Member Perspectives | TaaS: Treatment as a service

This article was written by Dr's Arpan Parikh, Amit Parikh, and Logan Dalal. You can also check out their work on their Substack, Two Docs and a Stack

TL;DR: While digital therapeutics hold real promise, we have hurdles to cross in order to bridge them from being overhyped to a more sustainable future.

Intro

Over the last 3-5 years, the idea of a digital therapeutic (DTx) has enamored 😍 the healthcare community. As we’ve entered a golden age of technological innovation and smartphone adoption 🤳🏽, the allure of creating evidence-based, clinically validated treatments that are delivered digitally, instead of orally, intranasally, or intramuscularly, has grown exponentially. However, despite record fundraising in 2021 by DTx companies, adoption by clinicians and uptake by patients has been slow. By exploring the history of DTx and reviewing the ‘how’ behind the ‘what,’ we hope to shed some light on why we think DTx are making their way from the peak of inflated expectations to the trough of disillusionment📉, and what might come next for this promising yet underutilized treatment modality. In this article, we will explore how three prominent conditions being targeted by DTx - insomnia, substance use disorder, and ADHD - are moving along the hype curve, and what we can learn from each other about how the DTx space will move forward.

We’re excited to have an expert contributor collaborate with us on this piece; Dr. Logan Dalal is a Columbus, OH based, Harvard-trained sleep doc 💤 with deep interests in digital sleep tech. As mentioned above, insomnia is one of the key conditions targeted by DTx manufacturers (is that the right word - should we call them platforms / builders instead?) and he brings a knowledgeable perspective on this disease state.

The history, and how they work

The concept of a digital therapeutic was first mentioned in peer-reviewed medical literature waaaay back in 1995, by Sepah et al. They defined a DTx as evidence-based behavioral treatments delivered online that can increase accessibility and effectiveness of healthcare. Fast forward a few years, and the Digital Therapeutics Alliance (DTA) has refreshed this definition to [the delivery of] evidence-based therapeutic interventions to patients that are driven by software to prevent, manage, or treat a medical disorder or disease.

The intention behind DTx is completely sound and it’s understandable why they generated so much hype: we now have a new means (digital) 📱 to deliver treatment for a subset of illnesses which are responsive to this modality. As our country’s shortage of clinicians to treat the population continues to grow, the idea of using a (relatively) infinitely scalable treatment becomes increasingly attractive.

Much of the work in this space has centered around behavioral health, for reasons that are apparent - of all the medical specialties, ours is the one that has best embraced non-medication and non-interventional treatments. This is a function of the diseases we treat being amenable to behavioral interventions and psychotherapy, a luxury not afforded to many other fields in medicine (good luck treating a cerebral aneurysm or hypothyroidism with psychotherapy).

The DTA has defined DTx using broad brushstrokes 🖌️. These broad brushstrokes have likely contributed to the hype that has been generated around DTx. A tool as simple as an app-based food diary, or an app-based sleep tracker, could be considered a DTx under this wide-casting net. However, we believe that in order to cross the bar from being a (no doubt helpful) digital tool, to a bonafide digital therapeutic, there must be an impact on the underlying pathophysiology of the disease. We advocate for focusing on evidence-based therapeutics with validated clinical efficacy as one means for the DTx industry to move forward successfully.

DTx Progress: Insomnia, SUD, and ADHD

For the three disease areas we’ll cover today (insomnia, substance use disorders, and ADHD), DTx development has largely revolved around existing, evidence-based psychotherapeutic treatments which can be translated to a digital, semi-automated modality of treatment. While we (as a society) tend to talk about psychotherapy with quite loose terminology, it’s important to remember that psychotherapy is a highly evidence-based, rigorous, and precise 🎯 treatment. We have a significant amount of data showing that psychotherapy leads to positive behavioral changes, impacts the sense of self and consciousness, and also impacts the pathophysiology in the brain 🧠that is responsible for the symptoms it treats. So let’s dive right into these three conditions, kicking off with insomnia…

Insomnia 🛏️

What is it: Insomnia, an inappropriate wakefulness, affects 30% of the world’s population (conservatively). Simply, it’s the inability to sleep with resulting daytime impairment. In reality, it's a complex disease process with multiple underlying mechanisms, including mismatched circadian rhythms (‘body clock’), neural-hormonal imbalances (think GABA, Histamine, and Hypocretin), psychiatric conditions and environmental factors which coalesce. 

Treatment challenges: Treatment is founded on two major mechanisms: optimization of neurotransmitter dysfunction and behavioral modifications. Medications include the use of sedative-hypnotics such as benzodiazepine receptor antagonists, colloquially called ‘z’ drugs and known to many Americans by their brand names (Ambien, Lunesta, etc.). Given the similarity of these drugs to benzodiazepines, there has been concern of potential side effects in the elderly such as dementia, and fall risk. Moreover, there are concerns about their misuse, given their tendency to create dependence and tolerance (which can over time even lead to addiction). As such, over the recent years Cognitive Behavior Therapy for Insomnia (CBT-i) has been heralded (rightly so) as the gold standard for initial care. Unfortunately, with limited providers, duration of treatment, and high cost, access has been sparse:

1. If you’ve tried to find a therapist for yourself (or refer your patients to see one), you know that wait times today for therapists are on the order of weeks to months 🗓️ (which is too long to wait when one can’t sleep).

