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Steve Olson, Sarah H. Beachy, Claire F. Giammaria, and
Adam C. Berger, Rapporteurs
Roundtable on Translating Genomic-Based Research for Health
Board on Health Sciences Policy
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NOTICE: The project that is the subject of this report was approved by the Govern-
ing Board of the National Research Council, whose members are drawn from the
councils of the National Academy of Sciences, the National Academy of Engineer-
ing, and the Institute of Medicine.
This project was supported by contracts between the National Academy of Sciences
and the American College of Medical Genetics (unnumbered contract); Ameri-
can Medical Association (unnumbered contract); American Nurses Association
(unnumbered contract); Blue Cross and Blue Shield Association (unnumbered con-
tract); Centers for Disease Control and Prevention (Contract No. 200-2011-38807);
College of American Pathologists (unnumbered contract); Department of the Air
Force (Contract No. FA7014-10-P-0072); Department of Veterans Affairs (Con-
tract No. V101(93) P-2238); Eli Lilly and Company (Contract No. LRL-0028-07);
Genetic Alliance (unnumbered contract); Health Resources and Services Adminis-
tration (Contract No. HHSH250201100119P); Johnson & Johnson (unnumbered
contract); Kaiser Permanente (unnumbered contract); National Cancer Institute
(Contract No. N01-OD-4-2139, TO#189); National Heart, Lung, and Blood Insti-
tute (Contract No. N01-OD-4-2139, TO#189); National Human Genome Research
Institute (Contract No. N01-OD-4-2139, TO#189 and 264); National Society of
Genetic Counselors (unnumbered contract); and Pfizer Inc. (Contract No. 140-N-
1818071). 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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Suggested citation: IOM (Institute of Medicine). 2012. Integrating Large-Scale
Genomic Information into Clinical Practice: Workshop Summary. Washington, DC:
The National Academies Press.
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“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
— Goethe
Advising the Nation. Improving Health.
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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 Acad-
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and technical matters. Dr. Ralph J. Cicerone is president of the National Academy
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The National Academy of Engineering was established in 1964, under the charter
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www.national-academies.org
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PLANNING COMMITTEE1
BRUCE BLUMBERG (Cochair), Institutional Director of Graduate
Medical Education, Northern California Kaiser Permanente, The
Permanente Medical Group, Oakland, CA
CATHERINE A. WICKLUND (Cochair), Past President, National Society
of Genetic Counselors; Director, Graduate Program in Genetic
Counseling; Associate Professor, Department of Obstetrics and
Gynecology, Northwestern University, Chicago, IL
PAUL R. BILLINGS, Chief Medical Officer, Life Technologies
Corporation, Carlsbad, CA
DENISE E. BONDS, Medical Officer, Division of Prevention and
Population Sciences, National Heart, Lung, and Blood Institute,
Bethesda, MD
W. GREGORY FEERO, Special Advisor to the Director for Genomic
Medicine, National Human Genome Research Institute, Bethesda, MD
KATHERINE JOHANSEN-TABER, Senior Scientist, American Medical
Association, Chicago, IL
SHARON KARDIA, Professor and Chair of Epidemiology; Director,
Public Health Genetics Program; Director, Life Science and Society
Program; Codirector, Center for Public Health and Community
Genomics, University of Michigan School of Public Health, Ann
Arbor
MOHAMED KHAN, Leader of Radiation Oncology, Vancouver Cancer
Centre, BC Cancer Agency, Vancouver, BC, Canada
MUIN KHOURY, Director, National Office of Public Health Genomics,
Centers for Disease Control and Prevention, Atlanta, GA
DEBRA LEONARD, Professor and Vice Chair for Laboratory Medicine;
Director of the Clinical Laboratories; Director of the Pathology
Residency Training Program, Weill Cornell Medical Center of Cornell
University, New York, NY
MICHELE LLOYD-PURYEAR, Chief, Genetic Services Branch, Health
Resources and Services Administration, Rockville, MD
MARTHA TURNER, Assistant Director, American Nurses Association
Center for Ethics and Human Rights, Silver Spring, MD
MICHAEL S. WATSON, Executive Director, American College of
Medical Genetics, Bethesda, MD
1 Institute of Medicine planning committees are solely responsible for organizing the work-
shop, identifying topics, and choosing speakers. The responsibility for the published workshop
summary rests with the workshop rapporteurs and the institution.
