Semiparametric Bayesian joint modeling of a binary and continuous outcome with applications in toxicological risk assessment

Many dose-response studies collect data on correlated outcomes. For example, in developmental toxicity studies, uterine weight and presence of malformed pups are measured on the same dam. Joint modeling can result in more efficient inferences than independent models for each outcome. Most methods for joint modeling assume standard parametric response distributions. However, in toxicity studies, it is possible that response distributions vary in location and shape with dose, which may not be easily captured by standard models. To address this issue, we propose a semiparametric Bayesian joint model for a binary and continuous response. In our model, a kernel stick-breaking process prior is assigned to the distribution of a random effect shared across outcomes, which allows flexible changes in distribution shape with dose shared across outcomes. The model also includes outcome-specific fixed effects to allow different location effects. In simulation studies, we found that the proposed model provides accurate estimates of toxicological risk when the data do not satisfy assumptions of standard parametric models. We apply our method to data from a developmental toxicity study of ethylene glycol diethyl ether.

[1]  S. MacEachern,et al.  Bayesian Nonparametric Spatial Modeling With Dirichlet Process Mixing , 2005 .

[2]  Louise Ryan,et al.  Bivariate Latent Variable Models for Clustered Discrete and Continuous Outcomes , 1992 .

[3]  Marie Davidian,et al.  Conditional Estimation for Generalized Linear Models When Covariates Are Subject‐Specific Parameters in a Mixed Model for Longitudinal Measurements , 2004, Biometrics.

[4]  Anindya Roy,et al.  Nonparametric Bayesian Methods for Benchmark Dose Estimation , 2013, Risk analysis : an official publication of the Society for Risk Analysis.

[5]  Geert Molenberghs,et al.  A hierarchical modeling approach for risk assessment in developmental toxicity studies , 2006, Comput. Stat. Data Anal..

[6]  R. Kohn,et al.  Regression Density Estimation Using Smooth Adaptive Gaussian Mixtures , 2007 .

[7]  S. Chib,et al.  Bayesian analysis of binary and polychotomous response data , 1993 .

[8]  David B Dunson,et al.  A Bayesian Approach for Joint Modeling of Cluster Size and Subunit‐Specific Outcomes , 2003, Biometrics.

[9]  D. Dunson,et al.  Nonparametric Bayes Testing of Changes in a Response Distribution with an Ordinal Predictor , 2008, Biometrics.

[10]  D. Dunson,et al.  Bayesian latent variable models for clustered mixed outcomes , 2000 .

[11]  M. Pennell,et al.  Efficient Bayesian joint models for group randomized trials with multiple observation times and multiple outcomes , 2012, Statistics in medicine.

[12]  D. Dunson,et al.  Nonparametric Bayes Conditional Distribution Modeling With Variable Selection , 2009, Journal of the American Statistical Association.

[13]  M M Regan,et al.  Likelihood Models for Clustered Binary and Continuous Out comes: Application to Developmental Toxicology , 1999, Biometrics.

[14]  S. MacEachern,et al.  An ANOVA Model for Dependent Random Measures , 2004 .

[15]  J. E. Griffin,et al.  Order-Based Dependent Dirichlet Processes , 2006 .

[16]  C. Antoniak Mixtures of Dirichlet Processes with Applications to Bayesian Nonparametric Problems , 1974 .

[17]  Wesley O Johnson,et al.  Bayesian Nonparametric Nonproportional Hazards Survival Modeling , 2009, Biometrics.

[18]  Jason A. Duan,et al.  Generalized spatial dirichlet process models , 2007 .

[19]  K S Crump,et al.  A new method for determining allowable daily intakes. , 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[20]  H. Ishwaran,et al.  Markov chain Monte Carlo in approximate Dirichlet and beta two-parameter process hierarchical models , 2000 .

[21]  C. McCulloch Joint modelling of mixed outcome types using latent variables , 2008, Statistical methods in medical research.

[22]  D. Dunson,et al.  Kernel stick-breaking processes. , 2008, Biometrika.

[23]  T. Hanson,et al.  A class of mixtures of dependent tail-free processes. , 2011, Biometrika.

[24]  P. Müller,et al.  Bayesian Inference in Semiparametric Mixed Models for Longitudinal Data , 2010, Biometrics.

[25]  Kassandra M. Fronczyk,et al.  A Bayesian approach to the analysis of quantal bioassay studies using nonparametric mixture models , 2014, Biometrics.

[26]  A. Agresti,et al.  A Correlated Probit Model for Joint Modeling of Clustered Binary and Continuous Responses , 2001 .

[27]  T. Ferguson A Bayesian Analysis of Some Nonparametric Problems , 1973 .

[28]  Kassandra Fronczyk,et al.  A Bayesian Nonparametric Modeling Framework for Developmental Toxicity Studies , 2014 .