Testing threshold and hormesis in a random effects dose-response model applied to developmental toxicity data.
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.
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Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
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D000818:Animals; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D015509:Developmental Biology / Q000379:methods; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004056:Differential Threshold; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D047109:Fetal Development / Q000187:drug effects*; D007928:Lethal Dose 50; D016013:Likelihood Functions; D051379:Mice; D008954:Models, Biological; D015233:Models, Statistical; D019055:No-Observed-Adverse-Effect Level; D016019:Survival Analysis; D018675:Toxicity Tests / Q000379:methods*
D004051:Diethylhexyl Phthalate