July 15, 2020
Dr. Francis Collins, National Institutes of Health
9000 Rockville Pike Bldg 10.
Bethesda, MD 20892
US: Challenge Trials for COVID-19
Dear Dr. Collins,
The COVID-19 pandemic must be fought urgently on many fronts, but it is hard to picture robust economic and social recoveries in the absence of a vaccine. We are writing to underscore the vast importance of human challenge trials as a method to help develop vaccines.
In April, thirty-five members of the US House of Representatives called upon U.S. regulators to consider allowing volunteers to be infected with the pandemic coronavirus to speed vaccine testing—in so-called human challenge or controlled infection trials. In addition, over a hundred vaccine candidates are already under development around the world, at least ten of which have moved into the clinical trial phase. In May, the World Health Organization published guidance supporting trials of that form, if done ethically, and in June published a draft laying out a practical roadmap for their implementation.
The undersigned urge the U.S. government (including, but not limited to the Coronavirus Task Force, the Department of Health and Human Services, the Food and Drug Administration, Centers for Disease Control and Prevention, National Institutes of Health, and Congress), its allies, international funders, and world bodies (e.g. the World Health Organization), to undertake immediate preparations for human challenge trials, including supporting safe and reliable production of the virus and any biocontainment facilities necessary to house participants.
Background
The rationale for human challenge trials is that they can greatly accelerate the development of a COVID-19 vaccine.
Human challenge trials can provide information much faster than conventional efficacy trials, which take months longer. In such trials, volunteers still receive the vaccine candidate or a control. Instead of resuming life as usual and waiting to “catch” a virus, volunteers are deliberately exposed to the pathogen under controlled conditions. Beyond being faster than conventional trials, a challenge test is likelier to conclude with interpretable results, e.g. should the presence of virus around the study site begin to fade over time.
If challenge trials can safely and effectively speed the vaccine development process, there is a formidable presumption in favor of their use, which would require a very compelling ethical justification to overcome.
Principles for an Effective COVID-19 Human Challenge Trial
Human research demands caution and oversight. Crucial protections must be extended to protect the health and autonomy rights of volunteers. Guidance from the World Health Organization clarifies that human challenge trials are ethical when they meet certain criteria. The following are some protections that should clearly be in place.
● Trial participants should be relatively young and in good health. The mortality risk of the coronavirus to 20-29 year-olds, healthy and unhealthy, is similar to that of living kidney donors , a relatively common procedure, similarly justified by the donor’s informed consent and the benefits to society. Excluding participants with preexisting conditions would lower the risk significantly.
● It is crucial that all trial participants be provided the highest quality medical care with frequent monitoring. A significant percentage of the population will likely become infected and their access to medical care may be limited. As a result, the guarantee of excellent medical care in the study means that infection would be safer in the controlled, medically supervised, and isolated conditions of a challenge trial.
● Ethical and scientific review must be of the highest quality. In the U.S., that would mean not only the usual FDA and IRB review but a vigorous public discussion and perhaps even an additional, independent ethics and science taskforce representing, among others, challenge volunteers.
● The autonomy of the volunteers is of paramount concern. This means that the informed consent process must be robust (e.g. no children, no prisoners, multiple tests of comprehension). It also means that the wish of informed volunteers to participate in the trial ought to be given substantial weight. Providing some input over trial development and procedure to those interested in becoming volunteers (e.g. in the design of isolation conditions) could both enhance their agency and improve study design. Decades of psychological research on highly altruistic behaviors has demonstrated that a large, and likely growing, fraction of the general population is willing to undergo meaningful risks to benefit others due to genuinely altruistic motivation rather than insensitivity to risk, psychopathology, or other ethically concerning motives.
If done properly, live Coronavirus human challenge trials can be an important way to accelerate vaccine development and, ideally, to save the lives of millions around the world as well as help rescue global economies. We strongly recommend that production of the unattenuated virus begin immediately consistent with good manufacturing practices for potential use in trials that balance risks and benefits and respect the safety and autonomy of volunteers. It is also vitally important that there is both full transparency on the vaccine development and trial process and a diverse group of trial participants necessary to provide a broadly effective and universally available vaccine. We appeal to the government and foundation funders around the world to support this effort.
