Incorporating Individual and Collective Ethics Into Phase I Cancer Trial Designs

Abstract

A general framework is proposed for Bayesian model based designs of Phase I cancer trials, in which a general criterion for coherence (Cheung, 2005, Biometrika 92, 863-873) of a design is also developed. This framework can incorporate both "individual" and "collective" ethics into the design of the trial. We propose a new design that minimizes a risk function composed of two terms, with one representing the individual risk of the current dose and the other representing the collective risk. The performance of this design, which is measured in terms of the accuracy of the estimated target dose at the end of the trial, the toxicity and overdose rates, and certain loss functions reflecting the individual and collective ethics, is studied and compared with existing Bayesian model based designs and is shown to have better performance than existing designs.