title: Designing dose finding studies with an active control for exponential families.
abstract: In a recent paper Dette et al. (2014) introduced optimal design problems for dose finding studies with an active control. These authors concentrated on regression models with normal distributed errors (with known variance) and the problem of determining optimal designs for estimating the smallest dose, which achieves the same treatment effect as the active control. This paper discusses the problem of designing active-controlled dose finding studies from a broader perspective. In particular, we consider a general class of optimality criteria and models arising from an exponential family, which are frequently used analyzing count data. We investigate under which circumstances optimal designs for dose finding studies including a placebo can be used to obtain optimal designs for studies with an active control. Optimal designs are constructed for several situations and the differences arising from different distributional assumptions are investigated in detail. In particular, our results are applicable for constructing optimal experimental designs to analyze active-controlled dose finding studies with discrete data, and we illustrate the efficiency of the new optimal designs with two recent examples from our consulting projects.
authors.affiliation: Ruhr-Universität Bochum, Fakultät für Mathematik, 44780 Bochum, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Dette
authors.affiliation: Ruhr-Universität Bochum, Fakultät für Mathematik, 44780 Bochum, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Kettelhake
authors.affiliation: Statistical Methodology, Novartis Pharma AG, 4002 Basel, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Bretz
keywords: active control; dose estimation; dose response; optimal designs