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I. Introduction
The recent rapid developments in digital technology and the Fourth Industrial Revolution have brought about changes in various industrial sectors, including healthcare. The coronavirus disease 2019 (COVID-19) pandemic also has limited access to healthcare, and demand for healthcare services for patients with chronic diseases is steadily increasing due to population aging and improvements in living standards. Effective health management is crucial for lowering medical expenses because the rise in chronic diseases due to population aging has increased the social and financial burden on health insurance. Against this backdrop, digital therapeutics (DTx) provide an example of how combining medical technology with digital technology could create additional value [1].
The term DTx refers to evidence-based therapeutic interventions using high-quality software programs to prevent, manage, and treat medical disorders or diseases (Digital Therapeutics Alliance). It was developed by fusing digital, medical, and pharmaceutical technologies. The widespread use of smartphones has increased the public’s ability to use digital devices, and the development of high-speed Internet networks has paved the way for more efficient medical services. DTx have comparatively low development costs and a short development period. They can be supplied in large quantities because they require less complicated manufacturing, transportation, and storage facilities and have fewer toxic and adverse effects than current medical devices. The emergence of non-face-to-face treatment due to COVID-19 has become a good testbed for evaluating the need for and potential efficacy of DTx. Therefore, it is expected that DTx will be crucial for developing future healthcare services that can reduce medical disparities in the prevention and management of diseases [2].
The development of DTx is currently mainly focused on psychiatric and chronic diseases, which can benefit greatly from behavioral interventions. In this paper, we examine different forms of DTx reflecting various treatment types and discuss their implications.
II. Treatment Types of Digital Therapeutics
To investigate the interaction types and representative cases of DTx, exploratory research was conducted in two phases. In the first phase, we collected literature on DTx treatment cases in Korea and abroad. We collected academic papers published in the 6-year period before January 2023, clinical trial lists of the US Food and Drug Administration (FDA) and Korea Ministry of Food and Drug Safety (MFDS), and newspaper articles from the websites of various government agencies (https://clinicaltrials.gov) and the Google portal site, using search terms such as “digital therapeutics,” “DTx,” “FDA approved DTx,” and “DTx clinical trials.”
In the second phase, two researchers confirmed and transcribed the interaction method of the collected cases. The types classified by each researcher were compared to see if they matched. If the types did not match, the final decision was made through discussion.
In the third phase, we selected seven major types of DTx that were used in numerous cases from the literature. We then summarized the indications and treatment components of each representative case of DTx. The seven types of interactions used in DTx identified were cognitive behavioral therapy (CBT) [3], distraction therapy [4], graded exposure therapy (GET) [5], reminiscence therapy [6], art therapy [7], therapeutic exercise [8], and gamification [9] (Table 1).
1. Cognitive Behavioral Therapy
CBT is a type of psychotherapy that combines cognitive and behavioral therapy to identify negative patterns in thinking or behavior and replace them with positive ones [10]. CBT methods include identifying negative thoughts, practicing new skills, goal-setting, and problem-solving. Self-monitoring involves tracking behaviors, symptoms, or experiences over time. During this process, mobile devices are used to measure physical and emotional health, and by self-identifying the outcomes, individuals are given an opportunity to work on changing their behavior or problem [11]. CBT requires individuals to perform tasks to improve their own behavior and necessitates constant evaluation and follow-up by medical personnel or psychological counselors. Thus, properly designed DTx can facilitate the implementation of these tasks and greatly advance treatment [12].
2. Distraction Therapy
Distraction therapy involves diverting attention away from pain or unpleasant thoughts using auditory, visual, and tactile stimuli to reduce the sense of pain or anxiety without eliminating the cause of the pain or allowing it to go unnoticed [13]. This attention-shifting mechanism is primarily used for virtual reality (VR) pain management. The main mechanism of distraction therapy is to disperse the attention needed for pain perception. VR requires extensive information processing, such as visual and auditory processing, and is more effective than conventional attention-distracting tools [14].
