Accelerating Diagnostics in a Time of Crisis The Response to

COVID 19 and a Roadmap for Future Pandemics

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Published online by Cambridge University Press
 Accelerating
Diagnostics in a Time
of Crisis
The Response to the COVID-19 Pandemic
and a Roadmap for Future Pandemics
Edited by
Steven C. Schachter
®
Rapid Acceleration of Diagnostics (RADx ) Chief, CIMIT

Wade E. Bolton
RADx–VentureWell

Published online by Cambridge University Press

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Information on this title: www.cambridge.org/9781009396981
DOI: 10.1017/9781009396998
© Cambridge University Press & Assessment 2024
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First published 2024
A catalogue record for this publication is available from the British Library.
Library of Congress Cataloging-in-Publication Data
Names: Schachter, Steven C., editor. | Bolton, Wade E., 1947– editor.
Title: Accelerating diagnostics in a time of crisis : the response to COVID-19 and a roadmap for future pandemics /
edited by Steven C. Schachter, Wade E. Bolton.
Description: Cambridge, United Kingdom ; New York, NY : Cambridge University Press, 2023. | Includes
bibliographical references and index.
Identifiers: LCCN 2023023826 (print) | LCCN 2023023827 (ebook) | ISBN 9781009396981 (paperback) | ISBN
9781009396998 (ebook)
Subjects: MESH: COVID-19 – diagnosis | Pandemics | Emergencies | Rapid Diagnostic Tests | Process Assessment,
Health Care | United States
Classification: LCC RA644.C67 (print) | LCC RA644.C67 (ebook) | NLM WC 506.1 | DDC 616.2/4144–dc23/eng/
20230828
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Every effort has been made in preparing this book to provide accurate and up-to-date information that is in
accord with accepted standards and practice at the time of publication. Although case histories are drawn
from actual cases, every effort has been made to disguise the identities of the individuals involved.
Nevertheless, the authors, editors, and publishers can make no warranties that the information contained
herein is totally free from error, not least because clinical standards are constantly changing through
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that they plan to use.

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 Dedicated to Lindley Hall for his mentorship, John Parrish for his pioneering work to
accelerate health-care solutions and to Wallace and Joe Coulter and their spirit of Science
Serving Humanity.
This work was supported by the National Institute of Biomedical Imaging and
Bioengineering under Grant 5U54EB015408-06. The views expressed in this manuscript
are those of the authors and do not necessarily represent the views of the National Institute
of Biomedical Imaging and Bioengineering; the National Heart, Lung, and Blood Institute;
the National Institutes of Health; or the US Department of Health and Human Services.
The editors and chapter authors are thankful for the visionary leadership of Francis
Collins, Bruce Tromberg, Jill Heemskerk, Tiffani Lash, and Todd Merchak in guiding the
development and implementation of the Rapid Acceleration of Diagnostics (RADx®) Tech
program and facilitating the close collaboration of crucially essential government agencies
and nongovernmental organizations in this effort.

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Published online by Cambridge University Press
 Contents
List of Contributors ix
Foreword xiii
Harvey V. Fineberg
Preface xv
Wade E. Bolton
Acknowledgments xvii

Introduction 1 Dolphin, Emily Muth, Jose Valdesuso,

Tania Fernandez and Brian Walsh
1 Early Detection, Response, 6 Quality and Risk Management
and Surveillance of the COVID-19 Processes for Diagnostic Assays
Pandemic Crisis 6 during an Emergency Pandemic
Enrique M. Rabellino, Alexandra Response 103
Smith, and Marta C. Cohen Devon C. Campbell and Christie Johnson

2 Immunology of COVID-19 7 Development of Assays to Diagnose

and Ineffective Immunity 31 COVID-19 125
Adolfo Firpo-Betancourt and Enrique Yukari C. Manabe and William Clarke
M. Rabellino 8 Laboratory Verification and Clinical
3 Clinical Management: A Roadmap Validation of COVID-19 Diagnostic
Based on One New York City Assays 143
Hospital’s Response to the COVID-19 Anuradha Rao, Leda Bassit, Julie
Pandemic 50 Sullivan, Wilbur Lam, and Jennifer
Barbara Barnett, Yvette Calderon, K. Frediani
Bethany Kranitzky, Young Im Lee, Erick 9 Importance of Timely Sequencing,
Eiting, Lina Miyakawa, Waleed Javaid, Tracking, and Surveillance
and Saralynne Brown of Emergent Variants 166
4 Contribution of RADx® Tech Jessica Lin, Morgan Greenleaf, Yang
to the Rapid Development Lu, Leda Bassit, Cassandra Wesselman,
of COVID-19 Diagnostic Tests 74 and Anne Piantadosi
Steven C. Schachter, John M. Collins, 10 The RADx® Regulatory Core
Michael K. Dempsey, Laura L. and Its Role in COVID-19 Emergency
Gibson, Matthew L. Robinson, and Use Authorizations 194
Paul Tessier Erika Tyburski and Cathryn Cambria
5 Coordination of Resources for the 11 Commercialization and Market
Manufacturing and Deployment of Assessment of COVID-19 Assays 211
COVID-19 Diagnostic Assays 88 Manuel Kingsley, Sunshine Moore,
Maren Downing, Mia Cirrincione, Heath Naquin, Eliseo Velasquez, Emily
Adam Samuta, Kevin Leite, Sam Kennedy, and Grace Bendinger
vii

