In silico trials for treatment of acute ischemic stroke: Design and implementation.

Miller, Claire ORCID: 0000-0003-0758-9447, Padmos, Raymond M ORCID: 0000-0001-7253-240X, van der Kolk, Max ORCID: 0000-0001-5761-5776, Józsa, Tamás I ORCID: 0000-0002-5082-0299, Samuels, Noor, Xue, Yidan ORCID: 0000-0001-9532-8671, Payne, Stephen J and Hoekstra, Alfons G (2021) In silico trials for treatment of acute ischemic stroke: Design and implementation. Computers in biology and medicine, 137. 104802-.

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Abstract

An in silico trial simulates a disease and its corresponding therapies on a cohort of virtual patients to support the development and evaluation of medical devices, drugs, and treatment. In silico trials have the potential to refine, reduce cost, and partially replace current in vivo studies, namely clinical trials and animal testing. We present the design and implementation of an in silico trial for treatment of acute ischemic stroke. We propose an event-based modelling approach for the simulation of a disease and injury, where changes to the state of the system (the events) are assumed to be instantaneous. Using this approach we are able to combine a diverse set of models, spanning multiple time scales, to model acute ischemic stroke, treatment, and resulting brain tissue injury. The in silico trial is designed to be modular to aid development and reproducibility. It provides a comprehensive framework for application to any potential in silico trial. A statistical population model is used to generate cohorts of virtual patients. Patient functional outcomes are also predicted with a statistical model, using treatment and injury results and the patient's clinical parameters. We demonstrate the functionality of the event-based modelling approach and trial framework by running proof of concept in silico trials. The proof of concept trials simulate the same cohort of patients twice: once with successful treatment (successful recanalisation) and once with unsuccessful treatment (unsuccessful treatment). Ways to overcome some of the challenges and difficulties in setting up such an in silico trial are discussed, such as validation and computational limitations.

Item Type:	Article
Uncontrolled Keywords:	Humans, Brain Ischemia, Reproducibility of Results, Computer Simulation, Stroke, Ischemic Stroke
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	24 Sep 2021 07:32
Last Modified:	18 Mar 2024 04:09
DOI:	10.1016/j.compbiomed.2021.104802
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3138067