Comparison of Isotonic Designs for Dose-Finding.

We compare several decision rules for allocating subjects to dosages that are based on sequential isotonic estimates of a monotone dose-toxicity curve. We conclude that the decision rule in which the next assignment is to the dose having probability of toxicity closest to target does not work well. The best rule in our comparison is given by the cumulative cohort design. According to this design, the dose for the next subject is decreased, increased, or repeated depending on the distance between the estimated toxicity rate at the current dose and the target quantile.