A view of Digital Therapeutics.

In July of 2011, while contemplating my relocation to Sweden from the UK, I wrote an opinion piece for The Chemical Engineer (issue 841), UK-based journal, published by the Institution of Chemical Engineers. In it, I described how the future of healthcare would be based on personalised treatments and digital technologies and that they would be more prevalent in the delivery of new medicines. Nine years on, where are we?

Digital Therapeutics Alliance (www.dtxalliance.org) defines digital therapeutics (DTx) as those that deliver evidence-based therapeutic interventions to patients that are driven by high quality software programs to prevent, manage, or treat a medical disorder or disease. They are used independently or together with medications, devices, or other therapies to optimise patient care and health outcomes.

The first instances of DTx were observed back in 2012, but the term has gained more use since 2015. There is no single methodology used in the practice of digital therapeutics, but the methods used in the development of DTx are rooted in cognitive behavioural therapy to encourage patients to make lifestyle changes. This is used to manage and prevent numerous conditions, including type II diabetes, Alzheimer’s disease, dementia, heart failure, chronic obstructive pulmonary disease, asthma, lung disease, obesity, substance abuse, ADHD, insomnia, hypertension, anxiety, depression, and others.

In most instances, DTx products are currently being manufac- tured by tech and device development companies, outside of the regulated environment of the pharmaceutical industry. Examples include companies such Welldoc, Sidekick Health, Voluntis, Kaia Health, and Propeller.

The Digital Therapeutics Alliance cites a number of examples backed by randomised clinical trials (RCTs):

• BlueStar, Welldoc’s software for type 1 and type 2 diabetes, helps diabetics with self-management in the home and clinical settings, in addition to delivering 1.7–2.0 A1c reductions in clinical and real-world studies.

• Kaia Health’s DTx product enables chronic pain sufferers to self-manage their condition and associated psychosocial aspects at home using only a smartphone, increasing healthcare access during this transitionary period for many workforces. In its latest RCT, users showed a 43% pain level decrease1 compared to control subjects.

There are new challenges with mental health conditions during the Covid-19 pandemic, with social distancing guidelines, long periods of lockdowns and social isolation:

• SilverCloud Health’s studies have shown in university students a 25–45% improvement in depression, anxiety and stress scores at 3 months2; and
• an RCT in a routine care setting showed lasting positive effects on depression, anxiety, and functional impairment up to 12 months after start of treatment.3
  DTx brings value to healthcare systems searching for ways to reduce clinical visits and hospitalisations for less acute conditions:
• Big Health’s product, Sleepio, demonstrated in a placebo- controlled RCT and 11 additional studies that 76% of users achieved healthy sleep levels4. Health economic data also suggest that Sleepio is associated with reductions in healthcare costs.
• Propeller Health’s DTx product for asthma has demonstrated a reduction of emergency department and related hospitalisations5 by 50%.
• Propeller Health’s DTx product for COPD results in
  a 35% improvement in symptom-free days6. Cleveland Clinic research indicated it could reduce annual hospitalisations from 3.9 to 2.3 visits7.

Another word about Covid

Covid-19. The single most significant event in most of our life- times. Ten months ago we could not have imagined a scenario where people would be restricted to their homes, working from home and having to limit social contact. The impact that this has had on all aspects of our lives is profound and what happens next, what changes will be introduced will also affect how we deliver healthcare.

Pharma companies were getting too grips with digital and how these technologies could help deliver new medicines. In fact, digital is on most pharma companies’ strategic agendas.

The plan was to implement these in the coming decade, but Covid-19 has accelerated this. The catalyst that is forcing all pharma companies look at how their current pipeline of medicines will continue to be delivered and commercialised.

• How can supply chains continue to deliver medicines?
• How can clinical trials continue when participants cannot visit clinical sites?
• How can we collect data, if participants are at home?
• How can participants be enrolled and consented onto studies?

Pharma companies have shown that they can continue their development and clinical programmes — and in a lot of cases, more efficiently than before Covid, by leveraging remote health solutions. Pharma companies have pivoted hard towards digital solutions. Pandora’s Box is ope and the lid will be impossible to close.

