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Neil Weisfeld, Rebecca A. English, and Anne B. Claiborne, Rapporteurs
Forum on Drug Discovery, Development, and Translation
Board on Health Sciences Policy
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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
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 study was supported by contracts between the National Academy of Sciences
and Department of Health and Human Services (Contract Nos. N01-OD-4-2139
TO #158 and HHSF223001003T), American Society for Microbiology, Amgen Inc.,
Association of American Medical Colleges, Bristol-Myers Squibb, Burroughs
Wellcome Fund, Celtic Therapeutics, LLLP, Critical Path Institute, Doris Duke
Charitable Foundation, Eli Lilly & Co., FasterCures, Foundation for the NIH,
Friends of Cancer Research, GlaxoSmithKline, Janssen Research & Development,
LLC, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, and Pfizer Inc.
The views presented in this publication do not necessarily reflect the views of the
organizations or agencies that provided support for the project.
International Standard Book Number-13: 978-0-309-25315-4
International Standard Book Number-10: 0-309-25315-2
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Copyright 2012 by the National Academy of Sciences. All rights reserved.
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The serpent has been a symbol of long life, healing, and knowledge among almost
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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). 2012. Envisioning a Transformed
Clinical Trials Enterprise in the United States: Establishing an Agenda for 2020:
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
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The Institute of Medicine was established in 1970 by the National Academy of
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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
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www.national-academies.org
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PLANNING COMMITTEE FOR THE WORKSHOP
SERIES ON IMPROVING THE CLINICAL TRIAL
PROCESS IN THE UNITED STATES1
JEFFREY M. DRAZEN (Chair), New England Journal of Medicine, Boston, MA
BARBARA ALVING,2 National Center for Research Resources,
Bethesda, MD
ANN BONHAM, Association of American Medical Colleges,
Washington, DC
LINDA BRADY, National Institute of Mental Health, Bethesda, MD
ROBERT CALIFF, Duke University Medical Center, Durham, NC
SCOTT CAMPBELL,3 Foundation for the National Institutes of Health,
Bethesda, MD
GAIL H. CASSELL, Harvard Medical School (visiting), Carmel, IN
JAMES H. DOROSHOW, National Cancer Institute, Bethesda, MD
PAUL R. EISENBERG, Amgen Inc., Thousand Oaks, CA
GARY L. FILERMAN, Atlas Health Foundation, McLean, VA
GARRET A. FITZGERALD, University of Pennsylvania School of
Medicine, Philadelphia
PETRA KAUFMANN, National Institute of Neurological Disorders and
Stroke, Bethesda, MD
RONALD L. KRALL, University of Pennsylvania Center for Bioethics,
Steamboat Springs, CO
FREDA LEWIS-HALL, Pfizer Inc., New York, NY
ELLEN SIGAL, Friends of Cancer Research, Washington, DC
JANET TOBIAS, Ikana Media and Mount Sinai School of Medicine,
New York, NY
JANET WOODCOCK, Food and Drug Administration, White Oak, MD
IOM Staff
ANNE B. CLAIBORNE, Forum Director
REBECCA A. ENGLISH, Associate Program Officer
ELIZABETH F. C. TYSON, Research Associate
ANDREW M. POPE, Director, Board on Health Sciences Policy
ROBIN GUYSE, Senior Program Assistant
1 Institute of Medicine planning committees are solely responsible for organizing the work-
shop, identifying topics, and choosing speakers. The responsibility for the published work-
shop summary rests with the workshop rapporteurs and the institution.
2 Barbara Alving was with the National Center for Research Resources until September 30,
2011.
