Abstract

Following the introduction of the continual reassessment method by OQuigley, Pepe and Fisher, there has been considerable interest in formal statistical procedures for phase I dose-finding studies. The great majority of published accounts relate to cancer patients treated once with a single dose of the test drug who return a single binary observation concerning the incidence of toxicity. However, most phase I dose-finding studies are not of such a simple form. Drugs being developed for milder conditions than cancer are usually first tested in healthy volunteers who participate in multiple dosing periods, returning a continuous pharmacokinetic response each time.

This talk will describe Bayesian decision procedures which have been developed for such dose-finding studies in healthy volunteers. The principles behind the approach will be described and an evaluation of its properties presented. An account will be given of an implementation of the approach in a study conducted in Scandinavia. Generalisation to studies in which more than one response is used will also be discussed.