Graham Gordon, Gueorguieva Ivelina, Dickens Kelly
Novartis Pharma AG, Lichtstrasse 35, Basel 4052, Switzerland.
Comput Methods Programs Biomed. 2005 Jun;78(3):237-49. doi: 10.1016/j.cmpb.2005.02.005. Epub 2005 Apr 22.
Planning any experiment includes issues such as how many samples are to be taken and their location given some predictor variable. Often a model is used to explain these data; hence including this formally in the design will be beneficial for any subsequent parameter estimation and modelling. A number of criteria for model oriented experiments, which maximise the information content of the collected data are available. In this paper we present a program, Optdes, to investigate the optimal design of pharmacokinetic, pharmacodynamic, drug metabolism and drug-drug interaction models. Using the developed software the location of either a predetermined number of design points (exact designs) or together with the proportion of samples at each point (continuous designs) can be determined. Local as well as Bayesian designs can be optimised by either D- or A-optimality criteria. Although often the optimal design cannot be applied for practical reasons, alternative designs can be readily evaluated.
规划任何实验都涉及一些问题，比如给定某些预测变量时要采集多少样本以及样本的位置。通常会使用一个模型来解释这些数据；因此，在设计中正式纳入这一点将有利于后续的任何参数估计和建模。有许多面向模型的实验标准，这些标准能使所收集数据的信息含量最大化。在本文中，我们展示了一个程序Optdes，用于研究药代动力学、药效学、药物代谢和药物 - 药物相互作用模型的最优设计。使用所开发的软件，可以确定预定数量的设计点（精确设计）的位置，或者确定每个点的样本比例（连续设计）。局部设计以及贝叶斯设计都可以通过D - 最优或A - 最优标准进行优化。尽管由于实际原因最优设计常常无法应用，但替代设计可以很容易地得到评估。
