Optimal Two-Stage Phase II Design Utilizing Partial Information for Long-Term Endpoints

• Activity Number: 130
• Type: Contributed
• Date/Time: Monday, August 2, 2010 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Bo Huang*+ and Enayet Talukder and Neal Thomas
• Companies: Pfizer Inc. and Pfizer Inc. and Pfizer Inc.
• Keywords: Clinical Trial ; Optimal Design ; Interim Analysis ; Adaptive Design ; Time-to-Event

Abstract

Phase II trials are often designed with an interim analysis so they can be stopped early if a drug is ineffective. One problem with interim analysis is incomplete follow-up for some patients. Standard designs such as Simon(1989) require suspension of accrual until patient follow-up is completed. Case and Morgan (2003) proposed a two-stage design that does not suspend accrual when the interim analysis is conducted. We review that design and propose modifications to ensure protection of Type I error rate and improved robustness to non-optimal conditions likely to be encountered in practice. Optimal designs for the broader randomized controlled trials are also proposed and discussed. Software (R package) is described to create the optimal designs and easily simulate their properties to check asymptotic approximations and robustness of the performance of the designs.