Digital Therapeutics - Reshaping the future of medicine

Digital Therapeutics – Reshaping the future of medicine

What is Digital Therapeutics?

With healthcare becoming digital, patients today are more empowered than ever before. As a result, digital health solutions have become the need of the hour to keep up with an increasing number of patients participating in their own treatment decisions. Digital health encompasses various platforms and systems that apply technological solutions to enhance healthcare delivery (1).

Over the last decade, the world has witnessed the explosion of digital health with the emergence of social media platforms, smartphones and mobile applications, wearable devices, cloud-based data platforms, real-world evidence studies, and the likes. As a result, general well-being and health monitoring are gradually extending from being space-bound activities restricted to hospitals and clinics to the widespread digital world through various smartphone applications (1).

The Digital Therapeutic Alliance (DTA) defines the DTx as “delivering medical interventions directly to patients using evidence-based, clinically evaluated software to treat, manage, and prevent a broad spectrum of diseases and disorders. They are used independently or in concert with medications, devices, or other therapies to optimize patient care and health outcomes.” DTx products are held to the same standards of evidence and regulatory oversight as traditional medical treatments and must demonstrate their safety, efficacy, quality, patient centricity, privacy, and ongoing clinical impact. These products should be reviewed and cleared or certified by regulatory bodies as required to support product claims of risk, efficacy and intended use (2). Best practices for DTx are related to design, clinical validation, usability, and data security (3).

Digital Therapeutics – Reshaping the future of medicine

What is Digital Therapeutics?

With healthcare becoming digital, patients today are more empowered than ever before. As a result, digital health solutions have become the need of the hour to keep up with an increasing number of patients participating in their own treatment decisions. Digital health encompasses various platforms and systems that apply technological solutions to enhance healthcare delivery (1).

Over the last decade, the world has witnessed the explosion of digital health with the emergence of social media platforms, smartphones and mobile applications, wearable devices, cloud-based data platforms, real-world evidence studies, and the likes. As a result, general well-being and health monitoring are gradually extending from being space-bound activities restricted to hospitals and clinics to the widespread digital world through various smartphone applications (1).

The Digital Therapeutic Alliance (DTA) defines the DTx as “delivering medical interventions directly to patients using evidence-based, clinically evaluated software to treat, manage, and prevent a broad spectrum of diseases and disorders. They are used independently or in concert with medications, devices, or other therapies to optimize patient care and health outcomes.” DTx products are held to the same standards of evidence and regulatory oversight as traditional medical treatments and must demonstrate their safety, efficacy, quality, patient centricity, privacy, and ongoing clinical impact. These products should be reviewed and cleared or certified by regulatory bodies as required to support product claims of risk, efficacy and intended use (2). Best practices for DTx are related to design, clinical validation, usability, and data security (3).

 How do Digital Therapeutics work?

DTx help (a) treat, (b) manage a disease or (c) improve health function including prevention of a disease through changes in patient behaviour and remote monitoring to yield enhanced and long-term health outcomes (1). DTx products empowers patients, healthcare providers, and payers with intelligent and accessible tools for addressing a wide range of conditions through data-driven interventions (3). Even though DTx is a part of the digital health domain, it is different from diagnostics, telehealth, and other digital health products.

Difference between Digital Health, Digital Medicine and DTx Products

Digital health acts as an umbrella entity that encompasses digital medicine which includes DTx. Products categorized under all these categories convey different levels of claims and risks. Moreover, their requirements for clinical evidence and regulatory oversight are different too. Digital health is a broad category comprising of technologies, platforms, and systems that engage consumers for lifestyle, wellness, and health-related purposes. Digital health entities can capture, store, and transmit health data to support clinical operations. Examples of digital health systems include health information technologies, telehealth systems, systems that use consumer health information, and clinical care administration tools, among others (1,2).

Digital medicine, on the other hand, consists of software or hardware products, typically supported by evidence, to measure or intervene in the service of human health. Digital diagnostics, digital biomarkers, and remote patient monitoring devices are a few examples of digital medicines (1,2).

DTx, as defined earlier, encompasses evidence-based therapeutic interventions that prevent, manage, or treat a medical disorder or a disease. Examples of DTx applications include digital sensors, wearable devices, certain virtual reality (VR), and artificial intelligence (AI) devices (1,2).

