A Computer Model of Renal Physiology for use as a FDA Medical Device Development Tool

 描述（由申请人提供）：本提案旨在开发经确认的心肾轴生理模型，以提交给FDA医疗器械开发工具试点项目。该模型将用于帮助开发和调节用于治疗高血压的器械。实例包括用于肾神经消融、颈动脉压力感受器的电刺激或动静脉瘘的形成的医疗器械。考虑到12-15%的美国高血压患者即使使用4种或更多种药物，价格标签为110 - 170亿美元，简化非药物器械设计、测试和监管时间的工具的重要性是显而易见的。高血压的多因素性质使其治疗复杂化，并且不能保证成功治疗每个患者。我们的生理模型是一个强大的工具，用于了解患者间的变异性和确认设备的使用环境的正确性。 在第一阶段，我们将证明一个经过验证和记录的肾脏模型，使用HumMod，我们现有的人体生理学模型作为新模型的基础。本研究的目的包括：1）将模型从专有模拟环境转移到更强大的验证框架中，2）通过将书目数据库与wiki链接来记录模型，以及3）验证套件以确保模型正确运行。该模型将在Modelica中实现，Modelica是一种用于复杂系统建模的多领域建模语言。在第二阶段，我们将使用第一阶段开发的工作流程来创建、记录和验证轴的心血管部分，包括神经反射弧和相关的内分泌系统。

 DESCRIPTION (provided by applicant): The purpose of this proposal is to develop a validated physiological model of the cardio- renal axis for submission to the FDA Medical Device Development Tool pilot program. The model will be used to aid in the development and regulation of devices intended to treat hypertension. Examples include medical devices for renal nerve ablation, electrical stimulation of the carotid baroreceptor or creation of an A-V Fistula. Given that 12-15% of US patients with uncontrolled hypertension even with the use of 4 or more drugs at a price tag of $11-$17 billion, the importance of a tool that streamlines the time for design, testing, and regulation of a non- pharmacological device is clear. The multifactorial nature of hypertension complicates its treatment, and no device intervention is guaranteed to successfully treat each patient. Our physiological model is a powerful tool for understanding interpatient variability and confirming the correctness of a device's context of use. In Phase I, we will demonstrate a validated and documented renal model, using HumMod, our existing model of human physiology as the basis for the new model. The aims of this study include: 1) the transfer of the model from a proprietary simulation environment into a more powerful, validated framework, 2) documentation of the model by linking a bibliographic database with a wiki, and 3) a validation suite to ensure that the model functions correctly. The model will be implemented in Modelica, a multi-domain modeling language for modeling of complex system. In Phase II, we will use the workflows developed in Phase I to create, document, and validate the cardiovascular part of the axis, including neural reflex arcs and the relevant endocrine systems.