Digital Therapeutics (DTx)

What is Digital Therapeutics?

Digital Therapeutics (DTx), also known as digital therapy, involves the use of software such as applications to deliver therapeutic interventions. For example, smartphone applications and IoT devices are utilized for treatment interventions in conditions such as hypertension, diabetes, and neuropsychiatric disorders.

DTx gained significant attention when WellDoc, a U.S. company, obtained clearance from the FDA (Food and Drug Administration) in 2010 for “BlueStar,” a therapeutic support application for patients with type 2 diabetes.

DTx refers to software-based therapies that improve treatment outcomes through standalone use or adjunctive use. Several DTx products have already been commercialized in the United States, which is a pioneer in this field.

DTx is a new category of medical device products that emerged approximately 10 to 15 years ago. DTx expands treatment options for both patients and physicians. Currently, the healthcare system is burdened with chronic issues such as “3-hour waits for 5-minute consultations.” However, with DTx, patients can receive treatment, diagnosis, and guidance at home without visiting medical facilities.

Patients can input their symptoms and measurement data in real-time, and physicians can conduct patient examinations and provide guidance during their available time slots.

In the industry, the number of emerging ventures developing DTx is increasing. The author continues to receive inquiries from numerous venture companies and software development companies seeking to enter the medical device industry.

Meanwhile, for pharmaceutical companies, DTx represents a potential revenue source beyond traditional pharmaceuticals. Historically, pharmaceutical companies have had to invest enormous funds over 10 to 15 years to develop new drugs. Moreover, there is a considerable possibility that development may be forced to halt midway. It is essentially an “all-or-nothing” gamble. Even if a drug successfully reaches the market, companies must continuously develop new drugs due to patent expiration issues and the emergence of generic products.

In contrast to pharmaceuticals, DTx can be developed in a relatively short period. Furthermore, functional additions and modifications after market launch can be implemented relatively easily.

DTx Pioneer: “Prescription App” BlueStar (WellDoc)

DTx gained widespread attention when the FDA cleared BlueStar, a medical device software developed by WellDoc in 2010, as a “prescription app” to assist in the self-management of type 2 diabetes.

A “prescription app” is one that becomes usable when a physician issues a code called an “unlock key” to a patient, who then enters that code into the application. In other words, it serves as a substitute for a traditional prescription.

BlueStar demonstrated results in large-scale clinical trials showing efficacy equal to or greater than that of pharmaceutical drugs for diabetes, leading to FDA clearance in 2010.

In fact, BlueStar was a successor product. While there was a predecessor DTx product for type 2 diabetes, it operated on personal computers. BlueStar’s innovation was its deployment on smartphones, meaning patients could now carry the medical device software with them at all times.

BlueStar’s functionality includes allowing patients to record blood glucose levels at home, displaying disease education and advice on lifestyle habits and motivation maintenance at appropriate times based on input information, and enabling patients to ask questions to specialists through the app.

Furthermore, the app provides learning opportunities for blood glucose control methods such as pharmacotherapy, dietary therapy, and exercise therapy.

For physicians, it serves as a diagnostic support system, providing the medical team with pre-consultation blood glucose readings, medication and health condition records, and progress reports before each examination.

“The World’s First DTx Prescribed for Treatment” reSET (Pear Therapeutics)

reSET, developed by Pear Therapeutics, demonstrates therapeutic effects on substance abuse and dependence through app-based cognitive behavioral therapy.

The key difference is that while BlueStar mentioned above was cleared as a tool to assist self-management, reSET was cleared as a treatment modality itself.

The approved indication for reSET is for patients aged 18 years and older with substance use disorder (including cannabis, cocaine, and alcohol) who are receiving outpatient treatment.

A 12-week (90-day) treatment period is established, with a total of 61 different content modules (therapy lessons) available. Patients are recommended to complete approximately four modules per week, selecting content related to their symptoms or recommended by their physician.

A multicenter, open-label randomized controlled trial was conducted in a population excluding opioid use disorder (399 patients). When comparing a control group receiving standard face-to-face counseling with a group that reduced face-to-face counseling and utilized reSET, the reSET group demonstrated evidence of a substance abstinence success rate twice as high as the control group.

