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Testing Threshold and Hormesis in a Random Effects Dose‐Response Model Applied to Developmental Toxicity Data
Author(s) -
Hunt D.,
Rai S. N.
Publication year - 2005
Publication title -
biometrical journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 63
eISSN - 1521-4036
pISSN - 0323-3847
DOI - 10.1002/bimj.200310129
Subject(s) - hormesis , threshold model , random effects model , statistics , toxicology , biology , mathematics , medicine , meta analysis , oxidative stress
Abstract Here we describe a random effects threshold dose‐response model for clustered binary‐response data from developmental toxicity studies. For our model we assume that a hormetic effect occurs in addition to a threshold effect. Therefore, the dose‐response curve is based on two components: relationships below the threshold (hormetic u‐shaped model) and those above the threshold (logistic model). In the absence of hormesis and threshold effects, the estimation procedure is straightforward. We introduce score tests that are derived from a random effects hormetic‐threshold dose‐response model. The model and tests are applied to clustered binary data from developmental toxicity studies of animals to test for hormesis and threshold effects. We also compare the score test and likelihood ratio test to test for hormesis and threshold effects in a simulated study. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)