DERIVING DRUG DISCOVERY
VALUE FROM LARGE-SCALE
GENETIC BIORESOURCES
Proceedings of a Workshop
Siobhan Addie, Amanda Wagner Gee, Steve Olson,
and Sarah H. Beachy, Rapporteurs
Roundtable on Genomics and Precision Health
Forum on Drug Discovery, Development, and Translation
Board on Health Sciences Policy
Health and Medicine Division
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
THE NATIONAL ACADEMIES PRESS • 500 Fifth Street, NW • Washington, DC 20001
This project was supported by contracts between the National Academy of Sciences and 23andMe (unnumbered contract); AbbVie Inc. (unnumbered contract); American Academy of Nursing (unnumbered contract); American College of Medical Genetics and Genomics (unnumbered contract); American Diabetes Association (unnumbered contract); American Heart Association (unnumbered contract); American Medical Association (unnumbered contract); American Society of Human Genetics (unnumbered contract); American Society of Microbiology (unnumbered contract); Amgen Inc. (Contract No. GHCCOPS-CSARF-85167); Association for Molecular Pathology (unnumbered contract); Association of American Medical Colleges (unnumbered contract); AstraZeneca (unnumbered contract); Baxter BioScience (unnumbered contract); Biogen (unnumbered contract); Blue Cross and Blue Shield Association (unnumbered contract); Burroughs Wellcome Fund (Contract No. 1016598); Centers for Disease Control and Prevention (Contract No. 200-2011-38807, Order No. 0039); College of American Pathologists (unnumbered contract); Critical Path Institute (unnumbered contract); Department of Veterans Affairs (Contract No. VA240-14-C-0037); Doris Duke Charitable Foundation (Contract No. 2015103); Eli Lilly and Company (unnumbered contract); FasterCures (unnumbered contract); Friends of Cancer Research (unnumbered contract); GeneDx (unnumbered contract); GlaxoSmithKline (Contract No. 016084); Health Resources and Services Administration (Contract No. HHSH250200976014I, Order No. HHSH25034017T and HHSH250201500001I, Order No. HHSH25034003T); International Society for Cardiovascular Translational Research (unnumbered contract); Janssen Research & Development, LLC (unnumbered contract); Johnson & Johnson (unnumbered contract); Kaiser Permanente Program Offices Community Benefit II at the East Bay Community Foundation (unnumbered contract); Merck & Co., Inc. (Contract No. CMO-140505-000393, Contract No. CMO-150107-000659, and Contract No. CMO-160208-001245); National Institutes of Health (Contract No. HHSN263201200074I; Task Order Nos. HHSN26300005/0002, HHSN26300066, and HHSN26300093: National Cancer Institute; National Center for Advancing Translational Sciences; National Human Genome Research Institute; National Institute of Allergy and Infectious Diseases; National Institute on Aging; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; and National Institute of Nursing Research); National Society of Genetic Counselors (unnumbered contract); New England Journal of Medicine (unnumbered contract); Northrop Grumman Health IT (unnumbered contract); Pfizer Inc. (unnumbered contract); PhRMA (unnumbered contract); Sanofi (unnumbered contract); and Takeda Pharmaceuticals (Contract No. 53108); and U.S. Food and Drug Administration (Contract No. 1R13FD005496-01). Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-44778-2
International Standard Book Number-10: 0-309-44778-X
Digital Object Identifier: 10.17226/23601
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Copyright 2016 by the National Academy of Sciences. All rights reserved.
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2016. Deriving drug discovery value from large-scale genetic bioresources: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/23601.
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PLANNING COMMITTEE1
NADEEM SARWAR (Chair), President, Andover Product Creation Innovation System, Eisai Inc.
REBECCA BLANCHARD, Executive Director, Genetics and Pharmacogenomics, Head of Clinical Pharmacogenomics, Merck & Co., Inc.