3. Graded Exposure Treatment
GET is an evidence-based psychotherapeutic method designed to help people overcome fear or anxiety about objects, activities, or situations by facing them [15]. It involves facing fear in a step-by-step manner and retraining the brain to recognize that fear is unnecessary by exposing people to fearful situations or objects.
Despite the scientific evidence for the effectiveness of GET, traditional exposure therapy has not been widely used in the healthcare industry due to space and time limitations, as well as the burden and fear that patients feel about exposure to real-world situations. GET, using VR exposure therapy, is a treatment that can compensate for these shortcomings. It can provide patients with environments that are difficult to provide in the real world and can also provide the optimal virtual environment that patients need during the treatment process [16].
4. Reminiscence Therapy
Reminiscence therapy is generally used to treat depression and dementia. It is a conscious process that helps individuals reflect on their past experiences, recall and remember significant events, revisit previously unresolved conflicts, maintain hope for the rest of their lives, and cope with conflict and frustration in the present and future. Through reminiscence, elderly people can recall and relive the past and come into contact with the times and events that were considered most significant, experiencing the feelings and emotions that arise as a result. This enables them to rediscover the meanings stored in their memories, enhancing their overall quality of life by enabling them to maintain their sense of independence and self-confidence. VR technology has recently been employed to reconstruct realistic past environments in the memories of the elderly, optimizing the effects of reminiscence therapy by allowing them to recall and relive experiences from their youth [17].
5. Art Therapy
Art therapy is a type of psychotherapy that enables patients to express themselves through various mediums of art, allowing them to explore and gain insights into their inner world, reflect on themselves, and engage in a conversation with themselves. Patients actively engage in art activities and their own healing activities. In the process of creative activities, serotonin, a neurotransmitter that lessens emotions of fear or anxiety, naturally increases, and positive changes occur in the body. One can feel a sense of accomplishment, regain self-confidence, and increase self-esteem by encouraging communication through pictorial works, realizing reality, enabling the acquisition of attitudes and self-management skills necessary for solving life difficulties and finishing tasks [18,19]. The use of various technologies allows an experience that goes beyond the actual art being created in the real world, especially in the case of art therapy. For example, VR can be used to provide art therapy to people who have not been able to receive conventional art therapy due to sensory, cognitive, or motor function problems [20].
6. Therapeutic Exercise
Another mechanism of DTx is to provide patients with therapeutic exercise. Depending on the types of injuries and disabilities, customized exercises can be provided to motivate patients to extend and intensify their workouts. By applying VR technology to exercise programs, it is feasible to accurately assess and evaluate the user’s exercise and provide individualized services accordingly, improving motivation and satisfaction. Therefore, therapeutic exercise using VR technology can be an alternative to overcome the temporal and spatial limitations faced by elderly or disabled people who have barriers to accessing healthcare. It can provide the elderly with satisfactory customized therapeutic exercises that support ongoing rehabilitation [21].
7. Gamification
Gamification is defined as the application of game design components and mechanisms to domains other than games. Gamification increases players’ enjoyment and immersion in problem-solving, knowledge transfer, and marketing [9].
The medical field is one area that can benefit greatly from gamification. Gamification can deliver medical services in a more patient-friendly manner due to the psychological anxiety and nebulous rejection often associated with healthcare services. While the effect may vary depending on the disease being treated (e.g., for mental illnesses, where people generally show severe resistance to and have difficulty immersing themselves in treatment), gamification can lower psychological barriers and foster more immersion, thereby improving the treatment effect. Additionally, individuals requiring treatment for mental illness often do not participate in treatment on their own, and the rate of quitting in the middle is high. Therefore, offering access to other types of treatment, such as gamification, is important [22].
III. Case Studies
When selecting DTx as the study subjects, exemplary cases of DTx that have met the following conditions were chosen: examples of DTx that have obtained government authorization for use, that have been granted health insurance coverage, or that have been approved for clinical trials by regulatory authorities in the corresponding nation and have proven to be efficacious.
