Vozeh S, Steimer J L, Rowland M, Morselli P, Mentre F, Balant L P, Aarons L
Intercantonal Office for the Control of Medicines, Bern, Switzerland.
Clin Pharmacokinet. 1996 Feb;30(2):81-93. doi: 10.2165/00003088-199630020-00001.
Currently, there is an increasing focus on the implementation of pharmacokinetic-pharmacodynamic (PK-PD) studies and modelling as essential tools for drug development. Strategies involving specifically the population approach, which are based on relatively recent statistical methodology (e.g. nonlinear mixed effects modelling, NONMEM) have been advocated for investigating pharmacokinetic and pharmacodynamic variability as well as dose-concentration-effect relationships. The present article outlines this approach, and discusses how it can be implemented within the framework of the studies currently performed as part of the clinical phases of new drug development. It also considers study design and performance, based on real-life experiences. Population approaches, if designed carefully and early, as part of the planning of the drug development programme, are expected to play a significant role at every phase of the programme and to contribute to providing information that is valuable for registration purposes. Statistical methodology and software are now widely available. However, practical issues such as integration of the population approach within existing protocols, quality control of the data, timing of laboratory and statistical analyses, as well as resource allocation, remain legitimate concerns to be considered in prospective studies.
目前，药代动力学-药效学（PK-PD）研究与建模作为药物研发的重要工具，受到越来越多的关注。有人提倡采用基于相对较新的统计方法（如非线性混合效应建模，NONMEM）的群体方法，以研究药代动力学和药效学变异性以及剂量-浓度-效应关系。本文概述了这种方法，并讨论了如何在新药临床研发阶段目前开展的研究框架内实施该方法。本文还基于实际经验考虑了研究设计与实施。如果在药物研发计划的规划阶段就精心设计并尽早采用群体方法，预计其将在该计划的每个阶段发挥重要作用，并有助于提供对注册有价值的信息。统计方法和软件现已广泛可用。然而，诸如将群体方法整合到现有方案中、数据质量控制、实验室和统计分析的时间安排以及资源分配等实际问题，仍是前瞻性研究中需要考虑的合理问题。
