Bivariate isotonic design for dose-finding with ordered groups.

We consider the problem of dose-finding where subjects can be stratified into two populations with possibly different susceptibility to toxicity. The goal is to find the maximally tolerated dose for each population. We propose a non-parametric design for this problem. Toxicity is estimated using the bivariate isotonic regression estimator. The new design is compared with the two-sample continual reassessment method. Copyright (c) 2005 John Wiley & Sons, Ltd.