3 Scott Campbell was with Foundation for the National Institutes of Health as of the dates
of the workshop.
v
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FORUM ON DRUG DISCOVERY,
DEVELOPMENT, AND TRANSLATION1
JEFFREY M. DRAZEN (Co-Chair), New England Journal of Medicine,
Boston, MA
STEVEN K. GALSON (Co-Chair), Amgen Inc., Thousand Oaks, CA
MARGARET ANDERSON, FasterCures, Washington, DC
HUGH AUCHINCLOSS, National Institute of Allergy and Infectious
Diseases, Bethesda, MD
LESLIE Z. BENET, University of California-San Francisco
ANN BONHAM, Association of American Medical Colleges,
Washington, DC
LINDA BRADY, National Institute of Mental Health, Bethesda, MD
ROBERT CALIFF, Duke University Medical Center, Durham, NC
C. THOMAS CASKEY, Baylor College of Medicine, Houston, TX
GAIL H. CASSELL, Harvard Medical School (visiting), Carmel, IN
PETER B. CORR, Celtic Therapeutics, LLLP, New York, NY
ANDREW M. DAHLEM, Eli Lilly & Co., Indianapolis, IN
TAMARA DARSOW, American Diabetes Association, Alexandria, VA
JAMES H. DOROSHOW, National Cancer Institute, Bethesda, MD
GARY L. FILERMAN, Atlas Health Foundation, McLean, VA
GARRET A. FITZGERALD, University of Pennsylvania School of
Medicine, Philadelphia
MARK J. GOLDBERGER, Abbott, Rockville, MD
HARRY B. GREENBERG, Stanford University School of Medicine, CA
STEPHEN GROFT, National Center for Advancing Translational
Sciences, Bethesda, MD
LYNN HUDSON, Critical Path Institute, Tuscon, AZ
THOMAS INSEL, National Center for Advancing Translational
Sciences, Bethesda, MD
MICHAEL KATZ, March of Dimes Foundation, White Plains, NY
PETRA KAUFMANN, National Institute of Neurological Disorders and
Stroke, Bethesda, MD
JACK D. KEENE, Duke University Medical Center, Durham, NC
RONALD L. KRALL, University of Pennsylvania Center for Bioethics,
Steamboat Springs, CO
FREDA LEWIS-HALL, Pfizer Inc., New York, NY
MARK B. McCLELLAN, The Brookings Institution, Washington, DC
CAROL MIMURA, University of California, Berkeley
1Institute of Medicine forums and roundtables do not issue, review, or approve individual
documents. The responsibility for the published workshop summary rests with the work -
shop rapporteurs and the institution.
vi
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ELIZABETH (BETSY) MYERS, Doris Duke Charitable Foundation,
New York, NY
JOHN ORLOFF, Novartis Pharmaceuticals Corporation, East Hanover, NJ
AMY PATTERSON, National Institutes of Health, Bethesda, MD
MICHAEL ROSENBLATT, Merck & Co., Inc., Whitehouse Station, NJ
JANET SHOEMAKER, American Society for Microbiology,
Washington, DC
ELLEN SIGAL, Friends of Cancer Research, Washington, DC
ELLIOTT SIGAL, Bristol-Myers Squibb, Princeton, NJ
ELLEN R. STRAHLMAN, GlaxoSmithKline, Research Triangle Park, NC
NANCY SUNG, Burroughs Wellcome Fund, Research Triangle Park, NC
JANET TOBIAS, Ikana Media and Mount Sinai School of Medicine,
New York, NY
JOANNE WALDSTREICHER, Janssen Research & Development, LLC,
Raritan, NJ
JANET WOODCOCK, Food and Drug Administration, White Oak, MD
IOM Staff
ANNE B. CLAIBORNE, Forum Director
RITA S. GUENTHER, Program Officer
REBECCA A. ENGLISH, Associate Program Officer
ELIZABETH F. C. TYSON, Research Associate
ANDREW M. POPE, Director, Board on Health Sciences Policy
ROBIN GUYSE, Senior Program Assistant
vii
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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 pub-
lished 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:
Deborah D. Ascheim, Department of Health Evidence and Policy
and the Cardiovascular Institute, Mount Sinai School of Medicine
Ralph I. Horwitz, GlaxoSmithKline
James R. O’Dell, Rheumatoid Arthritis Investigational Network,
University of Nebraska Medical Center
Deborah A. Zarin, National Library of Medicine, ClinicalTrials.gov
Although the reviewers listed above have provided many construc -
tive comments and suggestions, they did not see the final draft of the
report before its release. The review of this report was overseen by
Daniel R. Masys, University of Washington. Appointed by the Institute
ix
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x REVIEWERS
of Medicine, he was responsible for making certain that an independent
examination of this report was carried out in accordance with institu -
tional procedures and that all review comments were carefully consid -
ered. Responsibility for the final content of this report rests entirely with
the authors and the institution.
