THE ROLE OF DIGITAL
HEALTH TECHNOLOGIES
IN DRUG DEVELOPMENT
PROCEEDINGS OF A WORKSHOP
Eeshan Khandekar, Meredith Hackmann, Siobhan Addie,
Anna Nicholson, Sarah H. Beachy, and Carolyn Shore, Rapporteurs
Forum on Drug Discovery, Development, and Translation
Roundtable on Genomics and Precision Health
Board on Health Sciences Policy
Health and Medicine Division
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
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This activity was supported by contracts between the National Academy of Sciences and 23andMe; AbbVie Inc.; American Academy of Nursing; American College of Medical Genetics and Genomics; American Medical Association; Amgen Inc. (Contract No. GHCCOPS-CSARF-175837); Association for Molecular Pathology; Association of American Medical Colleges; AstraZeneca; Biogen; Blue Cross Blue Shield Association; Burroughs Wellcome Fund (Contract No. 1020264); College of American Pathologists; Color Genomics; Critical Path Institute; Department of Health and Human Services (Contract No. 75A50120C00006): Health Resources and Services Administration (Contract No. HHSH250201500001I; Task Order No. HHSH25034003T); Eisai Inc.; Eli Lilly and Company (Contract No. 4900709231); FasterCures–Milken Institute; Foundation for the National Institutes of Health; Friends of Cancer Research; Geisinger; Genome Medical Holding Company; Genosity; GlaxoSmithKline (Contract No. OTH-PPL-32245); Helix; Illumina; The Jackson Laboratory; Janssen Research & Development, LLC (Contract No. C2020004715); Johnson & Johnson; Kaiser Permanente; Merck & Co., Inc. (MRLCPO-19-5290 and MRLCPO-10-106723); Myriad Women’s Health; National Institutes of Health (Contract No. HHSN263201800029I; Task Order Nos. HHSN26300007 and HHSN26300010): All of Us Research Program, National Cancer Institute, National Center for Advancing Translational Sciences, National Human Genome Research Institute, National Institute of Allergy and Infectious Diseases, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Nursing Research, National Institute on Aging, Office of Disease Prevention, Office of Extramural Research, Office of Science Policy; National Society of Genetic Counselors; New England Journal of Medicine; Pfizer Inc.; Regeneron Pharmaceuticals; Sanofi (Contract No. 4472309 and Contract No. 57505685); Takeda Pharmaceuticals (Contract No. 53108); The University of Vermont Health Network Medical Group; U.S. Air Force Medical Service (Contract No. FA8052-17-P-0007); U.S. Food and Drug Administration (Grant No. 5R13FD005496-04 and Grant No. 5R13FD005496-05); and Vibrent Health. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-67959-6
International Standard Book Number-10: 0-309-67959-1
Digital Object Identifier: https://doi.org/10.17226/25850
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2020. The role of digital health technologies in drug development: Proceedings of a workshop. Washington, DC: The National Academies Press. http://doi.org/10.17226/25850.
