Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act

351 Pages·2012·5.6 MB·English

by  Marilyn J. Field

Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children and the Pediatric Research Equity Acts

Safe and Effective Medicines
for Children:
Studies Conducted Under the Best Pharmaceuticals for
Children Act and the Pediatric Research Equity Act

Committee on Pediatric Studies Conducted Under the Best Pharmaceuticals for
Children Act (BPCA) and the Pediatric Research Equity Act (PREA)

Board on Health Sciences Policy

Marilyn J. Field and Thomas F. Boat, Editors
Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children and the Pediatric Research Equity Acts
THE NATIONAL ACADEMIES PRESS • 500 Fifth Street, N.W. • Washington, DC 20001

NOTICE: The project that is the subject of this report was approved by the Governing Board of the
National Research Council, whose members are drawn from the councils of the National Academy of
Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the
committee responsible for the report were chosen for their special competences and with regard for
appropriate balance.

This study was supported by Contract No. DHHS-8598, TO #16, between the National Academy of
Sciences and the Food and Drug Administration, U.S. Department of Health and Human Services. Any
opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors
and do not necessarily reflect the views of the organizations or agencies that provided support for the
project.

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978-0-309-22549-6
International Standard Book Number— (prepublication)
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Suggested citation: IOM (Institute of Medicine). 2012. Safe and Effective Medicines for Children:
Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research
Equity Act. Washington, DC: The National Academies Press.
Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children and the Pediatric Research Equity Acts
Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children and the Pediatric Research Equity Acts

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Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children and the Pediatric Research Equity Acts

COMMITTEE ON PEDIATRIC STUDIES CONDUCTED
UNDER BPCA AND PREA

THOMAS F. BOAT (Chair), Vice President for Health Affairs, Christian R. Holmes
Professor and Dean of the College of Medicine, University of Cincinnati, Ohio
PETER C. ADAMSON, Professor of Pediatrics and Pharmacology at the University of
Pennsylvania School of Medicine, Chief of the Division of Clinical Pharmacology
and Therapeutics at The Children’s Hospital of Philadelphia, and Director of
Clinical and Translational Research at The Children’s Hospital of Philadelphia
Research Institute, Pennsylvania
RICHARD E. BEHRMAN, Consultant, Santa Barbara, California
F. SESSIONS COLE III, Park J. White, M.D., Professor of Pediatrics, Professor of Cell
Biology and Physiology, Washington University School of Medicine, and Chief
Medical Officer, St. Louis Children’s Hospital, Missouri
BRIAN FELDMAN, Professor of Pediatrics, Medicine, and Health Policy, Management
and Evaluation and Professor of the Dalla Lana School of Public Health,
University of Toronto, Canada
PAT FURLONG, Founding President and Chief Executive Officer of Parent Project
Muscular Dystrophy, Middletown, Ohio
ERIC KODISH, Director of the Center for Ethics, Humanities and Spiritual Care at
Cleveland Clinic, and F.J. O’Neill Professor and Chair of Bioethics and Professor
of Pediatrics, Lerner College of Medicine of Case Western Reserve University
Ohio
JENNIFER LI, Professor of Pediatrics (Cardiology), Professor of Medicine
(Cardiology), Director of Pediatric Clinical Research, Duke Clinical Research
Institute; Core Director of Pediatrics, Duke Translational Medicine Institute; and
Division Chief, Pediatric Cardiology, Duke University Health System, Durham,
North Carolina
CHRISTINA M. MARKUS, Partner and Deputy Practice Leader, FDA & Life Sciences
Group, King and Spalding LLP, Washington, D.C.
MILAP C. NAHATA, Division Chairman and Professor, College of Pharmacy, and
Professor of Pediatrics and Internal Medicine, College of Medicine of the Ohio
State University, Columbus
MARK A. RIDDLE, Professor of Psychiatry and Pediatrics and Director of the
Children’s Interventions Research Program in Psychiatry, Johns Hopkins
University School of Medicine, Baltimore, Maryland
JOSEPH ST. GEME III, James B. Duke Professor and Chair of Pediatrics and
Professor of Molecular Genetics and Microbiology, Duke University Medical
Center, Durham, North Carolina
ROBERT WARD, Professor of Pediatrics and Medical Director of Pediatric
Pharmacology, University of Utah, Salt Lake City

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Copyright © National Academy of Sciences. All rights reserved.
Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children and the Pediatric Research Equity Acts
Committee Consultants and Background Paper Authors

CHARLES J. COTÉ, Professor of Anaesthesia, Harvard Medical School, Cambridge,
Massachusetts
LARA ELLINGER, Department of Pharmacy Practice, College of Pharmacy,
University of Illinois at Chicago
MICHAEL GABAY, Department of Pharmacy Practice, College of Pharmacy,
University of Illinois at Chicago
ANDREW HERSHEY, Department of Neurology, Children’s Hospital Medical Center,
Cincinnati, Ohio
MATTHEW M. LAUGHON, Department of Pediatrics, University of North Carolina at
Chapel Hill
THE LEWIN GROUP, Falls Church, Virginia
P. BRIAN SMITH, Duke University Medical Center and Duke Clinical Research
Institute, Durham, North Carolina
JOAN M. STACHNIK, Department of Pharmacy Practice, College of Pharmacy,
University of Illinois at Chicago