v
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IOM Staff
ADAM C. BERGER, Project Director
CLAIRE F. GIAMMARIA, Research Associate
TONIA E. DICKERSON, Senior Program Assistant
vi
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ROUNDTABLE ON TRANSLATING
GENOMIC-BASED RESEARCH FOR HEALTH1
WYLIE BURKE (Chair), Professor and Chair, Department of Bioethics
and Humanities, University of Washington, Seattle
NAOMI ARONSON, Executive Director, Technology Evaluation Center,
Blue Cross and Blue Shield Association, Chicago, IL
BRUCE BLUMBERG, Institutional Director of Graduate Medical
Education, Northern California Kaiser Permanente, The Permanente
Medical Group, Oakland, CA
DENISE E. BONDS, Medical Officer, Division of Prevention and
Population Sciences, National Heart, Lung, and Blood Institute,
Bethesda, MD
C. THOMAS CASKEY, Professor, Baylor College of Medicine, Houston, TX
W. GREGORY FEERO, Special Advisor to the Director for Genomic
Medicine, National Human Genome Research Institute, Bethesda, MD
ANDREW N. FREEDMAN, Branch Chief, Clinical and Translational
Epidemiology Branch, Epidemiology and Genetics Research Program,
Division of Cancer Control and Population Sciences, National Cancer
Institute, Rockville, MD
GEOFFREY GINSBURG, Director, Center for Genomic Medicine, Institute
for Genomic Sciences and Policy, Duke University, Durham, NC
SHARON KARDIA, Professor and Chair of Epidemiology; Director,
Public Health Genetics Program; Director, Life Science and Society
Program; Codirector, Center for Public Health and Community
Genomics, University of Michigan School of Public Health, Ann
Arbor
MOHAMED KHAN, representative of the American Medical
Association; Leader of Radiation Oncology, Vancouver Cancer
Centre, BC Cancer Agency, Vancouver, BC, Canada
MUIN KHOURY, Director, National Office of Public Health Genomics,
Centers for Disease Control and Prevention, Atlanta, GA
DEBRA LEONARD, representative of the College of American
Pathologists; Professor and Vice Chair for Laboratory Medicine;
Director of the Clinical Laboratories; Director of the Pathology
Residency Training Program, Weill Cornell Medical Center of Cornell
University, New York, NY
MICHELE LLOYD-PURYEAR, Chief, Genetic Services Branch, Health
Resources and Services Administration, Rockville, MD
1 Institute of Medicine forums and roundtables do not issue, review, or approve individual
documents. The responsibility for the published workshop summary rests with the workshop
rapporteurs and the institution.
