Possible Contexts of Use for In Silico trials methodologies: a consensus-based review

TL;DR

This paper reviews potential applications of In Silico Trials methodologies in medical product development and regulation, based on expert consensus, and categorizes 46 possible contexts of use to guide future regulatory science.

Contribution

It provides a consensus-based taxonomy of 46 possible contexts of use for In Silico Trials, aiding regulatory and development processes.

Findings

Identified 46 possible contexts of use for In Silico Trials.

Organized these contexts into nine categories.

Reviewed 31 real-world examples from literature.

Abstract

The term "In Silico Trial" indicates the use of computer modelling and simulation to evaluate the safety and efficacy of a medical product, whether a drug, a medical device, a diagnostic product or an advanced therapy medicinal product. Predictive models are positioned as new methodologies for the development and the regulatory evaluation of medical products. New methodologies are qualified by regulators such as FDA and EMA through formal processes, where a first step is the definition of the Context of Use (CoU), which is a concise description of how the new methodology is intended to be used in the development and regulatory assessment process. As In Silico Trials are a disruptively innovative class of new methodologies, it is important to have a list of possible CoUs highlighting potential applications for the development of the relative regulatory science. This review paper presents the result of a consensus process that took place in the InSilicoWorld Community of Practice, an online forum for experts in in silico medicine. The experts involved identified 46 descriptions of possible CoUs which were organised into a candidate taxonomy of nine CoU categories. Examples of 31 CoUs were identified in the available literature; the remaining 15 should, for now, be considered speculative.