1. Cognitive Behavioral Therapy
Sommz is a software medical device developed by AIMMED that implements CBT to improve insomnia symptoms. On February 15, 2023, it became the first DTx to be approved by the MFDS in Korea.
Somzz is a wearable device-based treatment solution that combines CBT—the standard primary treatment according to insomnia clinical practice guidelines—and the circadian rhythm that most people adjust to in a 24-hour cycle. Six-month clinical trials conducted by three Korean medical institutions showed significant improvements in the Insomnia Severity Index between the pretest and posttest. The treatments include sleep habit training, real-time feedback, and behavioral interventions by the mobile app for 6–9 weeks. If non-pharmacological treatment using DTx is not effective, then drug treatment is initiated [23,24] (Figure 1).
2. Distraction Therapy
RelieVRx provides VR-based treatments to manage chronic pain. By using head-mounted displays (HMDs), RelieVRx distracts patients using games in a VR environment, thereby interrupting pain sensations and teaching pain management techniques such as relaxation therapy, diaphragmatic breath training, and behavior correction. It offers (1) pain relief programs based on biopsychological pain education, which is an evidence-based principle related to pain interventions, and (2) programs that regulate parasympathetic responses through diaphragmatic breathing. A clinical trial on patients with chronic back pain showed significant pain reduction compared to a control group that used conventional headsets [25,26] (Figure 2).
3. Graded Exposure Treatment
EASYHEiGHTS is a smartphone application developed by the University of Basel in Switzerland that employs VR to deliver exposure therapy to help overcome acrophobia. By changing the images captured by real drones, it creates a virtual environment where users can practice ascending to great heights.
According to clinical trial results, the group trained with EASYHEiGHTS showed less fear of heights and could ascend to higher altitudes compared to the control group. The application works by combining a smartphone app with an HMD to offer a 360° view of real-world scenery photographed by a drone, creating the impression of being at a high altitude. Users can gradually increase the height of the simulation, starting at 1 m, and train themselves to overcome their fear of heights [27,28] (Figure 3).
4. Reminiscence Therapy
LookBack VR is a reminiscence therapy-based app developed by the British startup Virtue Health that uses VR to improve the quality of life for patients with dementia. The app presents familiar items in a realistic style, including old photos, books, and sceneries from their homes, providing physical and visual stimulation that could enhance memory and mood. An additional app is provided to increase the patient’s communication capabilities, enabling the patient to communicate with the caregiver or family member’s smartphone or tablet [29,30] (Figure 4).
5. Art Therapy
In art therapy, VR is used to elicit positive emotions, and the technology allows sketching in 3D rather than 2D space, enabling the creation of works in 360°. Making digital creative works is easy because erasing or changing colors is uncomplicated. Furthermore, one can fully immerse themselves in the process of generating virtual works in a virtual environment. To investigate how VR technology might be used in the art therapy process, Drexel University College of Nursing and Health Professions facilitated the development of art therapy content utilizing VR headsets. After analyzing the participants’ experiences, the researchers discovered that production in a virtual environment led to embodied visual expressions, inspiring new artistic and imaginative responses. It also enhanced creativity, imagination, interaction, and problem-solving, as well as psychological stability [20,31,32].
6. Therapeutic Exercise
The Rehabilitation Gaming System is a virtual-/augmented-reality (VR/AR) neurorehabilitation treatment software program used in hospitals to treat stroke patients with symptoms caused by brain damage. Various rehabilitation gaming programs use technologies such as VR/AR, wearable sensors, and robotics to restore full body function and mobility in hands, arms, and legs. These technologies provide customized training, and games increase interest and sustainability in rehabilitation treatment. With data storage, games can also be used to monitor progress [33,34] (Figure 5).
7. Gamification
EndeavorRx is a tablet gaming app developed by Akili Interactive Labs to treat children with attention deficit hyperactivity disorder (ADHD). It is the first game-based DTx that can be used with a prescription to improve attention function in children with ADHD. The primary objective of the game is to avoid obstacles or locate a specific target, and concentration on the game improves attention. The child plays for 25 minutes a day, 5 days a week for 4 weeks to stimulate selective cognitive neural circuits.