JOHN CARULLI, Director, Precision Medicine, Biogen
GEOFFREY GINSBURG, Director, Center for Applied Genomics and Precision Medicine, Duke University
DAVID GOLDSTEIN, Director, Institute for Genomic Medicine, Columbia University
WILLIAM HOOS, Consultant, Pancreatic Cancer Action Network
GABRIELA LAVEZZARI, former Assistant Vice President, Science and Regulatory Advocacy, PhRMA
LAURA NISENBAUM, Advisor, Chorus Clinical Development, Eli Lilly and Company
DINA PALTOO, Senior Science Policy Analyst, Director of the Genetics, Health, and Society Program, Office of Science Policy, Office of the Director, National Institutes of Health
NALINI RAGHAVACHARI, Division of Geriatrics and Clinical Gerontology, National Institute on Aging
Genomics Roundtable Staff
SARAH H. BEACHY, Project Director
SIOBHAN ADDIE, Associate Program Officer
MEREDITH HACKMANN, Senior Program Assistant
Drug Forum Staff
ANNE B. CLAIBORNE, Project Director
REBECCA A. ENGLISH, Program Officer
AMANDA WAGNER GEE, Program Officer
MORGAN L. BONAME, Associate Program Officer
OLIVIA YOST, Senior Program Assistant
__________________
1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
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ROUNDTABLE ON GENOMICS AND PRECISION HEALTH1
GEOFFREY GINSBURG (Co-Chair), Director, Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC
SHARON TERRY (Co-Chair), President and Chief Executive Officer, Genetic Alliance, Washington, DC
NAOMI ARONSON, Executive Director, Technology Evaluation Center, Blue Cross and Blue Shield Association, Chicago, IL
REBECCA BLANCHARD, Executive Director, Genetics and Pharmacogenomics, Head of Clinical Pharmacogenomics, Merck & Co., Inc., West Point, PA
BRUCE BLUMBERG (until April 2016), Institutional Director of Graduate Medical Education, Northern California Kaiser Permanente, The Permanente Medical Group, Oakland, CA
JOHN CARULLI, Director, Translational Genomics, Biogen Idec, Cambridge, MA
ANN CASHION, Scientific Director, National Institute of Nursing Research, National Institutes of Health, Bethesda, MD
ROBERT B. DARNELL, President and Scientific Director, New York Genome Center; Investigator, Howard Hughes Medical Institute, Heilbrunn Cancer Professor and Senior Physician, Head, Laboratory of Molecular Neuro-Oncology, Rockefeller University, New York, NY
JOSEPH DONAHUE, Senior Vice President, Commerical Collaborations, GeneDx, Elmwood, NJ
MICHAEL J. DOUGHERTY, Director of Education, American Society of Human Genetics, Bethesda, MD
KAREN M. EMMONS, Vice President, Research, Director, Kaiser Foundation Research Institute, Kaiser Permanente, Oakland, CA
W. GREGORY FEERO, Representative of the Journal of the American Medical Association; Faculty, Maine Dartmouth Family Medicine Residency Program, Fairfield, ME
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
__________________
1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
JILL M. HAGENKORD, Chief Medical Officer, 23andMe, Mountain View, CA
JENNIFER L. HALL, Representative of the International Society for Cardiovascular Translational Research; Associate Professor of Medicine, University of Minnesota, Minneapolis
RICHARD J. HODES, Director, National Institute on Aging, Bethesda, MD
MUIN KHOURY, Director, National Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, GA
DAVID LANFEAR, Representative of the American Heart Association; Head, Advanced Heart Failure and Cardiac Transplant Section, Henry Ford Hospital, Detroit, MI
GABRIELA LAVEZZARI (until March 2016), Assistant Vice President, Scientific Affairs, PhRMA, Washington, DC
THOMAS LEHNER, Director, Office of Genomics Research Coordination, National Institute of Mental Health, Bethesda, MD
DEBRA LEONARD, Representative of the College of American Pathologists; Professor and Chair of Pathology at the University of Vermont College of Medicine; Physician Leader of Pathology and Laboratory Medicine at Fletcher Allen Health Care, University of Vermont College of Medicine, University of Vermont, Burlington
ELIZABETH MANSFIELD, Deputy Office Director for Personalized Medicine, Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD
JENNIFER MOSER, Health Science Specialist, Genomic Medicine Program, Office of Research and Development, Department of Veterans Affairs, Washington, DC
LAURA K. NISENBAUM, Advisor, Chorus Clinical Development, Eli Lilly and Company, Indianapolis, IN
ROBERT M. PLENGE (until February 2016), Vice President, Merck Research Labs; Head, Genetics and Pharmacogenomics, Merck Research Laboratories, Boston, MA
VICTORIA M. PRATT, Representative of the Association for Molecular Pathology; Associate Professor of Clinical Medical and Molecular Genetics and Director, Pharmacogenomics Diagnostic Laboratory, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis
MARY V. RELLING, Member and Chair, Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, TN
NADEEM SARWAR, President, Andover Product Creation Innovation System, Eisai Inc., Cambridge, MA
JOAN A. SCOTT, Chief, Genetic Services Branch, Division of Services for Children with Special Health Needs, Maternal and Child Health Bureau, Rockville, MD
SAM SHEKAR, Chief Medical Officer, Health Information Technology Program, Northrop Grumman Information Systems, McLean, VA
KATHERINE JOHANSEN TABER, Director, Personalized Medicine, American Medical Association, Chicago, IL
