Inclusion of Pregnant
and Lactating Persons
in Clinical Trials
_____
Theresa Wizemann, Andrew March,
and Carolyn Shore, Rapporteurs
Forum on Drug Discovery,
Development, and Translation
Board on Health Sciences Policy
Health and Medicine Division
Proceedings of a Workshop
NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by contracts between the National Academy of Sciences and Amgen Inc.; Association of American Medical Colleges; AstraZeneca; Biogen; Burroughs Wellcome Fund (Contract No. 1022279); Critical Path Institute; Eli Lilly & Co. (Contract No. 4900709231); FasterCures, Milken Institute; Foundation for the National Institutes of Health; Friends of Cancer Research; Johnson & Johnson; Medable, Inc.; Merck & Co., Inc. (Contract No. APA-21-151620); 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; Sanofi (Contract No. 70602577); Takeda Pharmaceuticals; and the U.S. Food and Drug Administration (Grant No. 1R13FD007302-01). 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: 978-0-309-69637-1
International Standard Book Number-10: 0-309-69637-2
Digital Object Identifier: https://doi.org/10.17226/26790
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2023. Inclusion of pregnant and lactating persons in clinical trials: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/26790.
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PLANNING COMMITTEE ON INCLUSION OF PREGNANT AND LACTATING PERSONS IN CLINICAL TRIALS1
RUTH FADEN (Cochair), Founder, Johns Hopkins Berman Institute of Bioethics and Phillip Franklin Wagley Professor, Johns Hopkins University
SHIRLEY SYLVESTER (Cochair), Senior Medical Director, Women’s Health, Johnson & Johnson
KAVITA SHAH ARORA, Associate Professor and Division Director of General Obstetrics and Gynecology, University of North Carolina, Chapel Hill
EBONY BOYCE CARTER, Associate Professor of Maternal Fetal Medicine, Washington University in St. Louis School of Medicine
NAHIDA CHAKHTOURA, Medical Officer, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
WILLIAM COOPER, Professor of Pediatrics and Health Policy, Vanderbilt University
BROWNSYNE TUCKER EDMONDS, Associate Professor and Obstetrics and Gynecology, Indiana University
DARCIE EVERETT, Medical Officer, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration
LESLIE MELTZER HENRY, Professor of Law, University of Maryland
STEVEN KERN, Deputy Director, Quantitative Sciences, Bill & Melinda Gates Foundation
LEYLA SAHIN, Deputy Director for Safety, Division of Pediatrics and Maternal Health, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
DIANE SPATZ, Professor of Perinatal Nursing and Nutrition, University of Pennsylvania
RAMAN VENKATARAMANAN, Professor of Pharmaceutical Sciences and Pathology, University of Pittsburgh
MICHELLE VICHNIN, Executive Director, Global Patient Advocacy and Strategic Alliances, Merck & Co.
CARMEN ZORRILLA, Interim Dean of Research and Professor of Obstetrics and Gynecology, University of Puerto Rico
___________________
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.
Health and Medicine Division Staff
CAROLYN K. SHORE, Director, Forum on Drug Discovery, Development, and Translation
DEANNA GIRALDI, Associate Program Officer
ANDREW MARCH, Associate Program Officer
MELVIN JOPPY, Senior Program Assistant
CLARE STROUD, Senior Director, Board on Health Sciences Policy (from June 2022)
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy (until June 2022)
Consultants
THERESA WIZEMANN, Science Writer
FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION1
GREGORY SIMON (Cochair), Kaiser Permanente Washington Health Research Institute and University of Washington
ANN TAYLOR (Cochair), Retired
CHRISTOPHER P. AUSTIN, Flagship Pioneering
LINDA BRADY, National Institute of Mental Health, NIH
JOHN BUSE, University of North Carolina School of Medicine
LUTHER CLARK, Merck & Co., Inc.
BARRY S. COLLER, The Rockefeller University
THOMAS CURRAN, Children’s Mercy, Kansas City
RICHARD DAVEY, National Institute of Allergy and Infectious Diseases, NIH
KATHERINE DAWSON, Biogen
JAMES H. DOROSHOW, National Cancer Institute, NIH
JEFFREY M. DRAZEN, New England Journal of Medicine
STEVEN K. GALSON, Retired
CARLOS O. GARNER, Eli Lilly and Company
DEBORAH HUNG, Harvard Medical School
LYRIC JORGENSON, Office of Science Policy, NIH
ESTHER KROFAH, FasterCures, Milken Institute
LISA M. LAVANGE, University of North Carolina
ARAN MAREE, The Janssen Pharmaceutical Companies of Johnson & Johnson
CRISTIAN MASSACESI, AstraZeneca
ROSS MCKINNEY JR., Association of American Medical Colleges
JOSEPH P. MENETSKI, Foundation for the National Institutes of Health
ANAEZE OFFODILE, University of Texas MD Anderson Cancer Center
SALLY OKUN, Clinical Trials Transformation Initiative
ARTI RAI, Duke University School of Law
MARK ROGGE, University of Florida
KLAUS ROMERO, Critical Path Institute
JONI RUTTER, National Center for Advancing Translational Sciences, NIH
SUSAN SCHAEFFER, Patients’ Academy for Research Advocacy
JOSEPH SCHEEREN, Retired
ANANTHA SHEKHAR, University of Pittsburgh
___________________
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.
