Drug Research and Development for Adults Across the Older Age Span
PROCEEDINGS OF A WORKSHOP
Erin Hammers Forstag and Carolyn Shore, Rapporteurs
Forum on Aging, Disability, and Independence
Forum on Drug Discovery, Development, and Translation
National Cancer Policy Forum
Board on Health Care Services
Board on Health Sciences Policy
Health and Medicine Division
THE NATIONAL ACADEMIES PRESS
Washington, DC
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This activity was supported by contracts between the National Academy of Sciences and the Administration for Community Living; American Association for Cancer Research; American Association for Retired Persons; American Cancer Society (Contract No. 66383); American College of Radiology; American Geriatrics Society; American Society of Clinical Oncology; Amgen Inc. (Contract No. GHCCOPS-CSARF-175837); Association of American Cancer Institutes; Association of American Medical Colleges; Association of Community Cancer Centers; AstraZeneca; Biogen; Biomedical Advanced Research and Development Authority; Bristol Myers Squibb (Contract No. 57015377); Burroughs Wellcome Fund (Contract No. 1020264); Cancer Support Community; Centers for Disease Control and Prevention (Contract No. 200-2011-38807; Task Order No. 75D30119F00080); CEO Roundtable on Cancer; Consumer Technology Association Foundation; Critical Path Institute; Eli Lilly and Company (Contract No. 4900709231); FasterCures, Milken Institute; Flatiron Health; Foundation for the National Institutes of Health; Friends of Cancer Research; The Gerontological Society of America; GlaxoSmithKline (Contract No. OTH-PPL-32245); The John A. Hartford Foundation; Johnson & Johnson; LeadingAge; Merck & Co., Inc. (Contract Nos. MRLCPO-19-9858 and MRLCPO-19-106723); National Comprehensive Cancer Network; National Institute on Disability, Independent Living, and Rehabilitation Research (Contract No. HHSP233201400020B); 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 Extramural Research, Office of Science Policy; National Institutes of Health (Contract No. HHSN263201800029I; Task Order No. HHSN26300008 and Contract No. HHSN263291800029I; Task Order No. 75N98019F00848): National Institute on Aging; National Patient Advocate Foundation; New England Journal of Medicine; Novartis Oncology (Contract No. NGC38403); Oncology Nursing Society; Paraprofessional Healthcare Institute; Pfizer Inc.; Sanofi (Contract No. 57505685); Society for Immunotherapy of Cancer; Takeda Pharmaceuticals (Contract No. 53108); and U.S. Food and Drug Administration (Grant No. 5R13FD005496-05). 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: 978-0-309-68568-9
International Standard Book Number-10: 0-309-68568-0
Digital Object Identifier: https://doi.org/10.17226/25998
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2021. Drug research and development for adults across the older age span: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/25998.
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PLANNING COMMITTEE FOR A WORKSHOP ON DRUG RESEARCH AND DEVELOPMENT FOR ADULTS ACROSS THE OLDER AGE SPAN1
JAMES APPLEBY (Chair), The Gerontological Society of America
MARIE A. BERNARD, National Institute on Aging, National Institutes of Health
BARRY S. COLLER, The Rockefeller University
DEBORAH COLLYAR, Patient Advocates in Research
DONALD HARVEY, Emory University School of Medicine
ALEX JOHN LONDON, Carnegie Mellon University
DAVID REUBEN, University of California, Los Angeles
MARK ROGGE, Takeda Pharmaceuticals
JANICE B. SCHWARTZ, University of California, San Francisco
MIRIAM MOBLEY SMITH, Northeastern University Bouvé College of Health Sciences School of Pharmacy
ROBERT TEMPLE, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
JONATHAN WATANABE, University of California, Irvine, School of Pharmacy and Pharmaceutical Sciences
BARBARA ZAROWITZ, University of Maryland School of Pharmacy
Health and Medicine Division Staff
CAROLYN K. SHORE, Director, Forum on Drug Discovery, Development, and Translation
LORI BRENIG, Research Associate (from May 2020)
AMANDA WAGNER GEE, Program Officer
JENNIFER HINNERS, Program Officer (through October 2020)
EESHAN KHANDEKAR, Associate Program Officer (through October 2020)
MELVIN JOPPY, Senior Program Assistant
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy
Consultant
ERIN HAMMERS FORSTAG, Science 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.
