Evaluation of Design Parameters for an Adaptive Seamless Phase 2b/3 Trial

• Activity Number: 221
• Type: Topic Contributed
• Date/Time: Monday, August 2, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Susan Y. Zhou*+ and Greg Soon and Xiao Ding and JungYeon Park and EunYoung Kim and Sue-Jane Wang
• Companies: CDER/FDA and CDER/FDA and CDER/FDA and CDER/FDA and CDER/FDA and FDA
• Keywords: adaptive seamless phase 2b/3 trial ; HIV-1 drug ; short-term efficacy endpoint ; long-term efficacy endpoint ; meta-analysis ; Missing

Abstract

Currently, an adaptive seamless Phase 2b/3 trial (ASPT) comparing the efficacy and safety of two doses of a new HIV-1 drug to a comparator HIV-1 drug was pursued. The design parameters include a short-term (ST) efficacy endpoint (EE) for dose confirmation and a long-term efficacy endpoint (LTEE) for regulatory purposes (Stallard and Todd, 2005), and an additional LTEE to formulate data structures. To ensure the quality of study design, simulation studies were performed to evaluate the type I/II errors. We derived formulae for the correlation coefficient of the originally defined EEs, and verified the adequacy of the proposed design parameters. Employing historical data, we conducted meta-analyses to model the designed parameters and predicted the treatment differences for selected scenarios. Research findings and the variability in the design parameters of the ASPT will be discussed.