Hierarchical Bayesian Benchmark Dose Analysis

Abstract

An important objective in statistical risk assessment is estimation of minimum exposure levels, called Benchmark Doses (BMDs) that induce a pre-specified Benchmark Response (BMR) in a target population. Established inferential approaches for BMD analysis typically involve one-sided, frequentist confidence limits, leading in practice to what are called Benchmark Dose Lower Limits (BMDLs). Appeal to hierarchical Bayesian modeling and credible limits for building BMDLs is far less developed, however. Indeed, for the few existing forms of Bayesian BMDs, informative prior information is seldom incorporated. Here, a new method is developed by using reparameterized quantal-response models that explicitly describe the BMD as a target parameter. This potentially improves the BMD/BMDL estimation by combining elicited prior belief with the observed data in the Bayesian hierarchy. Besides this, the large variety of candidate quantal-response models available for applying these methods, however, lead to questions of model adequacy and uncertainty. Facing this issue, the Bayesian estimation technique here is further enhanced by applying Bayesian model averaging to produce point estimates and (lower) credible bounds. Implementation is facilitated via a Monte Carlo-based adaptive Metropolis (AM) algorithm to approximate the posterior distribution. Performance of the method is evaluated via a simulation study. An example from carcinogenicity testing illustrates the calculations.