Accelerating the
Development and
Uptake of Rapid
Diagnostics to Address
Antibiotic Resistance
Erin Hammers Forstag and
Carolyn Shore, Rapporteurs
Forum on Drug Discovery,
Development, and Translation
Forum on Medical and
Public Health Preparedness for
Disasters and Emergencies
Forum on Microbial Threats
Board on Global Health
Board on Health Sciences Policy
Health and Medicine Division
Proceedings of a Workshop
NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by contracts between the National Academy of Sciences and Administration for Children and Families (Contract No. HHSP233201400020B; Task Order No. 75P00120F37103); American Burn Association; American College of Emergency Physicians; American College of Surgeons-Committee on Trauma; American Hospital Association; American Red Cross; American Society of Tropical Medicine and Hygiene; Amgen Inc.; Association of American Medical Colleges; Association of Public Health Laboratories; Association of State and Territorial Health Officials; AstraZeneca; Biogen; Burroughs Wellcome Fund (Contract No. 1023129, 1022390); Centers for Disease Control and Prevention (Contract No. 75D30121F00095, 75D30121D11240; Task Order No. 75D30121F00001): National Center for Emerging Zoonotic Infectious Diseases; Council of State and Territorial Epidemiologists; Critical Path Institute; East West Protection LLC; EcoHealthAlliance; Eli Lilly and Company; Emergency Nurses Association; ExxonMobil Foundation; FasterCures, Milken Institute; Foundation for the National Institutes of Health; Friends of Cancer Research; Healthcare Ready; Infectious Diseases Society of America; Johnson & Johnson (Contract No. C2022024120); Medable; Merck & Co., Inc. (Contract No. APA-21-151620; Grant No. MEM-22-160471); National Association of Chain Drug Stores; National Association of County and City Health Officials; National Association of Emergency Medical Technicians; National Fire Protection Association; National Highway Traffic Safety Administration (Contract No. 693JJ922P000037); National Institutes of Health (Contract No. HHSN263201800029I; Task Order No. HHSN26300007, HHSN26300011, HHSN26300026): National Cancer Institute, National Center for Advancing Translational Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, Office of the Director; New England Journal of Medicine; New Venture Fund (Contract No. NVF-NGDF-NAT10-Subgrant-017387-2022-04-01); Office of the Assistant Secretary for Preparedness and Response (Contract No. 75A50121P00089); Sanofi (Contract No. 70602577); Takeda; The MITRE Corporation; The Rockefeller Foundation; Trauma Center Association of America; Uniformed Services University of Health Sciences (Award No. HU00012210001); U.S. Agency for International Development (Grant No. 7200AA18GR00003); U.S. Department of Defense; U.S. Department of Homeland Security (Contract No. HSHQDC-17-A-B0001; Task Order No. 70RWMD21F00000031); U.S. Department of Veterans Affairs (Contract No. 36C25022C0273); U.S. Food and Drug Administration (Contract No. 1R13FD007302-01, 75F40120P00; Award No. 5R13FD006897-03). 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: 978-0-309-70240-9
International Standard Book Number-10: 0-309-70240-2
Digital Object Identifier: https://doi.org/10.17226/27008
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2023. Accelerating development and uptake of rapid diagnostics to address antibiotic resistance: Proceesings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/27008.
