[Feature: Post-COVID Healthcare Policy] Kota Satake: The Potential of Digital Medicine After the COVID-19 Pandemic

The environment surrounding digital medicine in Japan has undergone a major transformation over the past decade. Digital medicine is a broad general term for the application of digital technology to medical care, including electronic health records that digitize patient medical information, online consultations that enable remote medical care, and Software as a Medical Device (SaMD) such as "prescription apps." In particular, following the 2014 amendment to the Pharmaceutical Affairs Act, prescription apps became subject to pharmaceutical approval and insurance coverage as SaMD even as standalone software*1, and they have come into the spotlight as a new treatment strategy alongside traditional pharmaceuticals and hardware medical devices. In this article, I will introduce the trends in digital medicine and the role of prescription apps through development examples, while also touching upon the potential of digital medicine after the COVID-19 pandemic.

Nicotine Dependence Treatment App

Prescription apps belong to a category called Digital Therapeutics (DTx), which are Software as a Medical Device (SaMD) that require regulatory approval and are intended to treat a disease themselves. I will introduce the background of how prescription apps are developed and implemented in society.

One of the major social issues in Japan is the high smoking rate. Currently, 12-week treatments are covered by insurance at smoking cessation clinics, but the treatment completion rate remains at about 30% due to reasons such as the difficulty for the working-age population to visit clinics. As a new treatment method to address these issues, CureApp, Inc. developed the "CureApp SC Nicotine Addiction Treatment App and CO Checker" (hereafter, CureApp SC), a smoking cessation treatment support system*2 (Figure 1). This product consists of three components: a patient app, a doctor app, and a CO checker that can measure the concentration of carbon monoxide (CO) in exhaled breath at home. By using CureApp SC, automatic guidance based on medical evidence is displayed based on data entered into the app by patients and doctors, providing behavioral therapy, medication and visit management, and disease education. As evidence of clinical effectiveness, a domestic Phase III multicenter clinical trial showed a statistically significant difference in the continuous abstinence rate from weeks 9 to 24: 63.9% in the intervention group (CureApp SC added to smoking cessation aid) versus 50.5% in the control group (sham app used with smoking cessation aid), with an odds ratio of 1.73 (95% confidence interval 1.239–2.424) against the control group*3 (P=0.001). Following the efficacy and safety demonstrated in the clinical trials, new reimbursement categories were established: 140 points for the Smoking Cessation Treatment Support System Instruction and Management Fee and 2,400 points for the Smoking Cessation Treatment Support System Fee*4. This became an example of a prescription app using digital technology providing new value to traditional treatment schemes for challenges in the medical field.

Hypertension Treatment Support App

As another example, I will introduce a hypertension treatment support app combined with IoT (Internet of Things) devices such as commercially available blood pressure monitors. Hypertension is a significant risk factor for cerebrovascular and cardiovascular events. Among the approximately 43 million hypertension patients in Japan, only about 12 million are receiving treatment and have good control, leaving a challenge where many people remain untreated or poorly controlled*5. To solve these issues, the "CureApp HT Hypertension Treatment Support App" (hereafter, CureApp HT), a hypertension treatment support program, was developed (Figure 2). This product can be used to support hypertension treatment, such as lifestyle modifications, along with data obtained from home blood pressure monitors and guidance from doctors at outpatient clinics. The effectiveness and safety of CureApp HT were evaluated in a domestic Phase III multicenter randomized controlled trial*6. When 390 essential hypertension patients under 65 years of age who were not using antihypertensive drugs were assigned to a control group receiving lifestyle modification guidance and an intervention group using the hypertension treatment support app in addition to lifestyle modification guidance, the primary endpoint (change in 24-hour ambulatory systolic blood pressure 12 weeks after intervention) showed a significant decrease in systolic blood pressure in the intervention group (Intervention group: -4.9 mmHg, Control group: -2.5 mmHg, P=0.024). Furthermore, no serious adverse events derived from the product were observed in this clinical trial, and no safety issues were pointed out. Based on these results, pharmaceutical approval was obtained from the Ministry of Health, Labour and Welfare in April 2022 after review by the PMDA, and it became covered by insurance in September*7.