vii
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ELIZABETH MANSFIELD, Director of the Personalized Medicine
Staff, Office of In Vitro Diagnostic Device Evaluation and Safety,
Center for Devices and Radiological Health, U.S. Food and Drug
Administration, Silver Spring, MD
GARRY NEIL, Corporate Vice President, Corporate Office of Science and
Technology, Johnson & Johnson, New Brunswick, NJ
ROBERT L. NUSSBAUM, Chief, Division of Medical Genetics,
Department of Medicine and Institute of Human Genetics, University
of California, San Francisco, School of Medicine
MICHELLE A. PENNY, Senior Director, Translational Medicine Group,
Eli Lilly and Company, Indianapolis, IN
AIDAN POWER, Vice President and Global Head of Molecular
Medicine, Pfizer Inc., Groton, CT
VICTORIA M. PRATT, Chief Director, Molecular Genetics, Quest
Diagnostics Nichols Institute, Chantilly, VA
RONALD PRZYGODZKI, Associate Director for Genomic Medicine,
Biomedical Laboratory Research and Development, Department of
Veterans Affairs, Washington, DC
ALLEN D. ROSES, President and Chief Operating Officer, Cabernet,
Shiraz and Zinfandel Pharmaceuticals; and Jefferson-Pilot Professor
of Neurobiology and Genetics, Professor of Medicine (Neurology);
Director, Deane Drug Discovery Institute; Senior Scholar, Fuqua
School of Business, R. David Thomas Executive Training Center,
Duke University, Durham, NC
KEVIN A. SCHULMAN, Professor of Medicine and Business
Administration; Director, Center for Clinical and Genetic Economics;
Associate Director, Duke Clinical Research Institute, Duke University
School of Medicine, Durham, NC
SHARON TERRY, President and Chief Executive Officer, Genetic Alliance,
Washington, DC
MARTHA TURNER, Assistant Director, American Nurses Association
Center for Ethics and Human Rights, Silver Spring, MD
MICHAEL S. WATSON, Executive Director, American College of
Medical Genetics, Bethesda, MD
DANIEL WATTENDORF, Deputy Chief, Medical Innovations,
Department of the Air Force; Program Manager, DARPA/Defense
Sciences Office, Arlington, VA
CATHERINE A. WICKLUND, Past President, National Society
of Genetic Counselors; Director, Graduate Program in Genetic
Counseling; Associate Professor, Department of Obstetrics and
Gynecology, Northwestern University, Chicago, IL
viii
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IOM Staff
ADAM C. BERGER, Project Director
SARAH H. BEACHY, Christine Mirzayan Science and Technology Policy
Graduate Fellow (August to November 2011)
CLAIRE F. GIAMMARIA, Research Associate
TONIA E. DICKERSON, Senior Program Assistant
ANDREW POPE, Director, Board on Health Sciences Policy
ix
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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
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 process. We wish to thank the following individuals for
their review of this report:
James P. Evans, Bryson Distinguished Professor of Genetics &
Medicine, Department of Genetics, University of North Carolina
at Chapel Hill
W. Andrew Faucett, Director, Policy and Education, Genomic
Medicine Institute, Geisinger Health System, Danville, PA
Henry T. Greely, Deane F. and Kate Edelman Johnson Professor of
Law; Professor, by courtesy, of Genetics; Director, Center for Law
and the Biosciences, Stanford University
Mary V. Relling, Chair, Pharmaceutical Department, St. Jude Children’s
Research Hospital, Memphis, TN
Cindy L. Vnencak-Jones, Professor, Departments of Pathology
and Pediatrics; Director, Molecular Diagnostics Laboratory,
Vanderbilt University Medical Center, Nashville, TN
xi
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xii REVIEWERS
Although the reviewers listed above have provided many construc-
tive comments and suggestions, they were not asked to endorse the final
draft of the report before its release. The review of this report was over-
seen by Harold J. Fallon, Dean Emeritus of the University of Alabama at
Birmingham School of Medicine. Appointed by the Institute of Medicine,
he was 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 author and the institution.
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Acknowledgments
The support of the sponsors of the Institute of Medicine Roundta-
ble on Translating Genomic-Based Research for Health was crucial to the
planning and conduct of the workshop Integrating Large-Scale Genomic
Information into Clinical Practice. Federal sponsors are the Centers for Dis-
ease Control and Prevention; Department of the Air Force; Department of
Veterans Affairs; Health Resources and Services Administration; National
Cancer Institute; National Heart, Lung, and Blood Institute; and National
Human Genome Research Institute. Non-federal sponsorship was provided
by the American College of Medical Genetics, American Medical Associa-
tion, American Nurses Association, Blue Cross and Blue Shield Association,
College of American Pathologists, Eli Lilly and Company, Genetic Alliance,
Johnson & Johnson, Kaiser Permanente, National Society of Genetic Coun-
selors, and Pfizer Inc.
The Roundtable wishes to express its gratitude to the expert speakers
whose presentations helped outline the challenges and opportunities in
integrating large-scale genomic information into clinical practice. The
Roundtable also wishes to thank the members of the planning committee
for their work in developing an excellent workshop agenda. The project
director would like to thank project staff who worked diligently to develop
both the workshop and the resulting summary. Christine Mirzayan Science
and Technology Policy Fellow Sarah H. Beachy was involved in writ-
ing and editing of the report, as was research associate Claire F. Giammaria.
