The impact of litter effects on dose-response modeling in teratology.
The fitting of dose-response models to teratology data involving littermates in order to generate estimates of teratogenic risk is receiving increasing attention as a potential alternative to the "safety-factor" approach to risk estimation. In this paper, we utilize the beta-binomial distribution to introduce varying degrees of intralitter correlation, and, for purposes of illustration, consider a logistic dose-response model that describes the logit of risk as a straight-line function of ln(dose). The biases and (exact and asymptotic) variances of the maximum likelihood estimators of the intercept and slope are studied by simulation as a function of the intralitter correlation structure.
D000818:Animals; D001699:Biometry; D004305:Dose-Response Relationship, Drug; D005260:Female; D008098:Litter Size; D008954:Models, Biological; D011247:Pregnancy; D012107:Research Design; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens