In-depth: The path to market for digital tools for mental health and neurological conditions

By Heather Mack
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The human brain and the seemingly infinite number of health complications that can befall it are complex. As such, there aren’t universally agreed-upon therapies and treatments for conditions ranging from depression and chronic pain to stroke and Parkinson’s disease. But recent, rapid advances in neuroscience research and digital technology are enabling a new wave of tools to gain traction in neurological or mental health settings.

And while the conditions they are working to treat are anything but straightforward, the method by which these digital tools are coming to market is actually more clear-cut. The key? Partnerships.

Buoyed by new insights and capabilities, major medical and research institutions are sounding the call that they want to work with digital health companies in this space. For example, Duke Clinical Research Institute just hosted its first ever symposium on neuroscience in clinical digital health trials. Companies putting out these products aren’t finding a foothold in healthcare simply because the technology seems exciting, but also because they have demonstrated they are taking their innovations seriously, with rigorous clinical validation processes and an eye on regulation, and even teamed up with pharmaceutical companies.

One example is Akili Interactive Labs, which makes app and web-based neurocognitive assessment games to detect and, hopefully, one day help treat conditions like pediatric ADHD and Alzheimer’s. Akili is currently conducting multiple clinical trials across a variety of patient populations. Most recently, the company released results from a study conducted with Pfizer, and they are working towards completing the clinical trials necessary to receive FDA approval by the end of the year.

Eddie Martucci, CEO of Akili, said as his company has always worked with pharmaceutical companies, and, in the last year, they’ve noticed a cultural shift within the industry that is really starting to drive digital innovation.

“I’ve seen a big change mostly in the last year where there has been a shift been toward what we think about what we mean by digital,” he said during a recent panel at the Experiential Technologies Conference in San Francisco. “We don’t think about digital as helping to seek out another product. We don’t think about digital has helping to make some other really well-known old school product better. We think about digital as products. More conversations we are starting to have are not 'Hey, can you make my trial better?' They're like, 'Ok, so you have a monitor, you have a digital treatment. What's the long-term, commercial infrastructure for that and how does that figure in with us?' The fact that those conversations are being had means to me that the thought process is changing. And we're seeing the same level of things happening with big medical device companies as well.”
 
While pharma, which is in some ways a digital health latecomer, is learning how to work with tech companies to innovate, these newer companies are also learning how to work through better clinical trials and keep their eyes on regulation and reimbursement.

Andrea Serino, head neuroscientist at Switzerland-based MindMaze, which is working on VR product to help stroke victims through their recovery, said the need for regulation keeps his company focused on amassing solid evidence. For companies seeking multiple regulatory clearances (MindMaze has a CE Mark, but not FDA clearance), the right partnerships become even more important.

“It's really about combining the need [for] evidence one side, the clinical side, and [on the] other side to cope with regulation. And we are trying to make it so that it is more based in Europe, so we have to deal with regulation of different countries, which you might find strange because the patients are the same everywhere,” Serino said during the panel. “I think with the partnership with pharma and digital health --there are a couple of reasons to do it: one, to combine [digital treatments like VR with traditional pharmaceutical treatments]. The other is to try different messages and use multimodal approaches, especially when you are dealing with neuroplasticity problems. For instance, you can use several ways to promote plasticity in the brain and with VR.”

For AppliedVR, some of the burden of regulation is shifted to their hospital partners, since they don't make medical claims about their software or offer it directly to consumers for therapeutic purposes, but that doesn’t mean the company has been able to forgo proving they are worth it to patients as well as payers. Originally, AppliedVR didn’t know what their role would be in healthcare, but the opioid crisis in America created a huge need for methods to deal with non-medication based pain management, so Cedars-Sinai approached them with a call to be part of their TechStars accelerator program.

“By far, it was one of the best decisions in our lives because it got us to one of the top 20 hospitals in the country,” AppliedVR CEO Matthew Stoudt said during the panel. “They fully integrated us and are becoming our lead client. All the other healthcare systems are calling them up, and asking about their experience with us, now we are getting supported by payer side of the equation.”

Payer reimbursement remains one of the biggest challenges in healthcare innovation, and while Stoudt couldn’t share who their partner will be, he said AppliedVR is expecting to have the level of reimbursement that will make the technology available for many patients, even if they aren’t in a forward-thinking hospital in a major urban area. Since the company provides the healthcare-focused VR content and clinicians take it from there to design how it will be used, AppliedVR isn’t on the hook for regulatory clearance. That said, they couldn’t be where they are today without the Cedars-Sinai association and a reimbursement plan.