During this clinical trial, no adverse events related to reSET use were reported.

Digital Therapeutics in Japan

In Japan, when the Pharmaceutical Affairs Law was revised in November 2014 and renamed the “Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (PMD Act),” “standalone programs (software)” were added to the scope of covered medical devices. This paved the way for therapeutic apps to be prescribed by physicians and covered by health insurance.

In October 2017, CureApp Inc., a medical venture company, announced the initiation of clinical trials for a “nicotine dependence treatment app (smoking cessation treatment app).”

On May 30, 2019, the company announced the submission of an application for regulatory approval of a smartphone app for treating nicotine dependence. This was the first application for a therapeutic app in Japan and the world’s first for smoking cessation treatment. Health insurance coverage was approved on November 11, 2020.

Clinical trials were conducted at 31 domestic medical institutions, and the results were published. The study examined how much the 6-month continuous abstinence rate improved when the app was used in conjunction with 12 weeks of treatment at smoking cessation clinics. The trial was conducted with 584 patients with nicotine dependence. Patients who used the app in combination with standard treatment showed a continuous abstinence rate of 64%, an improvement of 13 percentage points.

The app was jointly developed by CureApp Inc. and Keio University School of Medicine. When patients input information such as the strength of their urge to smoke into the app, it displays advice such as “Please chew gum.”

For patients, achieving smoking cessation or improving diabetes management is a personal struggle. Quitting smoking can be quite difficult to accomplish alone. Additionally, diabetes often presents without noticeable symptoms, and when life gets busy, patients may inadvertently forget treatment or medication.

When patients experience “loss of motivation” during treatment, DTx support can increase the likelihood of continuation.

Thus, DTx appears to hold great promise. However, there are considerable challenges regarding the implementation of clinical trials to prove efficacy and issues related to insurance reimbursement. These issues will be addressed in a separate article.

Regulatory and Industry Update (2025)

As of 2025, the digital therapeutics landscape continues to evolve rapidly with important regulatory developments:

United States Regulatory Framework

The FDA continues to refine its approach to DTx through several key guidance documents. The FDA’s Digital Health Center of Excellence, established to advance digital health innovation, provides regulatory clarity through the Software as a Medical Device (SaMD) framework. The FDA has implemented a precertification program that allows certain companies with demonstrated quality systems to bring lower-risk digital health products to market more efficiently.

The FDA has also clarified that DTx products are evaluated based on their intended use and risk classification. Most DTx products fall under Class II medical devices, requiring 510(k) clearance or, less commonly, de novo classification for novel products. The FDA emphasizes the importance of clinical evidence demonstrating safety and effectiveness, with the level of evidence scaled to the product’s risk level.

European Union Regulatory Environment

In the European Union, DTx products are regulated under the Medical Devices Regulation (MDR 2017/745). Software intended for therapeutic purposes is typically classified as Class IIa or IIb medical devices, depending on the condition being treated and the potential risks. DTx developers must demonstrate compliance with the General Safety and Performance Requirements (GSPRs) and undergo conformity assessment by Notified Bodies for higher-risk products.

The EU has been working on specific guidance for software and artificial intelligence-based medical devices, with the Medical Device Coordination Group (MDCG) publishing guidance documents on qualification and classification of software.

Japan’s Evolving Framework

Japan has continued to advance its regulatory framework for DTx since the initial approvals. The Pharmaceuticals and Medical Devices Agency (PMDA) has been working to streamline the approval process for digital health products while maintaining safety standards. Japan established a specific consultation framework for program medical devices, recognizing the unique characteristics of software-based therapies.

The PMDA has issued guidance on clinical evaluation of program medical devices, emphasizing the importance of demonstrating clinical benefit through appropriate study designs. Japan has also been exploring innovative approaches to post-market surveillance and iterative improvement of DTx products, recognizing that software can be updated more frequently than traditional medical devices.

