Policy Issues in the
Development and Adoption of
Biomarkers for Molecularly
Targeted Cancer Therapies
WORKSHOP SUMMARY
Sharyl J. Nass, Jonathan Phillips, and Margie Patlak, Rapporteurs
National Cancer Policy Forum
Board on Health Care Services
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
NOTICE: The workshop that is the subject of this workshop summary 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.
This project was supported by Contract No. HHSN261200900003C and Contract No. HHSN263201200074I (Task Order No. HHSN26300052) between the National Academy of Sciences and the Centers for Disease Control and Prevention and the National Cancer Institute/National Institutes of Health, respectively, and by the American Association for Cancer Research, the American Cancer Society, the American Society for Radiation Oncology, the American Society of Clinical Oncology, the American Society of Hematology, the Association of American Cancer Institutes, AstraZeneca, Bristol-Myers Squibb, the Cancer Support Community, C-Change, the CEO Roundtable on Cancer, EMD Serono, Helsinn Healthcare SA, the LIVESTRONG Foundation, the National Comprehensive Cancer Network, Novartis Oncology, the Oncology Nursing Society, and Sanofi Oncology. The views presented in this publication do not necessarily reflect the views of the organizations or agencies that provided support for the activity.
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Suggested citation: IOM (Institute of Medicine). 2015. Policy issues in the development and adoption of biomarkers for molecularly targeted cancer therapies: Workshop summary. Washington, DC: The National Academies Press.
“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
THE NATIONAL ACADEMIES
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.
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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. Victor J. Dzau 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. C. D. Mote, Jr., are chair and vice chair, respectively, of the National Research Council.
WORKSHOP PLANNING COMMITTEE1
ADRIAN SENDEROWICZ (Chair), President, Oncology Drug Development, LLC
KENNETH ANDERSON, Kraft Family Professor of Medicine, American Cancer Society Clinical Research Director, Jerome Lipper Multiple Myeloma Center, Harvard Medical School, Dana-Farber Cancer Institute
MICHAEL A. CALIGIURI, CEO, James Cancer Hospital & Solove Research Institute, Director, Ohio State University Cancer Center
BARBARA CONLEY, Associate Director, Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute
CAROL A. HAHN, Associate Professor of Radiation Oncology, Duke University Medical Center, Medical Director of Radiation Oncology, Duke Raleigh Hospital, Clinical Affairs and Quality Council Chair, American Society for Radiation Oncology
ROY HERBST, Professor of Medicine & Chief, Section of Medical Oncology, Yale Cancer Center
SAMIR N. KHLEIF, Director, Georgia Health Sciences University Cancer Center, Georgia Regents University Cancer Center
ROBERT McDONOUGH, Head of Clinical Policy Research & Development, Aetna, Inc.
LISA McSHANE, Mathematical Statistician, Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute
RICHARD PAZDUR, Office of Oncology and Hematology Products, Food and Drug Administration
RICHARD SCHILSKY, Chief Medical Officer, American Society of Clinical Oncology
_______________
1 Institute of Medicine planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.
Project Staff
SHARYL J. NASS, Forum Director and Director, Board on Health Care Services
JONATHAN PHILLIPS, Research Associate
SARA THARAKAN, Research Assistant
HANNAH DURING, Senior Program Assistant
PATRICK ROSS, Senior Program Assistant
NATIONAL CANCER POLICY FORUM1
MICHAEL A. CALIGIURI (Chair), CEO, James Cancer Hospital & Solove Research Institute, Director, Ohio State University Comprehensive Cancer Center
PATRICIA A. GANZ (Vice Chair), Professor, University of California, Los Angeles, School of Medicine & Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center
AMY P. ABERNETHY, Associate Professor of Medicine, Duke University School of Medicine, and Director, Duke Cancer Care Research Program
LUCILE ADAMS-CAMPBELL, Professor of Oncology, Associate Director for Minority Health and Health Disparities Research, Georgetown University Lombardi Cancer Center
KENNETH ANDERSON, Kraft Family Professor of Medicine, American Cancer Society Clinical Research Director, Jerome Lipper Multiple Myeloma Center, Harvard Medical School, Dana-Farber Cancer Institute
LOYCE PACE BASS, Health Policy Director, LIVESTRONG Foundation
MONICA BERTAGNOLLI, Professor of Surgery, Harvard University Medical School
OTIS BRAWLEY, Chief Medical Officer and Executive Vice President, American Cancer Society
CARLTON BROWN, Director of Professional Services, Oregon Nurses Association, and Past President, Oncology Nursing Society
SERGIO CANTOREGGI, Chief Scientific Officer and Global Head of Research and Development, The Helsinn Group
ROBERT W. CARLSON, CEO, National Comprehensive Cancer Network
GREGORY CURT, U.S. Medical Science Lead, AstraZeneca
_______________
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.