FORUM ON AGING, DISABILITY, AND INDEPENDENCE1
STEPHEN EWELL (Co-Chair), Consumer Technology Association Foundation
REBECCA JACKSON STOECKLE (Co-Chair), Education Development Center
JOHN AUERBACH, Trust for America’s Health
MARIE A. BERNARD, National Institute on Aging, National Institutes of Health
JULIE BYNUM, University of Michigan Medical School
MARGARET L. CAMPBELL, Campbell & Associates Consulting
BRUCE CHERNOF, The SCAN Foundation
TAMALA DAVID, State University of New York College at Brockport
THOMAS E. EDES, U.S. Department of Veterans Affairs
ROBERT ESPINOZA, Paraprofessional Healthcare Institute
DONNA FICK, The Pennsylvania State University College of Nursing
TERRY T. FULMER, The John A. Hartford Foundation
KATHY GREENLEE, Greenlee Global LLC
ROBERT JARRIN, The Omega Concern LLC
SUSAN JENKINS, Administration for Community Living
JANNI LEHRER-STEIN, Disability Policy Consultant and Advocate
SARAH RUIZ, National Institute on Disability, Independent Living, and Rehabilitation Research
KATIE SMITH SLOAN, LeadingAge
ERWIN TAN, AARP
FERNANDO TORRES-GIL, University of California, Los Angeles
Forum Staff
TRACY A. LUSTIG, Forum Director
SIOBHAN ADDIE, Program Officer
RUKSHANA GUPTA, Senior Program Assistant
SHARYL NASS, Senior Director, Board on Health Care Services
___________________
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.
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, Office of the Commissioner, U.S. Food and Drug Administration
CHRISTOPHER P. AUSTIN, National Center for Advancing Translational Sciences
LINDA BRADY, National Institute of Mental Health, National Institutes of Health
BARRY S. COLLER, The Rockefeller University
THOMAS CURRAN, Children’s Mercy, Kansas City
RICHARD DAVEY, National Institute of Allergy and Infectious Diseases, National Institutes of Health
KATHERINE DAWSON, Biogen
JAMES H. DOROSHOW, National Cancer Institute, National Institutes of Health
JEFFREY M. DRAZEN, New England Journal of Medicine
STEVEN K. GALSON, Amgen Inc.
CARLOS O. GARNER, Eli Lilly and Company
JULIE L. GERBERDING, Merck & Co., Inc.
ANNE HEATHERTON, Takeda Pharmaceuticals
DEBORAH HUNG, Harvard Medical School
ESTHER KROFAH, FasterCures, Milken Institute
LISA M. LaVANGE, University of North Carolina
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, Patients’ Academy for Research Advocacy
JOSEPH SCHEEREN, Critical Path Institute
ANANTHA SHEKHAR, University of Pittsburgh
JAY SIEGEL, Retired
ELLEN V. SIGAL, Friends of Cancer Research
LANA R. SKIRBOLL, Sanofi
___________________
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.
