Office of Clinical Pharmacology, Office of Translational Sciences, US Food and Drug Administration, Silver Spring, Maryland, USA.
Clin Pharmacol Ther. 2019 Apr;105(4):899-911. doi: 10.1002/cpt.1363. Epub 2019 Mar 1.
Model-informed drug development (MIDD) refers to the application of a wide range of quantitative models in drug development to facilitate the decision-making process. MIDD was formally recognized in Prescription Drug User Fee Act (PDUFA) VI. There have been many regulatory applications of MIDD to address a variety of drug development and regulatory questions. These applications can be broadly classified into four categories: dose optimization, supportive evidence for efficacy, clinical trial design, and informing policy. Case studies, literature papers, and published regulatory documents are reviewed in this article to highlight some common features of these applications in each category. In addition to the further development and investment in these established domains of application, new technology, and areas, such as more mechanistic models, neural network models, and real-world data/evidence, are gaining attention, and more submissions and experiences are being accumulated to expand the application of model-based analysis to a wider scope.
模型引导的药物研发（MIDD）是指在药物研发中广泛应用各种定量模型，以促进决策过程。MIDD 在《处方药用户收费法》（PDUFA）第六部分中得到正式认可。已经有许多关于 MIDD 的监管应用，以解决各种药物研发和监管问题。这些应用可以大致分为四类：剂量优化、疗效支持证据、临床试验设计和政策制定。本文综述了案例研究、文献论文和已发布的监管文件，以突出这些应用在每个类别中的一些共同特征。除了在这些已建立的应用领域进一步开发和投资外，新技术和领域，如更具机制性的模型、神经网络模型和真实世界的数据/证据，也引起了关注，更多的提交和经验正在积累，以将基于模型的分析应用扩展到更广泛的范围。