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PLANNING COMMITTEE ON ACCELERATING THE DEVELOPMENT AND UPTAKE OF RAPID DIAGNOSTICS TO ADDRESS ANTIBIOTIC RESISTANCE1
KENT E. KESTER (Co-chair), Vice President, Translational Medicine, International AIDS Vaccine Initiative
BETSY WONDERLY TRAINOR (Co-chair), Alliance Director, Diagnostics, CARB-X
JOHN BILLINGTON, Head of Commercial Pipeline and Health Security Policy and Advocacy, GSK
CAREY-ANN BURNHAM, Chief Clinical Officer, Pattern Bioscience
PAUL EDER, Senior Scientific Officer, National Institute of Allergy and Infectious Diseases, NIH
DEBORAH HUNG, Associate Professor and Core Faculty Member, Harvard Medical School
AMANDA JEZEK, Senior Vice President of Public Policy and Government Relations, Infectious Diseases Society of America
ROBIN PATEL, Elizabeth P and Robert E Allen Professor of Individualized Medicine, Division of Clinical Microbiology, Mayo Clinic
RIBHI SHAWAR, Assistant Director, Division of Microbiology Devices, Center for Devices and Radiological Health, Food and Drug Administration
SUSAN VAN METER, President, American Clinical Laboratory Association
Health and Medicine Division Staff
JULIE LIAO, Forum Director
CAROLYN K. SHORE, Forum Director
LISA BROWN, Senior Program Officer
SCOTT WOLLEK, Senior Program Officer
BIANCA ESPINOSA, Associate Program Officer (from July 2022)
DEANNA GIRALDI, Associate Program Officer (until September 2022)
CLAIRE BIFFL, Research Associate
ASHLEY BOLOGNA, Senior Program Assistant (from July 2022)
MELVIN JOPPY, Senior Program Assistant
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy (until June 2022)
___________________
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.
CLARE STROUD, Senior Director, Board on Health Sciences Policy (from June 2022)
Consultant
ERIN HAMMERS FORSTAG, Science Writer
FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION1
GREGORY SIMON (Cochair), Kaiser Permanente Washington Health Research Institute and University of Washington
ANN TAYLOR (Cochair), Retired
CHRISTOPHER P. AUSTIN, Flagship Pioneering
LINDA BRADY, National Institute of Mental Health, NIH
JOHN BUSE, University of North Carolina, Chapel Hill School of Medicine
LUTHER T. CLARK, Merck & Co., Inc.
BARRY S. COLLER, The Rockefeller University
TAMMY R.L. COLLINS, Burroughs Wellcome Fund
THOMAS CURRAN, Children’s Mercy, Kansas City
RICHARD DAVEY, National Institute of Allergy and Infectious Diseases, NIH
KATHERINE DAWSON, Biogen
JAMES H. DOROSHOW, National Cancer Institute, NIH
JEFFREY M. DRAZEN, New England Journal of Medicine
STEVEN K. GALSON, Retired
CARLOS O. GARNER, Eli Lilly and Company
DEBORAH HUNG, Harvard Medical School
LYRIC JORGENSON, Office of Science Policy, NIH
ESTHER KROFAH, FasterCures, Milken Institute
LISA M. LaVANGE, University of North Carolina
ARAN MAREE, Johnson & Johnson
CRISTIAN MASSACESI, AstraZeneca
ROSS McKINNEY JR., Association of American Medical Colleges
JOSEPH P. MENETSKI, Foundation for the National Institutes of Health
ANAEZE C. OFFODILE II, University of Texas MD Anderson Cancer Center
SALLY OKUN, Clinical Trials Transformation Initiative
ARTI RAI, Duke University School of Law
MARK ROGGE, University of Florida
KLAUS ROMERO, Critical Path Institute
JONI RUTTER, National Center for Advancing Translational Sciences, NIH
SUSAN SCHAEFFER, Patients’ Academy for Research Advocacy
JOSEPH SCHEEREN, Retired
ANANTHA SHEKHAR, University of Pittsburgh
___________________
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.
JAY SIEGEL, Retired
ELLEN V. SIGAL, Friends of Cancer Research
MARK TAISEY, Amgen Inc.