2. Psychotherapy also takes a commitment - we’re talking about protocols that require weekly visits for multiple months before they reach full efficacy.

3. And finally, even if a patient is willing to put up with the lead time and time to onset, the cost of psychotherapy can be prohibitive to many Americans, as more and more mental health clinicians opt out of the insurance system altogether (as our colleague Dr. Muir has written about).

It's quite easy to see where DTx fits into the bigger picture. There is potential to expand access for insomnia care, as well as re-engage both patients and clinicians alike with gold standard therapy.

Illustrative example: Pear Therapeutics 🍐, once again, has shown to be a pioneer in this space, with the development of Somryst (previously SHUTi), an FDA approved 6 module, 9-week course encompassing the fundamentals of CBT-i therapy. Patients use this app to watch instructional videos, play games to test their knowledge, and receive algorithmic feedback on sleep timings. Studies show it works, with patients who completed the course reporting a significant reduction in insomnia symptom severity. It is relatively cost effective as well, at $899, while similar competing apps price themselves as low as $150 (not FDA-approved digital therapeutics); a course of traditional in-person CBT-i may cost upwards of $2000 with long waitlists for patients to get in to see a therapist.

DTx limitations: Gold standard therapy, comparative cost, and ease of access; DTx (‘digital pills’) have the potential to become a ‘one-size-fits-all’ solution, and therein lies a potential limitation we should all be cognizant of. Treatment of a complex disease like insomnia requires individualized care, with a comprehensive work-up (e.g., ensuring a patient isn’t actually suffering from sleep apnea), subtle titrations, feedback, and regular efficacy monitoring. Perhaps that is why some studies show dCBT-i platforms can have dropout rates >50% 😮. Treatments only work for patients who use them, and have the best shot at working when prescribed to the right patient. From where we sit, more clarity is needed on the particular subsets of patients that would benefit most from a DTx insomnia solution.

Substance use disorders 💊

What are they: Substance use disorders capture a wide array of disease processes, encompassing the pathological use of both legal (e.g., tobacco and alcohol), and illicit (e.g., cocaine, MDMA, etc.) substances. Today, from a pharmacologic perspective, we have FDA-approved medications to treat only three of the many substance use disorders that exist: alcohol use disorder (AUD), opioid use disorder (OUD), and tobacco use disorder. These diseases are destructive to the lives of those suffering from them, and also cause significant comorbidity with other chronic diseases as well as mortality. Far too few Americans have access to specialized care to treat OUD and AUD in particular, and these diseases are extra stigmatized (within the already stigmatized arena of psychiatry).

Treatment challenges: As such, the excitement around DTx to address SUDs (particularly OUD and AUD) is understandable. This is a group of patients who often lack access to the care they require (for a variety of reasons, including undersupply of treating clinicians and barriers to accessing care including stigma) and whose illness results in massive personal dysfunction and systemic costs. Furthermore, we know there are effective non-medication treatments that can be adjuncts to the medications a patient may take to treat OUD (e.g., buprenorphine) or AUD (e.g., naltrexone).

Classically, a combination of two psychotherapy techniques, cognitive behavioral therapy (CBT) and motivational interviewing (MI) / motivational enhancement treatment (MET) have been utilized by clinicians treating SUDs. The premise of DTx solutions in the SUD space has been to replicate much of the protocolized processes in the format of a digital tool that can be prescribed to engage patients asynchronously.

Illustrative example: One of the most exciting players in this space has been Pear (hello again), and its reSET (and reSET-o) products. Pear deserves much praise for being one of the first commercial DTx platforms, and for actually working with the FDA to create a unique clearance process for digital therapeutics. reSET consists of 12-week CBT-grounded and contingency-management driven programs meant to supplement the care a patient receives from an SUD treatment professional.

DTx limitations: However, despite its promise, reSET has achieved minimal adoption since its approval in 2017. In 2021 Pear reported ~14,000 total prescriptions, and in its latest quarterly report available (Q2 2022) reported ~12,000 prescriptions. Compare this to ~1.7 million Americans who were prescribed buprenorphine in 2019. The list price for a 90-day ‘course’ of reSET is ~$1700 💰, and despite Pear’s best efforts, there has not been widespread coverage by the major public and private payors (there have been a number of smaller, regional insurance plans entering into one-off coverage agreements with Pear). $550/month is a tough pill to swallow (pun intended) for patients, particularly when compared to the out-of-pocket costs of buprenorphine or naltrexone (which cost around 10x less out-of-pocket and are also generally very well covered by most payors). There is no doubt that we need better access to AUD and OUD care across the country, as we continue to lose hundreds of lives daily to substance use disorders; however, DTx have not been the savior we hoped they would be in treating these diseases.