These cases suggest that prescription apps have a high affinity for treatments that encourage "behavioral change," such as nicotine dependence and lifestyle-related diseases, and can support treatment by demonstrating their characteristic of filling "treatment gaps." Currently, Japan is keeping pace with the rest of the world, and development is progressing in various new areas such as insomnia, depression, and diabetes.

Digitalization Accelerated Rapidly During COVID-19

The COVID-19 pandemic changed various aspects of medical care. In particular, to prevent the spread of infection through face-to-face contact, online medical consultations using digital technology underwent deregulation. In 2020, online consultations for first-time visits were permitted on a temporary and exceptional basis, and their permanent implementation was subsequently announced. Regarding insurance points for online consultations, it was initially an era where "the first visit must be face-to-face," but through the pandemic, such regulations were removed. In the FY2022 medical fee revision, a new evaluation for first-time visits using information and communication equipment was established. In fact, the number of medical institutions supporting online consultations in Japan increased in one year from 10,812 (9.1%) as of April 2020 to 16,843 (15.2%) as of April 2021, and has been increasing gradually since then*8. However, compared to the rapid growth of online consultation adoption in other countries during the pandemic, there is still room for growth in Japan.

In the changing medical landscape of the COVID era, new intervention methods that integrate and utilize various digital devices are also being explored. Here, I will summarize the roles that the previously introduced prescription apps can play in the post-COVID era. First is the approach to the decrease in outpatient visit frequency and the avoidance of medical consultations. There are concerns that avoiding consultations due to fear of COVID-19 infection may lead to insufficient treatment management for diseases unrelated to COVID-19. Here, if the treatment gap between outpatient visits can be supplemented with prescription apps, it is expected to contribute to treatment management. Second is adaptation to the spread of online consultations. To adapt from face-to-face consultations to online consultations, it is important not to lower the quality of care. By using prescription apps in combination, it is expected to reduce regional disparities and maintain or improve the quality of medical care.

In fact, taking the smoking cessation app as an example, I will introduce evidence regarding the effectiveness of prescription apps using online consultations*9. In this study, the face-to-face consultation group was entirely face-to-face, while the online consultation group had the first visit face-to-face and the 2nd to 5th visits online, with both groups performing smoking cessation treatment using CureApp SC. The primary endpoint, the continuous abstinence rate from weeks 9 to 12, was 81.0% for the online consultation group and 78.9% for the face-to-face consultation group, with an odds ratio of 1.14 (95% confidence interval 0.45–2.88), demonstrating clinical non-inferiority. This suggests that online consultations combined with prescription apps are as effective as face-to-face consultations and can be considered an effective treatment strategy for patients who have difficulty visiting outpatient clinics.

In this way, there is increasing attention on developing "digitalization," which utilizes digital medicine in services and processes, and subsequently "digital transformation," which creates new value across the entire medical field.

Furthermore, the wave of COVID-19 is changing the flow not only of clinical practice but also of research and clinical trials. Decentralized Clinical Trials (DCT), a clinical trial method that does not depend on visits to medical institutions, and online clinical trials that technically guarantee the consistency between trial data and medical records through the use of blockchain technology have been proposed, and the creation of guidance such as proper use guidelines is underway*10.

Constantly Evolving Medical Devices and the Use of RWD

Software as a Medical Device (SaMD) using digital technology, including prescription apps, is constantly evolving. Therefore, in promoting its practical application, it is necessary to develop an approval review system and structure that takes its characteristics into account. In November 2020, the Ministry of Health, Labour and Welfare announced the "Strategy for DASH for SaMD (Digital Transformation Action Strategies in Healthcare for SaMD)" to promote the early practical application of cutting-edge SaMD. Furthermore, in the December 2022 interim report on promoting regulatory reform, discussions are being held to promote the development and market entry of SaMD, including (1) the use of real-world data (RWD) in a two-stage approval system and (2) flexible review of reimbursement prices based on actual use in clinical settings over a certain period*11.

Regarding the first point, the use of RWD, the United States released the "Framework for FDA's Real-World Evidence Program" in December 2018, and the FDA has approved the expansion of drug indications based on appropriately designed studies using RWD, showing progress in RWD utilization. In Japan as well, the establishment of consultation desks and guidelines for the use of RWD is progressing, starting with pharmaceutical-related data. Currently, the use of RWD in Japan is limited to cases where RCTs are difficult, such as rare diseases or pediatric cases. However, since research using RWD can focus on "usefulness" or "effectiveness in clinical practice," I believe it is possible to build the necessary evidence by properly organizing it alongside traditional research such as randomized controlled trials (RCTs).

