15 December 2022

Proof-of-principle of the SIMCor virtual cohort generator


The virtual cohort generator, by definition, is a pipeline of mathematical models able to generate virtual reproductions of human patients’ anatomy and physiology, and filter them using a multi-step strategy to obtain a population of high-fidelity ‘virtual patients’, able to accurately reproduce not only real patients’ features, but also their response to a device-based treatment of interest, mimicking the process of a real clinical trial.

The virtual cohort generator has been integrated in the project virtual research environment (VRE), a data repository and computing space developed for the generation of virtual cohorts and the conduction of simulated (‘in-silico’) biomedical device trials.



The validation of the generated virtual cohorts follows, articulated in three steps. The (1) patient-specific validation is used to demonstrate that the mechanistic model can realistically mimic the physiology of real patients. The (2) self-validation uses a sub-population of the real patient cohort – previously set aside – to assess whether the numerical distributions of the virtual patients mimic the real distributions used to create the virtual cohorts. Finally, in the (3) cross-validation, the outputs of interest of the virtual cohorts in the in-silico clinical trial are compared with independent patient cohorts of analogous real clinical trials, to verify whether the numerical outputs from the in-silico trial are comparable with real clinical trial outputs. 


SIMCor focuses on cardiologic diseases and device-based treatments. Particularly, on aortic valve stenosis and its treatment using transcatheter aortic valve replacement (TAVR), and heart failure, monitored using a pulmonary artery pressure sensor (PAPS). 

The initial proof-of-concept validation of the virtual cohort generator has been successfully conducted on the generation of synthetic geometries of the ascending aorta and left ventricular outflow tract of aortic stenosis patients using filters defined by clinical requirements, as well as on the exemplary transcatheter aortic valve implantation (TAVI) and the assessment of device effects on the virtual patient population. Further assessments will be conducted in the next months to validate the reliability of the method to mimic larger cohorts of real patients from independent clinical trials.




Visualisation of three different steps of the deployment simulation of a self-expanding TAVI device.
Schematic illustration (left) and 3D geometry (right)  of an aortic root geometry and the definition used to determine the angle between the ascending aorta and the left ventricular outflow tract. Credits: Eindhoven University of Technology. Licence: CC-BY 4.0.