IMMUNIZATION SAFETY REVIEW
HEPATITIS B VACCINE AND DEMYELINATING NEUROLOGICAL DISORDERS
Kathleen Stratton, Donna A.Almario, and Marie C.McCormick, Editors
THE NATIONAL ACADEMIES PRESS
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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.
Support for this project was provided by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health as part of a National Institutes of Health Task Order No. 74. The views presented in this report are those of the Institute of Medicine Immunization Safety Review Committee and are not necessarily those of the funding agencies.
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IMMUNIZATION SAFETY REVIEW COMMITTEE
MARIE C.McCORMICK, M.D., Sc.D., (Chair), Professor and Chair,
Department of Maternal and Child Health, Harvard School of Public Health
RONALD BAYER, Ph.D., Professor,
Division of Sociomedical Sciences, School of Public Health, Columbia University
ALFRED BERG, M.D., M.P.H., Professor and Chair,
Department of Family Medicine, University of Washington School of Medicine
ROSEMARY CASEY, M.D., Associate Professor of Pediatrics,
Jefferson Medical College and
Lankenau Faculty Pediatrics, Wynnewood, Pennsylvania
JOSHUA COHEN, Ph.D., Senior Research Associate,
Harvard Center for Risk Analysis, Harvard School of Public Health
CONSTANTINE GATSONIS, Ph.D., Professor of Medical Science and Applied Math, and Director,
Center for Statistical Sciences, Brown University
STEVEN GOODMAN, M.D., M.H.S., Ph.D., Associate Professor,
Department of Oncology, Division of Biostatistics, Johns Hopkins School of Medicine
ELLEN HORAK, M.S.N., Education and Nurse Consultant,
Public Management Center, University of Kansas
MICHAEL KABACK, M.D., Professor,
Pediatrics and Reproductive Medicine, University of California, San Diego
GERALD MEDOFF, M.D., Professor,
Department of Internal Medicine, Washington University School of Medicine, St. Louis
REBECCA PARKIN, Ph.D., Associate Research Professor,
Department of Occupational and Environmental Health, School of Public Health and Health Services, George Washington University
BENNETT SHAYWITZ, M.D., Professor of Pediatrics and Neurology, Co-Director,
Yale Center for the Study of Learning and Attention
The following individuals are members of the Immunization Safety Review Committee but were unable to attend the meeting on the topic of this report:
BETSY FOXMAN, Ph.D., Professor,
Department of Epidemiology, School of Public Health, University of Michigan
CHRISTOPHER B.WILSON, M.D., Professor and Chair,
Department of Immunology, University of Washington
Health Promotion and Disease Prevention Board Liaison
RICHARD B.JOHNSTON, Jr., M.D., Professor of Pediatrics, Associate Dean for Research Development,
University of Colorado School of Medicine and National Jewish Medical and Research Center
KATHLEEN STRATTON, Ph.D., Study Director
DONNA A.ALMARIO, M.P.H., Research Associate
KYSA CHRISTIE, Research Assistant
KATRINA J.LAWRENCE, M.S., Senior Project Assistant
ROSE MARIE MARTINEZ, Sc.D., Director,
Board on Health Promotion and Disease Prevention
JANE S.DURCH, M.A., Freelance Writer and Editor,
STEVEN J.MARCUS, Ph.D., Freelance Editor,
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 NRC’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 report 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:
Arthur K.Asbury, M.D., University of Pennsylvania
Ann Bostrom, Ph.D., Georgia Institute of Technology
Linda Cowan, Ph.D., University of Oklahoma
Bradley N.Doebbeling, M.D., M.Sc., University of Iowa Healthcare
Stephen L.Hauser, M.D., University of California, San Francisco
Christopher Karp, M.D., Children’s Hospital Research Foundation
Edgar K.Marcuse, M.D., M.P.H., Children’s Hospital & Regional Medical Center
John Menkes, M.D., Cedars Sinai Medical Center, University of California, Los Angeles
Peter H.Meyers, J.D., The George Washington University
Helen Ranney, M.D., Alliance Pharmaceutical Corporation
Richard Rheingans, Ph.D., Emory University
Harvey Sadow, Ph.D., Former Chairman, President and CEO of Boehringer Ingelheim Pharmaceuticals and Boehringer Ingelheim Corportaion
Brian Ward, M.D., Montreal General Hospital
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 Robert Lawrence, M.D., Johns Hopkins University and Ronald Estabrook, Ph.D., University of Texas Southwestern. Appointed by the National Research Council and Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures 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.
