Pappalardo F et al. published a recent paper (in the IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS) advocating for a roadmap towards the CE marking of medical devices based on in silico trials. In silico trials simply mean the use of computer modelling and simulation in healthcare and is in effect a clinical trial simulation. Although computational modelling may have been in use heavily in the pharmaceutical industry to identify new molecular targets and drug candidates, the use in the medical device industry is still very much under development.
The modelling may be used for three main purposes:
- Digital Patient solutions, where the model predictions operate as clinical decision support (CDS) systems mainly to be used by clinicians.
- In Silico Trials, where computer models and simulations enable the evaluation of the safety and efficacy of new medical products.
- Personal Health Forecasting solutions, where the end users are the patients themselves.
In silico trials are not widely recognised as a means of producing clinical evidence, although the EU MDR does not exclude the use of evidence produced using computer modelling and simulation; in annex VII it explicitly acknowledges computer modelling as one possible source of evidence. The regulation specifies that, where appropriate, “the results of biophysical or modelling research the validity of which has been demonstrated beforehand” may be considered in relation to the device requirements regarding design and manufacture.
Using a Roadmap
The paper proposes a roadmap that includes formulation of working groups within the ISO and IMDRF to study the integration of such solutions as well as the appropriate methodologies to be developed. Their proposed roadmap is well thought out and well described.
Although, the advantages are clear (reduction in costs, less use of animals for experiments, less human participants in trials) the pitfalls are also clear for anyone who understands the complexity of biological systems and their interactions. In addition, such generalisation in biological understanding (a model is the aggregate of multiple data points towards an average or mean model) clashes with the advent of personalised medicine which recognises the uniqueness of an individual at the genetic/ molecular level and their individual therapeutic and care needs.
It may, therefore, be the case that such in silico trials will only be able to provide a small fraction of useful evidence until the time we fully comprehend everything there is about the biological system or process to be studied, if such time ever arrives. Otherwise, wrong input will lead to wrong conclusions, and we may end up with situations like the PIP breast implant scandal 15 years down the line.
There is a natural appetite from a galloping data science industry to prove its real-life value and to some extent it will. In silico trials may be used as a pivot to provide a theoretical framework, not dissimilar to the multitude of molecular targets and drug candidates but as we know from the pharmaceutical industry, only a very limited number make it through to the market. Robust regulatory requirements to account for reproducibility of real-life results would be essential, lest we forget what these devices are meant to do. Namely, interaction with real flesh, bones and blood.
How can RQM+ help you?
Our clinical and regulatory experts, including our Medical Directors, have extensive experience to advise on the value of such trials and the best way to integrate them into your clinical development plan in producing sufficient evidence for your first regulatory submissions. Contact us today to learn more about our team of experts and how we can support your clinical and regulatory needs.
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