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A new threshold dose‐response model including random effects for data from developmental toxicity studies
Author(s) -
Hunt Daniel L.,
Rai Shesh N.
Publication year - 2005
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1092
Subject(s) - threshold model , statistics , random effects model , mathematics , developmental toxicity , correlation , litter , biology , medicine , pregnancy , meta analysis , gestation , geometry , agronomy , genetics
Usually, in teratological dose finding studies, there are not only threshold effects but also extra variations that cannot be accounted for by the beta‐binomial model alone. The beta‐binomial model assumes correlation between fetuses in the same litter. The general random effect threshold (RE) model allows the additional variability that arises due to correlation and between litter variability to be modeled, in combination with threshold in the model. The goal of this research was to investigate a threshold dose‐response model with random effects (RE) to model the variability that exists between litters of animals in studies of toxic agents. Data from a developmental toxicity study of a toxic agent were analysed, using the proposed RE threshold dose‐response model, which is an extension of logit in form. Also, an approximate likelihood function was used to derive parameter estimates from this model, and tests were performed to determine the significance of the model parameters, in particular, the RE parameter. A simulation study was conducted to assess the performance of the RE threshold model in estimating the model parameters. Copyright © 2005 John Wiley & Sons, Ltd.