Regarding the second point, insurance reimbursement prices, discussions that take the characteristics of SaMD into account are necessary. Considering the specific characteristics of SaMD, such as the need for updates and security maintenance, continuous evaluation within the medical fee system is required. This is a field where future treatment, including evaluation methods when performance improves, is attracting attention. Furthermore, when such SaMD receives insurance reimbursement, cost-effectiveness compared to traditional treatments is also discussed. Taking the previously introduced hypertension treatment support app as an example, research comparing the cost-effectiveness of treatments has produced data suggesting that the hypertension treatment support program is superior in cost-effectiveness when based on usual care (ICER; the incremental cost-effectiveness ratio was ¥1,199,880/QALY for the use of the prescription app, compared to the general standard of ¥5 million*12). In Japan, which faces the challenge of increasing medical costs, the spread of digital medicine may become a stepping stone for reducing medical expenditures.

Future Outlook

In the May 2022 proposal by the Liberal Democratic Party's Policy Research Council, "Medical DX Reiwa Vision 2030," it was announced that to fundamentally resolve the state of information in Japan's medical field, initiatives would be promoted for (1) the creation of a "National Medical Information Platform," (2) the standardization of electronic health record information, and (3) "Medical Fee Revision DX"*13. I believe these policies will further drive the digitalization of medical care and allow both healthcare providers and patients to reap the benefits. Following COVID-19, while the digitalization of medical care progresses, challenges such as ICT literacy on the part of users, in addition to regulations, have emerged. To maximize the characteristics of digital medicine with new value that compensates for what cannot be achieved through analog means, various efforts such as improving usability are required.

In this article, I have described the trends in digital medicine after the COVID-19 pandemic, the role of prescription apps, and the future potential of digital medicine. Digital medicine is highly flexible and adaptable, and it is expected that an uncountable number of types of solutions will emerge. I hope this will serve as a guide for looking toward the future, promoting the digitalization of medical care in Japan, and considering what can be done to steadily improve medical care.

*1 Ministry of Health, Labour and Welfare, Overview of the Act for Partial Amendment of the Pharmaceutical Affairs Act (Act No. 84 of 2013). Overview of the Act for Partial Amendment of the Pharmaceutical Affairs Act (Act No. 84 of 2013) (Accessed May 14, 2023)

*2 Ministry of Health, Labour and Welfare, Central Social Insurance Medical Council General-1-1, Regarding Insurance Coverage of Medical Devices (Listed in December 2020). Regarding Insurance Coverage of Medical Devices (Scheduled for Listing in December 2020) (Accessed March 13, 2023)

*4 Ministry of Health, Labour and Welfare, Overview of the FY2022 Medical Fee Revision. Overview of the FY2022 Medical Fee Revision (Accessed March 13, 2023)

*7 Ministry of Health, Labour and Welfare, Central Social Insurance Medical Council General-1-1, Regarding Insurance Coverage of Medical Devices (Listed in September 2022). Regarding Insurance Coverage of Medical Devices (Scheduled for Listing in September 2022) (Accessed March 13, 2023)

*8 Ministry of Internal Affairs and Communications, 2021 White Paper on Information and Communications, Status of Online Consultations Seen Through Data MIC | 2021 White Paper on Information and Communications | Status of Online Consultations Seen Through Data (Accessed May 30, 2023)

*10 Pmda. Administrative Initiatives Regarding Approval Review of Software as a Medical Device ~ DASH for SaMD. Administrative Initiatives Regarding Approval Review of Software as a Medical Device ~DASH for SaMD~ (Accessed May 16, 2023)

*11 December 2022, Council for Promotion of Regulatory Reform, Interim Report on Promotion of Regulatory Reform (Draft) Interim Report on Promotion of Regulatory Reform (Draft) (Accessed May 16, 2023)

*13 Proposal for "Medical DX Reiwa Vision 2030" (Liberal Democratic Party Policy Research Council) Proposal for "Medical DX Reiwa Vision 2030" (Accessed May 16, 2023)