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 viii Contents

12 Testing Strategies to Mitigate 14 Summary and Path Forward

COVID-19 Disease Spread 236 for Future Pandemics 263
Paul Tessier and Anette Wade E. Bolton and Steven
E. Hosoi C. Schachter
13 A Pandemic Not Just of Infection
but of Inequality: The Social
Impact of COVID-19 250
Mara Aspinall and Liz Ruark Index 274

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 Contributors

Mara Aspinall Marta C. Cohen

Health Catalysts, Tucson, AZ, USA Sheffield Children’s Hospital, Sheffield, UK

Barbara Barnett John M. Collins

Mount Sinai Health System, New York, CIMIT, Boston, MA, USA
NY, USA
Michael K. Dempsey
Leda Bassit CIMIT, Boston, MA, USA
Emory University, Atlanta, GA, USA Massachusetts Institute of Technology,
Cambridge, MA, USA
Grace Bendinger
Rapid Acceleration of Diagnostics Sam Dolphin
(RADx®)–VentureWell, Hadley, RADx–VentureWell, Hadley, MA, USA
MA, USA Frindle Health, Newnan,
GA, USA Maren Downing
RADx–VentureWell, Hadley, MA, USA
Wade E. Bolton
RADx–VentureWell, Hadley, MA, USA Erick Eiting
Bolton Consulting & Services, Delray Mount Sinai Health System, New York,
Beach, FL, USA NY, USA

Saralynne Brown Tania Fernandez

Mount Sinai Health System, New York, DreamCatcher Ventures, San Francisco,
NY, USA CA, USA
RADx-VentureWell, Hadley, MA, USA
Yvette Calderon
Mount Sinai Health System, New York, Harvey V. Fineburg
NY, USA Gordon & Betty Moore Foundation, Palo
Alto, CA, USA
Cathryn Cambria
Cambria Regulatory Consulting, Atlanta, Adolfo Firpo-Betancourt
GA, USA Mount Sinai Health System, New York,
NY, USA
Devon C. Campbell
Prodct, Boston, MA, USA Jennifer K. Frediani
Emory University, Atlanta, GA, USA
Mia Cirrincione
RADx–VentureWell, Hadley, Laura L. Gibson
MA, USA University of Massachusetts Medical
School, Worcester, MA, USA
William Clarke
Johns Hopkins University School of Morgan Greenleaf
Medicine, Baltimore, MD, USA Emory University, Atlanta, GA, USA
ix

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 x List of Contributors

Anette E. Hosoi Lina Miyakawa

Massachusetts Institute of Technology, Mount Sinai Health System, New York,
Boston, MA, USA NY, USA

Waleed Javaid Sunshine Moore

Mount Sinai Health System, New York, Sunshine Moore Consulting, Madison, WI,
NY, USA USA
RADx–VentureWell, Hadley, MA, USA
Christie Johnson
Prodct, Boston, MA, USA Emily Muth
RADx–VentureWell, Hadley, MA, USA
Emily Kennedy
RADx–VentureWell, Hadley, MA, USA Heath Naquin
University City Science Center,
Manuel Kingsley Philadelphia, PA, USA
Questus Healthcare, Atlanta, GA, USA RADx–VentureWell, Hadley, MA, USA
RADx–VentureWell, Hadley, MA, USA
Anne Piantadosi
Bethany Kranitzky Emory University, Atlanta, GA, USA
The Ohio State University Wexner
Medical Center, Columbus, Enrique M. Rabellino
OH, USA MedScience Services, Miami, FL, USA

Wilbur Lam Anuradha Rao

Emory University, Atlanta, GA, USA Emory University, Atlanta, GA, USA

Young Im Lee Matthew L. Robinson

Mount Sinai Health System, New York, Johns Hopkins University School of
NY, USA Medicine, Baltimore, MD, USA

Kevin Leite Liz Ruark

RADx–VentureWell, Hadley, MA, USA covidsafeschools.org, Boston, MA, USA

Jessica Lin Adam Samuta

Georgia Institute of Technology, Atlanta, RADx–VentureWell, Hadley, MA, USA
GA, USA
Steven C. Schachter
Yang Lu Harvard Medical School, Boston, MA, USA
Icahn School of Medicine at Mount Sinai, CIMIT, Boston, MA, USA
New York, NY, USA
Alexandra Smith
Yukari C. Manabe RADx–VentureWell, Hadley, MA, USA
Johns Hopkins University School University of South Carolina School of
of Medicine, Baltimore, Medicine Greenville, Greenville,
MD, USA SC, USA