Sincerely,
Initial Signatories in italics. Institutional affiliations for identification purposes only:
Initial Signatories
Scott Aaronson, David J. Bruton Centennial Professor of Computer Science, University of Texas at Austin
Amrita Ahuja, Director of the Douglas B. Marshall, Jr. Family Foundation
Chris Anderson, Head of TED
Alexander Berger, Managing Director at Open Philanthropy
Arthur Caplan, Drs. William F. and Virginia Connolly Mitty Professor of Bioethics, Department of Population Studies, NYU Langone Health
Nir Eyal, Henry Rutgers Professor of Bioethics and Director of the Center for Population-Level Bioethics (CPLB), Rutgers University
Ambassador James Glassman, Founding Executive Director at the George W. Bush Institute
Kim Krawiec, Kathrine Robinson Everett Professor of Law, Duke University School of Law
Marc Lipsitch, Professor of Epidemiology, Harvard University
Abigail Marsh, Professor of Psychology and Neuroscience, Georgetown University
Josh Morrison, Co-Founder and Executive Director at 1DaySooner
Stanley Plotkin, Emeritus Professor of Pediatrics, Perelman School of Medicine, University of Pennsylvania
Sophie Rose, Co-Founder and Director of Research at 1DaySooner
Nadine Rouphael, Associate Professor of Medicine and Acting Director, Hope Clinic, Emory Vaccine Center
Sally Satel, Resident Scholar at the American Enterprise Institute
Peter Singer, Ira W. DeCamp Professor of Bioethics in the University Center for Human Values, Princeton University
Kate Wharton, Senior Associate at CrossBoundary
Daniel Wikler, Mary B. Saltonstall Professor of Population Ethics and Professor of Ethics and Population Health, Harvard University
Nobel Laureates
Mario Capecchi, Distinguished Professor in the Department of Human Genetics, University of Utah School of Medicine
Carol Greider, Professor of Molecular Biology and Genetics, Johns Hopkins University School of Medicine
Oliver Hart, Lewis P. and Linda L. Geyser University Professor, Harvard University
Lou Ignarro, Professor Emeritus, UCLA School of Medicine
William G. Kaelin, Jr., Professor of Medicine, Howard Hughes Medical Institute, Harvard Medical School
Barry Marshall, Clinical Professor and UWA Brand Ambassador, The University of Western Australia
Craig Mello, Distinguished Professor in RNA Therapeutics, University of Massachusetts Medical School
Paul Modrich, James B. Duke Professor of Biochemistry, Duke University
Edvard Moser, Professor of Neuroscience, Kavli Institute for Systems Neuroscience, Norwegian University of Technology and Science
May-Britt Moser, Professor of Neuroscience, Kavli Institute for Systems Neuroscience, Norwegian University of Technology and Science
Sir Richard Roberts, Chief Scientific Officer, New England Biolabs
Michael Rosbash, Professor of Biology and Investigator, Howard Hughes Medical Institute, Brandeis University
Alvin Roth, The Craig and Susan McCaw Professor of Economics, Stanford University
Jack Szostak, Alex Rich Distinguished Investigator, Massachusetts General Hospital
Arieh Warshel, Dana and David Dornsife Chair in Chemistry, Distinguished Professor of Chemistry and Biochemistry, University of Southern California
Experts and Academics
Bolaji Akinyemi, Professor of Political Science, Nigerian Foreign Minister, 1985-1987
Inder Anand, Professor of Medicine, University of Minnesota,
Ralf Bader, Professor of Philosophy, University of Fribourg
Sayantan Banerjee, Lead Volunteer, Infectious Disease, PUBhealth
David Barnett, Assistant Professor of Philosophy, University of Toronto
Christian Barry, Professor of Philosophy, Australian National University
Daniel Batson, Professor Emeritus of Psychology, University of Kansas
Andy Bazar, Professor Emeritus, Mechanical Engineering, California State University
Matthew Bedke, Head of Philosophy Department, University of British Columbia
Karen Bennett, Professor of Philosophy and Department Chair, Rutgers University
Alcino Bonella, Professor of Bioethics, Federal University of Uberlândia, Brazil
Marcel Boyer, Professor Emeritus of Economics, University of Montreal