WILLIAM S. DALTON, CEO, M2Gen Personalized Medicine Institute, Moffitt Cancer Center, and Chair, American Association for Cancer Research Science Policy & Legislative Affairs Committee
GWEN DARIEN, Executive Vice President, Programs and Services, Cancer Policy Institute, Cancer Support Community
WENDY DEMARK-WAHNEFRIED, Associate Director for Cancer Prevention and Control, University of Alabama at Birmingham Comprehensive Cancer Center
JAMES DOROSHOW, Deputy Director, National Cancer Institute
CAROL A. HAHN, Associate Professor of Radiation Oncology, Duke University Medical Center, Medical Director of Radiation Oncology, Duke Raleigh Hospital, Clinical Affairs and Quality Council Chair, American Society for Radiation Oncology
LORI HOFFMAN HOGG, Veterans Health Administration National Oncology Clinical Advisor, Office of Nursing Services and Cancer Program Director, Albany Stratton VA Medical Center
CHARLES HUGH-JONES, Chief Medical Officer, Sanofi North America
SAMIR N. KHLEIF, Director, Georgia Health Sciences University Cancer Center, Georgia Regents University Cancer Center
RICHARD A. LARSON, Hematology/Oncology Director, University of Chicago
MICHELLE M. LE BEAU, Arthur and Marian Edelstein Professor of Medicine, Director, Comprehensive Cancer Center, University of Chicago
JOSEPH LEVEQUE, Vice President, Head U.S. Medical–Oncology, Bristol-Myers Squibb
SHARI LING, Deputy Chief Medical Officer, Center for Clinical Standards and Quality, Centers for Medicare & Medicaid Services
GRETA MASSETTI, Associate Director for Science, Division of Cancer Prevention and Control, Centers for Disease Control and Prevention
DANIEL R. MASYS, Affiliate Professor, Biomedical Informatics, University of Washington
MARTIN J. MURPHY, CEO, CEO Roundtable on Cancer
RICHARD PAZDUR, Director, Office of Oncology and Hematology Products, Food and Drug Administration
STEVEN PIANTADOSI, Phase One Foundation Endowed Chair and Director, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
JENNIFER A. PIETENPOL, Director, Vanderbilt-Ingraham Cancer Center, Benjamin F. Byrd, Jr., Professor of Oncology, Professor of Biochemistry, Vanderbilt University
ANDREW SCHIERMEIER, Senior Vice President, Head of Global Oncology, Merck Serono
RICHARD SCHILSKY, Chief Medical Officer, American Society of Clinical Oncology
DEBORAH SCHRAG, Chief, Division of Population Sciences, Professor of Medicine, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School
YA-CHEN TINA SHIH, Professor of Health Economics, Chief, Section of Cancer Economics and Policy, Department of Health Services Research, University of Texas MD Anderson Cancer Center
ELLEN V. SIGAL, Chair and Founder, Friends of Cancer Research
ELIZABETH THOMPSON, President and CEO, C-Change
RALPH WEICHSELBAUM, Daniel K. Ludwig Professor and Chair, Department of Radiation Oncology, Director, Ludwig Center for Metastasis Research, The University of Chicago Medical Center
GEORGE J. WEINER, Director, Holden Comprehensive Cancer Center, University of Iowa, President, Association of American Cancer Institutes
National Cancer Policy Forum Staff
SHARYL J. NASS, Forum Director and Director, Board on Health Care Services
JONATHAN PHILLIPS, Research Associate
SARA THARAKAN, Research Assistant
HANNAH DURING, Senior Program Assistant
PATRICK ROSS, Senior Program Assistant
PATRICK BURKE, Financial Associate
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Reviewers
This workshop summary 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 workshop summary as sound as possible and to ensure that the workshop summary 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 workshop summary:
David Eberhard, Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill
Stan Hamilton, University of Texas MD Anderson Cancer Center
Donna A. Messner, Center for Medical Technology Policy
Katherine L. Nathanson, Perelman School of Medicine at the University of Pennsylvania
William Pao, F. Hoffmann-La Roche Ltd.
Although the reviewers listed above have provided many constructive comments and suggestions, they did not see the final draft of the workshop
summary before its release. The review of this report was overseen by Eli Y. Adashi, Warren Alpert Medical School at Brown University. 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 rapporteurs and the institution.
