发表机构
University of Luebeck; Fraunhofer Research Institution for Individualized Medical Technology and Engineering IMTE; Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein; Centre for Regulatory Affairs in Biomedical Sciences, Technische Hochschule Lübeck（吕贝克大学; 弗劳恩霍夫个体化医疗技术与工程研究所 IMTE; 什未因-荷尔斯泰因大学医学中心麻醉与重症医学科; 吕贝克应用技术大学生物医药科学监管事务中心）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
研究针对机械通气中自动化控制策略临床转化慢的问题，应用符合标准的框架对计算呼吸模型进行可信度评估，通过多方面验证评估其可信度，为自动化撤机策略等提供适用模型及验证蓝图。
AI 中文摘要
计算建模和模拟是评估医疗设备性能和安全性的有力工具，尤其适用于自动化医疗系统的计算机模拟临床试验。在通气领域，由于在不断变化的病理生理学情况下需要管理气体交换、呼吸力学和患者-呼吸机相互作用，自动化控制策略的临床转化仍然缓慢且资源密集。本文应用了一个符合标准的框架对计算呼吸模型进行可信度评估，并通过自动撤机案例研究进行了展示。该框架在结构化、基于指南的验证工作流程中实施了ASME V&V 40和FDA原则。计算生理模型整合了呼吸力学、气体交换、呼吸控制和呼吸机表示，并在明确界定的使用背景和明确的感兴趣问题下进行了验证。通过校准、生理合理性、基于人群的评估和突发行为的再现来评估模型的可信度。在拟议的可信度评估计划中解决了从预期使用背景中得出的所有模型要求，并透明地报告了记录的差距。由此产生的可信度论证支持了该模型在其使用背景下的适用性。在基于人群的比较和机制合理性方面展示了优势，而剩余的局限性与体内证据的程度、人群代表性和外部验证有关。总体而言，该模型被认为适用于自动化撤机策略的中低风险临床前计算机模拟临床试验。此外，本文概述的验证程序为其他机械通气算法和相关用例中该模型及类似模型的验证提供了蓝图。
英文摘要
Computational modeling and simulation have emerged as powerful tools for assessing medical device performance and safety, particularly in silico clinical trials (ISCTs) for automated medical systems. In ventilation, where gas exchange, respiratory mechanics, and patient-ventilator interaction must be managed under evolving pathophysiology, clinical translation of automated control strategies remains slow and resource-intensive. These challenges are particularly relevant for AI-based therapy-control systems, whose data-driven decision-making must be evaluated across heterogeneous and safety-critical patient states that may be sparsely represented in clinical datasets. Mechanistic, physiology-based models provide a complementary and interpretable environment for testing such scenarios. This paper applies a standards-aligned framework for credibility assessment of a computational respiratory model, demonstrated using an automated weaning case study. The framework operationalizes ASME V&V 40 and FDA principles within a structured validation workflow. The model integrates respiratory mechanics, gas exchange, respiratory control, and a ventilator representation, with validation under a defined context of use and explicit questions of interest. Model credibility is assessed through calibration, physiological plausibility, population-based evaluation, and reproduction of emergent behavior. All model requirements derived from the intended context of use are addressed, and gaps are transparently reported. The resulting credibility argument supports applicability of the model for medium-low-risk preclinical ISCTs of automated weaning strategies. Residual limitations relate to the extent of in vivo evidence, population representativeness, and external validation. The validation procedure provides a blueprint for validation of this and similar models in mechanical ventilation and related use cases.
Comments49 pages, 10 figures. Submitted to PLOS Computational Biology
