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EpidEmiologic StudiES of VEtEranS ExpoSEd to dEplEtEd uranium Feasibility and Design Issues Committee on Gulf War and Health: Updated Literature Review of Depleted Uranium Board on Population Health and Public Health Practice
THE NATIONAL ACADEMIES PRESSâ 500 Fifth Street, NWâ 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 V101 (049A3) P-0066, Modification 2 between the National Academy of Sciences and the Department of Veterans Affairs. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that pro- vided support for this project. International Standard Book Number-13: 978-0-309-12006-7 International Standard Book Number-10: 0-309-12006-3 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, NW, Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at www.iom.edu. Copyright 2008 by the National Academy of Sciences. All rights reserved. Printed in the United States of America The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin. Suggested citation: IOM (Institute of Medicine). 2008. Epidemiologic studies of veterans exposed to depleted uranium: Feasibility and design issues. Washington, DC: The Na- tional Academies Press.
âKnowing is not enough; we must apply. Willing is not enough; we must do.â âGoethe Advising the Nation. Improving Health.
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examina- tion of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academyâs purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the Na- tional Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council. www.national-academies.org
COMMITTEE ON GULF WAR AND HEALTH: UPDATED LITERATURE REVIEW OF DEPLETED URANIUM DAVID G. HOEL, PhD (Chair), Distinguished University Professor, Medical University of South Carolina, Charleston MICHAEL ASCHNER, PhD, Gray E.B. Stahlman Professor of Neuroscience, Vanderbilt University, Nashville, TN MELISSA D. BEGG, ScD, Professor of Clinical Biostatistics and Director of Academic Programs, Mailman School of Public Health of Columbia University, New York VIVIEN W. CHEN, MPH, PhD, Professor and Director of Epidemiology Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans HAROLD I. FELDMAN, MD, MSCE, Professor of Medicine and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia PHILIP HARBER, MD, MPH, Professor and Chief, Division of Occupational and Environmental Medicine, David Geffen School of Medicine, University of California, Los Angeles PATRICK J. HEAGERTY, PhD, Professor of Biostatistics, University of Washington School of Public Health and Community Medicine, Seattle KIYOUNG LEE, MPH, ScD, Assistant Professor, University of Kentucky College of Public Health and Seoul National University School of Public Health, Republic of Korea JONATHAN LINKS, PhD, Professor and Director, Center for Public Health Preparedness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Staff ABIGAIL E. MITCHELL, PhD, Senior Program Officer JENNIFER E. SAUNDERS, MPH, MPP, Senior Program Associate RENEE WLODARCZYK, Research Assistant JOSEPH GOODMAN, Senior Program Assistant NORMAN GROSSBLATT, Senior Editor ROSE MARIE MARTINEZ, ScD, Director, Board on Population Health and Public Health Practice
Reviewers This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures ap- proved by the National Research Councilâs Report Review Committee. The pur- pose 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 of 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 for their review of this report: Patricia A. Buffler, School of Public Health, University of California, Berkeley Bernard L. Cohen, Department of Physics and Astronomy, Professor Emeritus, University of Pittsburgh Mitchell H. Gail, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health Robert Herrick, Department of Environmental Health, Harvard School of Public Health Margot Krauss, Independent Consultant, Kensington, Maryland Michael J. Thun, Epidemiology and Surveillance Research, American Cancer Society Although the reviewers listed above have provided many constructive com- ments and suggestions, they were not asked to endorse the conclusions or recom- mendations, nor did they see the final draft of the report before its release. The vii
viii REVIEWERS review of this report was overseen by David J. Tollerud, School of Public Health and Information Sciences, University of Louisville, and Johanna T. Dwyer, Tufts University School of Medicine and Friedman School of Nutrition Science, Tufts-New England Medical Center. Appointed by the Institute of Medicine and the National Research Council, respectively, they were responsible for making certain that an independent examination of this report was carried out in accor- dance 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.
Contents SUMMARY 1 1 INTRODUCTION 5 The Committeeâs Task, 6 The Committeeâs Approach to Its Task, 6 Organization of the Report, 7 References, 7 2 ELEMENTS OF AN EPIDEMIOLOGIC STUDY 9 Identifying Study Populations, 9 Exposure Assessment, 14 Outcome Assessment, 18 Assessing the Strength of the Evidence, 21 Epidemiologic Study Designs, 22 Summary, 22 References, 23 3 AVAILABLE DATASETS 25 Depleted-Uranium Exposure in the Military Population, 25 Available Datasets, 26 Summary, 38 References, 38 ix
CONTENTS 4 CONCLUSIONS AND RECOMMENDATIONS 41 Proposed Approaches to the Study of Health Outcomes of Exposure to Depleted Uranium, 42 Recommendations for Improving Future Epidemiologic Studies, 46 Additional Recommendations, 47 References, 48 Tables and Figures TABLE 2-1â Number of Subjects Required to Detect a Difference in Lung- Cancer Risk Due to DU Exposure, 11 TABLE 2-2â Number of Subjects Required to Detect a Difference in Serum Creatinine Concentration Due to DU Exposure, 12 TABLE 2-3â Number of Subjects Required to Detect an Increased Risk of Renal Disease Due to DU Exposure, 14 TABLE 3-1â Information in Available Datasets, 27 TABLE 3-2â Summary of DU Bioassay Results (2003-2007), 34 TABLE 4-1â Proposed Epidemiologic Study Designs to Assess Health Outcomes of Exposure to DU, 43 FIGURE 1-1â Stages of an epidemiologic study of DU exposure, 7