Definitions and Status Quo
Digital therapeutics (DTx), (‘software as medical device’,) are defined by the Digital Therapeutics Alliance (DTA) as “evidencebased therapeutic interventions that are driven by high-quality software programs to treat, manage, or prevent a disease or disorder. They are used independently or in concert with medications, devices, or other therapies to optimize patient care and health outcomes” . For pain, DTx typically use software to record pain perception and physiological signals (e.g., heart rate or blood oxygenation) or to manage pain-related health issues such as sleep or mood . Smartphone or online applications can provide treatment-specific content, including education or psychologically informed programs, or interaction with chatbots [2,20]. Wearables can be used to guide different lifestyle parameters related to pain reduction, such as exercise and stress [8,20,21]. An increasingly popular type of DTx showing great promise for the treatment of pain is immersive virtual reality (VR), pioneered by Hoffman and colleagues for acute pain control during wound care in burn patients . Since then, VR applications have shown robust efficacy for the management of acute pain and as adjunct treatment for burn pain and other painful medical procedures [6,12,22,23]. More recently, VR has emerged as a stand-alone treatment with the potential to achieve long-lasting relief in chronic pain, such as low back pain  or endometriosis . The promise of VR and other DTx to provide viable adjuncts or alternatives to side-effect-prone pharmacological options is reflected in the FDA’s recent first-time approval of a VR device for the treatment of chronic pain [3,4,16].
Potential Benefits for Integrative Health
As articulated by Keefe and colleagues a decade ago , DTx might improve clinical pain outcomes in several ways [6,12,22,23]. These include distraction-based methods, with greater treatment effects observed for high-tech immersive DTx utilizing multiple sensory inputs (haptic, audio, visual); by acting on pain-related movement patterns (e.g., in chronic pain disorders with pronounced kinesiophobia); and by simulating movement of avoided or missing body parts (e.g., CRPS or phantom limb pain) in safe (virtual) environments. Additionally, DTx can have direct neuromodulatory effects [6,22] as well as indirect effects on pain by improving mood outcomes [12,23]. Using the opportunities of DTx to promote treatment adherence and individualization , DTx can be integrated with evidence-based behavioral interventions to provide a more immersive and experiential pain intervention. This approach has the potential to enhance the efficacy and long-term benefits of such interventions , and to reduce cost and enhance access to care .
To date, DTx are mainly used as stand-alone interventions, often sought out by patients themselves, and the line to wellness applications is often blurred. Practitioners may on occasion recommend individual DTx or use them to provide digital exercise sheets or educational content. The use of telehealth, another digital approach to pain management, was accelerated by the COVID-19 pandemic , and continues to be used as a replacement for in-person care . For integrative models of pain care, however, DTx and other digital tools have the potential to be used as integrated treatment components alongside in-person care, as platforms where patients can interact with providers or experience peer support, to monitor patient progress, and to support self-management once in-person therapy has been completed. Further, electronic health records are important to harmonize care across providers, especially in interdisciplinary settings. As technology develops, DTx are beginning to influence clinical care, research, and healthcare policy .
Potential Issues and Future Needs
In the US and in Europe, DTx are becoming increasingly regulated, with the first pain-related applications already approved for prescribing and reimbursement . Regulation has also ushered in higher standards for the scientific evaluation of DTx through clinical trials , with the goal of improving the evidence base for DTx.
For research, data collection through smartphone applications and wearables holds the promise of large-scale high-density data from the real world. Not only can this make large clinical trials more feasible , but the analysis of such datasets may also improve scientific understanding of individual differences in pain and interventions. App developers and clinicians will then strive to use this information to personalize care to individuals. Drug companies are also highly active in the DTx space, for example, by exploring options to increase medication adherence . Whether these endeavors will also promote integration with non-pharmacological care remains to be seen.
Despite rapid and promising developments, there are challenges for the widespread use of technological solutions in healthcare, including the allocation of resources, ethical issues (including privacy and data security), governance, the development of eSkills and a technologyfriendly culture .
In pain management, as in other chronic disease areas, the potential for personalization, improved accessibility, and better care is significant. For DTx and other digital solutions to be effectively integrated with in-person care, however, joint efforts continue to be necessary from developers, healthcare providers, research, and policy-makers.
- Center for Devices, Radiological Health. Software as a Medical Device (SaMD). US Food and Drug Administration n.d. Available: https://www.fda.gov/medical-devices/digital-health-center-excellence/software-medical-device-samd. Accessed 3 Jan 2023.
- Gandy M, Pang STY, Scott AJ, Heriseanu AI, Bisby MA, Dudeney J, Karin E, Titov N, Dear BF. Internet-delivered cognitive and behavioural based interventions for adults with chronic pain: a systematic review and meta-analysis of randomized controlled trials. Pain 2022;163:e1041– e1053. doi:10.1097/j.pain.0000000000002606.
- Garcia LM, Birckhead BJ, Krishnamurthy P, Mackey I, Sackman J, Salmasi V, Louis R, Maddox T, Darnall BD. Three-Month Follow-Up Results of a Double-Blind, Randomized Placebo-Controlled Trial of 8-Week Self-Administered At-Home Behavioral Skills-Based Virtual Reality (VR) for Chronic Low Back Pain. J Pain 2022;23:822–840.
- Garcia LM, Birckhead BJ, Krishnamurthy P, Sackman J, Mackey IG, Louis RG, Salmasi V, Maddox T, Darnall BD. An 8-week self-administered at-home behavioral skills-based virtual reality program for chronic low back pain: double-blind, randomized, placebo-controlled trial conducted during COVID-19. J Med Internet Res 2021;23:e26292.
