Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester, UK.
Certara UK Limited (Simcyp Division), Sheffield, UK.
CPT Pharmacometrics Syst Pharmacol. 2021 May;10(5):420-427. doi: 10.1002/psp4.12615. Epub 2021 May 1.
As model-informed drug development becomes an integral part of modern approaches to the discovery of new therapeutic entities and showing their safety and effectiveness, modalities of incorporating the paradigm into widespread practice require a revisit. Traditionally, modeling and simulation (M&S) have been performed by specialized teams who create bespoke models for each case and have reservations about letting modeling be done by the greater mass of scientists engaged in various stages of drug development. An analogy can be drawn between M&S and automobiles: typical drivers of ordinary cars use them for daily tasks, such as going from point A to B whereas specialized Formula 1 drivers using bespoke individually made cars to test the latest technologies. The reliability and robustness of ordinary cars for the first group requires elements related to quality and endurance that are very different from those applicable to any Formula 1 car supported by a large team of engineers. In this commentary, we frame and analyze the problems concerning the structure and setup of various M&S tools, and their pros and cons. We demonstrate that many misconceptions have precluded having an open discussion on what each modality of M&S tools strives to achieve, and we provide data and evidence that support the move of M&S to main stream use by many, as opposed to specialized usage by few. Parallels are drawn in many other areas involving laboratory instrumentation, statistical analyses, and so on.
随着模型引导药物研发成为新药发现和展示其安全性和有效性的现代方法的一个组成部分，将该范例纳入广泛实践的方式需要重新审视。传统上，建模和模拟 (M&S) 是由专门的团队进行的，他们为每个案例创建定制模型，并对让更多从事药物研发各个阶段的科学家进行建模持保留态度。可以将 M&S 与汽车进行类比：普通汽车的典型驾驶员将其用于日常任务，例如从 A 点到 B 点，而专门的一级方程式驾驶员则使用定制的个人汽车来测试最新技术。对于第一组，普通汽车的可靠性和耐用性需要与适用于由大量工程师支持的任何一级方程式赛车相关的质量和耐久性元素非常不同。在这篇评论中，我们构建并分析了各种 M&S 工具的结构和设置及其优缺点所涉及的问题。我们表明，许多误解使得对 M&S 工具的每种模式努力实现的目标进行公开讨论变得不可能，并提供数据和证据支持将 M&S 推向许多人的主流使用，而不是少数人的专门使用。在涉及实验室仪器、统计分析等的许多其他领域也进行了类比。
