Dr Tina Morrison, US Food and Drug Administration, USA (TBC)
Dr Flora Musuamba, European Medicines Agency
Symposium Co-Chairs
Alfons Hoekstra, Assistant Professor, University of Amsterdam
Marco Viceconti, Professor of Computational Biomechanics, University of Bologna
Symposium Description
An important application of Virtual Human technology are In-Silico Trials (IST). ISTs should contribute to the three R’s, refinement, reduction, or replacement of pre-clinical and clinical trials. Driven forward by the Virtual Human community, the Food and Drug Administration (FDA) in the US, the European Medical Association (EMA), and the Avicenna Alliance, and with funding through, for example, the European Commission, a number of projects developing and applying ISTs are underway. The challenges they face are multifaceted, ranging from validating the underlying in-silico models of specific pathophysiology or applied virtual populations, via technological and infrastructural demands, to regulatory issues. The goal of this special symposium is to bring together key stake holders in the current development of ISTs, to highlight state-of-the-art developments, to discuss the challenges that ISTs are facing, and to contribute to next steps in successfully applying IST in actual (pre-)clinical settings.
Marketing approvals of (new) medicinal products (and combinations) generates large interests of both patients in need of new medicinal therapies and the sponsors (big pharmaceutical industry, SMEs, and academia). Before a new medical product can be used on humans in a country, it must be approved for that use by the relative Regulatory Authority of that country. In USA, this will be the remit of the Food and Drug Administration (FDA) drugs and medical devices whereas in the European Union pharmaceuticals are approved by the European Medicine Agency (EMA) mostly and by national competent authorities to a lesser extent. The approval of medical devices is delegated to the member states, through selected notified bodies.
Consequently, regulators have to find the appropriate balance between the need to ensure that decision-making is based on scientifically valid data and the need for access to the new medicines is considered. Full Abstract
Coronary Artery Disease (CAD) is the leading cause of death in Europe and worldwide with more than 17 million deaths [1]. Atherosclerosis, the major disease process of CAD, is a chronic inflammation driven by the build-up of atherosclerotic plaques inside the coronary arteries. Bioresorbable Vascular Scaffolds (BVS) revolutionised the field of interventional cardiology by providing targeted drug delivery, mechanical support and complete resorption overcoming the barriers of bare-metal and drug-eluting stents. In vitro and in vivo experiments followed by clinical trials are currently used in providing useful information on the safety and efficacy of BVS. However, these processes are time-consuming and costly. In parallel, they raise ethical considerations due to the uncertainty related to the extremely well performance in controlled laboratory experiments and pre-clinical studies, and potential under performance during or after clinical trials. Full Abstract
In-Silico Trials (IST) represent an innovative application of Virtual Human technology helpful in assisting and supporting the refinement, the reduction, or the replacement of pre-clinical and clinical trials. In this multifaceted challenge perspective, the regulatory authorities are facing with an increasing number of projects developing and applying ISTs ranging from validating underway in-silico models of specific pathophysiology or applied virtual populations, via technological and infrastructural demands. The last few years have been characterised by an intense activity around the so-called regulatory science, aimed to ensure a robust approach to assess the credibility of individual in-silico methods as sources of regulatory evidence (Viceconti et al., 2017; Pappalardo et al., 2018a; Morrison et al., 2018). Full Abstract
The clinical assessment of new drugs against osteoporosis is a particularly expensive one. Ideally a clinical trial should have fragility fractures as primary outcome, and should follow-up patients for at least five years, but this would bring the cost and time-to-market to unacceptable levels. A quick search on https://clinicaltrials.gov shows that Romosozumab, one of the latest drugs brought to market has been studies either with indirect outcome metrics (such as bone density), or at most observing fractures over 24 months. While this is probably adequate for the specific purposes of those trials, the possibility to assess the efficacy of these new drugs with in silico trials is of extreme interest. Full Abstract
Familial cardiomyopathies (FCM) are most commonly diagnosed, or progress of the disease is monitored, through in vivo imaging, with either echocardiography or, increasingly, cardiac magnetic resonance imaging (MRI). The treatment of symptoms of FCM by established therapies could only in part improve the outcome, but novel therapies need to be developed to affect the disease process and time course more fundamentally. In SILICOFCM project we are doing in silico multiscale modeling of FCMs that would take into consideration comprehensive list of patient specific features (genetic, biological, pharmacologic, clinical, imaging and patient specific cellular aspects) capable of optimizing and testing medical treatment strategy with the purpose of maximizing positive therapeutic outcome, avoiding adverse effects, avoiding drug interactions, preventing sudden cardiac death, shortening time between the drug treatment commencement and the desired result. Full Abstract