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PLANNING COMMITTEE FOR A WORKSHOP ON THE ROLE OF DIGITAL HEALTH TECHNOLOGIES IN DRUG DEVELOPMENT1
JENNIFER GOLDSACK (Co-Chair), Executive Director, Digital Medicine Society
JOSEPH P. MENETSKI (Co-Chair), Associate Vice President of Research Partnerships, Foundation for the National Institutes of Health
LINDA BRADY, Director, Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health
RAY DORSEY, Professor, University of Rochester Medical Center
DEBORAH ESTRIN, Associate Dean, Cornell Tech
GEOFFREY GINSBURG, Director, Center for Applied Genomics & Precision Medicine, Duke University School of Medicine
HUSSEINI K. MANJI, Global Therapeutic Head, Neuroscience, Janssen Research & Development, LLC
DEVEN MCGRAW, Chief Regulatory Officer, Ciitizen Corporation
LAUREN OLIVA, Global Regulatory Policy Lead, Biogen
BRAY PATRICK-LAKE, Director of Strategic Partnerships, Evidation Health
LEONARD SACKS, Associate Director of Clinical Methodology, Office of Medical Policy, Center for Drug Evaluation and Research; U.S. Food and Drug Administration
JOYCE TUNG, Vice President, Research, 23andMe
EFFY VAYENA, Professor, Health Ethics and Policy Lab; ETH Zurich
Board on Health Sciences Policy Staff
SARAH H. BEACHY, Senior Program Officer
CAROLYN SHORE, Senior Program Officer
SIOBHAN ADDIE, Program Officer
MEREDITH HACKMANN, Associate Program Officer
EESHAN KHANDEKAR, Associate Program Officer
MICHAEL BERRIOS, Research Associate (until March 2020)
KELLY CHOI, Senior Program Assistant (from March 2020)
MELVIN JOPPY, Senior Program Assistant
ANDREW M. POPE, Senior Board Director
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION1
ROBERT M. CALIFF (Co-Chair), Duke University and Verily Life Sciences
GREGORY SIMON (Co-Chair), Kaiser Permanente Washington Health Research Institute and University of Washington
AMY ABERNETHY, U.S. Food and Drug Administration
CHRISTOPHER P. AUSTIN, National Center for Advancing Translational Sciences
LINDA BRADY, National Institute of Mental Health
RICK BRIGHT, Biomedical Advanced Research and Development Authority
BARRY COLLER, The Rockefeller University
THOMAS CURRAN, Children’s Mercy, Kansas City
RICHARD DAVEY, National Institute of Allergy and Infectious Diseases
KATHERINE DAWSON, Biogen
JAMES H. DOROSHOW, National Cancer Institute
JEFFREY M. DRAZEN,New England Journal of Medicine
STEVEN K. GALSON, Amgen Inc.
CARLOS GARNER, Eli Lilly and Company
JULIE L. GERBERDING, Merck & Co., Inc.
ANNE HEATHERINGTON, Takeda Pharmaceuticals
DEBORAH HUNG, Harvard Medical School
ESTHER KROFAH, FasterCures–Milken Institute
LISA LaVANGE, University of North Carolina Gillings School of Global Public Health
ROSS McKINNEY, JR., Association of American Medical Colleges
JOSEPH P. MENETSKI, Foundation for the National Institutes of Health
ARTI RAI, Duke University School of Law
KELLY ROSE, Burroughs Wellcome Fund
SUSAN SCHAEFFER, The Patients’ Academy for Research Advocacy
JOSEPH SCHEEREN, Critical Path Institute
ROB SCOTT, AbbVie Inc.
ANANTHA SHEKHAR, Indiana University School of Medicine
JAY SIEGEL (retired)
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
ELLEN V. SIGAL, Friends of Cancer Research
LANA R. SKIRBOLL, Sanofi
AMIR TAMIZ, National Institute of Neurological Disorders and Stroke
ANN TAYLOR, AstraZeneca
PAMELA TENAERTS, Clinical Trials Transformation Initiative, Duke University
JOANNE WALDSTREICHER, Johnson & Johnson
JONATHAN WATANABE, University of California, San Diego
CARRIE WOLINETZ, Office of Science Policy, National Institutes of Health
ALASTAIR WOOD, Vanderbilt University
JANET WOODCOCK, U.S. Food and Drug Administration
Forum Staff
CAROLYN SHORE, Forum Director
AMANDA WAGNER GEE, Program Officer
JENNIFER HINNERS, Program Officer
EESHAN KHANDEKAR, Associate Program Officer
MELVIN JOPPY, Senior Program Assistant
ROUNDTABLE ON GENOMICS AND PRECISION HEALTH1
GEOFFREY GINSBURG (Co-Chair), Duke University
MICHELLE PENNY (Co-Chair), Goldfinch Bio
NAOMI ARONSON, Blue Cross Blue Shield Association
ARIS BARAS, Regeneron Pharmaceuticals
KARINA BIENFAIT, Merck and Co., Inc.
