Optimal designs for dose-finding experiments in toxicity studies
Optimal designs for dose-finding experiments in toxicity studies
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DOI：
10.3150/08-bej152
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发表时间：
2009-02-01
期刊：
影响因子：
1.5
通讯作者：
Wong, Weng Kee
中科院分区：
文献类型：
--
作者：
Dette, Holger;Pepelyshev, Andrey;Wong, Weng Kee
我们构建了最优设计，估计胎儿畸形率，产前死亡率和毒理学研究的总体毒性指数在广泛的模型假设。我们使用威布尔分布来模拟这些速率，并假设植入的数量取决于剂量水平。我们研究了当窝内相关系数以不同方式取决于剂量水平时最优设计的性质。局部最优设计被发现，沿着与鲁棒版本的设计，是不太敏感的模型参数的初始值中的误设定。我们还报告了在毒理学实验中常用的设计的效率和建议的最优设计的效率时，真实率有非威布尔分布。最佳的设计策略，发现在毒理学研究中的多目标设计的概述。
We construct optimal designs for estimating fetal malformation rate, prenatal death rate and an overall toxicity index in a toxicology study under a broad range of model assumptions. We use Weibull distributions to model these rates and assume that the number of implants depend on the dose level. We study properties of the optimal designs when the intra-litter con-elation coefficient depends on the dose levels in different ways. Locally optimal designs are found, along with robustified versions of the designs that are less sensitive to misspecification in the initial values of the model parameters. We also report efficiencies of commonly used designs in toxicological experiments and efficiencies of the proposed optimal designs when the true rates have non-Weibull distributions. Optimal design strategies for finding multiple-objective designs in toxicology studies are outlined as well.