Michael Bratman, Durfee Professor of Philosophy, Stanford University
John Broome, Emeritus White’s Professor of Moral Philosophy, University of Oxford
Allen Buchanan, Research Professor of Philosophy and Center for Philosophy of Freedom, University of Arizona; Emeritus Professor of Philosophy and Law, Duke University
Eric Budish, Steven G. Rothmeier Professor of Economics, University of Chicago Booth School of Business
Tyler Burge, Flint Professor of Philosophy, University of California, Los Angeles
Jim Buttery, Head, infection and Immunity, Monash Children's Hospital; Professor of Paediatric Epidemiology, Monash University
Bryan Caplan, Professor of Economics, George Mason University
David Chalmers, University Professor of Philosophy, New York University
Carolyn Riley Chapman, Faculty Affiliate, NYU Division of Medical Ethics
Richard Chappell, Assistant Professor of Philosophy, University of Miami
Andrew Charman, Lecturer in Physics, University of California, Berkeley
Catherine Constable, Assistant Professor, Department of Medicine at NYU Grossman School of Medicine
Lewis Conway, Campaign Strategist, American Civil Liberties Union
Philip Cook, Sanford Professor Emeritus of Public Policy, Duke University
Stephen Darwall, Andrew Downey Orrick Professor of Philosophy, Yale University
Ara Darzi, Professor the Lord Darzi of Denham, OM, KBE, PC, FRS; Director of the Institute of Global Health Innovation, Imperial College London
Sir Partha Dasgupta FBA FRS, Frank Ramsey Professor Emeritus of Economics, University of Cambridge
Daniel Dennett, Austin B. Fletcher Professor of Philosophy, Tufts University
Pedro Rosa Dias, Associate Professor of Health Economics, Imperial College Business School, Imperial College London
Thomas Douglas, Senior Research Fellow, University of Oxford
Frances Egan, Professor of Philosophy, Rutgers University
Tom Ellis, Professor of Synthetic Genome Engineering, Imperial College London
Gareth Evans, Former Australian Foreign Minister and President Emeritus of the International Crisis Group
Nita Farahany, Robinson O. Everett Professor of Law & Philosophy, Duke University School of Law
Kyle Ferguson, Postdoctoral Fellow, Division of Medical Ethics, NYU Grossman School of Medicine
Kit Fine, University Professor and Silver Professor of Philosophy and Mathematics, New York University
Stephen Finlay, Director and Professor of the Dianoia Institute of Philosophy, Australian Catholic University; Professor of Philosophy, University of Southern California
Stuart Firestein, Professor of Biological Sciences, Columbia University
Johann Frick, Assistant Professor of Philosophy and Human Values, Princeton University
Matteo M. Galizzi, Associate Professor of Behavioural Science, London School of Economics
Daniel Garber, A. Watson J. Armour III University Professor of Philosophy, Princeton University
Tobias Gerhard, Associate Professor of Pharmacy and Epidemiology, Director, Center for Pharmacoepidemiology and Treatment Science, Rutgers Biomedical and Health Sciences
Daniel Gilbert, Edgar Pierce Professor of Psychology, Harvard University
Rebecca Newberger Goldstein, Author; Research Associate, Harvard University
Robert Goodin, Distinguished Professor of Philosophy, Australian National University
Kenneth Goodman, Professor of Medicine and Philosophy, University of Miami
Joshua Greene, Professor of Psychology, Harvard University
Lori Gruen, William Griffin Professor of Philosophy, Wesleyan University
Alexander Guerrero, Associate Professor of Philosophy, Rutgers University
Saarthak Gupta, Research Fellow, Open Philanthropy
Jonathan Haidt, Professor of Ethical Leadership, New York University - Stern School of Business
Edward Hall, Norman E. Vuilleumier Professor of Philosophy, Harvard University
Hans Halvorson, Stuart Professor of Philosophy, Princeton University
Elizabeth Harman, Laurance S. Rockefeller Professor of Philosophy and Human Values, Princeton University
Stephan Hartmann, Alexander von Humboldt Professor and Director, Munich Center for Mathematical Philosophy, LMU Munich, Germany
