A new dose-finding design for bivariate outcomes.

Abstract

For some drugs, toxicity events lead to early termination of treatment before a therapeutic response is observed. That is, there are three possible outcomes: toxicity (therapeutic response unknown), therapeutic response without toxicity, and no response with no toxicity. The optimal dose is the dose that maximizes the probability of the joint event, response, and no toxicity. The optimal safe dose is the dose, from among the doses with toxicity rate less than the maximum tolerable level, that maximizes the probability of response and no toxicity. We present a new sequential design to maximize the number of subjects assigned in the neighborhood of the optimal safe dose in a dose-finding trial with two outcomes.