Bayesian semiparametric analysis of developmental toxicology data.
Modeling of developmental toxicity studies often requires simple parametric analyses of the dose-response relationship between exposure and probability of a birth defect but poses challenges because of nonstandard distributions of birth defects for a fixed level of exposure. This article is motivated by two such experiments in which the distribution of the outcome variable is challenging to both the standard logistic model with binomial response and its parametric multistage elaborations. We approach our analysis using a Bayesian semiparametric model that we tailored specifically to developmental toxicology studies. It combines parametric dose-response relationships with a flexible nonparametric specification of the distribution of the response, obtained via a product of Dirichlet process mixtures approach (PDPM). Our formulation achieves three goals: (1) the distribution of the response is modeled in a general way, (2) the degree to which the distribution of the response adapts nonparametrically to the observations is driven by the data, and (3) the marginal posterior distribution of the parameters of interest is available in closed form. The logistic regression model, as well as many of its extensions such as the beta-binomial model and finite mixture models, are special cases. In the context of the two motivating examples and a simulated example, we provide model comparisons, illustrate overdispersion diagnostics that can assist model specification, show how to derive posterior distributions of the effective dose parameters and predictive distributions of response, and discuss the sensitivity of the results to the choice of the prior distribution.
Dominici
F
F
Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland 21205, USA. fdominic@jhsph.edu
Parmigiani
G
G
D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000633:toxicity; D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D001499:Bayes Theorem; D001699:Biometry; D003627:Data Interpretation, Statistical; D004051:Diethylhexyl Phthalate / Q000633:toxicity; D005260:Female; D015233:Models, Statistical; D011247:Pregnancy; D012680:Sensitivity and Specificity; D018600:Teratology / Q000706:statistics & numerical data*; D014116:Toxicology / Q000706:statistics & numerical data*
D015085:2,4,5-Trichlorophenoxyacetic Acid; D004051:Diethylhexyl Phthalate