Sally Haslanger, Ford Professor of Philosophy and Women's Gender Studies, Massachusetts Institute of Technology
Dan Haybron, Theodore R. Vitali C.P. Chair in Philosophy, Saint Louis University
Fatemeh Heidary, Director, International Virtual Ophthalmic Research Center
Adrian Hill, Lakshmi Mittal and Family Professor of Vaccinology & Director of the Jenner Institute, University of Oxford
Karla FC Holloway, James B. Duke Professor Emerita of English and Law, Duke University
Richard Holton, Professor of Philosophy, University of Cambridge
Ching-Li Hu, Director Shanghai Ethics Committee of Clinical Research; Emeritus Professor, Shanghai Ruijin Hospital, Shanghai Jiaotong University, School of Medicine; Former Deputy Director-General of WHO and International Bioethics Committee of UNESCO
Thomas Hurka, Professor of Philosophy, University of Toronto
Dale Jamieson, Professor of Environmental Studies and Philosophy, New York University
Robin Jeshion, Professor of Philosophy, University of Southern California
Shelly Kagan, Clark Professor of Philosophy, Yale University
Justin Kalef, Director of Teaching Innovation, Department of Philosophy, Rutgers University
Gregory Keating, Maurice Jones, Jr. - Class of 1925 Professor of Law and Philosophy, Gould School of Law, University of Southern California
Stephen Kennedy, Professor of Reproductive Medicine, University of Oxford
Muhammad Ali Khalidi, Professor of Philosophy, City University of New York
Hadi Kharrazi, Johns Hopkins School of Public Health
David Killoren, Research Fellow in Philosophy at the Dianoia Institute of Philosophy, Australian Catholic University
A. Marm Kilpatrick, Professor of Ecology and Evolutionary Biology, University of California, Santa Cruz
Philip Kitcher, John Dewey Professor of Philosophy, Emeritus, Columbia University
Gene Kopp, Postdoctoral Fellow of Mathematics, University of Bristol
Christine M. Korsgaard, Arthur Kingsley Porter Professor of Philosophy, Harvard University
Colleen Kraft, Associate Professor of Pathology and Laboratory Medicine, Emory University
Zell Kravinsky, Investor and Philanthropist
Yamuna Krishnan, Professor of Chemistry, University of Chicago
Ruipeng Lei, Professor and Executive Director, Center for Bioethics, Huazhong University of Science and Technology; Member, WHO Ethics and COVID-19 Working Group
Béatrice Longuenesse, Silver Professor & Professor of Philosophy, New York University
Mario Macis, Associate Professor of Economics, Johns Hopkins University
Todd May, Class of 1941 Memorial Professor of the Humanities, Clemson University
James McCartney, Associate Professor Emeritus, Department of Philosophy, Villanova University
Trip McCrossin, Assistant Teaching Professor, Department of Philosophy, Rutgers University
Victoria McGeer, Professor of Philosophy at Australian National University; Senior Research Scholar at the University Center for Human Values, Princeton University
Jeff McMahan, White’s Professor of Moral Philosophy, University of Oxford
Aneesh Mehta, Associate Professor of Medicine, Emory University
Marisa Miraldo, Associate Professor in Health Economics, Imperial College London
Jessie Munton, Lecturer in Philosophy, University of Cambridge
Robert Myers, Professor of Philosophy, York University
Kim Nasmyth, Professor of Biochemistry, University of Oxford
Richard Nisbett, Theodore M. Newcomb Distinguished University Professor Emeritus of Psychology, University of Michigan
Akinlolu Ojo, Professor of Medicine and Population Health, University of Kansas School of Medicine
Bishr Omary, Senior Vice Chancellor for Academic Affairs and Research, Henry Rutgers Professor of Biomedical Sciences, Robert Wood Johnson Medical School, Rutgers University
Baroness Onora O’Neill, University of Cambridge, Emerita Professor of Philosophy, winner of Holberg and Berggruen prizes
Peter Openshaw, Professor of Experimental Medicine, Imperial College London
Steven Pinker, Johnstone Family Professor of Psychology, Harvard University
Philip Pettit, Laurance S. Rockefeller University Professor of University Center for Human Values, Princeton University; Distinguished Professor of Philosophy, Australian National University
