B0668
Title: Optimal designs for identifying alert concentrations
Authors: Kirsten Schorning - Technical University Dortmund (Germany) [presenting]
Kathrin Moellenhoff - University of Cologne, Faculty of Medicine and University Hospital, Cologne, Germany (Germany)
Abstract: The determination of alert concentrations, where a pre-specified threshold of the response variable is exceeded, is an important goal of concentration-response studies. Recently, several model-based testing procedures were developed that provide the identification of alerts at concentrations, which were not measured during the study. These model-based approaches are based on the fits of nonlinear concentration-response curves and therefore their quality strongly depends on the set of concentrations at which observations were taken. The optimal design problem is addressed for the identification of alert concentrations in order to improve these model-based testing procedures with respect to their power. Consequently, an optimal design minimizes the maximum variance of the estimator of potential alert concentration. Optimal design theory (equivalence theorem, efficiency bounds) is developed for this design problem and the results are illustrated in several examples identifying the alert concentration under the assumption of different dose-response relationships. In particular, it is demonstrated within a simulation study that using the optimal design results in more powerful tests for identifying alerts than using other commonly used non-optimal designs.
