Model-Based Bayesian Adaptive Dose-Finding Designs for a Phase II Trial

Abstract

We describe the planning of a dose-finding study for a compound currently in early Phase II clinical development. Data from a trial with the same primary endpoint are available for a marketed drug that has the same pharmacological mechanism, which provides strong prior information for some characteristics of the new compound. We develop and evaluate informative model-based Bayesian analyses. We also evaluate adaptive designs that change the allocation of patients to doses after an interim analysis. The performance of the model-based Bayesian analyses applied to the adaptive designs is compared to the performance of corresponding analyses applied to a nonadaptive design. The performance is also compared to model-based maximum likelihood estimation and simple pairwise comparison of treatment group means applied to the nonadaptive design to assess the contributions of the model, Bayesian prior distribution, and adaptive designs to improvements in decision and estimation performance.

Keywords: :

• Bayesian analysis
• Clinical trial
• Dose-finding
• Emax modeling
• Phase II