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An in silico-based approach to improve the efficacy and precision of drug REPurpOsing TRIALs for a mechanism-based patient cohort with predominant cerebro-cardiovascular phenotypes

An in silico-based approach to improve the efficacy and precision of drug REPurpOsing TRIALs for a mechanism-based patient cohort with predominant cerebro-cardiovascular phenotypes

Objective

Our programme will develop an innovative in-silico based approach to improve the efficacy and precision of drug repurposing trials. We have chosen drug repurposing as it has the shortest time for clinical validation and translation. Validation of all putatively de novo discovered drug repositionings within the time-frame of this programme would be unrealistic. To improve efficacy and precision, and to adopt our computer simulation parameters and models, we choose a systems medicine based in-silico approach that identifies mechanistically related disease phenotypes and, as a result, a virtual patient cohort. We then validate this in-silico drug repurposing via high precision clinical trials in patients with cerebro-cardiovascular phenotypes stratified using an exclusive mechanistic biomarker panel. We thus innovate two biomedical product classes, drugs and diagnostics. With this we will establish generally applicable in silico trials for other mechanistically related or defined disease phenotypes, for which size, duration, and risks will be reduced and precision increased. This generates rapid patient benefit, reduces drug development costs as well as risks, and enhances industrial competitiveness. Scientifically, we will contribute to reducing the uncertainty and vagueness of many of our current disease definitions that describe a symptom or apparent phenotype in an organ rather than defining diseases mechanistically as disturbance of self-regulation equilibria of biomolecular processes. Finally, we will reduce animal experimentation and animal numbers in general by applying a preclinical randomised confirmatory trial (pRCTs) concept and preclinical systematic reviews and meta-analyses facilitated by our open access pre-clinicaltrials.org platform, a pendant to clinicaltrials.gov.
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Coordinator

UNIVERSITEIT MAASTRICHT

Address

Minderbroedersberg 4-6
6200 Md Maastricht

Netherlands

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 270 089,50

Participants (10)

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SYDDANSK UNIVERSITET

Denmark

UNIVERSITY OF NEWCASTLE UPON TYNE

United Kingdom

EU Contribution

€ 844 728

UNIVERSITAETSKLINIKUM ESSEN

Germany

EU Contribution

€ 597 565

MEDIZINISCHE HOCHSCHULE HANNOVER

Germany

EU Contribution

€ 550 722

UNIVERSITAIR MEDISCH CENTRUM UTRECHT

Netherlands

EU Contribution

€ 550 722

BIOCRATES LIFE SCIENCES AG

Austria

EU Contribution

€ 157 789

SOMALOGIC LIMITED

United Kingdom

EU Contribution

€ 342 964

MUCKE HERMANN

Austria

EU Contribution

€ 125 122

Concentris Research Management GmbH

Germany

EU Contribution

€ 355 026

TECHNISCHE UNIVERSITAET MUENCHEN

Germany

EU Contribution

€ 742 045

Project information

Grant agreement ID: 777111

Status

Ongoing project

  • Start date

    1 February 2018

  • End date

    31 January 2023

Funded under:

H2020-EU.3.1.5.

  • Overall budget:

    € 5 536 775,64

  • EU contribution

    € 5 536 772,50

Coordinated by:

UNIVERSITEIT MAASTRICHT

Netherlands