VENCE BONHAM, JR., National Human Genome Research Institute
ROBERT B. DARNELL, The Rockefeller University and New York Genome Center
STEPHANIE DEVANEY, All of Us Research Program, National Institutes of Health
KATHERINE DONIGAN, U.S. Food and Drug Administration
W. GREGORY FEERO,Journal of the American Medical Association
JESSICA M. GILL, National Institute of Nursing Research
JENNIFER GOLDSACK, Digital Medicine Society
MARC GRODMAN, Genosity
RICHARD J. HODES, National Institute on Aging
PRADUMAN JAIN, Vibrent Health
SALLY JOHN, Biogen
SEKAR KATHIRESAN, Massachusetts General Hospital
MUIN KHOURY, Centers for Disease Control and Prevention
DAVID LEDBETTER, Geisinger
CHARLES LEE, The Jackson Laboratory for Genomic Medicine
THOMAS LEHNER, National Institute of Mental Health
DEBRA LEONARD, College of American Pathologists
PATRICK LOERCH, Johnson & Johnson
JAMES LU, Helix
SEAN MCCONNELL, American Medical Association
MONA MILLER, American Society of Human Genetics
JENNIFER MOSER, Department of Veterans Affairs
MAXIMILIAN MUENKE, American College of Medical Genetics and Genomics
ANNA PETTERSSON, Pfizer Inc.
VICTORIA M. PRATT, Association for Molecular Pathology
NADEEM SARWAR, Eisai Inc.
SHERI SCHULLY, Office of Disease Prevention, National Institutes of Health
JOAN A. SCOTT, Health Resources and Services Administration
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
SAM SHEKAR, American College of Preventive Medicine
NONNIEKAYE SHELBURNE, National Cancer Institute
NIKOLETTA SIDIROPOULOS, The University of Vermont Health Network Medical Group
KATHERINE JOHANSEN TABER, Myriad Women’s Health
RYAN TAFT, Illumina
JACQUELYN TAYLOR, Columbia University
SHARON TERRY, Genetic Alliance
JOYCE TUNG, 23andMe
JAMESON VOSS, Air Force Medical Support Agency
CATHERINE A. WICKLUND, National Society of Genetic Counselors
HUNTINGTON F. WILLARD, Genome Medical
JANET K. WILLIAMS, American Academy of Nursing
SARAH WORDSWORTH, University of Oxford
ALICIA ZHOU, Color Genomics
Roundtable Staff
SARAH H. BEACHY, Roundtable Director
SIOBHAN ADDIE, Program Officer
MEREDITH HACKMANN, Associate Program Officer
MICHAEL BERRIOS, Research Associate (until March 2020)
KELLY CHOI, Senior Program Assistant (from March 2020)
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Reviewers
This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.
We thank the following individuals for their review of this proceedings:
ANDREA CORAVOS, Elektra Labs
SUSAN SCHAEFFER, The Patients’ Academy for Research Advocacy
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by ERIC B. LARSON, Kaiser Permanente Washington. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.
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Acknowledgments
The support of the Forum on Drug Discovery, Development, and Translation was crucial to the planning and conduct of this workshop on The Role of Digital Health Technologies in Drug Development. Federal sponsors are Department of Health and Human Services; National Institutes of Health (National Cancer Institute, National Center for Advancing Translational Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, Office of Extramural Research, Office of Science Policy); and U.S. Food and Drug Administration. Nonfederal sponsorship was provided by AbbVie Inc.; Amgen Inc.; Association of American Medical Colleges; AstraZeneca; Burroughs Wellcome Fund; Critical Path Institute; Eli Lilly and Company; FasterCures–Milken Institute; Foundation for the National Institutes of Health; Friends of Cancer Research; GlaxoSmithKline; Johnson & Johnson; Merck & Co., Inc.; New England Journal of Medicine; Sanofi; and Takeda Pharmaceuticals.
The support of the Roundtable on Genomics and Precision Health was also very important for the workshop. Federal sponsors are Health Resources and Services Administration; National Institutes of Health (All of Us Research Program, National Cancer Institute, National Human Genome Research Institute, National Institute of Mental Health, National Institute of Nursing Research, National Institute on Aging, Office of Disease Prevention); and U.S. Air Force Medical Service. Nonfederal sponsorship was provided by 23andMe; American Academy of Nursing; American College of Medical Genetics and Genomics; American Medi-
cal Association; American Society of Human Genetics; Association for Molecular Pathology; Biogen; Blue Cross Blue Shield Association; College of American Pathologists; Color Genomics; Eisai Inc.; Geisinger; Genome Medical Holding Company; Genosity; Helix; Illumina; The Jackson Laboratory; Janssen Research & Development, LLC; Kaiser Permanente; Merck & Co., Inc.; Myriad Women’s Health; National Society of Genetic Counselors; Pfizer Inc.; Regeneron Pharmaceuticals; The University of Vermont Health Network Medical Group; and Vibrent Health.