AMIR TAMIZ, National Institute of Neurological Disorders and Stroke, NIH
PAMELA TENAERTS, Medable
MAJID VAKILYNEJAD, Takeda
JONATHAN WATANABE, University of California Irvine School of Pharmacy and Pharmaceutical Sciences
ALASTAIR WOOD, Vanderbilt University
CRIS WOOLSTON, Sanofi
Forum Staff
CAROLYN K. SHORE, Forum Director
BIANCA ESPINOSA, Associate Program Officer (from July 2022)
DEANNA GIRALDI, Associate Program Officer (until September 2022)
ANDREW MARCH, Associate Program Officer
ASHLEY BOLOGNA, Senior Program Assistant (from July 2022)
MELVIN JOPPY, Senior Program Assistant
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy (until June 2022)
CLARE STROUD, Senior Director, Board on Health Sciences Policy (from June 2022)
FORUM ON MEDICAL AND PUBLIC HEALTH PREPAREDNESS FOR DISASTERS AND EMERGENCIES1
SUZET MCKINNEY (Co-Chair), Sterling Bay
CRAIG VANDERWAGEN (Co-Chair), East West Protection, LLC
JOANNE ANDREADIS, Centers for Disease Control and Prevention
TOM COTTER, Healthcare Ready
BROOKE COURTNEY, U.S. Food and Drug Administration
CINNAMON DIXON, National Institute of Environmental Health Sciences
DAVID EISENMAN, University of California, Los Angeles
CARINA ELSENBOSS, National Association of County and City Health Officials
BRUCE EVANS, National Association of Emergency Medical Technicians
DAVID FERRARO, Society for Critical Care Medicine
PRITESH GANDHI, U.S. Department of Homeland Security
ASHA GEORGE, Bipartisan Commission on Biodefense
NATALIE GRANT, Administration for Children and Families
JANET HAMILTON, Council of State and Territorial Epidemiologists
DAN HANFLING, In-Q-Tel
DAVID (CHRIS) HASSELL, Administration for Strategic Preparedness and Response
JOHN HICK, Hennepin County Medical Center
THOMAS KIRSCH, Uniformed Services University of the Health Sciences
RICHARD KWOK, National Institute of Environmental Health Sciences
JAMES LAWLER, University of Nebraska Medical Center
NICOLETTE LOUISSAINT, Healthcare Distribution Alliance
FREDA LYON, Emergency Nurses Association
MONIQUE MANSOURA, The MITRE Corporation
BIRGITTE MESSERSCHMIDT, National Fire Protection Association
AUBREY MILLER, National Institute of Environmental Health Sciences
BARBARA MULACH, National Institute of Allergy and Infectious Diseases
IRA NEMETH, American College of Emergency Physicians
JOHN OSBORN, Mayo Clinic College of Medicine
TARA O’TOOLE, In-Q-Tel
ANDREW PAVIA, Infectious Diseases Society of America
LEWIS RADONOVICH, National Institute for Occupational Safety and Health
___________________
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.
TERRY RAUCH, U.S. Department of Defense
SARA ROSZAK, National Association of Chain Drug Stores
COLLEEN RYAN, American Burn Association
ROSLYNE SCHULMAN, American Hospital Association
RICHARD SERINO, Harvard T.H. Chan School of Public Health
SCOTT SHONE, Association of Public Health Laboratories
BRANNON TRAXLER, Association of State and Territorial Health Officials
TENER VEENEMA, Johns Hopkins Bloomberg School of Public Health
JENNIFER WARD, Trauma Center Association of America
GAMUNU WIJETUNGE, Department of Transportation
MATTHEW WYNIA, University of Colorado, Denver
DAVID ZONIES, Committee on Trauma—American College of Surgeons
Forum Staff
LISA BROWN, Senior Program Officer
SCOTT WOLLEK, Senior Program Officer
SHALINI SINGARAVELU, Program Officer
MICHAEL BERRIOS, Research Associate
CLARE STROUD, Senior Director, Board on Health Sciences Policy
FORUM ON MICROBIAL THREATS1
PETER DASZAK (Chair), EcoHealth Alliance
KENT E. KESTER (Vice Chair), International AIDS Vaccine Initiative
EMILY ABRAHAM, Johnson & Johnson
KEVIN ANDERSON, Retired
DANIEL BAUSCH, American Society of Tropical Medicine and Hygiene
CHRISTOPHER BRADEN, Centers for Disease Control and Prevention
CRISTINA CASSETTI, National Institute of Allergy and Infectious Diseases, NIH
ANDREW CLEMENTS, U.S. Agency for International Development
MALICK DIARA, ExxonMobil
SCOTT F. DOWELL, Bill & Melinda Gates Foundation
MARCOS A. ESPINAL, Pan American Health Organization
EVA HARRIS, University of California, Berkeley
JON H. HEINRICHS, Sanofi
ELIZABETH D. HERMSEN, Pfizer Inc.