IOM Staff

MARILYN J. FIELD, Senior Program Officer
CLAIRE F. GIAMMARIA, Research Associate
ROBIN E. PARSELL, Senior Program Assistant
ANDREW M. POPE, Director, Board on Health Sciences Policy
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Copyright © National Academy of Sciences. All rights reserved.
Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children and the Pediatric Research Equity Acts

Acknowledgments

In preparing this report, the committee and project staff benefited greatly from the
assistance and expertise of many individuals and groups. Important information and
insights came from three public meetings that the committee organized to collect
information and perspectives from officials from the Food and Drug Administration
(FDA) and the National Institutes of Health and individuals from organizations
representing pharmaceutical and biotechnology companies, pediatricians, researchers,
and advocates. A number of speakers at these meetings, including Anne Zajicek, Natella
Y. Rakhmanina, Samuel Maldonado, and Ronald Portman, also shared their knowledge at
other times during the course of the study. Appendix A includes the agendas of the public
meetings.
The committee appreciates the contributions of the authors of the background
papers and analyses that appear as Appendixes B, C, and D. We likewise appreciate the
analyses conducted by staff of The Lewin Group (including Nancy Walczak, Ian Glen,
and Cynthia Schuster) and their patience in discussing the details of these analyses, which
changed extensively over the course of the project. Consultants Andrew Hershey and
Charles Coté assisted with the analysis of studies and labeling changes involving
migraine and anesthetic products. At the College of Pharmacy, University of Illinois at
Chicago, Amy LoDolce was very helpful in initiating the work on what became
Appendix D of this report.
Robert Nelson, our project officer at FDA, and his colleague, Catherine Lee,
provided information and clarification on a seemingly endless number of questions about
FDA policies, procedures, and documents. They consulted with many others at FDA in
the process, and we appreciate those who helped them answer our questions. Lisa Mathis
and Julia Dunne at FDA also assisted staff in understanding additional aspects of FDA
activities related to pediatric drug studies. At the American Academy of Pediatrics,
Tamar Haro and Mark Del Monte provided helpful background information.
We also appreciate the work of copy editor Michael Hayes and Debra Gilliam,
Chanda Chay, and John Bowers at Caset Associates. Within the National Academies, we
acknowledge the assistance of Adam Berger, Laura Harbold, Donna Randall, Vilija Teel,
and Sarah Ziegenhorn, among many others.
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Copyright © National Academy of Sciences. All rights reserved.
Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children and the Pediatric Research Equity Acts

Reviewers

This report has been reviewed in draft form by individuals chosen for their
diverse perspectives and technical expertise, in accordance with procedures approved by
the National Research Council’s Report Review Committee. The purpose of this
independent review is to provide candid and critical comments that will assist the
institution in making its published reports as sound as possible and to ensure that the
report meets institutional standards for objectivity, evidence, and responsiveness to the
study charge. The review comments and draft manuscript remain confidential to protect
the integrity of the deliberative process. We wish to thank the following individuals for
their review of this report:

Jon S. Abramson, Wake Forest University School of Medicine
Marilee C. Allen, Johns Hopkins University School of Medicine
Daniel Benjamin, Duke Clinical Research Center
Susan S. Ellenberg, University of Pennsylvania School of Medicine
Chris Feudtner, Children’s Hospital of Philadelphia
Henry G. Grabowski, Duke University
Sean Hennessy, University of Pennsylvania School of Medicine
Raphael Hirsch, University of Pittsburgh School of Medicine
Steven Joffe, Dana-Farber Cancer Institute
Michael Katz, March of Dimes Birth Defects Foundation
Michael Labson, Covington & Burling LLP
Fernando D. Martinez, Arizona Health Sciences Center
Josef Neu, University of Florida
Arthur W. Nienhuis, St. Jude Children's Research Hospital
Alastair J. Wood, Symphony Capital LLC
Kathryn C. Zoon, National Institute of Allergy and Infectious Diseases

Although the reviewers listed above have provided many constructive comments
and suggestions, they were not asked to endorse the conclusions or recommendations, nor
did they see the final draft of the report before its release. The review of this report was
overseen by Ellen Wright Clayton, Vanderbilt University, and Charles E. Phelps,
University of Rochester. Appointed by the National Research Council and the Institute of
Medicine, these individuals were responsible for making certain that an independent
examination of this report was carried out in accordance with the institutional procedures
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Copyright © National Academy of Sciences. All rights reserved.
Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children and the Pediatric Research Equity Acts
and that all review comments were carefully considered. Responsibility for the final
content of this report rests entirely with the authoring committee and the institution.
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Copyright © National Academy of Sciences. All rights reserved.