JAY SIEGEL, Retired
ELLEN V. SIGAL, Friends of Cancer Research
MARK TAISEY, Amgen Inc.
AMIR TAMIZ, National Institute of Neurological Disorders and Stroke, NIH
PAMELA TENAERTS, Medable, Inc.
MAJID VAKILYNEJAD, Takeda Pharmaceutical Company, Inc.
JONATHAN WATANABE, University of California Irvine School of Pharmacy and Pharmaceutical Sciences
ALASTAIR WOOD, Vanderbilt University
JANET WOODCOCK, U.S. Food and Drug Administration
CRISPIN WOOLSTON, Sanofi
Forum Staff
CAROLYN K. SHORE, Forum Director
BIANCA ESPINOSA, Associate Program Officer (from July 2022)
DEANNA GIRALDI, Associate Program Officer (until September 2022)
ANDREW MARCH, Associate Program Officer
ASHLEY BOLOGNA, Senior Program Assistant (from July 2022)
MELVIN JOPPY, Senior Program Assistant
CLARE STROUD, Senior Director, Board on Health Sciences Policy (from June 2022)
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy (until June 2022)
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:
CHRISTINA BUCCI-RECHTWEG, Novartis Pharmaceuticals Corporation
JOSÉ F. CORDERO, University of Georgia
MARNI HALL, IQVIA
ANNA MASTROIANNI, Johns Hopkins University
ELAD SHARON, National Cancer Institute, National Institutes of Health
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 ELLEN WRIGHT CLAYTON, Vanderbilt University Medical Center. She 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.
Acknowledgments
Support from the sponsors of the Forum on Drug Discovery, Development, and Translation 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 opportunities to improve the inclusion of pregnant and lactating persons in clinical trials; to the members of the planning committee for their work in developing the workshop agenda and shaping the discussions; and to additional National Academies staff, without whom this workshop and the accounting thereof would not have been possible: Christie Bell, Samantha Chao, Robert Day, Rebekah Hanover Pettit, Benjamin Hubbert, Devona Overton, Marguerite Romatelli, Bettina Seliber, Lauren Shern, Maya Thirkill, Elizabeth Webber, and Taryn Young.
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Contents
Organization of the Proceedings
2 EFFECTS OF EVIDENCE GAPS IN CLINICAL TREATMENT FOR PREGNANT AND LACTATING PERSONS
Challenges for Pregnant and Lactating Persons
Willingness of Pregnant and Lactating Individuals to Participate in Clinical Trials
Navigating Legal Barriers and Liability Risks
Institutional Policies and Practices that Promote Inclusion in Research
Regulatory Efforts to Promote Inclusion in Research
Addressing Legal and Regulatory Concerns
Opportunities to Address Liability Concerns: Breakout Discussion Highlights
Lessons Learned from COVID-19 Vaccine Trials
Lessons Learned from Drug Trials for Mood Disorders
Perspectives on Evidence Generation
5 POTENTIAL PRACTICAL SOLUTIONS FOR INCLUDING PREGNANT AND LACTATING PERSONS IN CLINICAL TRIALS
6 PROMISING INNOVATIVE APPROACHES TO EVIDENCE GENERATION
Incorporating Real-World Evidence
Pharmacologic Approaches to Evidence Generation
Improving Safety in the Postmarket Setting: A Regulatory Perspective
Facilitating the Implementation of Innovative Approaches to Evidence Generation
Progress Toward Implementing the PRGLAC Task Force Recommendations
C BIOGRAPHICAL SKETCHES OF THE WORKSHOP PLANNING COMMITTEE, SPEAKERS, AND STAFF
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Abbreviations and Acronyms
AAP | American Academy of Pediatrics |
ACOG | American College of Obstetrics and Gynecology |
BPCA | Best Pharmaceuticals for Children Act |
CDER | Center for Drug Evaluation and Research (FDA) |
EHR | electronic health record |
FDA | U.S. Food and Drug Administration |
FDAMA | Food and Drug Administration Modernization Act |
FD&C | Food, Drug, and Cosmetic Act |
GBS | group B Streptococcus |
IRB | institutional review board |
JHU | Johns Hopkins University |
MPRINT | Maternal and Pediatric Precision in Therapeutics |
NICHD | National Institute of Child Health and Human Development (NIH) |
NIH | U.S. National Institutes of Health |
OBGYN | obstetrician/gynecologist |
PHASES | Pregnancy and HIV/AIDS: Seeking Equitable Study |
PREA | Pediatric Research Equity Act |
PREVENT | Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies |
PRGLAC | Task Force on Research Specific to Pregnant Women and Lactating Women |
RSV | respiratory syncytial virus |
SOP | standard operating procedure |
SSRI | selective serotonin reuptake inhibitor |
SWHR | Society of Women’s Health Research |
UW | University of Washington |