EndeavorRx has been proven to improve objective attention in a trial involving 348 children with ADHD aged 8–12. Based on the findings of five recent clinical trials involving over 600 children, 73% of those who used EndeavorRx increased their attention, with no serious adverse effects (0%). The FDA authorized EndeavorRx for its treatment effectiveness and safety in June 2020. Temporary effects included decreased frustration tolerance (2.8%), headache (1.7%), and emotional reactions (1.1%). Therefore, monitoring is required when applying gamification [35–37] (Figure 6).
IV. Discussion
The popularity of DTx is increasing due to its potential to provide additional value compared to conventional medical devices. The DTx market reached USD 2,117.8 million (KRW 2.497 trillion) in 2020 with an annual growth rate of 26.7% and is expected to reach USD 6,904.6 million (KRW 8.1398 trillion) in 2025 [38]. The expansion of information infrastructure has made it possible to use a variety of methodologies, and their effects can be tested through non-face-to-face treatment due to the COVID-19 pandemic.
The scope of DTx is also broadening to include other medical fields, such as pain management, exercise rehabilitation therapy, and preventive medicine. In this study, we classified DTx into seven interaction types. However, DTx applications using various interaction types are currently under development, and more interaction types are thus expected to be used in DTx in the future.
To expand the development and utilization of DTx and to lead the market, the following initiatives should be considered. First, medical practitioners in various fields should become familiar with DTx and its mechanisms and explore its potential in clinical practice. As technology advances, the possibility of using a wide range of devices and sensors is increasing. Therefore, a variety of sensors and devices should be utilized in healthcare services to conduct innovative and integrated research that can address unmet medical needs and add value.
Second, to develop and commercialize DTx, the government needs to establish standardized assessment techniques for verifying its effectiveness, safety, security, and ethics, which would ultimately reduce development time and costs. However, there are currently no clear international standards and regulations for DTx [39]. To address this issue, the Digital Therapeutics Alliance, a nonprofit organization that represents the DTx industry and stakeholders, is developing DTx product evaluation tools for various entities, such as patients, clinicians, and policymakers. They have also produced and disseminated DTx valuation and integration guides [34]. The International Electrotechnical Commission (IEC) is also collaborating with TC 62 to standardize information systems, safety, and ethics for medical electrical equipment that are easily understandable not only to professionals but also to the general public [39]. Korea, which currently chairs the International Medical Device Regulator Forum (IMDRF), has played a critical role in establishing international standards and guidelines for medical devices. The MFDS has demonstrated accomplishments within the artificial intelligence (AI) medical device working group of the IMDRF, including the establishment of international standard guidelines for AI medical devices [40]. We must maintain our efforts to lead the market of international standards. Additionally, guidelines should be provided for effectiveness assessment methodologies, considering cost-benefit and medical efficacy specific to DTx, based on such standards [41].
Lastly, the private sector should work with healthcare providers to forecast demand, conduct clinical trials, and establish academic evidence from the perspective of the medical device development life cycle. The development of medical devices requires navigating numerous hurdles and processes, including planning for research, clinical trials, and commercialization, and thus, the goal can be achieved through the collaboration of all involved parties. In particular, due to the medical industry’s nature, which must prioritize safety and effectiveness, it is essential to persuade stakeholders using clinical evidence based on real-world data [41].
Samsung Medical Center, through the hospital-centered research collaboration platform “K-DEM (Digital & Electronic Medicine) Station,” increases the feasibility of research and supports strategic designs to promote licensing, establishes clinical research strategies and creates evidence, usability tests, and information on unmet needs in the medical field. Efforts are being made to collaborate with hospitals and companies, such as supporting the development of innovative treatments through reflection. Based on these efforts, DTx will be able to be used in various fields of medical service [42].
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