The forum and roundtable wish to express gratitude to the members of the planning committee for their work in developing an excellent workshop agenda and to the expert speakers who explored the role of digital health technologies in drug development. The project directors would like to thank the project staff who worked diligently to develop both the workshop and the resulting proceedings.
Contents
Organization of the Proceedings
2 ETHICAL AND REGULATORY CONSIDERATIONS FOR DIGITAL HEALTH TECHNOLOGIES
Categories and Uses of Digital Health Technologies
Using Digital Health Technologies to Capture Real-World Evidence
Ethical, Legal, and Social Implications of Digital Health Technologies and Clinical Research
3 DIGITAL HEALTH TECHNOLOGIES FOR CHARACTERIZING DISEASE
Challenges in Deriving Health Insights from Real-World Sensor Data
Discovery Through Person-Generated Health Data
4 DIGITAL HEALTH TECHNOLOGIES FOR RECRUITMENT AND SAFETY
Regulatory Perspective on Drug Development Tools
Engaging the Public in Research Using Mobile Health
Digital Health Technologies and Remote Monitoring in Drug Development
Digital Health Technologies and the COVID-19 Pandemic
Deploying Digital Health Technologies at the Intersection of Clinical Care and Research
5 DIGITAL HEALTH TECHNOLOGIES FOR PIVOTAL TRIALS
Industry Perspective on Digital Health Technologies in Pivotal Trials
Performance Requirements for Digital Health Technologies in Pivotal Trials
Regulatory Perspective on the Use of Digital Health Technologies in Pivotal Trials
Digital Health Technologies for Post-Marketing Research and Surveillance
Use of Digital Health Technologies to Empower Patient Participation
Clinician Perspective on Digital Health Technologies for Post-Marketing Research and Surveillance
7 REFLECTIONS AND KEY TAKEAWAYS
Challenges Associated with the Use of Digital Health Technologies
Digital Health Technologies to Enable Patient-Centered Drug Development
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Boxes, Figures, and Table
BOXES
2-1 Digital Health Technology Methods
3-1 Guiding Questions for Evaluating the Scientific Value of a Data Type
3-2 Evidation Health’s Achievement Program
4-1 21st Century Cures Section 3011 Drug Development Tool Qualification
4-2 Evaluation of Digital Health Technology for Cardiovascular Monitoring
5-1 Verification and Validation of Digital Tools for Measuring Parkinson’s Disease Severity
6-1 Patient-Informed Measurement and Design Principles
7-1 Standards Needed for Evaluating Digital Health Technologies
FIGURES
3-1 Sources of person-generated health data
4-1 Conceptual framework for biomarker development for regulatory acceptance
4-2 Telehealth-based learning health system during an infectious disease outbreak
5-1 Conceptual map of technical and organizational capacity for biomedical big data
TABLE
2-1 Digital Health Technology Research and Information Gaps to Be Filled
Acronyms and Abbreviations
3-MST | 3-minute step test |
12-MRT | 12-minute run test |
ADAU | average daily accelerometry unit |
BYOD | bring your own device |
COA | clinical outcome assessment |
COVID-19 | coronavirus disease 2019 |
CPU | clinical pharmacology unit |
DDT | drug development tool |
DHT | digital health technology |
EHR | electronic health record |
FDA | U.S. Food and Drug Administration |
IND | investigational new drug |
IRB | institutional review board |
KCCQ | Kansas City Cardiomyopathy Questionnaire |
NIH | National Institutes of Health |
PD | Parkinson’s disease |
PGHD | person-generated health data |
PMC | post-marketing commitment |
PMR | post-marketing requirement |
R&D | research and development |
ReCODE | Research Center for Optimal Digital Ethics |
WHO | World Health Organization |