Tonia E. Dickerson arranged meetings and handled administrative tasks
that resulted in a highly successful workshop.
xiii
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Contents
ABBREVIATIONS AND ACRONYMS xix
1 INTRODUCTION 1
2 THE REALIZATION OF GENOMIC MEDICINE 5
Shifting Research Paradigms, 6
Clinical Applications of Genomics-Based Medicine, 6
Addressing Obstacles and Defining a Path Forward, 7
The ClinSeq Project, 8
An Evolution of Medicine, 10
3 THE ANALYSIS OF GENOMIC DATA 11
Challenges for Laboratories, 12
Laboratory-Based Solutions, 14
Meaningful Use of Test Results, 17
Genomic Medicine in Practice, 20
4 THE INTERPRETATION OF GENOMIC DATA 25
Data Interpretation from a Clinician’s Perspective, 26
Integrating Genomic Data with Pathology, 29
Using a Bioinformatics Model for Interpretation, 33
Envisioning Clinical Genomics in 2020, 36
xv
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xvi CONTENTS
5 THE DELIVERY OF GENOMIC DATA 39
Implementing Pharmacogenetics in Clinical Practice, 40
Granting Access to Personal Health Information, 43
Advancing the Utilization of Genomic Information, 45
Building a Business Case for Genetic Testing, 46
6 ETHICAL AND LEGAL ISSUES 47
Regulatory Issues, 48
Ethical Issues: The Doctor–Patient Relationship, 49
Privacy Issues, 50
Other Issues, 51
7 WORKFORCE DEVELOPMENT 53
Knowledge, Skill Sets, and Training Opportunities, 54
A Generation of Effort, 55
8 ENVISIONING THE FUTURE 57
Maintaining Curated Databases, 57
Databases for Genetic Variants Involved in Cancer, 59
A Public Health Approach to Genomic Medicine, 60
Return of Results, 62
Getting Health Care Providers Interested, 62
Reimbursement for Interpretative Services, 63
The Role of Industry, 63
Final Words, 63
REFERENCES 65
APPENDIXES
A WORKSHOP AGENDA 69
B SPEAKER BIOGRAPHICAL SKETCHES 75
C REGISTERED ATTENDEES 87
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Figures and Box
FIGURES
3-1 Genetic tests undergo a characteristic progression from gene discovery
to test application, 15
4-1 A model for future cancer care demonstrates how genomic sequencing
and network biology will enable personalized medicine, 30
BOX
8-1 Goals to Realize the Vision of Genomic Medicine, 61
xvii
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Abbreviations and Acronyms
ATM automated teller machine
BRCA1 breast cancer 1, early onset
BRCA2 breast cancer 2, early onset
CAP College of American Pathologists
CDC Centers for Disease Control and Prevention
CDG congenital disorders of glycosylation
CK creatine kinase
CLIA Clinical Laboratory Improvement Amendments
CLL chronic lymphocytic leukemia
CMAMMA combined malonic and methylmalonic aciduria
CMD congenital muscular dystrophy
CPMC Coriell Personalized Medicine Collaborative
CT computed tomography
EGFR epidermal growth factor receptor
EMR electronic medical record
FDA U.S. Food and Drug Administration
FISH fluorescent in situ hybridization
HCM hypertrophic cardiomyopathy
HIV human immunodeficiency virus
xix
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xx ABBREVIATIONS AND ACRONYMS
ICOB Informed Cohort Oversight Board
IRB institutional review board
IT information technology
NCBI National Center for Biotechnology Information
NIH National Institutes of Health
PCPGM Partners HealthCare Center for Personalized Genetic Medicine
PGRN Pharmacogenomics Research Network
PHR personal health record
SNP single nucleotide polymorphism
TPMT thiopurine S-methyltransferase
XLID X-linked intellectual disability
