From syringes to workflow management systems, healthcare is no stranger to adopting new technologies into standard care. As digital and connected technologies continue to stake their claim in the industry, the last few years have seen the rise of a new type of health technology product — one that promises measurable health outcomes validated by traditional clinical trials.
“You had a little burst of [these ideas] years ago which were consumer focused, … a lot of concept ideas that popped out in the consumer space, or the wellness space, or the App Store that purported to be related to health, and so that felt like it’s been happening for the past 10 years,” Eddie Martucci, CEO of Boston-based Akili Interactive Labs, told MobiHealthNews. “But I think what was really happening underneath, sort of in the background, is that a small, select group of companies that were getting funding decided to deploy in a non-consumer, non-launch phase to do serious medical validation. That tends to take the kind of time that we’re talking about, a handful of years, … [and] what we’re seeing now is that first burst of validation.”
Martucci’s company is best known for the Project: EVO ADHD treatment, a novel therapy for pediatric patients that takes the form of a mobile video game. Project: EVO is among the many offerings increasingly being referred to as “digital therapeutics,” an umbrella phrase that encompasses a range digitally-focused healthcare products targeting specific medical conditions and therapeutic outcomes.
“It feels like we’re at the point of an industry that’s just birthed — or is exploding — because no matter where you look, you have digital therapeutics being mentioned alongside other medical approaches or other scientific approaches,” Martucci said. “I’ve had a lot of folks come up to me from conferences, from publications, and [point out] this coincidence. I think [it’s partially] coincidence how quickly this happened, but it seemed like a lot of players in the industry were poised to … really have defining moments.”
For Martucci, these defining moments included Pear Therapeutics’ de novo FDA clearance for its software-only substance abuse therapy, reSET; Proteus Digital Health and Otsuka Pharmaceutical’s clearance of a sensor-equipped pill that pairs with a companion app; and Akili’s recently concluded multi-center trial and very public filing for FDA approval. These milestones and others each landed within the span of a few months and, according to Pear Therapeutics’s Chief Commercial Officer Alex Waldron, bestowed digital therapeutics with a legitimacy that is hard for major players in the health industry (such as Novartis) to ignore.
“Everyone is very curious about how this model is going to play out because the physicians, payers, and patients are looking at this as a third segment: small molecules, biologics, and then digital therapeutics,” Waldron told MobiHealthNews. “It’s another way to be able to treat diseases that maybe have not been able to be treated to date.”
What’s in a name?
Despite recent events, digital therapeutics still have a number of roadblocks to surpass before they can sit alongside more established therapies. Chief among these is a clear definition of which products, exactly, can be considered a digital therapeutic as opposed to some other kind of health technology.
“Broad definition, the way we see it, is that digital therapeutics are something that is digital or software by nature, that engages a patient, and by virtue of the mechanics of the software can by itself or in combination with something else lead to clinical outcomes,” Martucci said. “I think the important parts there are the obvious digital piece, because that is by definition what it’s supposed to be, but then also the clinical outcomes. That’s where the therapeutic piece is really important — validated clinical outcomes.”
Martucci said that these general guidelines can encompass the various forms and approaches that digital therapeutics take, whether that be digitally-enabled drug delivery, software-driven behavior modification or disease management, or standalone digital products that directly activate physiology to achieve outcomes. But whereas Martucci’s definition of a digital therapeutic was broad, Waldron’s vision of proper digital therapeutics includes some very clear requirements: randomized controlled trials, Current Good Manufacturing Practices, well-implemented quality management systems, and the nod from a regulatory body.
“My opinion is slightly more stringent in the fact that I think the only way to get that kind of a firm outcome is having it reviewed by a regulatory agency, whether that’s the FDA or the EMA,” Waldron said. “Unless you actually get that imprimatur of an objective third-party regulatory body whose job is to determine what legitimately is efficacious or not, I have a hard time calling that an outcome in my mind. And I think historically payers have had a hard time paying for something unless it has been objectively viewed as well.”
Waldron’s point was echoed by Glooko CEO Rick Altinger, who argued that any product that does not require at least Class 2 FDA clearance should not be considered a true therapeutic. Altinger — who said that he considers his company’s recently approved Mobile Insulin Dosing System as another example of a digital therapeutic — also stressed the outcome- and market-driven role a therapeutic should have within the industry as a whole.
