The SimInSitu project has successfully completed its final development milestone: the execution of an In-Silico Clinical Trial (ISCT) using one of the two sub-modules of the SimInSitu in-silico platform. The ISCT was designed as a patient-screening study aimed at refining inclusion and exclusion criteria for enrolment in a potential clinical trial involving an investigational pulmonary valve device.
Ten virtual paediatric patients, aged 5 to 18 years, were included in the screening. Each patient underwent a virtual treatment process conducted under strict clinical guidance, during which the appropriate device size was selected and aligned or trimmed to match the individual anatomy. At this stage, an initial clinical assessment evaluated potential patient risks based on the chosen device size and placement.
A second clinical assessment was performed using in-silico clinical data generated by the SimInSitu platform, enabling reliable predictions of valve kinematics, flow patterns, and key device-related clinical parameters – including Regurgitation Fraction (RF), Mean and Peak Pressure Gradient (MPG/PPG), and Effective and Geometric Orifice Area (EOA/GOA), among others. These in-silico results supported patient-specific risk evaluation and informed enrolment decisions, particularly in complex cases.
The SimInSitu in-silico platform has been developed over several years following a hierarchical, bottom-up modelling strategy that also shaped our credibility assessment framework. We defined and executed a comprehensive set of Verification, Validation, and Uncertainty Quantification (VVUQ) activities across all model complexity levels, collectively establishing the required trustworthiness of the platform. We are confident that this hierarchical modelling and VVUQ approach – supported by a wide range of validation comparators – can help achieve the level of credibility expected by international regulatory bodies.