Digital Medicines

But what could this mean for accessibility to medicines? A survey8 of COPD (chronic obstructive pulmonary disease) patients, in five countries, showed that people own some type of device that can connect to the internet. People use apps and wearables every day to track their steps, their diet and their weight. Heart rate and even ECG values can be monitored. Data is transmitted from their devices to their smartphones and they can monitor how they are doing against set goals or targets. That is a lot of data! How can this data be used for healthcare?

The Digital Therapeutics (DTx) market is expected to grow9, year on year, by 21%. This is a conservative estimate, based on pre-Covid data.

The development of digital therapeutics follows a process more associated with product design development, as opposed to traditional pharmaceutical development. Words and phrases like “agile” or “sprints” often crop up when developing a DTx. Think software development. But one thing is the same. The user is at the centre of the development. Or in the case of DTx, the patient. And there is evidence that patients are interested in DTx solutions, and could be willing to pay for them.

A key sticking point, data sharing. But, there is evidence that patients would accept sharing data with their doctor. Of course, some level of validation or approval is needed to assure people that these digital solutions work as intended, and protect patients’ data.

App or Pill?

We know how easy it is to download an app from the App Store or Google Play Store. And regularly, new apps or app versions are released with bug fixes and improved functionality. At this is important. Here there is an accessible ecosystem to put digital therapeutics directly into the hands of patients. But we already have hundreds of apps on our phones! And some have not been used for months, if not years! So how does pharma cut through that noise?

Patients may have chronic conditions and have to live with their diseases for years. A DTx solution must take this into account and be designed with “stickability” so that people will use it regularly. If the app is left unopened on the patient’s smart device, after a few weeks any benefit is lost.

Just as the efficacy of traditional medicines is assessed in randomised clinical trials, then so are DTx-based solutions. Evidence and data are important to show that these solutions work (see previous examples). Whether the solution is used to remind patients to take their medication, or to help them monitor key health parameters to better help understand disease progression, a DTx is a digital tool supported by clinical evidence.

Many people are living with chronic conditions, such as diabetes, NASH, asthma, COPD, heart failure and chronic kidney disease. This means taking medication for the rest of their lives. And multiple, different medications. So how do they make sure they remember to take their medication at the right time?

People forget. It happens. Or, if people start feeling better, they question why they need to continue to take their medication, and perhaps they just stop. Perhaps the side effects of the medication are too much to bear. Or there are financial or societal reasons or barriers that cause patients to stop taking their medication.

Poor medication adherence is often linked to negative health outcomes. This puts significant burden on healthcare systems, as patients need to visit their physicians more than maybe needed or are hospitalised. In fact, half to three- quarters of patients in the US stop taking their medication after one year of being prescribed. This equates to US$300bn in additional doctor visits, emergency department visits and hospitalisations11.

DTx methods like reminders and notifications help patients remember to take their medication. This improves time on therapy and health outcomes. As well as adherence, data from wearables (FitBits, smartwatches and the like) allow people to set meaningful targets and goals, and so take back control. An element of gamification, if you will.

The mental wellbeing of people suffering with diseases cannot be understated. DTx can provide guidance and encouragement on how to manage your disease and give support, minimising the risk of depression and other mental illnesses.

This results in fewer visits to the doctor and the hospital, more meaningful discussions between patients and physicians, and ultimately, reduced burden on already-stretched healthcare systems.

How do you develop a DTx? What is the problem companies are trying to solve with a DTx? It is important to understand the physical and emotional journey that patients, doctors and caregivers go through. Remember that the multi-step journey a patient goes through (from first experiencing symptoms, through tests, diagnosis and treatment) can be overwhelming.

An understanding of this journey will help identify the unmet need that can be solved using DTx. With this understanding, specifications and requirements will be drafted, prototypes manufactured, and human factors tests performed. Think product design development/lifecycle.

Using targeted surveys, chemical engineers working in pharmaceutical drug development project teams develop an understanding of what patients and healthcare providers (HCPs) need. Working with agencies that specialise in user experience and design, we develop questionnaires that try to quantify the needs from these different stakeholders. With these groups we are trying to design solutions for different personality types. They have different challenges that they seek to overcome: some patients may be struggling to stay on top of managing their disease; some may need validation and encouragement to help them; while others are in complete control and just want to keep improving.

