Enhancing population pharmacokinetic modeling efficiency and quality using an integrated workflow
Enhancing population pharmacokinetic modeling efficiency and quality using an integrated workflow
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DOI：
10.1007/s10928-014-9370-4
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发表时间：
2014-08-01
影响因子：
2.5
通讯作者：
Radivojevic, Andrijana
中科院分区：
文献类型：
--
作者：
Schmidt, Henning;Radivojevic, Andrijana
群体药代动力学（popPK）分析是药物计量学的核心，需要定期进行。虽然这些分析是相对标准的，但是在时间（效率）和执行方法（质量）上可以观察到很大的可变性。造成这种差异的主要原因包括建模者的经验水平、个人偏好和工具。本文旨在研究如何支持popPK模型构建过程，以提高其效率和质量。所提出的进行popPK分析的方法主要围绕三个关键组件：(1)识别最常见和最重要的popPK模型特征，(2)建模所需的信息内容和数据格式，以及(3)方法、工作流和工作流支持工具。这种方法已经在几个popPK建模项目中使用过，补充材料中提供了一个文档示例。通过避免重复编码和其他劳动密集型任务，并通过强调适合目的的模型，可以提高模型构建的效率。通过确保工作流和工具与组织内建立的popk建模指南保持一致，可以提高质量。本文的主要结论是，基于工作流的popk建模方法是可行的，并且具有改善其各个方面的巨大潜力。然而，在药物计量学组织中实施这种方法需要对创新和变化持开放态度——这是制药工业中整合和定量药物开发演变的关键因素。
Population pharmacokinetic (popPK) analyses are at the core of Pharmacometrics and need to be performed regularly. Although these analyses are relatively standard, a large variability can be observed in both the time (efficiency) and the way they are performed (quality). Main reasons for this variability include the level of experience of a modeler, personal preferences and tools. This paper aims to examine how the process of popPK model building can be supported in order to increase its efficiency and quality. The presented approach to the conduct of popPK analyses is centered around three key components: (1) identification of most common and important popPK model features, (2) required information content and formatting of the data for modeling, and (3) methodology, workflow and workflow supporting tools. This approach has been used in several popPK modeling projects and a documented example is provided in the supplementary material. Efficiency of model building is improved by avoiding repetitive coding and other labor-intensive tasks and by putting the emphasis on a fit-for-purpose model. Quality is improved by ensuring that the workflow and tools are in alignment with a popPK modeling guidance which is established within an organization. The main conclusion of this paper is that workflow based approaches to popPK modeling are feasible and have significant potential to ameliorate its various aspects. However, the implementation of such an approach in a pharmacometric organization requires openness towards innovation and change-the key ingredient for evolution of integrative and quantitative drug development in the pharmaceutical industry.