Comparison of Clinical Development of Digital Therapeutics among Japan, the United States, and Germany
Clinical Snapshot
PICO Framework
| P — Population | Digital therapeutics (DTx) products developed and/or approved in Japan (as of November 2023), the United States, and Germany across multiple therapeutic areas |
| I — Intervention | Digital therapeutics (software-based therapeutic interventions) undergoing or having completed clinical development and regulatory review |
| C — Comparator | Cross-national comparison: Japan (PMDA-regulated) vs. United States (FDA-regulated) vs. Germany (BfArM/DiGA-regulated) |
| O — Outcomes | Clinical trial design characteristics (confirmatory and exploratory study designs), regulatory approval pathways, market authorisation actions, and evidence standards applied to DTx across the three jurisdictions |
Bottom Line
This descriptive comparative study from Keio University provides a useful, if methodologically limited, landscape analysis of digital therapeutics (DTx) clinical development across Japan, the United States, and Germany. The core finding — that confirmatory trial designs are broadly similar across jurisdictions despite differing regulatory frameworks — is plausible and consistent with the broader DTx literature. The authors correctly highlight the persistent challenge of placebo control design in DTx trials, a genuine and underappreciated methodological problem. However, the study's value is constrained by non-transparent comparator selection, absence of quantitative analysis, a small total sample of 27 DTx, and potential institutional publication bias given the Keio-affiliated authorship and journal. The cross-sectional November 2023 snapshot will date quickly. For Australian clinicians and regulators, the study offers useful contextual framing but cannot be directly applied given the TGA's distinct SaMD framework and the absence of a PBS-linked DTx reimbursement pathway. Senior clinicians should treat this as hypothesis-generating background evidence (Oxford CEBM Level 3 at best) rather than practice-changing guidance. The field urgently needs prospective, patient-level outcome data to move beyond regulatory process comparisons toward evidence of real-world clinical benefit.
Key Findings
P Value: Not reported — no inferential statistics performed
Effect Size: Not reported — the study is descriptive and does not calculate comparative effect sizes between jurisdictions. Narrative finding: trial designs showed 'more similarities than differences' across countries and therapeutic areas.
Primary Outcome: By November 2023, Japan had developed DTx across 11 therapeutic areas; 7 had reached or completed the confirmatory study stage and 5 were in the exploratory phase. A total of 27 DTx (Japanese plus selected US/German comparators) were reviewed for confirmatory trial design and regulatory actions.
Nnt Or Sensitivity: Not applicable — this is a regulatory landscape and trial design comparison study, not a clinical efficacy or diagnostic accuracy study. No NNT, sensitivity, specificity, or hazard ratios are calculable from the reported data.
Confidence Interval: Not reported
Clinical Application
The findings are primarily relevant to regulatory and research planning rather than direct clinical practice. The identification of placebo control challenges is actionable for trial designers. The comparative regulatory framework analysis is useful for organisations seeking international DTx approval strategies. Australia is not represented in this study. The TGA regulates DTx as Software as a Medical Device (SaMD) under the Therapeutic Goods Act 1989, with ARTG inclusion required for Class IIa and above SaMD. Unlike Germany's DiGA reimbursement pathway (which allows provisional listing with post-market evidence generation) or the FDA's Breakthrough Device Designation, Australia does not yet have a dedicated fast-track DTx reimbursement pathway under the PBS or MBS. The RACGP has published guidance on digital health tools but lacks specific DTx prescribing frameworks. Australian DTx developers and regulators could draw on the trial design lessons from this paper — particularly regarding active comparator designs and sham control challenges — when planning PMDA/FDA/BfArM-aligned development programs. The TGA's 2023 Software as a Medical Device guidance is the most relevant local regulatory reference. PBS listing of DTx remains an unresolved policy challenge in Australia, making the German DiGA model of particular interest for future health policy consideration. Relevant to clinical researchers, regulatory scientists, health technology assessment bodies, and digital health developers involved in DTx clinical development. Indirectly relevant to clinicians considering prescribing or recommending DTx to patients across therapeutic areas including mental health, substance use disorders, chronic disease management, and rehabilitation.
Abstract
Digital therapeutics (DTx) have demonstrated promising potential as a novel therapeutic approach, with their clinical development gaining momentum. Comparison of DTx development between Japan, a relative newcomer, and Germany and the U.S., known for favorable circumstances, is a topic of interest. DTx developed in Japan as of November 2023 were identified on the Pharmaceuticals and Medical Devices Agency (PMDA) website and in the literature. Similar DTx available in the U.S. and Germany were identified in the databases maintained by the U.S. Food and Drug Administration (USFDA) and Federal Institute for Drugs and Medical Devices (BfArM). Data on their clinical trials and regulatory status were obtained from these databases and their respective national clinical trial registries. The data obtained were compared and analyzed. By November 2023, Japan had developed DTx, encompassing 11 therapeutic areas. Seven DTx had reached or completed the confirmatory study stage, whereas five DTx were in the exploratory phase. Twenty DTx in the therapeutic areas were selected from the U.S. and Germany. A total of 27 DTx were reviewed regarding the designs of confirmatory studies and regulatory actions taken. Trial designs demonstrated more similarities than differences across the countries and therapeutic areas. Placebo trial design-associated difficulties were conspicuous. Although regulatory actions to place DTx in the market differed across countries, they effectively ensured the efficacy and safety of DTx that were suitable for marketing considering the most current science. The regulatory measures in the three countries seem to have positively impacted DTx development.
References
- 1.Tominaga, T., Hasegawa, T., & Harada, E. (2025). Comparison of clinical development of digital therapeutics among Japan, the United States, and Germany. The Keio Journal of Medicine. Advance online publication. https://doi.org/10.2302/kjm.2025-0006-OA
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