The Living Heart: FDA renews contract with Dassault to evaluate 3D simulation, virtual patients
Dassault Systèmes today announced a five-year extension of its collaboration with the US Food and Drug Administration (FDA), through which the company will develop a new tool to increase efficiency in the regulatory review process.
As part of its work with the FDA, the company is exploring the use of heart simulation as a source of digital evidence and developing virtual patients based on computational modeling and simulation to improve the efficiency of clinical trials.
Since the initial collaboration was announced in November 2014, the Living Heart model has been refined considerably and a cloud-based commercial version is available on Dassault’s 3DExperience platform, said Steve Levine, chief strategy officer and senior director of virtual human modeling at Dassault Systèmes and founder of the Living Heart Project.
Over the last five years, Dassault has worked closely with the US agency to determine how it would interpret results provided by a medical device or pharmaceutical company that used the Living Heart model as digital evidence, showing “by virtue of running computations that they could prove with high confidence that their treatment works, is safe, et cetera,” said Levine.
“That’s been a big goal of our collaboration,” he said, and as part of this, the FDA published a guidance document addressing validation and verification with input from Dassault. “Through the process, we’ve helped [the FDA] understand the power of computational modeling and simulation,” Levine added.
Moving forward with a renewed collaboration, Dassault will conduct an in silico clinical trial, taking the Living Heart model and converting it to be representative of a specific patient population, with the goal of inventing a curative device. The trial will be run in collaboration with the FDA on Dassault’s platform and the agency will review the entire process digitally.
“We recognize that the process of bringing innovation and treatments to market are very much guided and gated by the clinical trial process, so it’s been a focus for us to see if we can help the industry reduce those costs, the time, and improve quality ... We’ve used the Living Heart Project and the collaboration with the FDA to help collectively understand how that’s possible," said Levine.
Ultimately, the FDA hopes to produce a template of a clinical trial or “review of the future” to demonstrate how it could conduct reviews faster, with more transparency, and at a lower cost for everyone, said Levine.
The second phase of the project is to use virtual patients based on computational modeling and simulation. As Levine explained, developing a virtual patient framework provides “a way of including virtual patients statistically into a real population.” This enables companies to “fill the gaps in-between the real patients,” he said.
Using virtual patients, researchers are not limited to the actual patient population who are able and willing to participate. But what is key, Levine said, is the ability to first conduct trials with virtual patient populations, “so you’ve already figured out how it works, when it fails, when it doesn’t, and now all you’re doing is validating on patients … And that’s a much smaller, faster, efficient process – that’s what we want to get to.”
Dassault has spent the last five years working side by side with the FDA and is ready to “take on this next big hurdle together,” said Levine. “The relationship that we’ve been able to build has given us really great insight into how they think and how they work, so that we can understand how to help all concerned.”
Discovering what’s possible
Dassault’s collaboration with the FDA was initially announced in November 2014, originally featuring 30 member organizations and 100 cardiovascular specialists.
In 2016, the team was able to simulate blood flow in the beating heart, and the platform was extended to simulate medical treatments of the brain. The following year, the Living Heart model was made available on the cloud.
Last year, the model was further developed to determine if a drug is going to cause an arrhythmia, which is the number one reason drugs fail in clinical trials, said Levine.
“So, if we can get it into virtual humans ten years before it gets into real humans we can also help identify the false positives,” he explained. “We can go all the way from the drug molecule all the way to blood flow.”
The Living Heart Project was founded five years ago as a so-called “lighthouse project,” to explore the possibilities of 3D heart simulation. Through its work since then, Levine and his team found “quite a bit” is possible. While the company has yet to organize other parts of the body in the way it has with the heart community, it is taking that learning and applying it to other areas, such as the brain, eyes, lungs, knees and elbows, to name a few.
“We’ve been quite productive on taking that methodology and knowledge that we’ve learned from the Living Heart Project and applying it to the rest of the body,” said Levine, “which was certainly one of my hopes back then, but I wasn’t sure whether that would be reasonable. But now I know it is.”
Today, there are 130 organizations across 24 countries participating in the Living Heart Project. Industry involved includes pharma giants such as Bayer and Pfizer, as well as Boston Scientific and Medtronic, among others.
Said Levine, “The industry requires a lot of momentum to move, but you’re definitely starting to see it.”
Moving forward: How to improve the industry?
Dassault’s customers include pharmaceutical and medical device companies all of which want to be more innovative and continue to provide safety – and are also trying to embrace digital technologies to make health care more mobile and patient-centric, said Levine.
“A lot of what they are thinking about is how to evolve their products, so they can work in a more open and dynamic environment,” he explained, noting that “open and dynamic is not usually consistent with a high degree of regulatory control.”
To help its customers achieve these goals, Dassault is drawing on its experience in other industries, such as in automotive and aerospace, where managing risk is pertinent, though as Levine said, “you can control what you build when it comes to a car, you can’t necessarily control the human body.”
“So, we have to reverse engineer how the human body works,” he explained, which is why it has taken longer to develop computational models in this space. Still, Levine said the problems are completely analogous.
The company also is interested in moving forward, downstream into the health care delivery space, working directly with clinicians to help create continuity between the companies that create the treatments and those who deliver them.
Levine said the goal is to create a better feedback loop, “so the patient experience becomes clearer to those companies that are creating those innovations … closing that entire lifecycle, which is the way that we’ve built our platform for other industries.”
While unable to comment on the company’s proposed acquisition of Medidata, announced last month, Levine said the deal is in line with the company’s goals.
“As we think about our investments going forward,” he said, “identifying a company like Medidata is logical, with respect to our hope about how we can improve the industry.”