Virtual Clinical Trials
CHALLENGES AND OPPORTUNITIES
PROCEEDINGS OF A WORKSHOP
Joe Alper, Eeshan Khandekar, and Carolyn Shore, Rapporteurs
Forum on Drug Discovery, Development, and Translation
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 AbbVie Inc.; American Society for Microbiology; Amgen Inc. (Contract No. GHCCOPS-CSARF-126570); Association of American Medical Colleges; AstraZeneca; Burroughs Wellcome Fund (Contract No. 1019001); Critical Path Institute; Eli Lilly and Company; FasterCures; Foundation for the National Institutes of Health; Friends of Cancer Research; GlaxoSmithKline (Contract No. OTH-PPL-30507); Johnson & Johnson; Merck & Co., Inc. (Contract No. CMO-180308-002499; MRLCPO-18-2641); National Institutes of Health (Contract No. HHSN263201800029I; Task Order No. HHSN26300007): 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 Science Policy; New England Journal of Medicine; Pfizer Inc.; Sanofi (Contract No. 38532911); Takeda Pharmaceuticals (Contract No. 53108); and U.S. Food and Drug Administration (Grant No. 5R13FD005496-03, 5R13FD005496-04): Center for Drug Evaluation and Research, Office of the Commissioner. 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: 978-0-309-49488-5
International Standard Book Number-10: 0-309-49488-5
Digital Object Identifier: https://doi.org/10.17226/25502
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2019. Virtual clinical trials: Challenges and opportunities: Proceedings of a workshop. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/25502.
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PLANNING COMMITTEE ON VIRTUAL CLINICAL TRIALS: CHALLENGES AND OPPORTUNITIES1,2
LINDA BRADY (Co-Chair), National Institute of Mental Health, National Institutes of Health
S. CLAIBORNE JOHNSTON (Co-Chair), Dell Medical School, The University of Texas at Austin
STEVEN ANDERSON, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration
ROBERT M. CALIFF, Duke University and Verily Life Sciences
JOSH DENNY, Vanderbilt University
ROBERT GENTLEMAN, 23andMe
ROBERT GOODWIN, Pfizer Inc.
KATHY L. HUDSON, People-Centered Research Foundation
DAVID H. LEDBETTER, Geisinger
DAVID MCCALLIE, Cerner Corp.
REBECCA PENTZ, Emory University
LEONARD SACKS, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
TODD SHERER, The Michael J. Fox Foundation for Parkinson’s Research
KELLY SIMCOX, Sanofi
JOHN WILBANKS, Sage Bionetworks
Project Staff
CAROLYN SHORE, Forum Director
REBECCA ENGLISH, Program Officer
EESHAN KHANDEKAR, Research Associate
MELVIN JOPPY, Senior Program Assistant
Consultant
JOE ALPER, Consulting Writer
___________________
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.
2 Affiliation listed at the time of the workshop.
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FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION1,2
RUSS B. ALTMAN (Co-Chair), Stanford University
ROBERT M. CALIFF (Co-Chair), Duke University and Verily Life Sciences
CHRISTOPHER P. AUSTIN, National Center for Advancing Translational Sciences, National Institutes of Health
LINDA BRADY, National Institute of Mental Health, National Institutes of Health
TANISHA CARINO, FasterCures, Milken Institute
RICHARD DAVEY, National Institute of Allergy and Infectious Diseases, National Institutes of Health
JAMES H. DOROSHOW, National Cancer Institute, National Institutes of Health
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.
LYNN D. HUDSON, Critical Path Institute
JEFF HURD, AstraZeneca
S. CLAIBORNE JOHNSTON, Dell Medical School, The University of Texas at Austin
KATHARINE KNOBIL, GlaxoSmithKline
FREDA C. LEWIS-HALL, Pfizer Inc.
ALLISON MCELVAINE, American Diabetes Association
ROSS MCKINNEY, JR., Association of American Medical Colleges
JOSEPH P. MENETSKI, Foundation for the National Institutes of Health
BERNARD MUNOS, InnoThink Center for Research in Biomedical Innovation
MICHAEL SEVERINO, AbbVie Inc.
RACHEL E. SHERMAN, Office of the Commissioner, U.S. Food and Drug Administration
ELLEN V. SIGAL, Friends of Cancer Research
LANA R. SKIRBOLL, Sanofi
BRIAN L. STROM, Rutgers, the State University of New Jersey
AMIR TAMIZ, National Institute of Neurological Disorders and Stroke, National Institutes of Health
___________________
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.
