In Silico World: Lowering barriers to ubiquitous adoption of In Silico Trials

Project Information

ISW

Grant agreement ID: 101016503

DOI

10.3030/101016503

Project closed

EC signature date 4 December 2020

Start date 1 January 2021

End date 31 December 2024

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 7 646 012,25

EU contribution

€ 7 646 012,25

Coordinated by

ALMA MATER STUDIORUM - UNIVERSITA DI BOLOGNA
Italy

Periodic Reporting for period 3 - ISW (In Silico World: Lowering barriers to ubiquitous adoption of In Silico Trials)

Reporting period: 2024-01-01 to 2024-12-31

Summary of the context and overall objectives of the project

The cost of developing a new medical product has been growing exponentially in the last 30 years; some experts suggest that it might cost more than a billion EUR to develop and bring to the market a blockbuster drug, and it usually takes between 5 and 15 years. This is primarily due to the “trial and error” approach used, which is safe and effective, but also wasteful. In many other industrial sectors, similar problems have been solved with the use of computer modelling and simulation, but in the biomedical sector, some barriers are slowing down the adoption of the so-called In Silico Trials, computer simulations aimed at assessing the safety and efficacy of new medical products. The objective of the In Silico World (ISW) project was to lower such barriers.
A cheaper and faster approach to the development and testing of medical products would mean cheaper medical products, and thus lower spending in healthcare, due to the ageing of the population. More and better products could reach the market faster, ensuring better care for all suffering citizens. Lower development costs would lower the entry barrier in this market. Smaller companies could start developing and commercialising their products, competition would increase, prices would lower, and innovation would accelerate. ISW aimed to accelerate the uptake of in silico trials in the biomedical sector by improving model credibility, regulatory readiness, scalability, and usability across clinical and industrial settings, but also by providing better information on In Silico Trials to all stakeholders, analyse the legal and ethical landscape in the EU, and testing different business models to commercialise such technologies. The consortium of 15 EU institutions, including 7 universities, 3 companies, 2 research hospitals, and 3 not-for-profit organisations, worked together to pursue such an objective.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

ISW project completed the development of 38 tangible results. 11 In Silico Trials solutions were further developed; 4 are now commercially available, and a well-defined certification and commercialisation trajectory has been defined for all. These simulation technologies can reduce, refine, and in some cases replace animal and human experimentation in developing treatments for osteoporosis, tuberculosis, multiple sclerosis, heart diseases, foot diseases, mammary cancer, brain aneurysms, muscle weakness, osteoarthritis, and COVID-19.
We also developed and publicly released 7 collections of experimental data to validate the accuracy of these and similar simulation technologies. The publicly available validation collections are precious, as researchers developing new In Silico Trials can compare their technologies using such collections. This will accelerate the development of new and better In Silico Trials.
We also made publicly and freely available 9 processes, including two complete qualification dossiers with the European Medicines Agency, initiated the development of a new technical standard valid in the EU, published a freely available book on Good Simulation Practices, various briefs and recommendations on better European policies to broaden the use of In Silico Trials, economic impact analyses to guide industrial investments, educational curricula and online course to train and re-train the workforce on the development and use of In Silico Trials.
We also completed 10 services, including an Inventory of all relevant legal and ethical issues related to In Silico Trials, and online Community of Practice involving over 700 experts worldwide, more efficient computational methods enabling computer simulations that test a new treatment on thousands of virtual patients, more efficient services to train AI surrogate models and to executed very large agent-based models, and four commercial exploitations including two software-as-a-service, one software-enabled consulting service, and one conventional software selling.
On the open-access online repository Zenodo (https://zenodo.org/communities/insilicoworld-openaccess/) we created an ISW community which now hosts 56 digital resources. The open-access book on Good Simulation Practice (https://link.springer.com/book/10.1007/978-3-031-48284-7) was released in February 2024 and has been downloaded more than 44,000 times so far. On YouTube, the VPH Institute channel (https://www.youtube.com/@VPHINST) hosts various informative videos on In Silico Trials.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The 7 barriers to the adoption of In Silico Trials we tackled were: better simulations, validation data, and regulatory barriers, better informed stakeholders, computationally efficient simulations, a better educated workforce, and better business models.
Our project further developed 11 In Silico Trials solutions: four are commercially available, and the others are on a trajectory to become available soon. Today, we have much better In Silico Trials simulations.
While it is a drop in the sea, our seven validation collections are inspiring much broader initiatives, such as the new EU flagship initiative named Virtual Human Twins (https://www.virtualhumantwins.eu/) whose centrepiece is the sharing of large validation collections.
The regulatory landscape around In Silico Trials is much better today than in 2021. For In Silico Trials aimed at developing medical devices, there are clear regulatory pathways in Europe and the USA, and technical standards that guide the credibility assessment of new solutions. There is cultural resistance to medicinal products, which is slowly being eroded. Already, EMA followed one of the ISW project recommendations and separated the scientific advice on drugs from that of drug development methodologies. Meanwhile, there is a well-defined space of opportunity for In Silico Trials as drug development tools to replace animal testing for preclinical testing, and in specific cases where clinical experimentation is challenging
Policy briefs, Info-kits, YouTube videos, podcasts: thanks to the ISW project, there is plenty of information on In Silico Trials for citizens, policymakers, clinicians, and industrialists.
Computational scalability and efficiency have improved dramatically. Our BoneStrength solution has now predicted the risk of hip fracture as a function of different treatments in more than 6000 virtual patients. Using an AI surrogate model can accelerate some In Silico Trials simulations 1000-fold.
The ISW has produced intended learning outcomes, curricula, and educational materials for teaching In Silico Trials in engineering and biomedical degrees, and also to re-train the technical and non-technical workforce in industry, regulatory agencies, healthcare, and governmental organisations. Less than one year after its release, our teaching materials are already in use in two master’s degrees, one PhD programme, and various professional re-training courses.
ISW has explored 3 different business models to sell In Silico Trials: software-as-a-service, software-support consulting services, and traditional software licensing. Compared to four years ago, meanwhile, there has been a rapid growth in the number of startups that sell In Silico Trials services and products; also, large simulation software companies such as Ansys or Dassault now have a biomedical division.
The ISW project has influenced European and national initiatives, with its outputs now leveraged in numerous ongoing projects (e.g. EDITH, ICS-C, DARE, Heal Italia, Metastra, InSilicoHealth).

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