- van Gemert-Pijnen JL. Implementation of health technology: Directions for research and practice. Front Digit Health 2022;4:1030194.
- Gupta A, Scott K, Dukewich M. Innovative Technology Using Virtual Reality in the Treatment of Pain: Does It Reduce Pain via Distraction, or Is There More to It? Pain Med 2017;19:151–159.
- Hackett A, Hung A, Leclerc O, Velamoor S. The promise of digital therapeutics. 2020. Available: https://www.mckinsey.com/industries/life-sciences/our-insights/the-promise-of-digital-therapeutics. Accessed 3 Jan 2023.
- Hickey BA, Chalmers T, Newton P, Lin C-T, Sibbritt D, McLachlan CS, Clifton-Bligh R, Morley J, Lal S. Smart Devices and Wearable Technologies to Detect and Monitor Mental Health Conditions and Stress: A Systematic Review. Sensors 2021;21. doi:10.3390/s21103461.
- Hoffman HG, Doctor JN, Patterson DR, Carrougher GJ, Furness TA 3rd. Virtual reality as an adjunctive pain control during burn wound care in adolescent patients. Pain 2000;85:305–309.
- Hohenschurz-Schmidt D, Scott W, Park C, Christopoulos G, Vogel S, Draper-Rodi J. Remote management of musculoskeletal pain: a pragmatic approach to the implementation of video and phone consultations in musculoskeletal practice. PAIN Reports 2020;5:e878. doi:10.1097/ pr9.0000000000000878.
- Hong JS, Wasden C, Han DH. Introduction of digital therapeutics. Comput Methods Programs Biomed 2021;209:106319.
- Honzel E, Murthi S, Brawn-Cinani B, Colloca G, Kier C, Varshney A, Colloca L. Virtual reality, music, and pain: developing the premise for an interdisciplinary approach to pain management. Pain 2019;160:1909–1919.
- Keefe FJ, Huling DA, Coggins MJ, Keefe DF, Rosenthal ZM, Herr NR, Hoffman HG. Virtual reality for persistent pain: a new direction for behavioral pain management. Pain 2012;153:2163–2166.
- Leroux A, Rzasa-Lynn R, Crainiceanu C, Sharma T. Wearable Devices: Current Status and Opportunities in Pain Assessment and Management. Digit Biomark 2021;5:89–102.
- Merlot B, Dispersyn G, Husson Z, Chanavaz-Lacheray I, Dennis T, Greco-Vuilloud J, Fougère M, Potvin S, Cotty-Eslous M, Roman H, Marchand S. Pain reduction with an immersive digital therapeutic tool in women living with endometriosis-related pelvic pain: Randomized controlled trial. J Med Internet Res 2022;24:e39531.
- Office of the Commissioner. FDA Authorizes Marketing of Virtual Reality System for Chronic Pain Reduction. US Food and Drug Administration n.d. Available: https://www.fda.gov/news-events/press-announcements/fda-authorizes-marketing-virtual-reality-system-chronic-pain-reduction. Accessed 13 Dec 2022.
- Pearl R, Wayling B. The telehealth era is just beginning. Harv Bus Rev 2022. Available: https://cmham.org/wp-content/uploads/2022/05/HBR-Telehealth-Article-05.2022.pdf.
- Rennie K, Taylor C, Corriero AC, Chong C, Sewell E, Hadley J, Ardani S. The Current Accuracy, Cost-Effectiveness, and Uses of Musculoskeletal Telehealth and Telerehabilitation Services. Curr Sports Med Rep 2022;21:247–260.
- Roundtable on Value and Science-Driven Health Care, Board on Health Sciences Policy, Forum on Drug Discovery, Development, and Translation, Institute of Medicine. Large Simple Trials and Knowledge Generation in a Learning Health System: Workshop Summary. National Academies Press, 2013.
- Shetty A, Delanerolle G, Zeng Y, Shi JQ, Ebrahim R, Pang J, Hapangama D, Sillem M, Shetty S, Shetty B, Hirsch M, Raymont V, Majumder K, Chong S, Goodison W, O’Hara R, Hull L, Pluchino N, Shetty N, Elneil S, Fernandez T, Brownstone RM, Phiri P. A systematic review and meta-analysis of digital application use in clinical research in pain medicine. Front Digit Health 2022;4:850601.
- Sommer B, Pauli C, McCaskey M, Behrendt F, Schuster-Amft C, Graf ES. Biomechanical comparison of walking with a new, wearable rehabilitation training device to Nordic walking and regular walking in people with chronic low back pain. Assist Technol 2022. doi:10.1080/10400435.202 2.2138634.
- Tack C. Virtual reality and chronic low back pain. Disabil Rehabil Assist Technol 2021;16:637–645.
- Trost Z, France C, Anam M, Shum C. Virtual reality approaches to pain: toward a state of the science. Pain 2021;162:325–331.
- Understanding DTx. Digital Therapeutics Alliance 2021. Available: http://dtxalliance.org/understanding-dtx/. Accessed 13 Dec 2022.
- Unsworth H, Dillon B, Collinson L, Powell H, Salmon M, Oladapo T, Ayiku L, Shield G, Holden J, Patel N, Campbell M, Greaves F, Joshi I, Powell J, Tonnel A. The NICE Evidence Standards Framework for digital health and care technologies – Developing and maintaining an innovative evidence framework with global impact. DIGITAL HEALTH 2021;7:205520762110186. doi:10.1177/20552076211018617.