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Contents
ACRONYMS xv
1 INTRODUCTION 1
Defining the Problem, 4
Linking the Transformation of the Clinical Trials Enterprise
and Improving Quality of Care, 5
Purpose and Structure of the Workshop, 7
Organization of the Report, 10
2 INTEGRATING COMMUNITY PRACTICE AND CLINICAL
TRIALS 13
A Call for Disruptive Innovation in the Clinical Trials
Enterprise, 13
A Framework for the Clinical Trials Enterprise in the Health
Care System of 2020, 17
The Learning Health System, 22
3 IMPROVING PUBLIC PARTICIPATION IN CLINICAL
TRIALS 27
Developing a Robust Clinical Trials Workforce, 27
Opportunities to Create a Sustainable Workforce for the
Clinical Trials Enterprise, 31
Sustaining Institutional Support and Patient Engagement
in Clinical Trials, 36
xi
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xii CONTENTS
4 CREATING A NEW BUSINESS MODEL FOR CLINICAL
TRIALS 43
Transforming the Economics of Clinical Trials, 43
Identifying Opportunities to Improve Regulatory Frameworks
for Clinical Trials, 47
Opportunities for Aligning Cultural and Financial Incentives
in Clinical Trials, 48
5 BUILDING AN INFRASTRUCTURE TO SUPPORT CLINICAL
TRIALS 53
Gaps and Challenges in the Current Clinical Trials
Infrastructure, 54
Establishing an Infrastructure to Support a Transformed
Clinical Trials Enterprise, 56
6 SUGGESTING AN AGENDA FOR TRANSFORMING
ELEMENTS OF THE CLINICAL TRIALS ENTERPRISE 63
Reflecting on Potential Paths Forward, 66
Building a Framework and Suggesting an Agenda, 73
REFERENCES 81
APPENDIXES
A WORKSHOP AGENDA 85
B PARTICIPANT BIOGRAPHIES 97
C REGISTERED WORKSHOP ATTENDEES 123
D DISCUSSION PAPER: The Clinical Trials Enterprise in the
133
United States: A Call for Disruptive Innovation
E DISCUSSION PAPER: Developing a Robust Clinical Trials
161
Workforce
F DISCUSSION PAPER: Transforming the Economics of Clinical
183
Trials
G DISCUSSION PAPER: Developing a Clinical Trials Infrastructure 193
H DISCUSSION PAPER: Canadian Strategy on Patient-Oriented
203
Research
I DISCUSSION PAPER: Health Research as a Public Good ˆ
J DISCUSSION PAPER: Novel Ways to Get Good Trial Data:
211
The UK Experience
K IOM STAFF PAPER: Context and Glossary of Select Terms
225
Associated with the Clinical Trials Enterprise
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Tables, Figures, and Boxes
TABLES
2-1 The Four “Laboratories” of a Transformed Clinical Trials
Enterprise, 15
2-2 Potential Features of the Clinical Trials Enterprise and Health Care
System of 2020, 18
3-1 Education and Training Needs of Groups in the Clinical Trials
Workforce, 30
5-1 Some Clinical Trials Infrastructure Challenges and Possible Courses
of Action Mentioned at the Workshop, 61
6-1 Illustrative Strategies for Action by Stakeholder Groups Suggested
by Individual Workshop Participants, 79
FIGURES
2-1 U.S. costs per clinical trial are noncompetitive, 16
2-2 Example of a sequential clinical trial design that administers and
tests three drugs (drug A1, A2 and B1) in a tiered fashion, 25
3-1 Five suggested tiers for the workforce to meet the demands of a
transformed clinical trials enterprise, 29
xiii
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xiv TABLES, FIGURES, AND BOXES
3-2 The protocol navigator interface at the National Institute of Allergy
and Infectious Diseases (NIAID), 39
5-1 The PACeR (Partnership to Advance Clinical electronic Research)
system fills the EMR clinical data gaps and captures uniform data