AMIR TAMIZ, National Institute of Neurological Disorders and Stroke, National Institutes of Health
ANN TAYLOR, AstraZeneca
PAMELA TENAERTS, Clinical Trials Transformation Initiative, Duke University
JOANNE WALDSTREICHER, Johnson & Johnson
ROBERT WALKER, Biomedical Advanced Research and Development Authority
JONATHAN WATANABE, University of California, Irvine, School of Pharmacy and Pharmaceutical Sciences
CARRIE WOLINETZ, Office of Science Policy, National Institutes of Health
ALASTAIR WOOD, Vanderbilt University
JANET WOODCOCK, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
Forum Staff
CAROLYN K. SHORE, Forum Director
JENNIFER HINNERS, Program Officer (through October 2020)
AMANDA WAGNER GEE, Program Officer
EESHAN KHANDEKAR, Associate Program Officer (through October 2020)
MELVIN JOPPY, Senior Program Assistant
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy
NATIONAL CANCER POLICY FORUM1
EDWARD J. BENZ, JR. (Chair), Dana-Farber Cancer Institute and Harvard Medical School
PETER C. ADAMSON, Sanofi
GARNET L. ANDERSON, Fred Hutchinson Cancer Research Center and University of Washington
KAREN BASEN-ENGQUIST, University of Texas MD Anderson Cancer Center
SMITA BHATIA, The University of Alabama at Birmingham
LINDA BOHANNON, Cancer Support Community
CHRIS BOSHOFF, Pfizer Inc.
CATHY J. BRADLEY, Colorado School of Public Health and University of Colorado Cancer Center
OTIS W. BRAWLEY, Johns Hopkins University
CYNTHIA BROGDON, Bristol Myers Squibb
WILLIAM G. CANCE, American Cancer Society
ROBERT W. CARLSON, National Comprehensive Cancer Network
GWEN DARIEN, National Patient Advocate Foundation
NANCY E. DAVIDSON, Seattle Cancer Care Alliance; Fred Hutchinson Cancer Research Center; and University of Washington
GEORGE D. DEMETRI, Harvard Medical School; Dana-Farber Cancer Institute; and Dana-Farber/Harvard Cancer Center
JAMES H. DOROSHOW, National Cancer Institute
NICOLE F. DOWLING, Centers for Disease Control and Prevention
SCOT W. EBBINGHAUS, Merck Research Laboratories
KOJO S. J. ELENITOBA-JOHNSON, University of Pennsylvania Perelman School of Medicine
STANTON L. GERSON, Case Western Reserve University and University Hospitals Seidman Cancer Center
HEDVIG HRICAK, Memorial Sloan Kettering Cancer Center
MIMI HUIZINGA, Novartis Oncology
ROY A. JENSEN, Association of American Cancer Institutes; The University of Kansas Cancer Center; and Kansas Masonic Cancer Research Institute
RANDY A. JONES, University of Virginia School of Nursing
BETH Y. KARLAN, University of California, Los Angeles
LISA KENNEDY SHELDON, Oncology Nursing Society
___________________
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.
SAMIR N. KHLEIF, Georgetown University Medical Center/Society for Immunotherapy of Cancer
KAREN E. KNUDSEN, Sidney Kimmel Cancer Center
MIA LEVY, Rush University Cancer Center and Rush System for Health
NEAL J. MEROPOL, Flatiron Health
MARTIN J. MURPHY, CEO Roundtable on Cancer
RANDALL A. OYER, Penn Medicine Lancaster General Health
CLEO A. SAMUEL-RYALS, University of North Carolina at Chapel Hill
RICHARD L. SCHILSKY, American Society of Clinical Oncology
JULIE SCHNEIDER, U.S. Food and Drug Administration
LAWRENCE N. SHULMAN, University of Pennsylvania
LARA STRAWBRIDGE, Centers for Medicare & Medicaid Services
GEORGE J. WEINER, The University of Iowa
ROBERT A. WINN, Virginia Commonwealth University Massey Cancer Center
Forum Staff
ERIN BALOGH, Senior Program Officer
LORI BRENIG, Research Associate (from May 2020)
ANNALEE GONZALES, Administrative Assistant
SHARYL NASS, Director, National Cancer Policy Forum, and Senior Director, Board on Health Care Services
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:
CONSTANCE CITRO, The National Academies of Sciences, Engineering, and Medicine
PATRICIA JONES, National Institute on Aging, National Institutes of Health
JONATHAN WATANABE, University of California, Irvine
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 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
Support from the sponsors of the National Academies’ Forum on Aging, Disability, and Independence; Forum on Drug Discovery, Development, and Translation; and National Cancer Policy Forum is crucial to support this and other work of the National Academies.
