Incorporating Integrated Diagnostics into Precision Oncology Care: Proceedings of a Workshop (2024)

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Incorporating Integrated Diagnostics into Precision Oncology Care Erin Balogh, Laurene Graig, Theresa Wizemann, and Sharyl Nass, Rapporteurs National Cancer Policy Forum Board on Health Care Services Health and Medicine Division Board on Human-Systems Integration Division of Behavioral and Social Sciences and Education Computer Science and Telecommunications Board Division on Engineering and Physical Sciences PREPUBLICATION COPY—Uncorrected Proofs Proceedings of a Workshop 

NATIONAL ACADEMIES PRESS  500 Fifth Street, NW  Washington, DC 20001 This activity was supported by Contract No. 75D30121D11240 (Task Order Nos. 75D30121F00002 and 75D30123F00024) and Contract No. HHSN263201800029I (Task Order Nos. HHSN26300008 and 75N98023F00019) with 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; American Cancer Society; American College of Radiology; American Society of Clinical Oncology; Association of American Cancer Institutes; Association of Community Cancer Centers; Bristol Myers Squibb; Cancer Support Community; Flatiron Health; Merck & Co., Inc.; National Comprehensive Cancer Network; National Patient Advocate Foundation; Novartis Oncology; Oncology Nursing Society; Partners in Health; Pfizer Inc.; Sanofi; and Society for Immunotherapy of Cancer. 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-XXXXX-X International Standard Book Number-10: 0-309-XXXXX-X Digital Object Identifier: https://doi.org/10.17226/27744 This publication is available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334- 3313; http://www.nap.edu. Copyright 2024 by the National Academy of Sciences. National Academies of Sciences, Engineering, and Medicine and National Academies Press and the graphical logos for each are all trademarks of the National Academies of Sciences. All rights reserved. Printed in the United States of America. Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2024. Incorporating integrated diagnostics into precision oncology care: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/27744. PREPUBLICATION COPY—Uncorrected Proofs 

The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president. The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. John L. Anderson is president. The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president. The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine. Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org. PREPUBLICATION COPY—Uncorrected Proofs 

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PLANNING COMMITTEE1 KOJO S. J. ELENITOBA-JOHNSON (Co-Chair), Memorial Sloan Kettering Cancer Center HEDVIG HRICAK (Co-Chair), Memorial Sloan Kettering Cancer Center CHRISTINA CHAPMAN, Baylor College of Medicine NANCY E. DAVIDSON, University of Washington ROY A. JENSEN, University of Kansas; Association of American Cancer Institutes BETH Y. KARLAN, University of California, Los Angeles MIA LEVY, Foundation Medicine, Inc. AANAND D. NAIK, University of Texas Health Sciences Center at Houston WENDY NILSEN, National Science Foundation JASON M. SLAGLE, Vanderbilt University Project Staff ANNA ADLER, Senior Program Assistant (from September 2023) LORI BENJAMIN BRENIG, Research Associate (until May 2023) TORRIE BROWN, Program Coordinator CHIDINMA CHUKWURAH, Senior Program Assistant THO NGUYEN, Senior Program Officer, Computer Science and Telecommunications Board DANIEL TALMAGE, Program Officer, Board on Human-System Integration EMMA WICKLAND, Research Associate (from September 2023) JULIE WILTSHIRE, Senior Finance Business Partner JENNIFER ZHU, Associate Program Officer (from January 2023) ERIN BALOGH, Co-Director, National Cancer Policy Forum SHARYL J. NASS, Co-Director, National Cancer Policy Forum; Senior Director, Board on Health Care Services 1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing s­ peakers. The responsibility for the published Proceedings of a Workshop rests with the workshop ­rapporteurs and the institution. v PREPUBLICATION COPY—Uncorrected Proofs 

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NATIONAL CANCER POLICY FORUM1 ROBERT A. WINN (Chair), Virginia Commonwealth University PETER C. ADAMSON, Sanofi JUSTIN E. BEKELMAN, University of Pennsylvania SMITA BHATIA, The University of Alabama at Birmingham GIDEON BLUMENTHAL, Merck CHRIS BOSHOFF, Pfizer Inc. OTIS W. BRAWLEY, Johns Hopkins University CHRISTINA CHAPMAN, Baylor College of Medicine; Michael E. DeBakey VA Medical Center GWEN DARIEN, National Patient Advocate Foundation CRYSTAL DENLINGER, National Comprehensive Cancer Network JAMES H. DOROSHOW, National Cancer Institute S. GAIL ECKHARDT, Baylor College of Medicine CHRISTOPHER R. FRIESE, University of Michigan STANTON L. GERSON, Case Western Reserve University SCARLETT LIN GOMEZ, University of California, San Francisco JULIE R. GRALOW, American Society of Clinical Oncology ROY S. HERBST, Yale University; American Association for Cancer Research HEDVIG HRICAK, Memorial Sloan Kettering Cancer Center CHANITA HUGHES-HALBERT, University of Southern California ROY A. JENSEN, University of Kansas; Association of American Cancer Institutes RANDY A. JONES, University of Virginia BETH Y. KARLAN, University of California, Los Angeles SAMIR N. KHLEIF, Georgetown University; Society for Immunotherapy of Cancer SCOTT M. LIPPMAN, University of California, San Diego ELENA MARTINEZ, University of California, San Diego LARISSA NEKHLYUDOV, Brigham and Women’s Hospital; Dana- Farber Cancer Institute; Harvard Medical School 1 The National Academies of Sciences, Engineering, and Medicine’s forums and round- tables 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. vii PREPUBLICATION COPY—Uncorrected Proofs 

