On the Use of Nonparametric Curves in Phase I Trials with Low Toxicity Tolerance

Gasparini and Eisele (2000, Biometrics56, 609–615) propose a design for phase I clinical trials during which dose allocation is governed by a Bayesian nonparametric estimate of the dose-response curve. The authors also suggest an elicitation algorithm to establish vague priors. However, in situations where a low percentile is targeted, priors thus obtained can lead to undesirable rigidity given certain trial outcomes that can occur with a nonnegligible probability. Interestingly, improvement can be achieved by prescribing slightly more informative priors. Some guidelines for prior elicitation are established using a connection between this curve-free method and the continual reassessment method.