Acknowledgments
Support from the many annual sponsors of the Institute of Medicine’s National Cancer Policy Forum is crucial to the work of the Forum. Current sponsors include the Centers for Disease Control and Prevention, the National Cancer Institute/National Institutes of Health, the American Association for Cancer Research, the American Cancer Society, the American Society for Radiation Oncology, the American Society of Clinical Oncology, the American Society of Hematology, the Association of American Cancer Institutes, AstraZeneca, Bristol-Myers Squibb, the Cancer Support Community, C-Change, the CEO Roundtable on Cancer, EMD Serono, Helsinn Healthcare SA, the LIVESTRONG Foundation, the National Comprehensive Cancer Network, Novartis Oncology, the Oncology Nursing Society, and Sanofi Oncology.
The Forum wishes to express its gratitude to the expert speakers whose presentations helped define the current challenges and opportunities in the development and adoption of biomarkers for molecularly targeted cancer therapies. The Forum also wishes to thank the members of the planning committee for their work in developing an excellent workshop agenda.
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Contents
MOLECULAR BIOLOGY REVOLUTION IN CANCER DIAGNOSIS AND TREATMENT
Lessons Learned from Single Analyte Tests
Tests for Circulating Tumor DNA
Business Climate for Developing Diagnostic Tests
CHALLENGES IN BIOMARKER TEST DEVELOPMENT
Assessing Analytical Validity, Clinical Validity, and Clinical Utility
REGULATORY OVERSIGHT CHALLENGES
Evolving Regulation of Laboratory-Developed Tests
CLINICAL IMPLEMENTATION CHALLENGES
Investigational and Off-Label Uses
Greater Expense, But Not Necessarily Greater Value
GATHERING THE EVIDENCE: INNOVATIVE CLINICAL TRIALS
Challenges with Basket and Umbrella Trials
GATHERING THE EVIDENCE: COVERAGE DECISIONS
Coverage with Evidence Development
The MolDx Approach to Test Reimbursement
Green Park Collaborative Recommendations
GATHERING THE EVIDENCE: DATABASES AND REGISTRIES
Targeted Agent and Molecular Profiling Utilization Registry
Boxes, Figures, and Tables
BOXES
1 Suggestions Made by Individual Workshop Participants
2 Actionable Genome Consortium
3 Steps to Validating a Next-Generation Sequencing Assay System for Use in a Clinical Trial
FIGURES
1 Genotyping time line for non-small-cell lung cancer
2 High-level strategy for drug and test co-development
3 Neratinib basket study schema
6 Proposed collaborative multipharma network to advance multibiomarker diagnostics
| AACR |
American Association for Cancer Research |
| ACMG |
American College of Medical Genetics and Genomics |
| AM |
Abbott Molecular |
| ASCO |
American Society of Clinical Oncology |
| BI |
Boehringer Ingelheim |
| BLA |
biologic license application |
| CAP |
College of American Pathologists |
| CDD |
coverage with data development |
| CDP |
Cancer Diagnosis Program |
| CED |
coverage with evidence development |
| CF |
cystic fibrosis |
| CFTR |
cystic fibrosis transmembrane conductance regulator |
| CLIA |
Clinical Laboratory Improvement Amendments |
| CMS |
Centers for Medicare & Medicaid Services |
| CPT |
current procedural terminology |
| CT |
computerized tomography |
| DCTD |
Division of Cancer Treatment and Diagnosis |
| Dx |
diagnostic |
| EGFR |
epidermal growth factor receptor |
| FDA |
Food and Drug Administration |
| FGFR |
fibroblast growth factor receptor |
| GSK |
GlaxoSmithKline |
| HHS |
U.S. Department of Health and Human Services |
| IDE |
investigational device exemption |
| IRB |
institutional review board |
| IVD |
in vitro diagnostics |
| LCMC |
Lung Cancer Mutation Consortium |
| LDT |
laboratory-developed test |
| LMM |
Laboratory of Molecular Medicine |
| Lung-MAP |
lung cancer master protocol |
| MATCH |
Molecular Analysis for Therapy Choice |
| NCCN |
National Comprehensive Cancer Network |
| NCI |
National Cancer Institute |
| NCTN |
National Clinical Trial Network |
| NDA |
new drug application |
| NGS |
next-generation sequencing |
| NIH |
National Institutes of Health |
| NSCLC |
non-small-cell lung cancer |
| OS |
overall survival |
| PCR |
polymerase chain reaction |
| PDQ |
Physician Data Query |
| PMA |
premarket approval |
| PSS |
Partner Specialty Society |
| TAPUR |
Targeted Agent and Molecular Profiling Utilization Registry |
| UCLA |
University of California, Los Angeles |
| UCSF |
University of California, San Francisco |
| UNC |
University of North Carolina |
