Likelihood models for clustered binary and continuous outcomes: Application to developmental toxicology
Likelihood models for clustered binary and continuous outcomes: Application to developmental toxicology
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DOI：
10.1111/j.0006-341x.1999.00760.x
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发表时间：
1999-09-01
期刊：
影响因子：
1.9
通讯作者：
Catalano, PJ
中科院分区：
文献类型：
--
作者：
Regan, MM;Catalano, PJ
在发育毒理学方面，正在积极采用基于剂量-反应模型和定量风险评估的方法。在活胎中，主要关注畸形和胎仔体重减轻的存在，但通常情况下，在适当解释窝内聚类的同时，单独表征每种结局的剂量-反应关系。联合对结局进行建模，允许与剂量的不同关系，同时纳入胎儿与结局之间的相关性。可能更合适。我们提出了一个基于似然的模型，它是一个相关的概率模型的扩展，将连续的结果。我们的模型保持了一个边际剂量-反应解释的个人结果，同时考虑到对单个胎儿的结果之间的相关性和那些由于聚类。畸形和低出生体重的联合风险可以直接估计。这种方法特别适合于作为定量风险评估的一部分来估计安全剂量水平。
In developmental toxicology, methods based on dose-response modeling and quantitative risk assessment are being actively pursued. Among live fetuses, the presence of malformations and reduction in fetal weight are of primary interest, but ordinarily, the dose-response relationships are characterized in each of the outcomes separately while appropriately accounting for clustering within litters. Jointly modeling the outcomes, allowing different relationships with dose while incorporating the correlation between the fetuses and the outcomes. may be more appropriate. We propose a likelihood-based model that is an extension of a correlated probit model to incorporate continuous outcomes. Our model maintains a marginal dose-response interpretation for the individual outcomes while taking into account both the correlations between outcomes on an individual fetus and those due to clustering. The joint risk of malformation and low birth weight can then be estimated directly. This approach is particularly well suited to estimating safe dose levels as part of quantitative risk assessment.