MARK G. KORTEPETER, Uniformed Services University of the Health Sciences
MICHAEL MAIR, U.S. Food and Drug Administration
JONNA MAZET, University of California, Davis
VICTORIA McGOVERN, Burroughs Wellcome Fund
SALLY A. MILLER, The Ohio State University
SUERIE MOON, The Graduate Institute of International and Development Studies, Geneva
RAFAEL OBREGON, United Nations Children’s Fund
KUMANAN RASANATHAN, World Health Organization
GARY A. ROSELLE, U.S. Department of Veterans Affairs
PETER A. SANDS, The Global Fund to Fights AIDS, Tuberculosis, and Malaria
THOMAS W. SCOTT, University of California, Davis
MATTHEW ZAHN, Orange Country Health Care Agency
Forum Staff
JULIE LIAO, Forum Director
LIZ ASHBY, Associate Program Officer
CLAIRE BIFFL, Research Associate
JUSTIN HAMMERBERG, Senior Program Assistant (until November 2022)
___________________
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.
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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 responsiveness 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:
CAROLE ANN BEWLEY, National Institute of Diabetes and Digestive Kidney Diseases, NIH
BRIAN RAUX, bioMérieux
ANTHONY SO, Johns Hopkins Bloomberg School of Public Health
Although the reviewers listed above provided many constructive comments 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 JIM E. RIVIERE, North Carolina State University. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with 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.
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Acknowledgments
Support from the sponsors of the Forum on Drug Discovery, Development, and Translation, the Forum on Medical and Public Health Preparedness for Disasters and Emergencies, and the Forum on Microbial Threats is crucial to support this and other work of the National Academies.
The National Academies’ staff wish to express their gratitude to the speakers whose presentations helped inform workshop discussions; to the members of the planning committee for their work in developing the workshop agenda and shaping the discussions; and to additional National Academies staff, without whom this workshop and the accounting thereof would not have been possible: Christie Bell, Samantha Chao, Robert Day, Rebekah Hanover Pettit, Benjamin Hubbert, Noah Ontjes, Devona Overton, Marguerite Romatelli, Bettina Seliber, Lauren Shern, Elizabeth Webber, and Taryn Young.
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Contents
2 EXPLORING THE NEED FOR RAPID DIAGNOSTICS
3 LESSONS LEARNED FROM THE COVID-19 PANDEMIC
Lessons Learned from the COVID-19 Pandemic
Programs to Accelerate the Development of Diagnostics
4 INCENTIVES AT THE INTERSECTION OF DRUG DEVELOPMENT AND COMPLEMENTARY DIAGNOSTICS
Boxes, Figures, and Tables
BOXES
7-2 Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria
FIGURES
2-1 Criteria for point-of-care testing
3-2 COVID-19 tests conducted per 1000 individuals per day
4-1 Clinical trial with diagnostic screening
5-1 Comparison of lives saved by a new diagnostic for bacterial pneumonia
TABLES
2-1 Challenges to the Use of mNGS and Potential Solutions
2-2 Examples of Microfluidics-Based Tests Developed for SARS-CoV-2
2-3 Pugh Matrix of AST and AMR Testing Approaches
6-1 Observational Studies: Rapid Blood Culture Diagnostic and Outcomes
6-2 Randomized Controlled Trials: Rapid Blood Culture Diagnostic and Outcomes
Acronyms and Abbreviations
| ABC | Acinetobacter calcoaceticus-baumannii complex |
| AI | artificial intelligence |
| AMR | antimicrobial resistance |
