Jongjin Kim, Juan Francisco Morales, Sanghoon Kang, Marian Klose, Rebecca J Willcocks, Michael J Daniels, Ramona Belfiore-Oshan, Glenn A Walter, William D Rooney, Krista Vandenborne, Sarah Kim
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引用次数: 0
摘要
基于定量模型的临床试验模拟工具在实际执行前通过模拟为研究设计提供信息方面发挥着至关重要的作用。这些工具可以帮助药物开发人员在硅学中探索各种试验方案,从而选择临床试验设计,更有效地检测治疗效果,从而减少时间、费用和参与者的负担。为提高工具的可用性,应开发用户友好的交互式平台,以浏览各种模拟场景。然而,开发此类工具对研究人员提出了挑战,需要建模和界面开发方面的专业知识。本教程以我们为杜氏肌营养不良症(DMD)开发的基于模型的临床试验模拟工具为例,旨在指导开发人员创建量身定制的 R Shiny 应用程序,从而弥补这一不足。本教程介绍了结构框架、基本控制器和可视化分析技术,以及标准选择和功率计算等关键代码示例。使用机器学习算法创建了一个虚拟人群,以扩大可用样本量,从而在介绍的工具中模拟临床试验场景。此外,还使用最近发表的一项 DMD 试验的安慰剂臂对模拟输出进行了外部验证。本教程对于开发基于 DMD 进展模型、适用于其他终点和生物标记物的临床试验模拟工具特别有用。所介绍的策略也可应用于其他疾病。
A model-informed clinical trial simulation tool with a graphical user interface for Duchenne muscular dystrophy.
Quantitative model-based clinical trial simulation tools play a critical role in informing study designs through simulation before actual execution. These tools help drug developers explore various trial scenarios in silico to select a clinical trial design to detect therapeutic effects more efficiently, therefore reducing time, expense, and participants' burden. To increase the usability of the tools, user-friendly and interactive platforms should be developed to navigate various simulation scenarios. However, developing such tools challenges researchers, requiring expertise in modeling and interface development. This tutorial aims to address this gap by guiding developers in creating tailored R Shiny apps, using an example of a model-based clinical trial simulation tool that we developed for Duchenne muscular dystrophy (DMD). In this tutorial, the structural framework, essential controllers, and visualization techniques for analysis are described, along with key code examples such as criteria selection and power calculation. A virtual population was created using a machine learning algorithm to enlarge the available sample size to simulate clinical trial scenarios in the presented tool. In addition, external validation of the simulated outputs was conducted using a placebo arm of a recently published DMD trial. This tutorial will be particularly useful for developing clinical trial simulation tools based on DMD progression models for other end points and biomarkers. The presented strategies can also be applied to other diseases.