Kupper L L, Portier C, Hogan M D, Yamamoto E
Biometrics. 1986 Mar;42(1):85-98.
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.
为了生成致畸风险估计值，将剂量反应模型拟合到涉及同窝仔畜的致畸学数据上，作为风险估计“安全系数”方法的一种潜在替代方法，正受到越来越多的关注。在本文中，我们利用贝塔二项分布来引入不同程度的窝内相关性，并且为了说明目的，考虑一个逻辑剂量反应模型，该模型将风险的对数几率描述为ln(剂量)的线性函数。通过模拟研究了截距和斜率的最大似然估计量的偏差和（精确和渐近）方差，作为窝内相关结构的函数。
