Optimal designs for composed models in pharmacokinetic-pharmacodynamic experiments.

Optimal designs for composed models in pharmacokinetic-pharmacodynamic experiments.
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DOI:
10.1007/s10928-012-9251-7
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发表时间:
2012-06
影响因子:
2.5
通讯作者:
Wong, Weng Kee
Wong, Weng Kee
中科院分区:
医学4区
文献类型:
--
作者:
Dette, Holger;Pepelyshev, Andrey;Wong, Weng Kee

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我们考虑两个常用的PK/PD模型,并提供封闭形式的描述局部最优设计估计个别参数。在一个新的方式,我们使用这些最优设计和构造局部标准化的最大最小最优设计,估计任何子集的模型参数的兴趣。我们通过最大化所有相关参数的估计的最小效率来实现这一点,以便这些最优设计较少依赖于单个参数或感兴趣的参数。此外,鲁棒设计,提出了进一步减少对标称值的参数的依赖。我们比较效率,我们提出的最优设计与局部最优设计和设计中使用的四个真实的研究文献,并表明,我们提出的设计提供的优势,在实践中使用的。
We consider two frequently used PK/PD models and provide closed form descriptions of locally optimal designs for estimating individual parameters. In a novel way, we use these optimal designs and construct locally standardized maximin optimal designs for estimating any subset of the model parameters of interest. We do this by maximizing the minimal efficiency of the estimates across all relevant parameters so that these optimal designs are less dependent on the individual parameter or parameters of interest. Additionally, robust designs are proposed to further reduce the dependence on the nominal values of the parameters. We compare efficiencies of our proposed optimal designs with locally optimal designs and designs used in four real studies from the literature and show that our proposed designs provide advantages over those used in practice.
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