An international consortium coordinated by the Academic Medical Center in Amsterdam (AMC) received funding from the H2020 programme to implement INSIST - IN Silico trials for treatment of acute Ischemic STroke
The main goal of INSIST is to realize in silico clinical stroke trials for biomedical products for endovascular treatment of acute ischemic stroke. Such an in silico clinical ischemic stroke trial consists of the generation of populations of virtual stroke patients, in silico models of treatments, and in silico models of the biophysiological aspects of the human response to stroke. The main vision underpinning the project is that an in silico clinical stroke trial will be very important for patient stratification and treatment development. It will contribute to more effective clinical trial design, reduction of animal testing and reducing the size and duration of human clinical trials.
Time is crucial in stroke. Each hour without successful treatment, the brain loses as many neurons as it does in 3-4 years of aging, but the choice of treatment is limited. Until very recently, only thrombolysis with intravenous administration of an enzyme to help break down unwanted blood clots seemed beneficial. As recently as 2015, the introduction of intra-arterial thrombectomy truly revolutionized treatment of ischemic stroke. Still almost 2 out of 3 patients with an acute ischemic stroke have an unfavorable outcome and become functionally dependent. Further improvement of medical products for treatment is therefore still urgently needed. The new generation of stroke intervention treatments requires testing in clinical trials before they can be introduced into the market. However, most of the treatments that are tested in clinical trials fail to be introduced in clinical practice.
Computer modelling plays an increasingly important role in research and development of biomedical products. In silico models hold the promise that, in combination with patient models that accurately represent important patient characteristics, they can be used to set up in silico clinical trials in which “virtual” patients are treated with “virtual” treatments. In silico clinical trials can potentially reduce, refine, and partially replace human clinical trials. With the advent of new stroke treatments, new trials are being planned. Because in silico modelling allows early and fast hypothesis testing and supports trial design, the next generation clinical stroke trials can greatly benefit from in silico clinical stroke trials. INSIST will advance in silico clinical trial methods in the field of acute ischemic stroke by simulating randomized controlled trials for novel acute ischemic stroke treatments.
In a collaborative effort of health professionals (Erasmus Medical Centre and AMC), (animal and computer) modellers (University of Oxford, University of Amsterdam, Politecnico di Milano, Lomonosov Moscow State university, University of Geneva, National University of Ireland and the Katholic university Leuven), and pharma and device industry (Neuravi, Servier), the INSIST consortium is uniquely positioned to realize these in silico clinical trials for acute ischemic stroke through providing the essential building blocks;
1. access to large amounts of patient data from 7 landmark trials on endovascular treatment of acute ischemic stroke, a large stroke registry of 2300 patients, and new human trials that will start early 2017 that together form the basis for building virtual populations of stroke patients and offer data for validation.
2. availability of in silico models of thrombosis and thrombolysis;
3. emerging in silico models of stent-retriever placements and subsequent thrombectomy;
4. in silico models for perfusion of brain tissue and brain tissue death as response to impaired perfusion.
Further information on the project can be found on the official website.