Advantages of Digital Therapeutics in today’s world:

DTx products can help patients, healthcare professionals and payors in the following ways (2).

1. Patients

• Improve patient health
• Deliver a highly engaging and user-friendly experience
• Provide meaningful results and insights on personalized goals and outcomes
• Easily scale and be accessible via smartphones and tablets
• Ensure patient safety and privacy protection

 Healthcare professionals

• Directly impact disease state measures and clinical outcomes
• Expand access to safe, confidential, and effective medical treatments
• Provide therapies for previously un- or undertreated conditions
• Extend clinicians’ ability to care for patients
• Maximize patient engagement
• Close gaps in care
• Lower overall healthcare costs

 Payors

• Reduce the overall cost of care
• Enhance, support, and optimize current medical treatments
• Optimize patient engagement
• Improve provider network efficiency
• Support value- and outcomes-based care initiatives
• Expand care delivery outside of traditional clinic settings
• Improve member experience and satisfaction

The COVID-19 pandemic has led to significant increase in use of digital therapeutics by increase in patient demand, regular flexibility that has expanded the access to digital health products and addressing the ever-increasing mental health and chronic disease burdens caused or exacerbated by COVID-19 (2).

Examples of use of DTx in Different Health Conditions

• reSET® and reSET-O® – to treat opioid use disorder (OUD) (4)
• WellDoc DiabetesManager System – to manage Type 2 Diabetes, hypertension and obesity (3,5)
• Insulia® – An aid in the management of diabetes for patients treated with long acting insulin analogs (6)
• Deprexis® - for online treatment of depression (7)
• Abilify MyCite – an ingestible sensor combined with aripiprazole to measure the effectiveness of medication treatment and help physicians improve clinical outcomes for schizophrenia, bipolar disorder and depression (8,9)
• EndeavorRx – a game-based digital therapeutic to improve the attention span of children with attention deficit hyperactivity disorder (ADHD) (3,10)
• GENUS (gamma entrainment using sensory stimuli) – a next-generation digital therapeutic designed to treat memory and cognition symptoms in Alzheimer’s disease (11)
• SpleepioTM – Sleep improvement program featuring Cognitive Behavioral Therapy (CBT) techniques (3,12)
• Kaia Health – mobile application for self-management of musculoskeletal pain based on multimodal rehabilitation (MMR) (2,13)
• Kaiku Health – app to improve the quality of life for cancer patients (2,14)
• Nerivio – wireless wearable remote electrical neuromodulation unit controlled by a phone app (2,15)

There are many more digital therapeutics currently on market or are under development (2,3).

Health Canada and Digital Health Technologies

Given the fast pace of innovation in digital health technologies, Health Canada has undertaken an initiative to adapt its approach to support better access to therapeutic products based on healthcare system needs. Under the “Regulatory Review of Drugs and Devices” initiative, Health Canada is establishing a new Digital Health Division within the Pharmaceutical Drugs Directorate’s (formerly known as TPD) Medical Devices Bureau to allow for a more targeted pre-market review of digital health technologies, to adapt to rapidly changing technologies in digital health, and to respond to fast innovation cycles (16).

Key areas of focus for Health Canada under this initiative include (16):

• Wireless Medical Devices
• Mobile Medical Apps (MMA)
• Telemedicine
• Software as a Medical Device (SaMD) which includes DTx products
• Artificial Intelligence
• Cybersecurity
• Medical Device Interoperability

Health Canada expects that establishing the new Digital Health Division will bring increased expert review capacity for medical devices integrating digital health technologies, which will benefit Canadian patients and the health care system by improving access to innovative digital health technologies that have rapid development cycles while potentially saving health care system costs (16).

Author: Pratibha Duggal, ICON Plc.

