Ritz, Christian4; Gerhard, Daniel3; Hothorn, Ludwig A.3
1 Administration, Department of Chemistry, Faculty of Science, Københavns Universitet2 Paediatric and International Nutrition, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet3 Leibniz Universität4 Paediatric and International Nutrition, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
This article develops a framework for benchmark dose estimation that allows intrinsically nonlinear dose-response models to be used for continuous data in much the same way as is already possible for quantal data. This means that the same dose-response model equations may be applied to both continuous and quantal data, facilitating benchmark dose estimation in general for a wide range of candidate models commonly used in toxicology. Moreover, the proposed framework provides a convenient means for extending benchmark dose concepts through the use of model averaging and random effects modeling for hierarchical data structures, reflecting increasingly common types of assay data. We illustrate the usefulness of the methodology by means of a cytotoxicology example where the sensitivity of two types of assays are evaluated and compared. By means of a simulation study, we show that the proposed framework provides slightly conservative, yet useful, estimates of benchmark dose lower limit under realistic scenarios.
Statistics in Biopharmaceutical Research, 2013, Vol 5, Issue 1, p. 79-90