Performance Measures in Dose-Finding Experiments

Abstract

In the first phase of pharmaceutical development, and assuming that the probability of positive response increases with dose, the main statistical goal is to estimate a percentile of the dose–response function for a given target value (Formula presented.). We compare the Maximum Likelihood and centred isotonic regression estimators of the target dose and we discuss several performance criteria to assess inferential precision, the amount of toxicity exposure and the trade-off between them for a set of some exemplary adaptive designs. We compare these designs using graphical tools. Several scenarios are considered using simulation, including the use of several start-up rules, the change of slope of the dose-toxicity function at the target dose and also different theoretical models, as logistic, normal or skew-normal distribution functions.