Revisiting Approved Digital Biomarkers: A Context-of-Use Perspective on Evidence Design

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

doi:10.51094/jxiv.6720

##article.authors##

Osamu Takenouchi 株式会社テックドクター
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
Yuya Imai argenx BV
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.
Takanori Fujita Tokyo Foundation for Policy Research
Toshikazu Fukami TechDoctor, Inc.
Kenta Hosomi Kyowa Kirin Co., Ltd.
Keisuke Izumi TechDoctor, Inc.
Taishiro Kishimoto Hills Joint Research Laboratory for Future Preventive Medicine and Wellness, Keio University School of Medicine
Naoki Kubota Eisai Co., Ltd.
Shuta Mitomo CMIC HOLDINGS Co., Ltd.
Hideki Oi Department of Healthcare Management, Kyorin University School of Medicine
Yuichiro Yano Department of General Medicine, Juntendo University Faculty of Medicine
Katsuhiko Yoshimoto Nippon Shinyaku Co., Ltd.
Yoichi Ito M. Data Science Center, Promotion Unit, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital
Kazumichi Minato TechDoctor, Inc.

DOI:

https://doi.org/10.51094/jxiv.6720

キーワード:

Digital Biomarker、 V3 Framework、 Validation、 Context of Use

抄録

Background

Digital biomarkers (dBMs) with adequate sensor accuracy and algorithm performance do not necessarily reach implementation. We examined whether the barrier lies less in the quantity of validation evidence than in a mismatch with the evidence a dBM's context of use (CoU) demands.

Summary

Using the V3+ framework of the Digital Medicine Society (DiMe) as a diagnostic lens, we retrospectively mapped the public regulatory record of five purposively selected cases: stride velocity 95th centile (SV95C), the Apple Watch atrial fibrillation (AF) History Feature, FreeStyle Libre, Mobilise-D digital mobility outcomes (DMOs), and 24-h cough frequency in chronic cough. No single model of success emerged; the load-bearing requirement differed by CoU and by implementation pathway. The load-bearing requirement was agreement with the reference method and usability for the two device cases, and a narrowly specified CoU for SV95C. The Mobilise-D DMOs remain at a letter of support, with cross-disease transferability and the minimal important difference (MID) still to be established; for cough frequency, the contested requirement shifted from validation of the counting method to the clinical meaningfulness of the change.

Key Messages

V3+ is most useful not as a uniform pass/fail scorecard but as a diagnostic lens that reveals which requirement is load-bearing in a given CoU. Because the CoU granted for the same device can differ across markets, and the evidence demanded follows the CoU, setting the target regulatory authority and the CoU is the first and most consequential decision in evidence design.

利益相反に関する開示

The authors' institutional affiliations are listed on the title page. During the three years preceding submission, no author received any grant, consultancy fee, honorarium, speaker fee, travel support, stock or stock options, patent royalty, or other fin

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