Biomarkers Consortium – Remote Digital Monitoring and Patient-Centric Medical Product Development

Workshops

On February 18 and 19, 2020, the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium held a public meeting titled Remote Digital Monitoring for Medical Product Development Workshop. The purpose of this workshop was to provide a forum for discussing opportunities and issues related to remote sensing technologies to increase the likelihood that drug development and therapeutic clinical trials will be successful.

The workshop focused on critical issues in assessing the maturity of digitally measured biomarkers and identifying future paths to enable more extensive usage of digital tools in human Research. These case studies, presentations, and open panel discussions are available via the links below.

Workshop participants prioritized a list of high-impact endpoints or measures that can be recorded by mobile sensing and created a framework to direct the development of remote monitoring measures. To enable a framework for the analytical and clinical validation required for drug developers and to build and improve operational/regulatory guidelines, the workshop planning team combined the meeting’s insights into several manuscripts and significant recommendations.

The FNIH Biomarkers Consortium co-hosted a second workshop, titled “Reverse Engineering of Digital Measures,” in 2022 with ETH, a public Research university in Zurich, Switzerland. This workshop expanded on the first meeting’s success by presenting insights from four extended case studies and assessing advancements, possibilities, and difficulties. The interactive case studies highlighted how patient-centricity impacts the production and validation of new evidence across settings, including regulatory interactions, reimbursement, and product development. Participants included regulators, industry, patients, and innovators. An important outcome of the session was a greater understanding of the importance of patient-centricity in creating new digital measures.

The group looked at how human-centered, comprehensive, evidence-based science is applied in the field. As a result, they also examined how this application affects interactions with payers and regulators, patient and human engagement, product development, and incorporating digital measures into decision-making throughout healthcare delivery.

Workshop Goals

• Convene diverse stakeholders in the field of digital health technology to establish a shared vocabulary for regulatory purposes.
• Present and examine real-world case studies of remote monitoring in clinical trials to highlight concepts that may require development of a new vocabulary.
• Identify areas of high unmet medical need that could be addressed using digital system technologies.
• Align stakeholders to apply an evidence-based framework for the use of digital health technologies in therapeutic Research and development.

Results & Accomplishments

• Remote Cardiac Safety Monitoring through the Lens of the FDA Biomarker Qualification Evidentiary Criteria Framework: A Case Study Analysis. Izmailova EA, Wood WA, Liu Q, et al. Digital Biomarkers (2021) 5, 103-113. https://doi.org/10.1159/000515110
• Remote digital monitoring in clinical trials in the time of COVID-19. Goldsack JC, Izmailova ES, Menetski JP, Hoffmann SC, Groenen PM, Wagner JA. Nature Reviews Drug Discovery 19, 378-379 (2020). doi: https://www.nature.com/articles/d41573-020-00094-0
• Remote Digital Monitoring for Medical Product Development. Izmailova EA, Wagner JA, Ammour N, et al. Clin Transl Sci (2020) 0, 1–8. doi: https://doi.org/10.1111/cts.12851
• Reverse Engineering of Digital Measures: Inviting Patients to the Conversation. Ieuan Clay, Nele Peerenboom, Dana E Connors, et al. Digit Biomark 2023;7:28–44. doi: https://fnih.org/sites/default/files/2023-05/Clay%20et%20al._Rev%20Eng%20of%20Dig%20Measures_DigBMx_May2023.pdf

Scientific Publications

• What evidence do we need for biomarker qualification? C. Leptak, J. P. Menetski, J. A. Wagner, J. Aubrecht, L. Brady, M. Brumfield, W. W. Chin, S. Hoffmann, G. Kelloff, G. Lavezzari, R. Ranganathan, J.-M. Sauer, F. D. Sistare, T. Zabka, D. Wholley, Sci Transl Med. 2017 Nov 22;9(417). pii: eaal4599. doi: 10.1126/scitranslmed.aal4599.
• Traditional and Digital Biomarkers: Two Worlds Apart? L. Babrak, J. Menetski, M. Rebhan, G. Nisato, M. Zinggeler, N. Brasier, K. Baerenfaller, T. Brenzikofer, L. Baltzer, C. Vogler, L. Gschwind, C. Schneider, F. Streiff, P. Groenen, E. Miho, Digit Biomark 2019;3:92–102, DOI: 10.1159/000502000
• Digital Medicine: A Primer on Measurement. A. Coravos, J. Goldsack, D.R. Karlin, C. Nebeker, E. Perakslis, N. Zimmerman, M.K. Erb, Digit Biomark 2019;3:31–71,DOI: 10.1159/000500413
• Workshop Overview and Pre-Read Resources
• CTTI Recommendations: Developing Novel Endpoints Generated by Mobile Technology for Use in Clinical Trials
• BEST Resource Taxonomy

Guidance Documents

• Draft Guidance Document – Biomarker Qualification: Evidentiary Framework
• Draft Guidance Document – Qualification Process for Drug Development Tools
• EMA Guidance – Questions and answers: Qualification of digital technology-based methodologies to support approval of medicinal products
• FDA Guidance – Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints For Regulatory Decision-Making
• FDA Resource – Framework for the Use of Digital Health Technologies in Drug and Biological Product Development