In silico trials for treatment of acute ischemic stroke: Design and implementation
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...
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| Veröffentlicht in: | Computers in biology and medicine 2021-10, Vol.137, p.104802-104802, Article 104802 |
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| container_title | Computers in biology and medicine |
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| creator | Miller, Claire Padmos, Raymond M. van der Kolk, Max Józsa, Tamás I. Samuels, Noor Xue, Yidan Payne, Stephen J. Hoekstra, Alfons G. |
| description | 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.
•Details the implementation of an in silico clinical trial for acute ischemic stroke and demonstrates proof of concept trials.•Event-based modelling approach combines a diverse set of models for simulating acute ischemic stroke injury and therapies.•A generalisable modular framework has been developed for running in silico clinical trials for event-based simulations.•A challenge for in silico trials is proving credibility, including access to in vitro and clinical data for trial validation. |
| doi_str_mv | 10.1016/j.compbiomed.2021.104802 |
| format | Article |
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•Details the implementation of an in silico clinical trial for acute ischemic stroke and demonstrates proof of concept trials.•Event-based modelling approach combines a diverse set of models for simulating acute ischemic stroke injury and therapies.•A generalisable modular framework has been developed for running in silico clinical trials for event-based simulations.•A challenge for in silico trials is proving credibility, including access to in vitro and clinical data for trial validation.</description><identifier>ISSN: 0010-4825</identifier><identifier>EISSN: 1879-0534</identifier><identifier>DOI: 10.1016/j.compbiomed.2021.104802</identifier><identifier>PMID: 34520989</identifier><language>eng</language><publisher>OXFORD: Elsevier Ltd</publisher><subject>Acute ischemic stroke ; Biology ; Blood pressure ; Brain injury ; Brain Ischemia - drug therapy ; Clinical trials ; Computational biology ; Computational neuroscience ; Computer Science ; Computer Science, Interdisciplinary Applications ; Computer Simulation ; Disease ; Drug development ; Engineering ; Engineering, Biomedical ; Event-based modelling ; Health services ; Humans ; In silico clinical trial ; In vivo methods and tests ; Injuries ; Ischemia ; Ischemic Stroke ; Life Sciences & Biomedicine ; Life Sciences & Biomedicine - Other Topics ; Mathematical & Computational Biology ; Mathematical models ; Medical equipment ; Medical research ; Modular design ; Patients ; Precision medicine ; Product development ; Regulatory approval ; Reproducibility of Results ; Science & Technology ; Simulation ; Statistical models ; Stroke ; Stroke - drug therapy ; Technology ; Traumatic brain injury</subject><ispartof>Computers in biology and medicine, 2021-10, Vol.137, p.104802-104802, Article 104802</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.</rights><rights>2021. 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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.
•Details the implementation of an in silico clinical trial for acute ischemic stroke and demonstrates proof of concept trials.•Event-based modelling approach combines a diverse set of models for simulating acute ischemic stroke injury and therapies.•A generalisable modular framework has been developed for running in silico clinical trials for event-based simulations.•A challenge for in silico trials is proving credibility, including access to in vitro and clinical data for trial validation.</description><subject>Acute ischemic stroke</subject><subject>Biology</subject><subject>Blood pressure</subject><subject>Brain injury</subject><subject>Brain Ischemia - drug therapy</subject><subject>Clinical trials</subject><subject>Computational biology</subject><subject>Computational neuroscience</subject><subject>Computer Science</subject><subject>Computer Science, Interdisciplinary Applications</subject><subject>Computer Simulation</subject><subject>Disease</subject><subject>Drug development</subject><subject>Engineering</subject><subject>Engineering, Biomedical</subject><subject>Event-based modelling</subject><subject>Health services</subject><subject>Humans</subject><subject>In silico clinical trial</subject><subject>In vivo methods and tests</subject><subject>Injuries</subject><subject>Ischemia</subject><subject>Ischemic