Andreas Peichl, Professor of Macroeconomics and Public Finance, University of Munich; Director of the ifo Center for Macroeconomics and Surveys
Michael Potter, Professor of Logic, University of Cambridge
Huw Price, Bertrand Russell Professor of Philosophy, University of Cambridge
Naresh Punjabi, Professor of Medicine and Epidemiology, Johns Hopkins University
Renzong Qiu, Professor Emeritus, Institute of Philosophy, Honorary Director of Center for Applied Ethics, Chinese Academy of Social Sciences, Fellow of the Hastings Center, Member of International Institute of Philosophy
Ofer Raban, Professor of Constitutional Law, University of Oregon
Janet Radcliffe-Richards, Professor of Practical Philosophy & Distinguished Research Fellow, Oxford Uehiro Centre for Practical Ethics, University of Oxford
Martin Rees, Astronomer Royal, University of Cambridge
Ora John Reuter, Associate Professor of Political Science, University of Wisconsin-Milwaukee
Justin Roberts, Director, Rikers Debate Project
Zachary Robinson, Research Fellow, Open Philanthropy
Sherrilyn Roush, Professor of Philosophy, University of California, Los Angeles
Ross Salawitch, Professor of Atmospheric Sciences and Chemistry & Biochemistry, University of Maryland, College Park
Julian Savulescu, Uehiro Chair in Practical Ethics, University of Oxford
Thomas M. Scanlon, Jr., Alford Professor of Natural Religion, Moral Philosophy, and Civil Polity, Emeritus, Harvard University
G. Owen Schaefer, Assistant Professor, Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore
Jonathan Schaffer, Distinguished Professor of Philosophy, Rutgers University
Susanna Schellenberg, Distinguished Professor of Philosophy and Cognitive Science, Rutgers University
Thomas Schmidt, Professor of Philosophy, Humboldt-Universität zu Berlin
Volker H. Schmidt, Professor of Sociology, National University of Singapore
Gina Schouten, Assistant Professor of Philosophy, Harvard University
Michael Schur, Screenwriter and Television Producer, Creator of The Good Place
Jeff Sebo, Clinical Assistant Professor of Environmental Studies, Affiliated Professor of Bioethics, Medical Ethics, and Philosophy, New York University
Andrew Sepielli, Associate Professor of Philosophy, University of Toronto
Michael Smith, McCosh Professor of Philosophy, Princeton University
Peter Smith, Professor of Tropical Epidemiology, London School of Hygiene & Tropical Medicine
Jesse Snedeker, Professor of Psychology, Harvard University
Christopher Snyder, Joel and Susan Hyatt Professor of Economics, Dartmouth College
Scott Soames, Distinguished Professor of Philosophy, University of Southern California
Ernest Sosa, Board of Governors Professor of Philosophy, Rutgers University
Stephen Stich, Distinguished Professor of Philosophy and Cognitive Science, Rutgers University
Brian L. Strom, Chancellor, Rutgers Biomedical & Health Sciences; Executive Vice President for Health Affairs; University Professor, Rutgers University
John Sullivan, Professor, Program in Molecular Medicine, University of Massachusetts Medical School
Alex Tabarrok, Bartley J. Madden Chair in Economics and Professor of Economics, George Mason University
Larry Temkin, Distinguished Professor of Moral Philosophy, Rutgers University
Lorna E. Thorpe, Professor and Director in the Division of Epidemiology, NYU Grossman School of Medicine, NYU Langone Health
Benjamin Tolchin, Assistant Professor of Neurology, Yale School of Medicine
Deborah VandenBroek, Principal Consultant, VandenBroek LLC
Alec Walen, Professor of Law and Philosophy, Rutgers University
Dominic Wilkinson, Consultant Neonatologist, John Radcliffe Hospital Oxford; Professor of Medical Ethics, Oxford Uehiro Centre for Practical Ethics, University of Oxford
Alex Wood, Professor of Psychology and Centennial Chair, London School of Economics and Political Science
Ramnik Xavier, Core Institute Member of the Broad Institute & Professor of Medicine, Massachusetts General Hospital & Harvard Medical School
David Zuckerman, Professor of Computer Science, University of Texas at Austin