2 Affiliation listed at the time of the workshop.
PAMELA TENAERTS, Clinical Trials Transformation Initiative, Duke University
JOHN WAGNER, Takeda Pharmaceuticals
JOANNE WALDSTREICHER, Johnson & Johnson
CARRIE WOLINETZ, Office of Science Policy, National Institutes of Health
JANET WOODCOCK, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
Forum on Drug Discovery, Development, and Translation Staff
CAROLYN SHORE, Forum Director
REBECCA ENGLISH, Program Officer
AMANDA WAGNER GEE, Program Officer
SYLVIA NCHA, Associate Program Officer
EESHAN KHANDEKAR, Research Associate
MELVIN JOPPY, Senior Program Assistant
ANDREW M. POPE, Director, Board on Health Sciences Policy
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
PENNY RANDALL, Central Nervous System Center of Excellence, IQVIA
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of this proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by LESLIE BENET, University of California, San Francisco. 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 following people from the Health and Medical Division at the National Academies of Sciences, Engineering, and Medicine was essential for the planning and conduct of the workshop and for the development of the Proceedings of a Workshop: Rebecca English, Bettina Seliber, Lauren Shern, and Taryn Young. The assistance of Laura Penny, independent health and medical editor, was also essential for the editing of the proceedings.
The support of the sponsors of the Forum on Drug Discovery, Development, and Translation was crucial to the planning and conduct of the workshop Virtual Clinical Trials: Challenges and Opportunities and for the development of the proceedings.
This project was funded in whole or in part with federal funds from the National Institutes of Health, U.S. Department of Health and Human Services, under Contract No. HHSN263201800029I: 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, and the Office of Science Policy; along with the U.S. Food and Drug Administration: Center for Drug Evaluation and Research and Office of the Commissioner.
Nonfederal sponsorship for this project was provided by AbbVie Inc., Amgen Inc., American Society for Microbiology, Association of American Medical Colleges, AstraZeneca, Burroughs Wellcome Fund, Critical Path Institute, Eli Lilly and Company, FasterCures, Foundation for the National
Institutes of Health, Friends of Cancer Research, GlaxoSmithKline, Johnson & Johnson, Merck & Co., Inc., New England Journal of Medicine, Pfizer Inc., Sanofi, and Takeda Pharmaceuticals.
Contents
Defining Virtual Clinical Trials
Organization of the Proceedings of a Workshop
2 OPPORTUNITIES TO IMPROVE CLINICAL TRIALS
3 EXPLORING VIRTUAL CLINICAL TRIALS
Lessons Learned from Clinical Care
Lessons Learned from Observational Studies
Lessons Learned from Interventional Studies
Recruitment for Clinical Trials
Underserved Community Outreach and Engagement
Clinical Trials Transformation Initiative: Decentralized Clinical Trials Project
Privacy Protections for Virtual Clinical Trials
Informed Consent for Passive Data Collection
6 REFLECTIONS ON THE WORKSHOP AND POTENTIAL FUTURE DIRECTIONS
Session 1: Opportunities to Improve Clinical Trials
Session 2: Exploring Clinical Trials
Session 4: Policy Considerations
B WORKSHOP SPEAKER BIOGRAPHICAL SKETCHES
C EXAMPLES OF VIRTUAL CLINICAL TRIALS INCLUDED IN THE WORKSHOP HANDOUT
D VIRTUAL CLINICAL TRIALS PRESENTED BY SPEAKERS AT THE WORKSHOP
Boxes, Figures, and Tables
BOXES
1-1 Workshop Statement of Task
3-1 Investigation of Genetics Data to Identify Drug Targets and Drug Response
FIGURES
2-1 Drug discovery, development, and approval process
2-2 Typology of clinical research based on location and methods of data captured
3-1 Attrition of interested and eligible participants at each step of the REMOTE trial protocol
4-1 Our Healthy Community model for community engagement
4-2 Mobile phone and smartphone ownership trends across socioeconomic demographic groups
4-3 Reasons for minority participation and non-participation in mHealth research
Acronyms and Abbreviations
| ALS | amyotrophic lateral sclerosis |
| CCPA | California’s Consumer Privacy Act |
| CTTI | Clinical Trials Transformation Initiative |
| CYP2C19 | Cytochrome P450 2C19 Enzyme |
| D2P | direct-to-participant |
| EHR | electronic health record |
| FDA | U.S. Food and Drug Administration |
| GDPR | Global Data Protection Regulation |
| GWAS | genome-wide association study |
| HbA1c | Hemoglobin A1c (glycated hemoglobin) |
| HiMSS | Healthcare Information and Management Systems Society |
| HIPAA | Health Insurance Portability and Accountability Act |
| ICD | International Statistical Classification of Diseases and Related Health Problems |
| IRB | Institutional Review Board |
| LRRK2 | leucine-rich repeat kinase gene |
| MCT | Mobile Clinical Trials |
| NIH | National Institutes of Health |
| ONC | The Office of the National Coordinator for Health Information Technology |
| PCSK9 | Proprotein Convertase Substillsin/KexIn Type 9 |
| UNC13A | Unc-13 Homolog A gene |
| VA | U.S. Department of Veterans Affairs |
