Current Landscape of Digital Biomarkers: Device Authorization, Regulatory Qualification, and Clinical-Trial Endpoints

Osamu Takenouchi; Toshikazu Fukami; Takanori Fujita; Kenta Hosomi; Keisuke Izumi; Naoki Kubota; Shuta Mitomo; Yuichiro Yano; Katsuhiko Yoshimoto; Kiyoyuki Chinzei; Megumi Furukawa; Tadashi Hosoya; Yuya Imai; Yoichi Ito M.; Norihiro Kawabata; Takashi Moriya; Yuka Suzuki; Mizuki Yoshida; Hideki Oi; Taishiro Kishimoto; Kazumichi Minato

doi:10.51094/jxiv.6687

##article.authors##

Osamu Takenouchi 株式会社テックドクター
Toshikazu Fukami TechDoctor, Inc.
Takanori Fujita Tokyo Foundation for Policy Research, Tokyo, Japan
Kenta Hosomi Kyowa Kirin Co., Ltd.
Keisuke Izumi TechDoctor, Inc.
Naoki Kubota Eisai Co., Ltd.
Shuta Mitomo CMIC HOLDINGS Co., Ltd.
Yuichiro Yano Department of General Medicine, Juntendo University Faculty of Medicine
Katsuhiko Yoshimoto Nippon Shinyaku Co., Ltd.
Kiyoyuki Chinzei Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)
Megumi Furukawa Johnson & Johnson Innovative Medicine
Tadashi Hosoya Department of Rheumatology, Institute of Science Tokyo, Tokyo, Japan
Yuya Imai argenx BV
Yoichi Ito M. Data Science Center, Promotion Unit, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital
Norihiro Kawabata Chugai Pharmaceutical Co., Ltd.
Takashi Moriya Edwards Lifesciences Japan Ltd.
Yuka Suzuki International Affairs, Clinical Research Innovation and Education Center, Tohoku University Hospital
Mizuki Yoshida Department of Biometrics & Data Management, Development Japan, Pfizer R&D Japan G.K.
Hideki Oi Department of Healthcare Management, Kyorin University School of Medicine
Taishiro Kishimoto Hills Joint Research Laboratory for Future Preventive Medicine and Wellness, Keio University School of Medicine
Kazumichi Minato TechDoctor, Inc.

DOI:

https://doi.org/10.51094/jxiv.6687

キーワード:

Digital Biomarker、 Medical Device、 Qualification、 Digital Endpoint、 Regulatory Landscape

抄録

Introduction

Digital biomarkers (dBMs), which provide objective measures of individuals’ performance in daily life, are expected to promote patient-centered care, to create new value in routine clinical practice and in treatment, and to be used in clinical trials. The adoption of dBMs can be categorized into three distinct pathways: (i) regulatory authorization as a medical device, (ii) qualification for a specific context of use (CoU), and (iii) adoption as a digital endpoint (dEP) in clinical trials, each of which requires different evidence. The lack of comprehensive overviews of these structural differences has led to increased rework during development. This review aimed to systematically map the structure of this adoption gap.

Methods

This study was conducted as a scoping review in accordance with the PRISMA-ScR guidelines. Drawing on publicly available regulatory information from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), public registries, clinical-trial databases, and academic literature, medical devices incorporating dBMs, dBMs qualified or supported by regulatory authorities, and dEPs used in clinical trials were collected and organized.

Results

A total of 225 medical devices had been authorized by the FDA, 10 dBMs had been qualified or supported by the FDA and the EMA, and 65 dEPs had been adopted as primary or secondary endpoints across 20 Phase 3 clinical trials listed in the Digital Medicine Society (DiMe) Library of Digital Endpoints. Maturity markedly differed across disease areas, with many areas having a substantial track record in medical devices but not progressing to qualification or primary endpoints in clinical trials. Comparison of advancing and lagging areas suggests that this maturity gap reflects three conditions: a reliable gold standard in the disease, consensus on the value of continuous measurement, and a clearly defined CoU.

Conclusion

Each of the three adoption pathways carries distinct evidence requirements, and a dBM established in one pathway is not automatically accepted in another. A fit-for-purpose evidence strategy needs to be designed from the earliest stages, anchored in the target CoU and the intended adoption pathway.

利益相反に関する開示

The conflict of interest statement is included in the main text of the manuscript.

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