• Mark Chang and Shein-Chung Chow.
• Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, USA. mark.chang@mpi.com
• J Biopharm Stat. 2005 Jan 1; 15 (4): 677-91.

AbstractIn recent years, the use of adaptive design methods based on accrued data of on-going trials have become very popular for dose response trials in early clinical development due to their flexibility (EMEA, 2002). In this paper, we developed a hybrid frequentist-Bayesian continual reassessment method (CRM) in conjunction with utility-adaptive randomization for clinical trial designs with multiple endpoints. The proposed hyperlogistic function family with multiple parameters gives users flexibility for probability modeling. CRM reassesses a dose-response relationship based on accrued data of the on-going trial, which allows investigators to make decisions based on a constantly updated dose-response model. The proposed utility-adaptive randomization for multiple-endpoint trials allows more patients to be assigned to superior treatment groups. The performance of the proposed method was examined in terms of its operating characteristics through computer simulations.

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