Retout S, Duffull S, Mentré F
INSERM U436, CHU Pitié-Salpétrière, 91 Bd de l'Hôpital, 75013, Paris, France.
Comput Methods Programs Biomed. 2001 May;65(2):141-51. doi: 10.1016/s0169-2607(00)00117-6.
In population pharmacokinetic studies, the precision of parameter estimates is dependent on the population design. Methods based on the Fisher information matrix have been developed and extended to population studies to evaluate and optimize designs. In this paper we propose simple programming tools to evaluate population pharmacokinetic designs. This involved the development of an expression for the Fisher information matrix for nonlinear mixed-effects models, including estimation of the variance of the residual error. We implemented this expression as a generic function for two software applications: S-PLUS and MATLAB. The evaluation of population designs based on two pharmacokinetic examples from the literature is shown to illustrate the efficiency and the simplicity of this theoretic approach. Although no optimization method of the design is provided, these functions can be used to select and compare population designs among a large set of possible designs, avoiding a lot of simulations.
在群体药代动力学研究中，参数估计的精度取决于群体设计。基于费舍尔信息矩阵的方法已得到发展并扩展到群体研究中，以评估和优化设计。在本文中，我们提出了简单的编程工具来评估群体药代动力学设计。这涉及为非线性混合效应模型开发费舍尔信息矩阵的表达式，包括估计残余误差的方差。我们将此表达式实现为两个软件应用程序（S-PLUS和MATLAB）的通用函数。通过对文献中两个药代动力学实例的群体设计评估，展示了这种理论方法的效率和简便性。尽管未提供设计的优化方法，但这些函数可用于在大量可能的设计中选择和比较群体设计，避免大量模拟。
