Optimal designs for dose-response models with restricted design spaces
Optimal designs for dose-response models with restricted design spaces
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DOI：
10.1198/016214505000001087
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发表时间：
2006-06-01
影响因子：
3.7
通讯作者：
Zhu, Wei
中科院分区：
文献类型：
--
作者：
Biedermann, Stefanie;Dette, Holger;Zhu, Wei
在密切反应研究中，由于对药物毒性和/或疗效的考虑，剂量范围往往受到限制。我们根据广泛的最优性准则，推导出在有限或无限制剂量范围内估计潜在剂量-反应曲线的最优设计。下面的曲线属于一组适合于剂量-反应研究的多种联系函数，具有共同的标准形式。这些包括基本的二元响应模型——logit和probit，以及这些模型的扭曲版本。我们的方法是基于一个新的几何解释的最佳设计相对于基弗的Phi(p)标准的回归模型与两个参数，这是独立的兴趣。它直观地说明了Phi(p)优化设计的支撑点的数量和位置。此外，几何结果将经典的最小覆盖椭球的d -最优设计特征推广到基弗的Phi(p)准则。结果是通过重新设计剂量范围试验来说明的。
In close-response studies, the dose range is often restricted because of concerns over drug toxicity and/or efficacy. We derive optimal designs for estimating the underlying dose-response curve for a restricted or unrestricted dose range with respect to a broad class of optimality criteria. The underlying curve belongs to a diversified set of link functions suitable for the dose-response studies and having a common canonical form. These include the fundamental binary response models-the logit and the probit, as well as the skewed versions of these models. Our methodology is based on a new geometric interpretation of optimal designs with respect to Kiefer's Phi(p) criteria in regression models with two parameters, which is of independent interest. It provides an intuitive illustration of the number and locations of the support points of Phi(p)-optimal designs. Moreover, the geometric results generalize the classical characterization of D-optimal designs by the minimum covering ellipsoid to the class of Kiefer's Phi(p) criteria. The results are illustrated through the redesign of a dose ranging trial.