The National Academies staff wish to express their gratitude to the speakers whose presentations helped inform workshop discussions on the state of drug research and development for adults across the older age span; the members of the planning committee for their work in developing the workshop agenda and shaping the discussions; Harpreet Singh for her valuable contributions; and National Academies staff without whom this workshop and the accounting thereof would not have been possible: Christie Bell, Robert Day, Sadaf Faraz, Andrew Grafton, Devona Overton, Bettina Seliber, Lauren Shern, Victor Stewart, and Taryn Young.
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Contents
2 INCLUSION OF OLDER ADULTS IN CLINICAL TRIALS: AN EVOLVING LANDSCAPE
Knowledge Gaps and Issues Unique to Older Adults
Age-Related Changes That Impact Drug Metabolism
Barriers to Conducting Clinical Trials That Include Older Adults
Inclusion/Exclusion Criteria and Trial Design
Organ Function Criteria Expansion
4 ALTERNATIVE STUDY APPROACHES
5 STRATEGIES FOR ENGAGING OLDER ADULTS IN CLINICAL RESEARCH
Outreach and Networking Strategies for Engaging Older Adults
Los Angeles Barbershop Blood Pressure Study
A Community Provider Perspective
6 CLINICAL TRIALS IN THE ERA OF COVID-19 AND BEYOND 65
7 REFLECTIONS AND KEY TAKEAWAYS
Practical Application of Science and Policy
APPENDIXES
Boxes, Figures, and Tables
BOXES
5-1 Personal Stories from the Los Angeles Barbershop Blood Pressure Study
FIGURES
2-1 Systems-based approaches to drug metabolism
2-2 Top perceived benefits and risks to clinical research participation
3-1 Common chronic conditions for adults age 65 and older
3-3 Utility of clinical trial attributes
4-1 Number of women who passed each step in the REMOTE protocol
4-2 Impact of quantitative systems pharmacology modeling: clarifying mechanisms reduces risk
6-1 COVID-19-associated hospitalizations by age
6-2 Medicare fee-for-service beneficiaries receiving telehealth services per week
6-3 Internet and home broadband access for adults age 65 and older
Acronyms and Abbreviations
ASPREE | Aspirin in Reducing Events in the Elderly |
BiTE | Bispecific T-Cell Engager |
CDER | Center for Drug Evaluation and Research |
CDN | Clinical Directors Network |
CHW | community health worker |
CMS | Centers for Medicare & Medicaid Services |
COVID-19 | coronavirus disease 2019 |
eHealth | electronic health |
EHR | electronic health record |
EMR | electronic medical record |
FDA | U.S. Food and Drug Administration |
FQHC | federally qualified health center |
GI | gastrointestinal |
IAL | Inclusion Across the Lifespan |
ICECAP | Influence of Cooling duration on Efficacy in Cardiac Arrest Patients |
IRB | Institutional Review Board |
LABBPS | Los Angeles Barbershop Blood Pressure Study |
mHealth | mobile health |
MRI | magnetic resonance imaging |
NIA | National Institute on Aging |
NIH | National Institutes of Health |
PACE | Programs for All-inclusive Care for the Elderly |
PBRN | Practice-Based Research Network |
PCORI | Patient-Centered Outcomes Research Institute |
PD | pharmacodynamics |
PK | pharmacokinetics |
PRO | patient-reported outcome |
PTZ | Piperacillin/Tazobactam |
QSP | Quantitative Systems Pharmacology |
R&D | research and development |
RCT | randomized controlled trial |
REMAP | randomized, embedded, multifactorial adaptive platform |
TAVR | transcatheter aortic valve replacement |
USC | University of Southern California |