SIMCor final meeting
The SIMCor project met last week for the final project meeting in Warnemünde, Rostock, Germany at the Institute for Implant Technology and Biomaterials. Over the course of the two days, the consortium highlighted all that was accomplished since the project began in January 2021. The Simcor project aimed to enhance the development, validation, and regulatory approval of cardiovascular implantable devices through a computational platform. The project's objectives include providing proof of validation for virtual cohorts and computer-based simulations of cardiovascular device implantation and performance. It also focuses on developing standards and protocols for in-silico testing, quantifying the benefits of such testing for healthcare, industry, and society, accelerating the integration of in-silico testing into medical device regulatory approval processes, and contributing to the European Open Science Cloud by sharing data, virtual cohorts, simulation models, methodologies, standards, and guidelines.
By providing a robust platform for the virtual testing of cardiovascular devices, Simcor will help reduce the dependency on traditional clinical trials, which are often lengthy and costly. The use of virtual cohorts and simulations can accelerate the approval process, improve device safety and effectiveness, and enhance personalised medicine approaches. As a result, healthcare providers can expect more rapid integration of innovative cardiovascular solutions into clinical practice, benefiting patients through quicker access to advanced therapeutic options.
In SIMCor, TAVI (Transcatheter aortic valve replacement) and PAPS (Pulmonary artery pressure sensors) are used as target use cases to evaluate a generalizable framework for assessing the impact of in-silico methods. A review of existing statistical tools revealed that currently no R-package exists that covers the needs of the SIMCor project. For this reason, ECRIN led a work package for the development of a new R-package, called R-statistical environment, allowing validation of virtual cohorts as well as application of validated cohorts in in-silico trials.
Four application scenarios were selected by the consortium to assess the predictive value of in-silico trials with respect to real clinical and preclinical trials. For each scenario, standardised templates were filled in covering key assessment criteria (e.g., Context of Use, Question of Interest, engineering outputs, targeted clinical outcomes, impact on clinical trials and medical device design). As a next step, standardised study protocols for three trials (TAVI-1, TAVI-3 and PAPS-1) specifying the hypotheses, the outcome criteria, a detailed description of the datasets to be collected, evidence on sample size if available and the statistical analysis plan, have been defined. The virtual datasets were generated and analysed. The results of the in silico clinical trials (ISCT) cover cleaning of the dataset, basic descriptive )statistics and a collection of univariate and multivariate analysis techniques dependent on the type of ISCT. Those results were put in perspective to the available literature, and conclusions for the application of in silico methods were drawn. The application of the CDISC standard for ISCT was also discussed during the consortium meeting, as usage of this standard is mandatory by the FDA and Japanese Medical Device Authorities.
The performance of the ISCTs in SIMCor and the intensive discussion among consortium members have clearly shown that there is a high potential of this approach to support preclinical and clinical trials but due to the high level of complexity and considerable uncertainty, it requires a steep learning curve to become a useful and accepted tool for medical device developers, researchers, regulatory bodies and policy makers.