“Unless you’re driving a measure that has some economic benefit as well, I don’t think you’re a digital therapeutic. There’s a lot of Silicon Valley companies around here that are offering digital health solutions to people who are already healthy, and they don’t create a measurable outcome that has an economic impact on the payer,” Altinger said. “Really, you might want to also define a new category of product — digital health [versus] digital wellness.”
The importance of differentiating between “legitimate” digital therapeutics and these other digital health products is one of the key challenges that led a handful of startups to launch the Digital Therapeutics Alliance in October, Waldron explained. Among the goals of the industry group — which includes Pear, Akili, Propeller Health, WellDoc, Omada Health, and Voluntis — is the eventual release of a whitepaper that will provide a standardized definition of what its members consider a digital therapeutic, Waldron said.
To this end, the Alliance joined industry players and digital therapeutic hopefuls together this week for a two-day conference, the inaugural Digital Therapeutics Summit. Although the sold-out event was bookended by panels discussing how best to define a true digital therapeutic, Jason Green, cofounder and head of production at Grey Green Media, the life science conference company that organized and conducted the summit, said that participants and attendees alike are still searching for an answer to the question.
“The consensus leaving the conference was that we’re still not close to a finalized definition — there’s obviously high degrees of commonalities between these companies … [and] when it comes to attracting investors, having a name that sets them aside from general digital health wellness apps is really important to these guys,” Green told MobiHealthNews. “I think that will formalize and become more clear in the next few months, and there’s definitely going to be a lot of interest from people outside the industry looking in.”
Investigation and regulation
Finding a definition for digital therapeutics is a multilayered issue, largely driven by the mixed approaches to product validation that many digital health companies have taken.
Some, like Pear and Akili, have set out on a traditional FDA therapeutic approval path well worn by the pharmaceutical industry. While admittedly slow and costly, Martucci said that following established medical research protocols is the best way for a new product to establish its clinical value.
“If I’m going to use something in my treatment of a patient or in the mainstream medical world, I’d better believe it works roughly at the same level I would prescribe any other treatment or intervention,” Martucci said. “The excitement and the new and the shiny gives way to if this actually works, and that’s where I think the medical world is pretty unique. On the one hand, you can probably say that’s why the medical world moves a lot slower than other industries, because they’re hesitant to trust when they don’t have data that something works. On the other hand, it’s kind of the DNA of what makes medicine medicine: they’re not going to start using things until they know or have a really strong sense that this is positive for patients.”
An equally important of this approach for Waldron is that it legitimizes digital therapeutics across the industry. He said that with his company’s approval, others have a working model on how to conduct research, submit it to the FDA, and, assuming Pear’s plans pan out, see use in clinical care.
“Back in 2015 Pear went to the FDA and said we want to be regulated. And the FDA said ‘Well no one’s ever said those words to us before. Why would you want to be regulated?’” Waldron said. “… The answer is legitimacy. There’s a lot of digital health products, digital wellness, and diagnostic products that were out there, but nothing that actually had been validated by the FDA in a rigorous review process. Because of that, customers — and when I say customers I mean patients, patients’ physicians — didn’t really know what to make of the data that various company were coming out [with].”
Aside from recent approvals, the FDA does appear to be paving the way for more digital products. The agency’s pilot of a pre-certification program looks to limit the hassles of approving frequently updated health tech products, and includes a number of digital health companies ranging from Apple and Verily to the therapeutics-focused Pear.
“What I’ve seen from the precertification program is an acknowledgement by the agency that they are very enthusiastic, that they recognize that digital therapeutics are effectively a different animal than traditional pharmaceuticals or biologic products might be,” Waldron said. “The FDA has already come out to [our] San Francisco office this year trying to understand how we create things, how the quality management systems come into place, and how we’re likely to take data and improve the efficacy of the product.”
The decision now for many companies developing products that could potentially be considered a full therapeutic is whether or not to follow Pear and Akili’s lead. Jo Masterson, cofounder and chief operating officer of 2Morrow, said that her company has a handful of clinical trials completed and another on the way for its behavioral therapy app. While her company does consider its products to be digital therapeutics and is ultimately interested in FDA, she said that 2Morrow is willing to give the process some time.
“We’re on the behavioral side, which definitely gives you a little bit more flexibility than, say, prescribing or diagnosing. If you want to diagnose or treat, especially if it affects medication, the FDA says that that’s where [they] are going to focus their energy initially, people who are trying to diagnose and treat things where there are substantial risks of something going wrong,” Masterson told MobiHealthNews. “I’m excited to see what the FDA does, but it’s crazy. The cost of doing clinical trials and the time to do it are both not very supportive of the technology world, innovation, and what people are willing to spend.”