| ASSURED | affordable, sensitive, specific, user-friendly, rapid, equipment-free, and deliverable |
| AST | antimicrobial susceptibility testing |
| ATTACK | Acinetobacter Treatment Trial Against Colistin |
| BAA | Broad Agency Announcement |
| BARDA | Biomedical Advanced Research and Development Authority |
| BCID | Blood Culture Identification |
| BEI | Biological Exposure Indices |
| BIO | Biotechnology Innovation Organization |
| BPP | BIOFIRE® Pneumonia Panel |
| CAP | Concept Acceleration Program |
| CARB-X | Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator |
| CDC | Centers for Disease Control and Prevention |
| C. diff | Clostridioides difficile |
| CFUs | colony-forming units |
| CLFS | Clinical Laboratory Fee Schedule |
| CLIA | Clinical Laboratory Improvement Amendments |
| CLSI | Clinical and Laboratory Standards Institute |
| CMS | Centers for Medicare & Medicaid Services |
| COVID-19 | coronavirus disease 2019 |
| CPT | Current Procedural Terminology |
| CRE | carbapenem-resistant Enterobacterales |
| DARPA | Defense Advanced Research Projects Agency |
| DNA | deoxyribonucleic acid |
| DRG | Diagnosis Related Group |
| E. Coli | Escherichia coli |
| ED | emergency department |
| ESBL | extended spectrum beta-lactamase |
| EU | European Union |
| EUA | Emergency Use Authorization |
| EUCAST | European Committee on Antimicrobial Susceptibility Testing |
| FDA | U. S. Food and Drug Administration |
| HHS | Health and Human Services |
| IDEA | Innovation + Design Enabling Access |
| IDSA | Infectious Diseases Society of America |
| IRB | institutional review board |
| IRS | Internal Revenue Service |
| ITAP | Independent Test Assessment Program |
| IV | intravenous |
| LDTs | laboratory developed tests |
| LMIC | low- and middle-income countries |
| MALDI-TOF | MSMatrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry |
| MAAP | Mapping Antimicrobial Resistance and Antimicrobial Use Partnership |
| MDR | multidrug resistant |
| MIPS | Merit-Based Incentive Payment System |
| mNGS | metagenomic next generation sequencing |
| MRSA | methicillin-resistant Staphylococcus aureus |
| MSF | Médecins Sans Frontières/Doctors Without Borders |
| MTB | Mycobacterium tuberculosis |
| NG | Neisseria gonorrhoeae |
| NGS | next generation sequencing |
| NIAID | National Institute of Allergy and Infectious Diseases |
| NIH | National Institutes of Health (U.S.) |
| NLA | National Limitation Amounts |
| NTAP | new technology add-on payment |
| NWSS | National Wastewater Surveillance System |
| OECD | Organization for Economic Cooperation and Development |
| PACCARB | Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria |
| PCR | polymerase chain reaction |
| PCS | Pre-Clinical Services |
| POC | point-of-care |
| RADx | Rapid Acceleration of Diagnostics |
| R&D | research and development |
| RAPIDS GN | Randomized Trial Evaluating Clinical Impact of Rapid Identification and Susceptibility Testing for Gram-negative Bacteremia |
| RCT | randomized controlled trial |
| REASSURED | real-time connectivity, ease of specimen, affordable, sensitive, specific, user-friendly, rapid, equipment-free, and deliverable |
| RIF | rifampin |
| RSV | respiratory syncytial virus |
| SALSA | Saving Access to Laboratory Services Act |
| SARS-CoV-2 | severe acute respiratory syndrome coronavirus 2 |
| STIs | sexually transmitted infections |
| SUL-DUR | sulbactam-durlobactam |
| UTI | urinary tract infection |
| VA | Department of Veterans Affairs |
| VRE | Vancomycin-resistant enterococci |
| WHO | World Health Organization |
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