RANDALL A. OYER, University of Pennsylvania; Penn Medicine Lancaster General Health; Association of Community Cancer Centers CLEO A. RYALS, Flatiron Health RICHARD L. SCHILSKY, ASCO TAPUR Study; University of Chicago JULIE SCHNEIDER, Oncology Center of Excellence, U.S. Food and Drug Administration SUSAN M. SCHNEIDER, Duke University LAWRENCE N. SHULMAN, University of Pennsylvania HEIDI SMITH, Novartis Pharmaceuticals KATRINA TRIVERS, Centers for Disease Control and Prevention ROBIN YABROFF, American Cancer Society National Cancer Policy Forum Staff ANNA ADLER, Senior Program Assistant TORRIE BROWN, Program Coordinator CHIDINMA CHUKWURAH, Senior Program Assistant JULIE WILTSHIRE, Senior Finance Business Partner EMMA WICKLAND, Research Associate JENNIFER ZHU, Associate Program Officer ERIN BALOGH, Co-Director, National Cancer Policy Forum SHARYL J. NASS, Co-Director, National Cancer Policy Forum; Senior Director, Board on Health Care Services viii PREPUBLICATION COPY—Uncorrected Proofs 

Reviewers This Proceedings of a Workshop was 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 National Academies of Sciences, Engineering, and Medicine in ­making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and respon- siveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process. We thank the following individuals for their review of this proceedings: JOCHEN K. LENNERZ, BostonGene MY T. THAI, University of Florida MARY M. ZUTTER, Vanderbilt University Medical Center Although the reviewers listed above provided many constructive com- ments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by MICHELLE LE BEAU, Cancer Prevention and Research Institute of Texas. She was responsible for making certain that an independent examination of this proceedings was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies. ix PREPUBLICATION COPY—Uncorrected Proofs 

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Acknowledgments The National Cancer Policy Forum is grateful for the support of our many annual sponsors. Federal sponsors include the Centers for Disease Control and Prevention and the National Cancer Institute/National Institutes of Health. Nonfederal sponsors include the American Association for Cancer Research; American Cancer Society; American College of Radiology; American Society of Clinical Oncology; Association of American Cancer Institutes; Associa- tion of Community Cancer Centers; Bristol Myers Squibb; Cancer Support Community; Flatiron Health; Merck & Co., Inc.; National Comprehensive Cancer Network; National Patient Advocate Foundation; Novartis Oncology; Oncology Nursing Society; Partners in Health; Pfizer Inc.; Sanofi; and Society for Immunotherapy of Cancer. The forum wishes to express its gratitude to the expert speakers whose presentations and discussions helped inform efforts to advance progress in the development and use of integrated diagnostics for precision oncology care. The forum also wishes to thank the members of the planning committee for their work in developing an excellent workshop agenda. xi PREPUBLICATION COPY—Uncorrected Proofs 

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Contents ACRONYMS AND ABBREVIATIONS xix PROCEEDINGS OF A WORKSHOP 1 WORKSHOP OVERVIEW 1 OVERVIEW OF THE CURRENT STATUS OF AND VISION FOR INTEGRATED DIAGNOSTICS 2 An Evolving Integrated Data Science Approach to Personalized Oncology Care, 2 An Expanding Role for AI, 10 Implementation Challenges, 11 Efforts to Improve Interoperability, 12 EFFORTS TO DEVELOP, IMPLEMENT, AND USE INTEGRATED DIAGNOSTICS 16 Perspectives from Academic Medical Centers, 16 Perspectives from Industry, 23 Perspectives from Large Health Care Organizations, 28 IMPROVING EVIDENCE GENERATION FOR INTEGRATED DIAGNOSTICS 31 A Cancer Risk Management Learning System for Evidence Generation, 32 xiii PREPUBLICATION COPY—Uncorrected Proofs 

