analysis in confirmatory clinical trials. A dialogue between the sponsor and the FDA regarding prospective adaptive designs can begin as early as during an end of phase IIa meeting or during the planning of pivotal phase III trials. An example of an adaptive design using conditional power calculations for sample size re-estimation in HIV clinical trials will be presented. Adaptive design considerations used to plan further phase II and phase III clinical trials reviewed by the Division of Antiviral Products at FDA/CDER will also be discussed.