“Once you start to see that momentum – that flywheel spinning – it starts to completely accelerate what you are doing, but you've gotta have an advocate,” he said. “For us, we couldn't do it unless someone completely bought into it and said, 'This is the future.' So that was what helped us the most.”

For those who don’t have a health system approaching them, working alongside pharma and meeting early and often with regulators is helping them prepare to enter the market. Corey McCann, CEO of Pear Therapeutics, actually started his company specifically thinking about pharmaceutical companies for a number of reasons: the clinical efficacy would be there, as would the intellectual property and nuanced understanding of regulatory and reimbursement environment. Like Akili, Pear has yet to bring products to market, but the company is working on eFormulations, which combines medication for conditions like substance abuse disorder with a digital therapy program. While McCann himself had a solid background in neuroscience and venture investing, breaking into digital neurotherapies wasn’t easy for Pear or for pharma.

“It's absolutely been a steep learning curve for us. These are very different worlds and I often joke that for roughly the first six months of the company's life, the tech team was using the acronym API and so was the healthcare team, but we were meaning entirely different things. So these are different languages, and I think because of that, it’s been hard for pharma to approach,” McCann said during the panel. “Frankly, the digitalization of the pill is somewhat obvious, but this is still not terribly emergent. That said, it's been a very tough business for them to wrap their minds around.”

What digital health innovation has changed is pharma now has the ability to streamline tactics to run their big phase III steps, and that comes from a close eye on regulation requirements.

While Stoudt acknowledged their position with Cedars-Sinai relieves them of that burden, he said he sees AppliedVR and other digital neurotherapy hopefuls are becoming more involved with the FDA as a means of education, even if it may scare off investors and entrepreneurs initially.

“Of course, that creates a fear on the investment side. I think if they see, hey, you are going to go down this FDA approval path, that's a lot of money, a lot of time, I think if you can kind of avoid it a bit if someone is trying to figure out that workaround,” he said. “The other one is the FDA is this notion is that it is 1,000 shades of gray. We had a call with someone recently and we only found him because we were buried 15 pages deep on their website.”

Getting more familiar with the FDA may make for more tech-friendly policies within the agency, and the FDA has shown recently they are more willing to have interactions not just with tech companies but with patients to learn about real world evidence and early-stage digital clinical trials.

“I don't want to regulate, our preference is not to,” said Stoudt. “But we have to think about the three things: claims you make, risk factor and use. But if we can avoid regulating, we want to, but I do wish they would be more open to at least having conversations about this. The more we get engaged with them, the more we can actually help to shape the policy as much as we interact with the policy.”

For Akili and Pear, they are different than other digital health tools that may avoid making outright claims, as they are driving straight towards FDA clearance. They believe the rewards are worth it: they will reap quick adoption by healthcare providers and users as well as payers.

“There, the evidence bar is relatively clear: large, randomized controlled trials, usually a couple different data sets, not just a trial data set. And by both a safety and efficacy profile that justifies it as a true medical device,” said Martucci. “We have a pretty solid path we are working towards, so it would be like, ‘For the treatment of ADHD. Full stop.’ and similar for cognitive decline or depression. Those kinds of claims are very clear medical claims, very clear evidence claims, and the FDA does have ways to handle them. And it's not just about FDA. When we sit with docs, you know, your average prescriber of an ADHD medication is not an early adopter tech nerd. Your average prescriber of an ADHD medication is a doc that is very used to and quite frankly, very comfortable writing a script for Adderall or Ritalin. So, from that perspective, you need something that can very neatly and very cleanly stand there as a treatment alongside Adderall. For that, there is a clear FDA path and a clear medical claim path.”

And of course, in healthcare, getting paid is not nearly as straightforward as tech companies may wish.

“Reimbursement is flatly the bottom line,” said McCann. “For most of us up here, we've got two strikes against us. We are dealing with something that has something to do with mental health, and that's easy to say no to. Number two, we're providing a new treatment modality, and that is also something that is easy to say no to. So the deck is stacked against us. That said, reimbursement is really key to see that through.”

While we are still waiting for many of the digital tools for neurological and mental health therapies to officially launch, the go-to-market strategies are already evident. Understanding the brain may still be the final frontier in healthcare, but digital innovation targeting it is finding its path.