DAVID VEENSTRA, Professor, Pharmaceutical Outcomes Research and Policy Program, Department of Pharmacy, University of Washington, Seattle
MICHAEL S. WATSON, Executive Director, American College of Medical Genetics and Genomics, Bethesda, MD
DANIEL WATTENDORF (until May 2016), Deputy Chief, Medical Innovations, Department of the Air Force; Program Manager, Defense Advanced Research Projects Agency/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
ROBERT WILDIN, Chief, Genomic Healthcare Branch, National Human Genome Research Institute, Bethesda, MD
JANET K. WILLIAMS, Representative of the American Academy of Nursing; Professor of Nursing, University of Iowa, College of Nursing, Chair of Behavioral and Social Science, Iowa City
Genomics Roundtable Staff
SARAH H. BEACHY, Project Director
SIOBHAN ADDIE, Associate Program Officer
MEREDITH HACKMANN, Senior Program Assistant
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FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION1
RUSS ALTMAN (Co-Chair), Stanford University, CA
STEVEN GALSON (Co-Chair), Amgen Inc., Thousand Oaks, CA
MARGARET ANDERSON, FasterCures, Washington, DC
HUGH AUCHINCLOSS, National Institute of Allergy and Infectious Diseases, Bethesda, MD
CHRISTOPHER AUSTIN, National Center for Advancing Translational Sciences, Bethesda, MD
ANN BONHAM, Association of American Medical Colleges, Washington, DC
LINDA BRADY, National Institute of Mental Health, Bethesda, MD
GAIL CASSELL, Harvard Medical School Department of Social and Global Medicine (Visiting), Carmel, IN
ANDREW DAHLEM, Eli Lilly and Company, Indianapolis, IN
JAMES DOROSHOW, National Cancer Institute, Bethesda, MD
JEFFREY DRAZEN, New England Journal of Medicine, Boston, MA
JODIE GILLON, AstraZeneca, Summit, NJ
KATHY HUDSON, National Institutes of Health, Bethesda, MD
LYNN HUDSON, Critical Path Institute, Tucson, AZ
S. CLAIBORNE JOHNSTON, Dell Medical School, University of Texas, Austin
RUSTY KELLEY, Burroughs Wellcome Fund, Research Triangle Park, NC
KATE KNOBIL, GlaxoSmithKline, Collegeville, PA
FREDA LEWIS-HALL, Pfizer Inc., New York, NY
BERNARD MUNOS, InnoThink Center for Research in Biomedical Innovation, Indianapolis, IN
JOHN ORLOFF, Baxalta, Deerfield, IL
ROBERT RATNER, American Diabetes Association, Alexandria, VA
MICHAEL ROSENBLATT, Merck & Co., Inc., Kenilworth, NJ
MICHAEL SEVERINO, AbbVie Inc., North Chicago, IL
LANA SKIRBOLL, Sanofi, Washington, DC
BRIAN STROM, Rutgers, the State University of New Jersey, Newark
JOHN WAGNER, Takeda Pharmaceuticals, Cambridge, MA
__________________
1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
JOANNE WALDSTREICHER, Johnson & Johnson, New Brunswick, NJ
CARRIE WOLINETZ, National Institutes of Health, Bethesda, MD
JANET WOODCOCK, U.S. Food and Drug Administration, Silver Spring, MD
HMD Staff
ANNE B. CLAIBORNE, Project Director
REBECCA A. ENGLISH, Program Officer
AMANDA WAGNER GEE, Program Officer
MORGAN L. BONAME, Associate Program Officer
OLIVIA YOST, Senior Program Assistant
Board on Health Sciences Policy Staff
ANDREW M. POPE, Director
HILARY BRAGG, Program Coordinator
Reviewers
This Proceedings of a Workshop has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published Proceedings of a Workshop as sound as possible and to ensure that the Proceedings of a Workshop 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 Proceedings of a Workshop:
LINDA BRADY, National Institute of Mental Health
COLLEEN A. CAMPBELL, University of Iowa
KATHERINE LAMBERTSON, Genetic Alliance
AIDAN C. POWER, Alzheon, Inc.
Although the reviewers listed above have provided many constructive comments and suggestions, they did not see the final draft of the Proceedings of a Workshop before its release. The review of this Proceedings of a Workshop was overseen by MELVIN WORTH. He was responsible for making certain that an independent examination of this Proceedings of a Workshop was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this Proceedings of a Workshop rests entirely with the rapporteurs and the institution.
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Acknowledgments
The support of the sponsors of the Roundtable on Genomics and Precision Health was crucial to the planning and conduct of the workshop Deriving Drug Discovery Value from Large-Scale Genetic Bioresources and for the development of the workshop proceedings. Federal sponsors are the Centers for Disease Control and Prevention; Department of Veterans Affairs; Health Resources and Services Administration; and National Institutes of Health (National Cancer Institute; National Human Genome Research Institute; National Institute of Mental Health; National Institute of Nursing Research; and National Institute on Aging). Nonfederal sponsorship was provided by 23andMe; American Academy of Nursing; American College of Medical Genetics and Genomics; American Heart Association; American Medical Association; American Society of Human Genetics; Association for Molecular Pathology; Biogen; Blue Cross and Blue Shield Association; College of American Pathologists; Eli Lilly and Company; GeneDx; International Society for Cardiovascular Translational Research; Janssen Research & Development, LLC; Kaiser Permanente Program Offices Community Benefit II at the East Bay Community Foundation; Merck & Co., Inc.; National Society of Genetic Counselors; Northrop Grumman Health IT; and PhRMA.