Masterson noted that her company’s product is primarily a digital delivery system of an already well-proven behavioral therapy, called Acceptance and Commitment Therapy (ACT). As such, jumping through the same regulatory hoops as a completely new therapeutic is not entirely reasonable for 2Morrow or similar digital products that are on the market, but unregulated.
“We’re not trying to prove that ACT can be effective for chronic pain — there’s 19 randomized controlled trials published already saying it can, it has strong empirical evidence. But we’re just trying to prove that we can also deliver this approach via the technology,” she said. “To expect people to do five-year randomized controlled trials is not very relevant because the technology will be old by the time the data comes out. If what you’re testing is the technology itself, we have to figure out reasonable ways to quickly assess things.”
Aside from those pursuing or interested in pursuing FDA clearance, both Waldron and Green noted a third group of digital health companies in attendance at the Digital Health Summit. Comprised of the digital health or wellness services who have few — if any — large trials under their belt, Waldron said these companies would likely forego the clinical trial route altogether and focus on disseminating their health products to as many users as possible to collect data and court future partners.
This approach may lack the FDA’s seal of approval, but Green suspected that the large number of summit attendees that fell into this camp indicates that they will still play a role in how the market will shape up.
“It’s was clear [from this week’s summit] that there’s obviously a small pocket of companies driving this space forward, certainly with going down that commercialization and regulation pathway. But there’s also a lot of companies that may not be about to really get their product paid for and regulator-approved, but are still far enough to have an impact on patients and make an impact on the space as well,” he said. “It’s an interesting dynamic from different business models. … Some of these companies that were in the room were certainly very interested, but wouldn’t have known what a digital therapeutic was before the conference.”
Engaging the industry
FDA approvals and the formation of an industry group are a shoe in the door for any nascent health tech space, and recent years have led to a marked change in how the healthcare industry’s biggest players are viewing digital technologies, Martucci explained.
“Back when these ideas were popping out and companies like Akili were getting formed, when we were sitting with pharmas there was a big dose of skepticism,” he said. “So, you’d get a meeting, and people would say ‘huh, that’s kind of interesting,’ but they’d also say ‘why are we talking about a videogame?’ … The fact that you’re seeing real mindshare and real [full-time employees] at pharmas put toward thinking through the tactics, not just the big pie in the sky vision but the tactics of how digital can either be directly used in R&D or even commercially, I certainly think it’s a turning point.”
Despite these gains and the eventual support from drugmakers, however, Martucci said that the market’s biggest hurdle for these novel products is still ahead.
“The high level is the initial nuanced commercial model and foothold — I think that’s the biggest challenge and opportunity. And I mean the whole bit of that, everything from the marketing, to the reimbursement, the deployment,” Martucci said. “It won’t be exactly like therapeutics today, nor should it be. I think the early companies in this space and anyone that partners with them get to define that in some way, and that’s pretty exciting, but to some groups it can be daunting.”
To successfully push into the healthcare market, Martucci said digital therapeutics makers will take new approaches to win over providers, pharmas, and payers. Courting the first of these should involve sales strategies generally similar to those of traditional therapeutics, Waldron advised, with special effort taken to stress the strengths of a digital platform.
“As our salespeople are walking into doctors’ offices, they’re not going to be going through the same thing a pharma rep would do on a regular basis, talking about features and benefits,” Waldron. “They’ll be doing all of that, but they’ll also be talking about how the product has gotten better since the last time the physician saw it. Was there a software update, was there a firmware update, or have we been able to take all of the efficacy data that we’ve seen from all the patients that are currently using this product and literally improve the efficacy of the product as the product continues to go on?”
So far, digital therapeutics have also managed to make some gains amongst healthcare’s entrenched infrastructure. Just yesterday, Novartis and Pear announced what the latter claims to be the first development deal between a pharma and a digital therapeutic. The agreement affects two therapeutics: Pear’s Thrive for schizophrenia, and another targeting mental health conditions affecting multiple sclerosis that will be developed jointly between the two companies.
“Our mission here at Novartis is to find innovative ways to improve and extend people’s lives and about 18 months ago we started seeing evidence around us that digital technologies might truly have that potential,” Joris Van Dam, executive director of digital therapeutics at Novartis, told MobiHealthNews. “We started our journey at that time speaking with a lot of academia and startups to understand which digital technologies truly have the potential to have a therapeutic effect on patients. We were very impressed with what Pear has done, and that was the start of our collaboration.”