References:

1. Dang A, Arora D, Rane P. Role of digital therapeutics and the changing future of healthcare. Journal of Family Medicine and Primary Care. 2020 May; 9(5):2207.
2. Digital Therapeutics: Combining Technology and Evidence-based Medicine to Transform Personalized Patient Care. [Accessed 29 April 2022]. https://www.dtxalliance.org/wp-content/uploads/2018/09/DTA-Report_DTx-Industry-Foundations.pdf.
3. Chung JY. Digital therapeutics and clinical pharmacology. Translational and Clinical Pharmacology. 2019 Mar 1;27(1):6-11.
4. Campbell AN, Nunes EV, Matthews AG, Stitzer M, Miele GM, Polsky D, Turrigiano E, Walters S, McClure EA, Kyle TL, Wahle A, Van Veldhuisen P, Goldman B, Babcock D, Stabile PQ, Winhusen T, Ghitza UE. Internet-delivered treatment for substance abuse: a multisite randomized controlled trial. Am J Psychiatry. 2014 Jun;171(6):683-90.
5. Quinn CC, Clough SS, Minor JM, Lender D, Okafor MC, Gruber-Baldini A. WellDoc mobile diabetes management randomized controlled trial: change in clinical and behavioral outcomes and patient and physician satisfaction. Diabetes Technol Ther. 2008 Jun;10(3):160-8.
6. Franc S, Joubert M, Daoudi A, Fagour C, Benhamou PY, Rodier M, Boucherie B, Benamo E, Schaepelynck P, Guerci B, Dardari D, Borot S, Penfornis A, D'Orsay G, Mari K, Reznik Y, Randazzo C, Charpentier G; TeleDiab study group. Efficacy of two telemonitoring systems to improve glycaemic control during basal insulin initiation in patients with type 2 diabetes: The TeleDiab-2 randomized controlled trial. Diabetes Obes Metab. 2019 Oct;21(10):2327-2332.
7. Meyer B, Berger T, Caspar F, Beevers CG, Andersson G, Weiss M. Effectiveness of a novel integrative online treatment for depression (Deprexis): randomized controlled trial. J Med Internet Res. 2009 May 11;11(2):e15.
8. Press release. Otsuka And Proteus® Announce The First U.S. FDA Approval of A Digital Medicine System: ABILIFY MYCITE® (aripiprazole tablets with sensor). November 2017. [Accessed 04 May 2022] https://www.otsuka-us.com/discover/articles-1075
9. Food and Drug Administration (FDA) Clinical Review. APPLICATION NUMBER: 207202Orig1s000. [Accessed 04 May 2022] https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207202Orig1s000MedR.pdf
10. Kollins SH, DeLoss DJ, Cañadas E, Lutz J, Findling RL, Keefe RS, Epstein JN, Cutler AJ, Faraone SV. A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial. The Lancet Digital Health. 2020 Apr 1;2(4):e168-78.
11. Does Synchronizing Brain Waves Bring Harmony? International Conference on Alzheimer’s and Parkinson Diseases 2021. April 2021 [Accessed 04 May 2022]. https://www.alzforum.org/news/conference-coverage/does-synchronizing-brain-waves-bring-harmony#Overture
12. Espie CA, Emsley R, Kyle SD, et al. Effect of Digital Cognitive Behavioral Therapy for Insomnia on Health, Psychological Well-being, and Sleep-Related Quality of Life: A Randomized Clinical Trial. JAMA Psychiatry. 2019;76(1):21–30.
13. Priebe JA, Haas KK, Moreno Sanchez LF, Schoefmann K, Utpadel-Fischler DA, Stockert P, et al. Digital Treatment of Back Pain versus Standard of Care: The Cluster-Randomized Controlled Trial, Rise-uP. J Pain Res. 2020;13:1823-1838.
14. Iivanainen S, Alanko T, Vihinen P, Konkola T, Ekstrom J, Virtanen H, Koivunen J Follow-Up of Cancer Patients Receiving Anti-PD-(L)1 Therapy Using an Electronic Patient-Reported Outcomes Tool (KISS): Prospective Feasibility Cohort Study JMIR Form Res 2020;4(10):e17898
15. Stewart J Tepper, MD, Tamar Lin, PhD, Tal Montal, MA, Alon Ironi, MSEE, Carrie Dougherty, MD, Real-world Experience with Remote Electrical Neuromodulation in the Acute Treatment of Migraine, Pain Medicine, Volume 21, Issue 12, December 2020, Pages 3522–3529.
16. Health Canada Notice: Health Canada’s Approach to Digital Health Technologies. April 2018. [Accessed on 04 May 2022] https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-devices/activities/announcements/notice-digital-health-technologies.html