Credibility Assessment of a Subject-Specific Mathematical Model of Blood Volume Kinetics for Prediction of Physiological Response to Hemorrhagic Shock and Fluid Resuscitation.

Subject-specific mathematical models for prediction of physiological parameters such as blood volume, cardiac output, and blood pressure in response to hemorrhage have been developed. studies using these models may provide an effective tool to generate pre-clinical safety evidence for medical devices and help reduce the size and scope of animal studies that are performed prior to initiation of human trials. To achieve such a goal, the credibility of the mathematical model must be established for the purpose of pre-clinical testing.

Evaluation of Fluid Resuscitation Control Algorithms via a Hardware-in-the-Loop Test Bed.

Objective: This paper presents a hardware-in-the-loop (HIL) testing platform for evaluating the performance of fluid resuscitation control algorithms. The proposed platform is a cyber-physical system that integrates physical devices with computational models and computer-based algorithms.

Methods: The HIL test bed is evaluated against in silico and in vivo data to ensure the hemodynamic variables are appropriately predicted in the proposed platform.

Credibility Evidence for Computational Patient Models Used in the Development of Physiological Closed-Loop Controlled Devices for Critical Care Medicine.

Physiological closed-loop controlled medical devices automatically adjust therapy delivered to a patient to adjust a measured physiological variable. In critical care scenarios, these types of devices could automate, for example, fluid resuscitation, drug delivery, mechanical ventilation, and/or anesthesia and sedation. Evidence from simulations using computational models of physiological systems can play a crucial role in the development of physiological closed-loop controlled devices; but the utility of this evidence will depend on the credibility of the computational model used.

Applying a Computational Model Credibility Framework to Physiological Closed-loop Controlled Medical Device Testing.

Physiological closed-loop controlled medical devices are safety-critical systems that combine patient monitors with therapy delivery devices to automatically titrate therapy to meet a patient's current need. Computational models of physiological systems can be used to test these devices and generate pre-clinical evidence of safety and performance before using the devices on patients. The credibility, utility, and acceptability of such model-based test results will depend on, among other factors, the computational model used.

Control-oriented physiological modeling of hemodynamic responses to blood volume perturbation.

This paper presents a physiological model to reproduce hemodynamic responses to blood volume perturbation. The model consists of three sub-models: a control-theoretic model relating blood volume response to blood volume perturbation; a simple physics-based model relating blood volume to stroke volume and cardiac output; and a phenomenological model relating cardiac output to blood pressure. A unique characteristic of this model is its balance for simplicity and physiological transparency.

Regulatory Considerations for Physiological Closed-Loop Controlled Medical Devices Used for Automated Critical Care: Food and Drug Administration Workshop Discussion Topics.

Part of the mission of the Center for Devices and Radiological Health (CDRH) at the US Food and Drug Administration is to facilitate medical device innovation. Therefore, CDRH plays an important role in helping its stakeholders such as manufacturers, health care professionals, patients, patient advocates, academia, and other government agencies navigate the regulatory landscape for medical devices. This is particularly important for innovative physiological closed-loop controlled (PCLC) devices used in critical care environments, such as intensive care units, emergency settings, and battlefield environments.