Using virtual subjects for clinical trials can be as effective as using real patients, the results of a recent study have shown.
In an evaluation of a medical device designed to treat brain aneurysms, which used virtual as opposed to real patients, the results proved successful in replicating those seen in traditional clinical methods.
The results of the study were published in Nature Communications.
Known as in-silico trials, researchers conducting this type of study create digital simulations of patient groups. These trials have the potential to reduce the time and costs associated with the development and testing of new medical devices and medicines, whilst also reducing human and animal harm in testing.
Using virtual populations to test a flow diverter
The international research, led by the University of Leeds, investigated whether an in-silico trial could replicate the results of three, real-life clinical trials that assessed the effectiveness of a device called a flow diverter, used in the treatment of brain aneurysms.
A flow diverter is a small, flexible mesh tube which is guided to the site of the aneurysm by a doctor using a catheter. Once in place, the flow diverter directs blood along the blood vessel and reduces flow into the aneurysm, initiating a clotting process that eventually cuts the aneurysm off from blood circulation, thus healing it. Without successful treatment, the aneurysm can burst causing a bleed on the brain and a stroke.
To establish their proof of concept, the researchers had to see if the results from their in-silico study mirrored the results from three previous major clinical trials into the effectiveness of flow diverters.
Conducting a virtual trial
The researchers built a virtual population using real patient data drawn from clinical databases, ensuring that the anonymised virtual patients closely resembled the patients used in real flow diverter clinical trials in terms of age, sex, and aneurysm characteristics. They then built a computational model that analysed how the implanted device would affect blood flow in each of the virtual patients. They were able to study different physiological conditions for each patient, such as normal and high blood pressure, and perform analyses on patient sub-groups, such as those with large aneurysms or aneurysms with a branch vessel.
The in-silico trial had 82 virtual cases. The traditional clinical trials had 109, 141, and 207 patients, respectively. Around half the cases in the traditional trials had high blood pressure.
The results of the in-silico trial predicted that 82.9% of the virtual patients with normal blood pressure would be successfully treated with a flow diverter. In the traditional clinical trials, the number of people who were successfully treated was 86.8%, 74.8% and 76.8%, respectively, showing that the in-silico trial closely replicated the results of the traditional clinical trials.
Benefits of in-silico trials
Professor Alex Frangi, Diamond Jubilee Chair in Computational Medicine and Royal Academy of Engineering Chair in Emerging Technologies at the University of Leeds, who supervised the study, said: “The results demonstrate the huge potential of in-silico trials. We have shown that the approach can replicate the findings of traditional clinical trials – and they do that in a fraction of the time it normally takes, and at a fraction of the cost.”
In the in-silico trial, the researchers were also able to adapt their computational model to investigate new hunches or emerging scientific findings.
By modelling the physics of blood flow and the biochemistry of blood clotting in aneurysms under different physiological conditions, they were able to identify sub-groups of patients at higher risk of stroke, with patients with large complex-shaped aneurysms at higher risk of haemorrhagic stroke and patients with hypertension at higher risk of ischaemic stroke. Being able to rigorously analyse medical device performance in this way will allow biomedical engineers to optimise the device design and reduce the risks associated with treatment.
Reducing the time of clinical trials
Professor Frangi said: “In-silico trials offer an opportunity to do virtual experiments that could explain concepts that are difficult to study in conventional clinical trials.
“The current approach to improve our understanding of new medical devices is slow, as conventional trials can easily take five to eight years, from their design to completion.
“In-silico trials could reduce this period to less than six months in some circumstances, making knowledge and therapeutic technologies safer and more promptly available to clinicians and patients.”
The research involved an international collaboration of scientists from Leeds, the University of Oxford, Radbound University Medical Centre in the Netherlands, and KU Leuven in Belgium.