Bayesian Hierarchical Analysis for Multiple Health Endpoints in a Toxicity Study

Abstract

Bayesian hierarchical models are built to fit multiple health endpoints from a dose-response study of a chemical contaminant, perchlorate. Perchlorate exposure results in iodine uptake inhibition in the thyroid, with health effects manifested by changes in blood hormone concentrations and histopathological effects on the thyroid. We propose empirical models to fit blood hormone concentration and thyroid histopathology data for rats exposed to perchlorate in the 90-day study of Springborn Laboratories Inc. (1998), based upon a mechanistic model derived from the assumed toxicological relationships between dose and the various endpoints. All of the models are fit in a Bayesian framework, and predictions about each endpoint in response to dose are simulated based on the posterior predictive distribution. A hierarchical model tries to exploit possible similarities between different combinations of sex and exposure duration, and it allows us to produce more stable estimates of dose-response curves. We also illustrate how the Bayesian model specification allows us to address additional questions that arise after the analysis.