Improving Early Development of Infectious Disease Treatments and Vaccines via Adaptive Designed Trials

• Activity Number: 534
• Type: Invited
• Date/Time: Wednesday, August 6, 2014 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): James A. Bolognese*+
• Companies: Cytel
• Keywords: adaptive design ; simulation ; combination treatment ; infectious disease ; vaccine ; early phase drug development

Abstract

Development of vaccines and treatments for an infectious disease sometimes, if not often, involve choosing the best combination of drugs or vaccine entities as well as the best regimen for administration. Traditional trial designs to address multiple combinations of compound/dose/regimen in early phase infectious disease trials focus on bacteriocidal effects and in vaccine trials focus on titer response. These are followed by large Phase 2b or 3 efficacy trials in which 1 or a few of the most promising combinations are studied. The large early Phase trials needed to assess the multiple combinations lead to huge investments of money, human resources, and time. Often sample sizes are kept small to limit the expense and time, and lead to inferior treatment choices. In addition, many subjects will receive inferior treatments since only a small subset will be administered the optimal one(s). Adaptive designs offer opportunity to reduce the number of subjects needed for these sorts of trials since they can focus assignment to treatments showing the best responses. Simulation studies were carried out to compare the traditional versus adaptive design approach in the early phase comb