Division of Pharmacometrics, Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, MD, USA.
Clin Pharmacokinet. 2011 Oct;50(10):627-35. doi: 10.2165/11593210-000000000-00000.
Pharmacometric analyses have become an increasingly important component of New Drug Application (NDA) and Biological License Application (BLA) submissions to the US FDA to support drug approval, labelling and trial design decisions. Pharmacometrics is defined as a science that quantifies drug, disease and trial information to aid drug development, therapeutic decisions and/or regulatory decisions. In this report, we present the results of a survey evaluating the impact of pharmacometric analyses on regulatory decisions for 198 submissions during the period from 2000 to 2008. Pharmacometric review of NDAs included independent, quantitative analyses by FDA pharmacometricians, even when such analysis was not conducted by the sponsor, as well as evaluation of the sponsor's report. During 2000-2008, the number of reviews with pharmacometric analyses increased dramatically and the number of reviews with an impact on approval and labelling also increased in a similar fashion. We also present the impact of pharmacometric analyses on selection of paediatric dosing regimens, approval of regimens that had not been directly studied in clinical trials and provision of evidence of effectiveness to support a single pivotal trial. Case studies are presented to better illustrate the role of pharmacometric analyses in regulatory decision making.
药代动力学分析已成为向美国 FDA 提交新药申请 (NDA) 和生物制品许可申请 (BLA) 的越来越重要的组成部分，以支持药物批准、标签和试验设计决策。药代动力学分析被定义为一种定量药物、疾病和试验信息的科学，以帮助药物开发、治疗决策和/或监管决策。在本报告中，我们介绍了一项调查的结果，该调查评估了 2000 年至 2008 年期间 198 项提交物的药代动力学分析对监管决策的影响。NDA 的药代动力学审查包括 FDA 药代动力学专家的独立、定量分析，即使这种分析不是由赞助商进行的，还包括对赞助商报告的评估。2000-2008 年期间，进行药代动力学分析的审查数量大幅增加，对批准和标签产生影响的审查数量也以类似的方式增加。我们还介绍了药代动力学分析对儿科剂量方案选择、批准未在临床试验中直接研究的方案以及提供支持单一关键试验的有效性证据的影响。案例研究的介绍旨在更好地说明药代动力学分析在监管决策中的作用。
