Design and Trial Operational Considerations for a Phase II Two-Stage Adaptive Trial

• Activity Number: 663
• Type: Topic Contributed
• Date/Time: Thursday, August 5, 2010 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Weili He*+ and Madhuja Mallick and Yevgen Tymofyeyev and James A. Bolognese
• Companies: Merck & Co., Inc. and Merck & Co., Inc. and Merck & Co., Inc. and Cytel Inc.
• Keywords: adaptive design trial ; Type I error ; sample size re-estimation ; futility check ; trial operation issues

Abstract

We design a two-stage adaptive design for the purposes of proof of concept and obtaining preliminary dose response information for a new chemical entity. Patients will be randomized to receive a high dose of test drug, placebo, and an active control during Stage I. During Stage II, a lower dose of test drug will be added in addition to the treatment arms in Stage I. Since the trial serves multiple purposes, we consider several design issues: a) assessment of futility, b) evaluation of assay sensitivity, and c) sample size re-estimation. We propose criteria for these evaluations. We consider and discuss the methods and the implications on the type I error rate. A simulation study evaluating the study design characteristics will be presented. Additionally, trial operation issues arise from the implementation of a complex adaptive design trial. We will describe the issues and the imple