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

2023/07/05

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 medical records that digitize patient medical information, online consultations that enable remote medical care, and software-based medical devices such as "therapeutic apps." In particular, with the 2014 amendment to the Pharmaceutical Affairs Act, therapeutic apps became subject to pharmaceutical approval and insurance coverage as program medical devices even as standalone software*1, and they have come into the spotlight as a new treatment strategy alongside conventional pharmaceuticals and hardware medical devices. In this article, I will introduce the trends in digital medicine and the role of therapeutic apps through development examples, while also touching upon the potential of digital medicine following the COVID-19 pandemic.

Nicotine Dependence Treatment App

Therapeutic 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 therapeutic 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 provided under insurance at smoking cessation clinics, but the treatment completion rate remains at about 30% due to reasons such as the difficulty for the working generation to visit clinics. As a new treatment method to address these issues, CureApp, Inc. developed the "CureApp SC Nicotine Dependence Treatment App and CO Checker" (hereafter, CureApp SC)*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/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 aids) versus 50.5% in the control group (sham app used with smoking cessation aids), 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 categories were established: the Smoking Cessation Treatment Support System Instruction and Management Fee (140 points) and the Smoking Cessation Treatment Support System Fee (2,400 points)*4. This became an example of how therapeutic apps using digital technology provided new value to conventional 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 considered to have good control through treatment, leaving a challenge where many remain untreated or poorly controlled*5. To solve this issue, the "CureApp HT Hypertension Treatment Support App" (hereafter, CureApp HT) was developed (Figure 2). This product can be used to support hypertension treatment, such as lifestyle modifications, alongside data obtained from home blood pressure monitors and doctor's guidance during outpatient visits. The efficacy and safety of CureApp HT were evaluated in a domestic Phase III multicenter randomized controlled trial*6. When 390 essential hypertension patients under 65 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 guidance, the primary endpoint (change in 24-hour ambulatory systolic blood pressure over 12 weeks post-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 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 therapeutic 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, therapeutic apps in Japan are keeping pace with the rest of the world, with development progressing in various new areas such as insomnia, depression, and diabetes.

Rapid Acceleration of Digitalization During COVID-19

The COVID-19 pandemic changed various aspects of healthcare. Notably, 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 adoption was later 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 from 10,812 (9.1%) as of April 2020 to 16,843 (15.2%) as of April 2021 within one year, and has been gradually increasing 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.

Within the changing medical landscape of the COVID era, new intervention methods that integrate and utilize various digital devices are being explored. Here, I will summarize the roles that the previously introduced therapeutic apps can play in the post-Corona 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 leads to insufficient treatment management for unrelated diseases. If therapeutic apps can fill the treatment gap between outpatient visits, they are expected to contribute to treatment management. Second is adaptation to the spread of online consultations. To adapt from face-to-face to online consultations, it is important not to lower the quality of care. By using therapeutic apps in combination, it is expected that regional disparities can be reduced and the quality of medical care can be maintained or improved.

In fact, taking the smoking cessation therapeutic app as an example, I will introduce evidence regarding the effect of therapeutic apps using online consultations*9. In this trial, the face-to-face group had all visits in person, while the online group had the first visit in person 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 group and 78.9% for the face-to-face 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 therapeutic apps are as effective as face-to-face consultations and can be considered an effective treatment strategy for patients who have difficulty visiting clinics.

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

Furthermore, the COVID-19 wave 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 appropriate usage guidelines is underway*10.

Constantly Evolving Medical Devices and the Use of RWD

Program medical devices using digital technology, including therapeutic apps, are constantly evolving. Therefore, to promote their practical application, it is necessary to establish approval review systems and structures that take their characteristics into account. In November 2020, the Ministry of Health, Labour and Welfare announced the "Digital Transformation Action Strategies in Healthcare for SaMD (DASH for SaMD)" to promote the early practical application of cutting-edge program medical devices. Furthermore, in the December 2022 interim report on regulatory reform promotion, discussions were held on (1) the utilization of Real-World Data (RWD) in a two-stage approval system and (2) flexible review of reimbursement prices based on actual usage records in clinical settings for a certain period, in order to promote the development and market entry of Software as a Medical Device (SaMD)*11.

Regarding the first point, the utilization of RWD, progress is being made in the United States, such as the release of the "Framework for FDA's Real-World Evidence Program" in December 2018 and the FDA's approval of expanded indications for drugs based on appropriately designed trials using RWD. 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 pediatrics. However, since research using RWD can focus on "usefulness" or "effectiveness in actual clinical practice," I believe it is possible to build the necessary evidence by properly organizing it alongside conventional research such as randomized controlled trials (RCTs).

Regarding the second point, insurance reimbursement prices, discussions taking the characteristics of program medical devices into account are necessary. Considering the specific characteristics of program medical devices, 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 drawing attention. Furthermore, when such program medical devices receive insurance reimbursement, their cost-effectiveness compared to conventional treatments is also discussed. Taking the previously introduced hypertension treatment support app as an example, research comparing the cost-effectiveness of treatment suggests data showing that the hypertension treatment support program is superior in cost-effectiveness when based on standard treatment (ICER; the incremental cost-effectiveness ratio was ¥1,199,880/QALY for the use of the therapeutic app, compared to the general standard of 5 million yen*12). In Japan, which faces the challenge of increasing medical costs, the spread of digital medicine may become a foothold for reducing medical expenditures.

Future Outlook

In the May 2022 proposal by the Liberal Democratic Party 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 medical record information, and (3) "Medical Fee Revision DX"*13. I believe these policies will further push the digitalization of healthcare and allow both medical providers and patients to reap the benefits. Following COVID-19, while the digitalization of healthcare progresses, challenges such as ICT literacy on the user side, 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 following the COVID-19 pandemic, the role of therapeutic 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 serves as a help in considering what can be done to promote the digitalization of Japanese healthcare and steadily improve medical care with an eye toward the future.

*1 Ministry of Health, Labour and Welfare, Overview of the Act for Partial Revision of the Pharmaceutical Affairs Act (Act No. 84 of 2013). Overview of the Act for Partial Revision 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 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 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 Ministry of Internal Affairs and Communications | 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 Program Medical Devices ~ DASH for SaMD. Administrative Initiatives Regarding Approval Review of Program Medical Devices ~DASH for SaMD~ (Accessed May 16, 2023)

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