Robust benchmark dose estimation using an infinite family of response functions

Abstract

ABSTRACTResearchers usually estimate benchmark dose (BMD) for dichotomous experimental data using a binomial model with a single response function. Several forms of response function have been proposed to fit dose–response models to estimate the BMD and the corresponding benchmark dose lower bound (BMDL). However, if the assumed response function is not correct, then the estimated BMD and BMDL from the fitted model may not be accurate. To account for model uncertainty, model averaging (MA) methods are proposed to estimate BMD averaging over a model space containing a finite number of standard models. Usual model averaging focuses on a pre-specified list of parametric models leading to pitfalls when none of the models in the list is the correct model. Here, an alternative which augments an initial list of parametric models with an infinite number of additional models having varying response functions has been proposed to estimate BMD for dichotomous response data. In addition, different methods for estimating BMDL based on the family of response functions are derived. The proposed approach is compared with MA in a simulation study and applied to a real dataset. Simulation studies are also conducted to compare the four methods of estimating BMDL.