ADHD ⚠️

What is it: Attention-Deficit/Hyperactivity Disorder is one of the most common neurodevelopmental disorders (impairments of brain development).  The symptoms can encompass three domains: hyperactivity, inattention and impulsivity, and must be severe enough to lead to functional impairments in at least two domains of the person’s life. ADHD has become a ‘popular’ diagnosis people gravitate towards - however we would be remiss to not mention here that oftentimes, the symptoms of ADHD (particularly difficulty concentrating) are frequently not due to ADHD but rather the result of other underlying diseases (most commonly depressive and anxiety disorders). There’s an entirely other piece to be written here about the way some companies have (in our opinion) inappropriately marketed to potential patients through various channels, including social media, leading to many people thinking they have ADHD and need treatment (when they really don’t). We’ll save that for another time 😏.

‍Treatment challenges: The good news is that the medications we use to treat ADHD are highly effective! The gold standard treatments are stimulant medications (amphetamine- or methylphenidate-based compounds). They are among the most effective medications in all of mental health when used correctly. The bad news is these medications can also be used inappropriately to achieve a euphoria like feeling (potentially leading to misuse and potential addiction) or as performance enhancers.

Beyond the misuse and misinformation campaigns around ADHD, those who are accurately diagnosed have medications that work well - so why do we need alternative treatments? Well, while the medications work well, they also have many side effects such as loss of appetite/weight loss, abdominal pain, headaches and emotional blunting (a reduced ability to feel and express emotions). And these can be particularly difficult to manage in patients under the age of 18. So, you can imagine the potential gap DTx solutions can fill as a means to to improve symptoms while minimizing risks and side-effects.

Illustrative example: The first company to release a product is Akili, which released EndeavorRx, an FDA authorized (not approved) video game (!!) 🕹️ for children 8-12 years old with inattentive symptoms. They describe their DTx as an adjunctive treatment to improve inattention by targeting certain brain regions and improving the ability to multitask and ignore distractions over at least a 4 week period. Kudos to the team for innovating and developing a digitally nativesolution rather than converting a current modality (such as the CBT example we discussed above) into a DTx.

DTx limitations: The studies Akili initially used to gain authorization supported that the product can improve a computer-based measure of inattention. However, the data did not show that there are benefits to the actual behavioral symptoms that children with inattentive-type ADHD experience (although Akili is releasing more data to attempt to prove this).

Per Akili’s website: Patients who engage with EndeavorRx demonstrate improvements in a digitally assessed measure, Test of Variables of Attention (TOVA®), of sustained and selective attention and may not display benefits in typical behavioral symptoms, such as hyperactivity.

Even if we move past the questions around true clinical benefit, despite EndeavorRx’s authorization by the FDA in 2020, our conversations with many Child and Adolescent Psychiatrists have reinforced that adoption has been spotty at best, partly due to questions of efficacy but also due to clinicians having difficulty adopting the idea of recommending a video game as a treatment to families. It is also inconsistently covered by insurance, and currently costs $99/month; note that again, this is on the order of magnitude of 10x more expensive than a typical stimulant prescription might cost out-of-pocket (and add a few turns on top of that when considering stimulants are often covered by most major payors).

What’s next?

By now, you might think that DTx will never gain widespread acceptance amongst clinicians and patients - but that’s actually not what we believe ‼️ We are in the early innings of optimizing the below three processes, which have driven the fall of DTx down the hype cycle and will be key in the opportunity for DTx to march forward towards a more sustainable future:

1. Building DTx to effectively engage patients and treat disease - as we discussed, we’d like to see more robust data with regards to sub-populations within patients suffering from insomnia, SUD, and ADHD who might be more likely to engage with and respond to DTx treatment

2. Engaging clinicians to think about prescribing DTx just as they do traditional medications or interventions - we have a hunch that this will partially happen naturally as more boomer and Gen X clinicians retire and the proportion of millenial and Gen Z clinicians increases; we also predict that DTx will not gain widespread adoption until and unless DTx platforms can show more robust clinical data

3. Convincing payors to consistently cover DTx - you now know that DTx are multiple orders of magnitude more expensive than the typical medications used to treat these three diseases; we predict that payors will want to see more robust efficacy data (and perhaps a march towards value for therapeutics) in order to be more confident in broadly covering DTx prescription

Additionally, more data ℹ️ around who is best poised to respond to a DTx will be helpful in not only targeting the right patients, but also in convincing clinicians 🥼 that they are worth the lift to prescribe.

Insomnia, Substance Use Disorders, and ADHD are all chronic conditions 🩺 that impact a large swath of patients with potentially debilitating symptoms, and are also conditions in which patients face significant barriers to seeking treatment (from both the stigma and access perspectives). We remain optimistic that the smart clinicians 👩🏽‍⚕️, researchers 🔬, and builders 👷🏽‍♀️ addressing these conditions and solving these challenges will achieve these goals, particularly by creating digital native treatments that are less so digital adaptations of existing treatments and more so truly unique modalities. This is how we will unlock the most value (and reduce the most suffering) for the patients we care for every day.

Two questions:

1. The process of clinicians adopting new therapeutics has been written about robustly; from your experience, what steps could (/should) DTx platforms take to drive adoption of this totally new therapeutic class by clinicians?

2. How far from the slope of enlightenment do you think DTx are?

✌🏽 A + A 

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