The support of the Forum on Drug Discovery, Development, and Translation was also very important for the workshop. Federal sponsors are the U.S. Food and Drug Administration and National Institutes of Health (National Cancer Institute; National Center for Advancing Translational Sciences; National Institute of Allergy and Infectious Diseases; National Institute of Mental Health; and National Institute of Neurological Disorders and Stroke). Nonfederal sponsorship was provided by AbbVie Inc.; American Diabetes Association; American Society of Mi-
crobiology; Amgen Inc.; Association of American Medical Colleges; AstraZeneca; Baxter BioScience; Burroughs Wellcome Fund; Critical Path Institute; Doris Duke Charitable Foundation; Eli Lilly and Company; FasterCures; Friends of Cancer Research; GlaxoSmithKline; Johnson & Johnson; Merck & Co., Inc.; New England Journal of Medicine; Pfizer Inc.; Sanofi; and Takeda Pharmaceuticals.
The Roundtable on Genomics and Precision Health and the Forum on Drug Discovery, Development, and Translation wish to express gratitude to the expert speakers who explored how progress could be made in discovering and validating promising targets and medicines for those targets by using the data collected from large-scale genetic studies. The Roundtable and Forum also wish to thank the members of the planning committee for their work in developing an excellent workshop agenda. The project directors would like to thank project staff who worked diligently to develop both the workshop and the resulting proceedings.
Contents
1 INTRODUCTION AND THEMES OF THE WORKHOP
Organization of the Proceedings
2 MAXIMIZING DISCOVERY CAPABILITIES THROUGH COHORT DESIGN
Genetic Bioresources and Discovery Efforts in Iceland
Improving Genomics and Cohort Studies
Longitudinal Studies at the Community Health Level
Genetics-Guided Drug Development at Regeneron
Drug Discovery Through Direct-to-Consumer Genetics
Participation, Data Sharing, and Privacy
3 DISCOVERY ACTIVITIES RELATED TO GENETIC BIORESOURCES
Informatics Approaches to Understanding Pharmacogenomics
Using Human Genetic Data to Support Target Prioritization
Stepping Stones to Understanding the Underlying Biology of Drug Targets
A Public–Private Collaborative Approach to Target Validation
Collecting and Sharing Data to Treat a Neurological Disorder
Exploring the Definition of the Precompetitive Research Space
4 BUSINESS MODELS THAT SUPPORT BIORESOURCE DISCOVERY AND COLLABORATION
Engaging Patients for Drug Discovery
Collaborative Approaches to Genomic Drug Discovery
The Sustainability of Business Models
5 POTENTIAL NEXT STEPS IN USING GENOMICS TO ADVANCE DRUG DISCOVERY
Disruptive Technologies for Driving Drug Discovery
Linking Genetic Data to Basic Research on Biological Function
Challenges Associated with Collecting Phenotypic Data
Considering the Needs of Patients
Promoting Information Sharing and Collaboration
Boxes and Figures
BOXES
1-1 Objectives of the Workshop
2-1 Examples of Survey Questions Posed by 23andMe to Participants (as presented by Richard Scheller)
3-1 Specific Needs That Could Accelerate Genomics-Driven Drug Discovery (as proposed by Russ Altman)
5-1 Possible Next Steps Proposed by Individual Workshop Participants
FIGURES
4-1 The actionable genome for pancreatic cancer contains a wide variety of potential drug targets
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Abbreviations and Acronyms
| AMP | Accelerating Medicines Partnership |
| CTTV | Centre for Therapeutic Target Validation |
| EHR | electronic health record |
| FNIH | Foundation for the National Institutes of Health |
| FOP | fibrodysplasia ossificans progressiva |
| GSK | GlaxoSmithKline |
| GWAS | genome-wide association study |
| ITMI | Inova Translational Medicine Institute |
| LDL | low-density lipoprotein |
| NCATS | National Center for Advancing Translational Sciences |
| NIH | National Institutes of Health |
| PANCAN | Pancreatic Cancer Action Network |
| PEER | Platform for Engaging Everyone Responsibly |
| PMI | Precision Medicine Initiative |
| PPMI | Parkinson’s Progression Markers Initiative |
| SGC | Structural Genomics Consortium |
| SIK | salt-inducible kinase |
| SNP | single-nucleotide polymorphism |
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