xiv CONTENTS Building the Evidence Generation Infrastructure to Scale Precision Diagnostics, 35 Opportunities to Leverage EHRs for Clinical Evidence Generation, 36 Lessons from AACR Project GENIE to Inform Evidence Generation, 40 The Role of Equitable Access in the Diversity of Registry Data, 43 DESIGN AND USE OF INTEGRATED DIAGNOSTICS 43 Ethical AI by Design, 43 A Diagnostic Management Team Approach to Reducing Diagnostic Errors, 45 Multimodal Data Integration for Research and Clinical Practice, 46 Implementing Integrated Diagnostics into Precision Oncology Care, 47 Trust and Acceptance of AI in Clinical Settings, 50 Risk Communication and Decision Support, 52 Reproducibility of ML Models for Integrated Diagnostics, 54 Overcoming Design and Use Challenges, 55 REGULATORY OVERSIGHT AND INSURANCE COVERAGE OF INTEGRATED DIAGNOSTICS 56 Pathways for Regulatory Review of Integrated Diagnostics, 56 Coverage Considerations for Integrated Diagnostics, 60 ENSURING PATIENT ACCESS AND PROMOTING HEALTH EQUITY 62 Developing Equitable AI Algorithms, 52 Integrated Diagnostics in Community-Based Settings of Care, 64 Promoting Health Equity Through Patient Access to Integrated Diagnostics, 67 Understanding and Addressing Disparities in Access and Use, 69 CURRENT FEDERAL INITIATIVES IN PRECISION CANCER CARE 70 NCI Precision Medicine Cancer Trials, 70 ARPA-H and Cancer Moonshot, 72 Promoting a Culture of Data Sharing, 75 REFLECTING ON THE WORKSHOP DISCUSSIONS 76 Envisioning the Future for Integrated Diagnostics, 76 Highlighting Insights from Academia, Industry, and Health Care Organizations, 76 PREPUBLICATION COPY—Uncorrected Proofs 

CONTENTS xv Improving Evidence Generation, 77 Enhancing Design and Use of Integrated Diagnostics, 77 Regulatory Oversight and Insurance Coverage, 78 Access and Equity, 79 REFERENCES 80 APPENDIX A Statement of Task 89 APPENDIX B Workshop Agenda 91 PREPUBLICATION COPY—Uncorrected Proofs 

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Boxes, Figures, and Table BOXES 1 Observations on the Development and Use of Integrated Diagnostics in Cancer Care: Highlights of Points Made by Individual Workshop Participants, 3 2 Opportunities to Advance the Development, Implementation, and Use of Integrated Diagnostics in Precision Cancer Care: Highlights of Points Made by Individual Workshop Participants, 6 3 FDA Risk Classification–Based Approval Pathways, 57 4 Overview of the NCI-MATCH Precision Cancer Medicine Trial, 71 5 Overview of ARPA-H, 73 FIGURES 1 Integrated data science approach to personalized treatment, 9 2 Examples of where patient data is generated across the health grid, 26 3 Reference implementation for a breast cancer risk management learning system, 33 4 Integrated real-world evidence generation platform, 39 TABLE 1 Settings of Cancer Care in the United States, 65 xvii PREPUBLICATION COPY—Uncorrected Proofs 

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Acronyms and Abbreviations AACR American Association for Cancer Research AI artificial intelligence ARPA-H Advanced Research Project Agency for Health CDRH Center for Devices and Radiological Health CID Center for Integrated Diagnostics CMS Centers for Medicare & Medicaid Services COVID-19 coronavirus disease 2019 CPT Current Procedural Terminology CT computed tomography DMT diagnostic management team EHR electronic health record FDA U.S. Food and Drug Administration 18F-FDG 18F-Fluorodeoxyglucose FHIR Fast Healthcare Interoperability Resources GENIE Genomics Evidence Neoplasia Information Exchange HIPAA Health Insurance Portability and Accountability Act of 1996 xix PREPUBLICATION COPY—Uncorrected Proofs 

xx ACRONYMS AND ABBREVIATIONS ICR Institute for Cancer Research, London IRB institutional review board IVD in vitro diagnostic MC Medical Center mCODE minimal Common Oncology Data Elements ML machine learning MRI magnetic resonance imaging MSK Memorial Sloan Kettering Cancer Center MSK-IMPACT MSK-Integrated Mutation Profiling of Actionable Cancer Targets NAII National Artificial Intelligence Institute NCATS National Center for Advancing Translational Sciences NCI National Cancer Institute NCORP NCI Community Oncology Research Program NIH National Institutes of Health NSF National Science Foundation OHDSI Observational Health Data Sciences and Informatics OHSU Oregon Health & Science University Penn University of Pennsylvania PET positron emission tomography PFS progression free survival PRISSMM pathology, radiology, imaging, signs and symptoms, tumor markers, oncology medical provider assessment RECIST Response Evaluation Criteria in Solid Tumors SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 UC University of California UCH University of California Health UTMB University of Texas Medical Branch VA U.S. Department of Veterans Affairs PREPUBLICATION COPY—Uncorrected Proofs