The same is true for physicians and doctors. They will have unmet needs that can be solved with DTx, but while they are reviewing their needs through a different lens, they are somewhat similar to their patients. They need more time, so that they can focus their care on their patients. They want to educate their patients to have a healthy lifestyle.

Through a good understanding of insights and the person- alities that drive some of these behaviours, we begin the task of developing the first DTx prototypes.

Prototype

The design is further refined through focus groups, and human factor and behavioural analyses. As with all product design, putting something real into the hands of a user, the patient or physician in our case, yields interesting feedback that really helps to ensure we develop a user-friendly product.

Manufacture and Distribution

What next? We have a product. How do we put the DTx into the hands of the users? What about the payers? What business model is appropriate for this? After all, this is not the same as a tablet or an inhaler.

Software as a Medical Device

The regulatory pathways for DTx are emerging and this would take another article to explain in more detail. But like a traditional medicine, these DTx solutions need to approved by the regulator, and most will take the “Software as a Medical Device” route.

Monetisation Strategy

What is the most appropriate business model? How do we promote and raise awareness of the DTx and ensure users can access it? Then how do we distribute it? What is the route to download through App Stores?

Revenue from the product itself comes via different channels:

• Traditional reimbursement: pricing a standalone DTx or premium price for the combination product.
  Increased sales volume through improved adherence. This applies to a DTx in combination with a medication.
• “Lite” or non-prescription versions for cash-pay consumers (similar to the over-the-counter approach).
• License the access or use of the digital platform to other manufacturers and HCPs through employer or personal health plans.
• Selling data to other manufacturers for insight, real- world evidence or R&D.
• There are indirect benefits that can be gained, for example, more robust data capture
• Differentiating strategy to drive preference for prescription drugs amongst HCPs and patients.
• Strategic competitive advantage using data mining or AI for insight generation or R&D.
• Outcome-based contracts with metrics enabled by DTx data capture.
• Value story for pricing and market access negotiations; real-world evidence.
• Capabilities, expertise and know-how to become partner of choice for licensing or co-development deals.

There are three go-to-market approaches that are used:

Business to consumer (B2C). Provide the product as: Free; Out of pocket, as a one-off payment; or Freemium, with in-app purchases for premium features.

Business to payer (B2P). For either a public payer or
a private payer — price per user; unlimited users for a fixed fee; and value-based contracting (outcome-based models).

Business to business (B2B). For provider organisation/ employer scheme/pharma companies — price per user; unlimited users for a fixed fee; value-based contracting (outcome-based models); fees for data access and analytics; and overall licensing with milestone payments (for pharma companies).

Is The Future is Now?

Covid has catalysed and accelerated the use of digital technology across the healthcare industry. The genie is well and truly out of the bottle, and it will be difficult to get it back in again, even if we wanted to.

DTx help patients adhere to their prescribed medications, thereby increasing time-on-therapy and improving health outcomes.

Data shared with physicians helps them to monitor their patients’ treatment and, if connected to electronic medical records, can reduce some of the administration burden. This leads to more focussed discussions with patients. This reduces the burden on healthcare systems.

For pharma companies, the opportunity to gather real-world data for medicines used in combination with DTx provides valuable insights into product performance and informs continued R&D of future products.

Integrity and privacy of patients’ data needs to be assured. And the proper regulatory pathways must be followed to provide assurance that these new types of medicines work. That digital future is a little bit closer.

References

1. https://go.nature.com/2GEMQHA
2. https://bit.ly/34pu27E
3. https://bit.ly/30QSIoL
4. www.bighealth.com/outcomes
5. https://dtxalliance.org/productpropeller
6. https://bit.ly/3jxFMuV
7. https://bit.ly/3iz4hXk
8. Internal Company survey, DTx Research, The view of the general public, September 2020
9. The Insight Partners, December 2018, https://bit.ly/37ofdFr
10. Decision Resource Group, Will CVS’s Digiceuticals Market- place Open the Floodgates to Digital Health Solutions?, July 2019, https://bit.ly/3mbcvrb
11. https://bit.ly/2StbkX8