Reimbursement Challenges and Progress

One of the significant challenges for DTx globally has been establishing appropriate reimbursement models. Traditional healthcare reimbursement systems were designed for conventional therapies such as pharmaceuticals and medical procedures, making it difficult to apply these models to software-based interventions.

In Japan, the process for health insurance coverage of DTx involves demonstrating clinical value and cost-effectiveness to the Ministry of Health, Labour and Welfare (MHLW). The reimbursement amount must reflect development costs, clinical evidence generation expenses, and ongoing software maintenance requirements. The challenge lies in balancing fair compensation for innovation with healthcare system sustainability.

Several countries are experimenting with novel reimbursement approaches, including outcome-based pricing, subscription models, and integration into existing diagnostic related group (DRG) payment systems. Germany’s Digital Health Applications (DiGA) program, launched in 2020, provides a structured pathway for DTx reimbursement and has been studied as a potential model by other countries.

Clinical Evidence Requirements

A critical aspect of DTx development is generating robust clinical evidence. Regulatory authorities require randomized controlled trials (RCTs) for higher-risk DTx products, similar to pharmaceutical development. However, the specific design of these trials must account for the unique characteristics of digital interventions, such as user engagement, adherence patterns, and the potential for rapid iteration and improvement.

The clinical evidence must demonstrate not only efficacy in controlled settings but also effectiveness in real-world use. This includes consideration of user interface design, accessibility, digital literacy requirements, and integration with existing healthcare workflows.

International Standards

Several international standards have been developed to support DTx development and regulation:

IEC 62304 provides requirements for the lifecycle processes of medical device software, covering development, maintenance, and risk management activities.

IEC 62366-1 addresses usability engineering for medical devices, which is particularly crucial for DTx products where patient engagement and ease of use directly impact therapeutic outcomes.

ISO 14971 establishes requirements for risk management throughout the medical device lifecycle, including specific considerations for software-related risks.

ISO 27001 provides a framework for information security management, increasingly important as DTx products handle sensitive patient health data.

These standards help ensure that DTx products meet consistent safety, effectiveness, and quality requirements across different markets.

Cybersecurity and Data Privacy

As DTx products collect, transmit, and store patient health information, cybersecurity and data privacy have become paramount concerns. Regulatory authorities worldwide have issued guidance on cybersecurity for medical devices, requiring manufacturers to implement appropriate safeguards throughout the product lifecycle.

In the United States, the FDA has issued guidance on cybersecurity in medical devices, requiring premarket cybersecurity information and postmarket management of cybersecurity vulnerabilities. The Health Insurance Portability and Accountability Act (HIPAA) establishes privacy requirements for protected health information.

In the European Union, the General Data Protection Regulation (GDPR) provides comprehensive data protection requirements, including provisions for obtaining patient consent, ensuring data security, and enabling data portability.

Japan’s Act on the Protection of Personal Information (APPI) governs the handling of personal health data, with specific provisions for medical information. DTx developers must ensure compliance with these privacy regulations while maintaining the functionality needed for therapeutic effectiveness.

Future Outlook

The future of DTx appears promising, with continued growth expected across various therapeutic areas. Emerging applications include mental health conditions, chronic pain management, neurodegenerative diseases, and pediatric conditions. The integration of artificial intelligence and machine learning technologies promises to enhance DTx capabilities through personalized treatment algorithms and adaptive interventions.

However, several challenges remain. These include establishing appropriate reimbursement models that incentivize innovation while ensuring healthcare system sustainability, generating long-term safety and effectiveness data, addressing digital divide issues to ensure equitable access, and developing interoperability standards to enable integration with electronic health records and other healthcare systems.

Regulatory authorities worldwide continue to work toward harmonization of DTx regulations to facilitate global development and market access while maintaining appropriate safety and effectiveness standards. Industry collaboration, including organizations such as the Digital Therapeutics Alliance, plays an important role in establishing best practices and advocating for appropriate regulatory frameworks.

As the field matures, DTx is likely to become an increasingly important component of healthcare delivery, complementing traditional therapies and expanding treatment options for patients worldwide.