Waldron said that the partnership is another step toward legitimizing their digital therapeutics and moving their other products into the wider healthcare market. On the payer side, he hinted at another upcoming announcement from Pear of “a full payer coverage with a national plan.” Speaking from experience, he explained that many of these companies are more than willing to give digital therapeutics a fair chance, so long as they prove that they can deliver results and drive savings.
“The way that I describe this to people when we specifically talk about the payer world and the way we think about our long-term strategy [is that] if you were to take our product, or any therapeutic product, and covered that with a cloth, and you didn’t know what was under the cloth but you talked … about the outcomes for patients that this therapeutic product would produce, they wouldn’t care, when you pulled that cloth off at the end of the discussion, if that was a pill, a vial, a biologic, or even a smartphone,” he said.
In a separate discussion with MobiHealthNews, Dr. Rhonda Randall, an osteopathic physician and chief medical officer at UnitedHealth Group, outlined a similar kind of outcome-focused mindset when describing her company’s interest in digital technologies and therapies.
“When we think about digital technologies and using data and technology to address the challenges of the healthcare system, we think about it very broadly,” Randall said. “There are many disease areas that are ripe for testing in special populations … whether that is a fitness tracker, which may not be a digital therapeutic, to something that is fully FDA approved and could be considered a digital therapeutic, like a CGM for example. I think we consider all of that … with certain goals in mind — can this technology help us take some of the fragmentation out of the system? Can this technology help it be a better experience for this consumer? Can this technology help take cost out of the system? So, asking those broader strategic questions rather than picking a particular [technology].”
Public payers, on the other hand, have shown less enthusiasm. Stephanie Tilenius, CEO of Vida Health, which offers digital coaching for chronic disease care, said that her company has found partnerships with providers, payers, self-insured employers, and pharma, but that reimbursement from CMS is still uniformly off the table.
“I really believe that you’re going to see digital therapeutics be bundled as part of the fabric of healthcare, so instead of going to the ER or your doctor or the hospital, you’ll pick up the phone or talk to Alexa and you’ll be able to get immediate care and help with your chronic condition,” Tilenius said. “But the one holdout is the CMS. Medicare is now reimbursing for diabetes prevention, but they’re only reimbursing for an in-person visit, whereas we have great outcomes for diabetes prevention; for example, we’re one one of the CDC-approved programs. … CMS needs to come around and accept these digital solutions as a standard of care. That would be a milestone.”
A rising tide
Since establishing the Digital Therapeutics Alliance, Martucci said that he’s been exposed to dozens of digital therapeutic hopefuls developing novel products and initiating their own clinical trials. Of note, the questions with which many of these companies have reached out to him and Akili have largely moved from the abstract toward more concrete sales and distribution tactics, a shift that he sees as a major sign of progress for the field.
Once a handful of these contenders have established their product and made it the market, though, he said that he expects the digital therapeutics industry to mold itself into a landscape of leading technology platforms backed by a handful of major players.
“That transition from one-off to true portfolio is something that tends, across any industry, to start to define the main players, the behemoths, and the growth of the industry is companies that have multiple products and core capabilities,” he said. “I think that you’re starting to see with some of these early players, the move … away from single-product validation to platform validation.”
At the moment, however, collective efforts such as the Digital Therapeutics Alliance and the Summit — recently reworked from an annual event to a biannual event due to high demand — suggest a budding industry that welcomes collaboration.
“I don’t think that we [in the Digital Therapeutics Alliance] see it as competition at this point,” Waldron said. “I think the bigger concern for that group, quite frankly, is to further legitimize that digital therapeutics are a new sector, that they are driven on a lot of the same parameters as small molecules and biologics, ... and to clear up a lot of the confusion that has existed within the digital world for a long time in terms of what is a legitimate therapy that is approved by the agency, as opposed to those therapies that have gone and conducted their own studies."
Waldron and Martucci's sentiment is shared by those outside of the alliance as well.
“We’ve been at this six years, we consider ourselves [among the] early people trying to do this, [so] we make friends with as many of the digital therapeutics, digital health people as we can," Masterson, from 2Morrow, said. "We kind of feel like when the credibility of the whole industry rises it helps everyone. They say ‘rising water floats all boats' … and when you’re early in things, I think it’s really critical that we learn from each other and try to figure out how the industry is going to move forward, not just individual businesses.”Nike Air Jordan 11Lab4 Retro 4 Patent Leather