Dose-response modeling of continuous endpoints
Dose-response modeling of continuous endpoints
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DOI：
10.1093/toxsci/66.2.298
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发表时间：
2002-04-01
影响因子：
3.8
通讯作者：
Slob, W
中科院分区：
文献类型：
--
作者：
Slob, W
本文介绍了一系列（嵌套）剂量-反应模型，可用于描述作为剂量函数的任何连续终点的变化。可以使用似然比检验作为标准来选择来自该模型家族的成员，以防止过度参数化。拟议的方法提供了一个正式的模型选择方法，和一个透明的方式来评估基准剂量。除了一些自然的约束，模型表达式遵循一个明显的方式量化人口之间的敏感性差异。因此，通过将两种性别的数据合并到同一分析中，可以有效地分析与两种性别相关的剂量-反应数据，即使两种性别对所研究的化合物的敏感性不同。敏感性差异的概念与风险评估中使用的评估因子密切相关。因此，如果可以获得关于要比较的人口的数据，这些模型可直接用于估计这些因素。这些信息对于违约评估因子的进一步验证或调整以及告知概率风险评估中的分布评估因子是有价值的。真实的数据集说明了所提出的方法的各种应用。
A family of (nested) dose-response models is introduced herein that can be used for describing the change in any continuous endpoint as a function of dose. A member from this family of models may be selected using the likelihood ratio test as a criterion, to prevent overparameterization. The proposed methodology provides for a formal approach of model selection, and a transparent way of assessing the benchmark dose. Apart from a number of natural constraints, the model expressions follow from an obvious way of quantifying differences in sensitivity between populations. As a consequence, dose-response data that relate to both sexes can be efficiently analyzed by incorporating the data from both sexes in the same analysis, even if the sexes are not equally sensitive to the compound studied. The idea of differences in sensitivity is closely related to the assessment factors used in risk assessment. Thus, the models are directly applicable to estimating such factors, if data concerning populations to be compared are available. Such information is valuable for further validation or adjustment of default assessment factors, as well as for informing distributional assessment factors in a probabilistic risk assessment. The various applications of the proposed methodology are illustrated by real data sets.