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 List of Contributors xi

Julie Sullivan Jose Valdesuso

Emory University, Atlanta, RADx–VentureWell, Hadley, MA, USA
GA, USA
Eliseo Velasquez
Paul Tessier Investors of Color Network, Boston, MA,
CIMIT, Boston, MA, USA USA RADx–VentureWell, Hadley, MA, USA

Erika Tyburski Brian Walsh

Atlanta Center for Microsystems RADx–VentureWell, Hadley, MA, USA
Engineered Point-of-Care
Technologies, Atlanta, Cassandra Wesselman
GA, USA ROSALIND Inc., San Diego, CA, USA

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Published online by Cambridge University Press
 Foreword
Harvey V. Fineberg

A deadly pandemic demands a response at multiple levels of government and society and
across myriad needs for public health and medical care. As the COVID-19 pandemic took
hold in early 2020, the US response faltered. Hospitals lacked sufficient personal protective
equipment for staff and, as cases surged, some were overwhelmed by sick patients. Optimal
care for extremely ill patients was uncertain. The federal response lacked a clear leadership
structure and chain of command. Antivirals were lacking, and an effective vaccine was yet to
be developed. Moreover, the Centers for Disease Control and Prevention initially distrib-
uted a test kit with a faulty reagent, setting back the national testing strategy for COVID-19.
The nation’s premier biomedical research organization, the National Institutes of Health
(NIH), focused its COVID-19 efforts on three main goals of research: vaccines, therapeutics,
and diagnostics. By April 2020, the NIH had activated a public–private partnership to
accelerate the development of COVID-19 therapeutics and vaccines. Through funding and
active collaboration, the NIH was instrumental in the development of the Moderna vaccine.
With the active engagement of 20 companies and scores of scientists, the NIH screened
hundreds of therapeutic candidates, embarked on clinical trials for more than three dozen of
the most promising, and obtained six therapeutics approved for clinical use. Fueled by
a special congressional appropriation in April 2020, the NIH launched the Rapid
Acceleration of Diagnostics (RADx®) initiative. Within six months, the Food and Drug
Administration granted emergency use authorization to the first point-of-care – rapid
COVID-19 tests funded through RADx – and since then more than four dozen RADx-
supported tests (20 point-of-care, 16 laboratory-based, and 13 home-based tests) have
received emergency use authorization.
The pandemic demanded unaccustomed speed, intensity, and flexibility in research. All
of the institutes of the NIH responded to these pandemic exigencies. However, RADx stands
out for its degree of innovativeness and readiness to embrace non-traditional ways of doing
business at the NIH.
Led by the National Institute of Biomedical Imaging and Bioengineering, RADx built on
years of experience gained through CIMIT and the Point-of-Care Technology Research
Network that is coordinated by CIMIT. Rather than consider the aim to be funding brilliant
research, RADx adopted an outcomes-oriented approach that embraced every stage, from
scientific idea through proof of concept, product development, manufacturing, clinical
evaluation, regulatory review, and authorization for use. Rather than traditional peer
review, RADx developed a shark-tank approach of presentation, assessment of promise,
and investment, followed by an innovation funnel with development milestones and
sequential winnowing or intensifying investment. Rather than a hands-off approach after
grant approval, RADx adopted venture-capital-like continued support and coaching to
overcome any obstacles along the way.
These innovations meant that RADx would seek and foster ideas that had the promise of
success and not simply look for reasons that a project might fail. Thus, RADx did not accept
an inevitable “valley of death” for biomedical product development; RADx established oases
of support that carried easier-to-use, faster, and more reliable diagnostic tests from scientific
xiii

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 xiv Foreword

ideas to clinical laboratories, sites of clinical care, and homes. Because of RADx, as many as
3 billion COVID-19 tests have entered the US market, and rapid home and point-of-care
tests have become the norm.
This book describes the concept, organization, implementation, and results of the RADx
initiative. It provides many cases to illustrate the varied ways that the RADx model,
combining the best of public and private capacities, contributed to the success. It shows
how RADx adapted and learned from failures in real time to strengthen its approach. The
book positions the quest for more and better diagnostic tests – accurate, easy to use, and
widely available – against the backdrop of multiple pandemic demands on clinical care and
public health. The RADx experience holds lessons not only for the development of future
diagnostics but also for any situation in which multiple scientific scenarios may yield
technologies to help meet an urgent health need.
More than three years after the start of COVID-19, the United States and much of the
world appear to have weathered the brunt of the pandemic, although the toll on lives and the
financial impact continue to mount, and post-acute sequelae of severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) remain an ongoing clinical dilemma. China, whose
zero-tolerance policies held off the full force of COVID-19 for a couple of years, has since
found itself in the throes of the pandemic and has lent its weight to the growing, global
burden of disease.
With time, we can anticipate many assessments of the pandemic response at the global,
national, and subnational levels. Many will proffer lessons, and some will be worth heeding.
The RADx story told here meets that high standard, worthy of heeding, in preparing for the
next pandemic or for any similarly severe and urgent health threat.

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