Stroke</subject><subject>Life Sciences & Biomedicine</subject><subject>Life Sciences & Biomedicine - 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drug therapy</topic><topic>Clinical trials</topic><topic>Computational biology</topic><topic>Computational neuroscience</topic><topic>Computer Science</topic><topic>Computer Science, Interdisciplinary Applications</topic><topic>Computer Simulation</topic><topic>Disease</topic><topic>Drug development</topic><topic>Engineering</topic><topic>Engineering, Biomedical</topic><topic>Event-based modelling</topic><topic>Health services</topic><topic>Humans</topic><topic>In silico clinical trial</topic><topic>In vivo methods and tests</topic><topic>Injuries</topic><topic>Ischemia</topic><topic>Ischemic Stroke</topic><topic>Life Sciences & Biomedicine</topic><topic>Life Sciences & Biomedicine - Other Topics</topic><topic>Mathematical & Computational Biology</topic><topic>Mathematical models</topic><topic>Medical equipment</topic><topic>Medical research</topic><topic>Modular design</topic><topic>Patients</topic><topic>Precision medicine</topic><topic>Product development</topic><topic>Regulatory approval</topic><topic>Reproducibility of Results</topic><topic>Science & Technology</topic><topic>Simulation</topic><topic>Statistical models</topic><topic>Stroke</topic><topic>Stroke - 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Academic</collection><jtitle>Computers in biology and medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miller, Claire</au><au>Padmos, Raymond M.</au><au>van der Kolk, Max</au><au>Józsa, Tamás I.</au><au>Samuels, Noor</au><au>Xue, Yidan</au><au>Payne, Stephen J.</au><au>Hoekstra, Alfons G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In silico trials for treatment of acute ischemic stroke: Design and implementation</atitle><jtitle>Computers in biology and medicine</jtitle><stitle>COMPUT BIOL MED</stitle><addtitle>Comput Biol Med</addtitle><date>2021-10</date><risdate>2021</risdate><volume>137</volume><spage>104802</spage><epage>104802</epage><pages>104802-104802</pages><artnum>104802</artnum><issn>0010-4825</issn><eissn>1879-0534</eissn><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.
•Details the implementation of an in silico clinical trial for acute ischemic stroke and demonstrates proof of concept trials.•Event-based modelling approach combines a diverse set of models for simulating acute ischemic stroke injury and therapies.•A generalisable modular framework has been developed for running in silico clinical trials for event-based simulations.•A challenge for in silico trials is proving credibility, including access to in vitro and clinical data for trial validation.</abstract><cop>OXFORD</cop><pub>Elsevier Ltd</pub><pmid>34520989</pmid><doi>10.1016/j.compbiomed.2021.104802</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-9532-8671</orcidid><orcidid>https://orcid.org/0000-0003-0758-9447</orcidid><orcidid>https://orcid.org/0000-0001-7253-240X</orcidid><orcidid>https://orcid.org/0000-0003-1156-2810</orcidid><orcidid>https://orcid.org/0000-0001-5761-5776</orcidid><orcidid>https://orcid.org/0000-0002-5082-0299</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Computers in biology and medicine, 2021-10, Vol.137, p.104802-104802, Article 104802 |
| issn | 0010-4825 1879-0534 |
| language | eng |
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| source | MEDLINE; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; Access via ScienceDirect (Elsevier); ProQuest Central UK/Ireland |
| subjects | Acute ischemic stroke Biology Blood pressure Brain injury Brain Ischemia - drug therapy Clinical trials Computational biology Computational neuroscience Computer Science Computer Science, Interdisciplinary Applications Computer Simulation Disease Drug development Engineering Engineering, Biomedical Event-based modelling Health services Humans In silico clinical trial In vivo methods and tests Injuries Ischemia Ischemic Stroke Life Sciences & Biomedicine Life Sciences & Biomedicine - Other Topics Mathematical & Computational Biology Mathematical models Medical equipment Medical research Modular design Patients Precision medicine Product development Regulatory approval Reproducibility of Results Science & Technology Simulation Statistical models Stroke Stroke - drug therapy Technology Traumatic brain injury |
| title | In silico trials for treatment of acute ischemic stroke: Design and implementation |
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