—Goethe

INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES

Advising the Nation. Improving Health.

Advisers to the Nation on Science, Engineering, and Medicine

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. Wm. A. Wulf 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 examination 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 Academy’s 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 National 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. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council.

www.national-academies.org

This page intentionally left blank.

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:

Gerard Anderson, PhD, Johns Hopkins Bloomberg School of Public Health

Stanley Hefta, PhD, Bristol-Myers Squibb

Hedvig Hricak, MD, PhD, Memorial Sloan-Kettering Cancer Center

Carolyn D. Jones, JD, MPH, AdvaMed

Lawrence A. Loeb, MD, PhD, University of Washington

Beverly S. Mitchell, MD, Stanford University Medical Center

Scott D. Patterson, PhD, Amgen, Inc.

Eric Schadt, PhD, Rosetta Inpharmatics, LLC

Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclu-

sions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Melvin Worth, MD, Scholar-in-Residence at the Institute of Medicine, and Gilbert S. Omenn, MD, PhD, University of Michigan Medical School. Appointed by the National Research Council and the 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.

The Committee is grateful to many individuals who provided valuable input and information for the study, either through formal presentations or through informal communications with study staff and Committee members. In addition to the speakers, moderators, and invited discussants at the IOM workshop on developing biomarkers, as noted in the appendix, contributors to the study include Peter Bach (Centers for Medicare and Medicaid Services), Carol Bigelow (Centers for Disease Control and Prevention), Ellen Feigal (The Critical Path Institute), Arthur Holden (Pharmaceutical Biomedical Research Consortium), Gail Javitt (Center for Genetics and Public Policy), Dan McGowan (SEMATECH Media Relations), Barbara Mittleman (NIH Office of Science Policy), Greg Raab (Raab and Associates, Inc.), Wolf Rogowski (Institute of Health Economics and Health Care Management), Todd Skaar and David Flockhart (Indiana University), Sudhir Srivastava and Donald Johnsey (NCI Cancer Biomarkers Research Group), Sean Tunis (Health Technology Center), Judith Wagner (IOM Scholar in Residence), Sidney Wolfe (Public Citizen’s Health Research Group), and Janet Woodcock (Food and Drug Administration). In addition, Margie Patlak assisted the committee by preparing some written background material on FDA oversight, CLIA, and the evaluation and adoption of clinical diagnostics for the report.

This page intentionally left blank.