In silico clinical trials: how computer simulation will transform the biomedical industry

Abstract

<p class="abstract">The term ‘in silico clinical trials indicates the use of individualised computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical intervention. This review article summarises the research and technological roadmap developed by the Avicenna Support Action during an 18 month consensus process that involved 577 international experts from academia, the biomedical industry, the simulation industry, the regulatory world, etc. The roadmap documents early examples of in silico clinical trials, identifies relevant use cases for in silico clinical trial technologies over the entire development and assessment cycle for both pharmaceuticals and medical devices, identifies open challenges and barriers to a wider adoption and puts forward 36 recommendations for all relevant stakeholders to consider<span lang="EN-US">.</span></p>

An engineering paradigm in the biomedical sciences: Knowledge as epistemic tool

“…Several authors hold that understanding complex biological systems by means of systems biology and synthetic biology will lead to practical innovations in medicine, drug discovery and biomedical engineering (e.g., Ideker et.al. 2001, Kitano 2002a, Somvanshi and Venkatesh 2014, Carusi 2014, Dev 2015, Viceconti et al 2016). Somvanshi and Venkatesh (2014), for instance, defend in their Conceptual Review on Systems Biology in Health and Diseases -from Biological Networks to Modern Therapeutics that understanding diseases at systems level -which they conceptualize as 'disease systems engineering' -will facilitate work on cures for diseases, for instance, "by identification of rational drug targets, effective drug design with least side effects, effective therapeutic strategies, diagnosis of actual source of disease state, treatment on disease source rather than symptoms, early and reliable diagnosis of diseases using predictive models, rational toxicological and drug safety assessments leading to improved healthcare."…”

“…It is a framework that aims to be descriptive, integrative and predictive, and so have the potential to deliver personalized care solutions, reduced need for experiments on animals, more holistic approach to medicine, and preventative approach to treatment of disease" (http://www. Viceconti et al, 2016). In this document, the term 'in silico clinical trials' refers to the use of individualized computer simulation (i.e., in silico medicine technologies) in the development or regulatory evaluation of a medicinal product, medical device or medical intervention (Avicenna roadmap 2016, 10).…”

Precision Imaging: more descriptive, predictive and integrative imaging

“…Combined with virtual interventions (e.g. Larrabide et al, 2012;Morales et al, 2013), this approach enables execution of in silico clinical trials (Viceconti et al, 2016) or supporting of regulatory processes (Center for Devices and Radiological Health, 2014) especially in scenarios that could be impractical, costly or unethical (e.g. Larrabide et al, 2013;Morales et al, 2011) to carry out in animals or humans as a first line of choice.…”

In silico assessment of biomedical products: The conundrum of rare but not so rare events in two case studies

“…In the case of biomedical products these assessment activities are codified in regulatory evaluation frameworks, which are surveilled by agencies such as the Food and Drug Administration (FDA) in USA. Here we focus our attention on the so so-called In Silico Clinical Trials (ISCT), defined as ÒThe use of individualized computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical interventionÓ 1 . The keyword is ÒindividualizedÓ.…”

“…The United States Food and Drug Administration (US-FDA) is leading this trend, worldwide. In January 2014 they produced a draft guidance for FDA staff and industry on ÒReporting of Computational Modeling Studies in Medical Device SubmissionsÓ 1 . In parallel they contributed to the establishment of an ASME Standardisation Committee V&V-40 ÒVerification and validation in computational modeling of medical devicesÓ 7 .…”