across all clinical data capture sites, which is needed for evidence-
based research, 59
BOXES
1-1 Stakeholders in the U.S. Clinical Trials Enterprise, 2
1-2 Selected Challenges Facing the U.S. Clinical Trials Enterprise, 5
1-3 Workshop Task and Objectives, 8
2-1 Some Aspects of the Challenge of Persuading Clinicians to Engage
in Research, 21
3-1 NIH Clinical Center Key Services for Researchers and Patients, 37
4-1 Selected Potential Strategies for Avoiding Unnecessary Costs in
Clinical Trials, 46
5-1 Elements of the Clinical Trials Infrastructure Discussed at the
Workshop, 55
6-1 Key Themes of Clinical Trials Enterprise Transformation Suggested
at the Workshop, 64
6-2 CEOs of Integrated Health Systems Could Promote Clinical
Research, 67
6-3 Aspects of a High-Performance Clinical Research System, 69
6-4 Possible Ways to Manage the Research Portfolio in the United
States, 71
6-5 One NIH Official’s Reflections on Collaborating with Patient
Advocates, 71
6-6 Components of the Canadian Strategy for Patient-Oriented
Research, 73
6-7 Public Engagement in Clinical Trials, 75
6-8 Individual Workshop Participants’ Suggestions for Simplifying the
IRB Process, 77
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Acronyms
ACO Accountable Care Organization
AHRQ Agency for Healthcare Research and Quality
AHSS academic health science system
AMI acute myocardial infarction
CDC U.S. Centers for Disease Control and Prevention
CED Coverage with Evidence Development
CER comparative effectiveness research
CERN European Organization for Nuclear Research
CF cystic fibrosis
CMS Centers for Medicare & Medicaid Services
CRO contract research organization
CTE clinical trials enterprise
CTSA Clinical and Translational Science Award
CTTI Clinical Trials Transformation Initiative
DoD U.S. Department of Defense
EDC electronic data capture
EHR electronic health record
EMA European Medicines Agency
FDA U.S. Food and Drug Administration
FNIH Foundation for the National Institutes of Health
xv
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xvi ACRONYMS
GCP Good Clinical Practice
GenISIS Genomic Informatics System for Integrative Science
GMP Good Manufacturing Practice
HCA Hospital Corporation of America
HHS Department of Health and Human Services
HIPAA Health Insurance Portability and Accountability Act
HITECH Health Information Technology for Economic and
Clinical Health
HMORN HMO (health maintenance organization) Research
Network
i2b2 Informatics for Integrating Biology and the Bedside
IHS integrated health system
IND Investigational New Drug
INTERMACS Interagency Registry for Mechanically Assisted
Circulatory Support
IOM Institute of Medicine
IRB Institutional Review Board
IT information technology
MRSA methicillin-resistant Staphylococcus Aureus
NCI National Cancer Institute
NHLBI National Heart, Lung, and Blood Institute
NIAID National Institute of Allergy and Infectious Diseases
NIH National Institutes of Health
NINDS National Institute of Neurological Disorders and Stroke
OAT Occluded Artery Trial
PACeR Partnership to Advance Clinical electronic Research
PCORI Patient-Centered Outcomes Research Institute
RCT randomized controlled trial
REDUCE-MRSA Randomized Evaluation of Decolonization versus
Universal Clearance to Eliminate-MRSA
SEMATECH Semiconductor Manufacturing Technology consortium
VA U.S. Department of Veterans Affairs
VINCI VA Informatics and Computing Infrastructure