Vaccines are among the greatest public health accomplishments of the past century. In recent years, however, a number of concerns have been raised about the safety of, and need for, certain immunizations. Indeed, immunization safety is a contentious area of public health policy, with discourse around it having become increasingly polarized and exceedingly difficult. The numerous controversies and allegations surrounding immunization safety signify an erosion of public trust in those responsible for vaccine research, development, licensure, schedules, and policy making. Because vaccines are so widely used—and because state laws require that children be vaccinated to enter daycare and school, in part to protect others—immunization safety concerns should be vigorously pursued in order to restore this trust.
It is in this context that the Institute of Medicine (IOM) was approached more than a year ago by the Centers for Disease Control and Prevention and the National Institutes of Health to convene an independent committee that could provide timely and objective assistance to the Department of Health and Human Services in reviewing emerging immunization safety concerns.
The IOM was chartered by the National Academy of Sciences in 1970 to serve as an adviser to the federal government on issues affecting the public’s health, as well as to act independently in identifying important issues of medical care, research, and education. The IOM thus brings to this mission three decades of experience in conducting independent analyses of significant public health policy issues. In particular, as described in more detail in this report, the IOM has a long history of involvement in vaccine safety. The IOM published its first
major vaccine safety report in 1977, followed by a subsequent report in 1988; both focused on the safety of polio vaccines. Two subsequent major reports, published in 1991 and 1994, examined the adverse events of childhood vaccines. Since then, the IOM has conducted several smaller studies and workshops focused on various vaccine safety topics. These studies were all well received by both the public and policy makers, and previous IOM committees on vaccine safety issues have been viewed as objective and credible.
Given the sensitive nature of the present immunization safety review study, the IOM felt it was especially critical to establish strict criteria for committee membership. These criteria prevented participation by anyone with financial ties to vaccine manufacturers or their parent companies, previous service on major vaccine advisory committees, or prior expert testimony or publications on issues of vaccine safety.
The rationale for imposing these stringent criteria was twofold. First, given growing public concern about vaccine safety and the public scrutiny surrounding this committee’s work, it was important to establish standards that would preclude any real or perceived conflict of interest or bias on the part of the committee members. While the committee members all share a belief in the benefits of vaccines to the public health, none of them has any vested interest in any of the vaccine safety issues that will come before them. Second, the IOM wanted to ensure consistency in the committee membership and avoid having members recuse themselves from the deliberations because they had participated in the development or evaluation of a vaccine under study.
Thus, the IOM has convened a distinguished panel of 15 members who possess significant breadth and depth of expertise in a number of fields, including pediatrics, neurology, immunology, internal medicine, infectious diseases, genetics, epidemiology, biostatistics, risk perception and communication, decision analysis, public health, nursing, and ethics. The committee members were chosen because they are leading authorities in their respective fields, are well respected by their colleagues, and have no conflicts of interest. This committee brought a fresh perspective to these critically important issues and approached its charge with impartiality and scientific rigor.
The IOM does not propose the use of the criteria it has laid out above in selecting members for federal vaccine advisory committees. The IOM committee was convened for a very different purpose from the usual federal vaccine advisory committees and, as such, required different standards.
As with all reports from the IOM, the committee’s work was reviewed by an independent panel of experts. The purpose of the review process is to enhance the clarity, cogency, and accuracy of the final report and to ensure that the authors and the IOM are creditably represented by the report published in their names. The report review process is overseen by the National Research Council’s (NRC) Report Review Committee (RRC), comprised of approximately 30 members of the National Academy of Sciences, National Academy of Engineer-
ing, and IOM. The IOM, in conjunction with the RRC, appoints a panel of reviewers with a diverse set of perspectives on key issues considered in the report. Unlike the selection criteria for committee membership (discussed above), many reviewers will have strong opinions and biases about the report topic. The composition of the review panel is not disclosed to the committee until after the report is approved for release. While the committee must consider and evaluate all comments from reviewers, it is not obligated to change its report in response to the reviewers’ comments. The committee must, however, justify its responses to the reviewers’ comments to the satisfaction of the RRC’s review monitor and the IOM’s review coordinator. A report may not be released to the sponsors or the public, nor may its findings be disclosed, until after the review process has been satisfactorily completed and all authors have approved the revised draft.
This report represents the unanimous conclusions and recommendations of that dedicated committee whose members deliberated a critical health issue. The report’s conclusions and recommendations should be of value to all concerned about these important matters.
President, Institute of Medicine (until June 30th2002)
The committee would like to acknowledge the many speakers and attendees at its open meeting held on March 11, 2002, in Washington, DC. The discussions were informative and helpful. The committee would also like to thank those people who submitted information to the committee through the mail or e-mail. Finally, the committee would like to thank the IOM staff for their dedication to this project. Without their commitment, attention to detail, creativity, sensitivity, and hard work, this project would be unworkable.