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Dose‐Response Models for Correlated Multinomial Data from Developmental Toxicity Studies
Author(s) -
Zhu Y.,
Krewski D.,
Ross W. H.
Publication year - 1994
Publication title -
journal of the royal statistical society: series c (applied statistics)
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.205
H-Index - 72
eISSN - 1467-9876
pISSN - 0035-9254
DOI - 10.2307/2986259
Subject(s) - multinomial distribution , developmental toxicity , statistics , econometrics , mathematics , biology , pregnancy , gestation , genetics
SUMMARY Developmental anomalies induced by toxic chemicals may be identified by using laboratory experiments with rats and mice. This paper examines dose‐response models for correlated multinomial data arising in studies of developmental toxicity. A hierarchical probability structure is used to unify and extend previous methods of modelling correlated binary data arising in such studies. Generalized estimating equations in conjunction with an extended Dirichlet‐multinomial covariance function are used to estimate jointly the regression parameters in Weibull dose‐response models for both embryolethality and fetal malformations. Quadratic estimating equations are used to estimate the overdispersion (correlation) parameters. Maximum likelihood estimates based on a Dirichlet‐multinomial distribution are also computed for comparison. The modelling procedures proposed are illustrated through the analysis of data from a recent large scale study of the developmental toxicity of the herbicide 2,4,5‐trichlorophenoxyacetic acid.