Zhang Liping, Pfister Marc, Meibohm Bernd
Bristol Myers Squibb Research and Development, Princeton, New Jersey, USA.
AAPS J. 2008 Dec;10(4):552-9. doi: 10.1208/s12248-008-9062-3. Epub 2008 Nov 12.
Model-based drug development (MBDD) has been recognized as a concept to improve the efficiency of drug development. The acceptance of MBDD from regulatory agencies, industry, and academia has been growing, yet today's drug development practice is still distinctly distant from MBDD. This manuscript is aimed at clarifying the concept of MBDD and proposing practical approaches for implementing MBDD in the pharmaceutical industry. The following concepts are defined and distinguished: PK-PD modeling, exposure-response modeling, pharmacometrics, quantitative pharmacology, and MBDD. MBDD is viewed as a paradigm and a mindset in which models constitute the instruments and aims of drug development efforts. MBDD covers the whole spectrum of the drug development process instead of being limited to a certain type of modeling technique or application area. The implementation of MBDD requires pharmaceutical companies to foster innovation and make changes at three levels: (1) to establish mindsets that are willing to get acquainted with MBDD, (2) to align processes that are adaptive to the requirements of MBDD, and (3) to create a closely collaborating organization in which all members play a role in MBDD. Pharmaceutical companies that are able to embrace the changes MBDD poses will likely be able to improve their success rate in drug development, and the beneficiaries will ultimately be the patients in need.
基于模型的药物研发（MBDD）已被公认为一种提高药物研发效率的理念。监管机构、行业和学术界对MBDD的接受度一直在不断提高，但如今的药物研发实践与MBDD仍有明显差距。本文旨在阐明MBDD的概念，并提出在制药行业实施MBDD的实用方法。对以下概念进行了定义和区分：药代动力学-药效学（PK-PD）建模、暴露-反应建模、药理计量学、定量药理学和MBDD。MBDD被视为一种范式和思维方式，其中模型构成了药物研发工作的工具和目标。MBDD涵盖了药物研发过程的全领域，而非局限于某一类型的建模技术或应用领域。实施MBDD要求制药公司在三个层面进行创新和变革：（1）建立愿意熟悉MBDD的思维模式；（2）调整适应MBDD要求的流程；（3）创建一个紧密协作的组织，所有成员都在MBDD中发挥作用。能够接受MBDD带来的变革的制药公司，可能会提高其药物研发的成功率，最终受益的将是有需要的患者。
