Application of the continual reassessment method to a phase I dose-finding trial in Japanese patients: East meets West.

After cancer-related phase I dose-finding trials are completed in Western countries, further phase I trials are often conducted to determine recommended doses (RDS) for Japanese patients. This may be due to concerns about possible differences in treatment tolerability between Caucasians and Japanese. In most of these, a conventional '3 +3' cohort study design is used in making dose escalation decisions, possibly due to its relatively easy implementation. Since its proposal by O'Quigleybiet al. (1990; Biometrics, 46:33-48), the continual reassessment method (CRM) has been used increasingly in cancer-related phase I dose-finding studies as an alternative to '3 +3' designs. One of the principal advantages of applying a Bayesian CRM may be the utilization of all available prior information to estimate RDS through prior distributions that are assumed for model parameters representing the dose-toxicity relationship. In this paper, we present an application of the Bayesian CRM to a phase I dose-finding study in Japanese patients with advanced breast cancer using an informative prior elicited from clinical investigators. In some settings, it may be appropriate to use an informative prior that reflects the accurate and comprehensive previous knowledge of clinical investigators. On the other hand, for a model-based Bayesian outcome-adaptive clinical trial, it is necessary to establish sufficiently vague priors so that accumulating data dominate decisions as the amount of observed data increases. Thus, we retrospectively investigated the relative strength of the prior using a recently proposed method to compute a prior effective sample size.