October 14, 2020

Mr. Matt Hancock MP

Secretary of State for Health and Social Care

United Kingdom of Great Britain and Northern Ireland

UK: Challenge Trials for COVID-19

Dear Mr. Hancock,

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, treatments, and our scientific understanding of the disease.

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 forty-one 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 you and other  international institutions and governments around the world to endorse and advance immediate preparations for human challenge trials, including supporting safe and reliable production of the virus, design of an infectious dosing study, 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 and improve our scientific understanding of the virus.

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. Challenge trials may be the only way to test the second generation of vaccines necessary to protect the developing world.

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 lower than 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. That would mean not only the usual review process, but also 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  have 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 innumerable lives 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 international institutions and governments around the world to support this effort.

Sincerely,

Initial Signatories in italics. Institutional affiliations for identification purposes only:

Initial Signatories

  1. Scott Aaronson, David J. Bruton Centennial Professor of Computer Science, University of Texas at Austin

  2. Amrita Ahuja, Director of the Douglas B. Marshall, Jr. Family Foundation

  3. Chris Anderson, Head of TED

  4. Alexander Berger, Managing Director at Open Philanthropy

  5. Arthur Caplan, Drs. William F. and Virginia Connolly Mitty Professor of Bioethics, Department of Population Studies, NYU Langone Health

  6. Nir Eyal, Henry Rutgers Professor of Bioethics and Director of the Center for Population-Level Bioethics (CPLB), Rutgers University

  7. Ambassador James Glassman, Founding Executive Director at the George W. Bush Institute

  8. Kim Krawiec, Kathrine Robinson Everett Professor of Law, Duke University School of Law

  9. Marc Lipsitch, Professor of Epidemiology, Harvard University

  10. Abigail Marsh, Professor of Psychology and Neuroscience, Georgetown University

  11. Josh Morrison, Co-Founder and Executive Director at 1DaySooner

  12. Stanley Plotkin, Emeritus Professor of Pediatrics, Perelman School of Medicine, University of Pennsylvania

  13. Sophie Rose, Co-Founder and Director of Research at 1DaySooner

  14. Nadine Rouphael, Associate Professor of Medicine and Acting Director, Hope Clinic, Emory Vaccine Center

  15. Sally Satel, Resident Scholar at the American Enterprise Institute

  16. Peter Singer, Ira W. DeCamp Professor of Bioethics in the University Center for Human Values, Princeton University

  17. Kate Wharton, Senior Associate at CrossBoundary

  18. Daniel Wikler, Mary B. Saltonstall Professor of Population Ethics and Professor of Ethics and Population Health, Harvard University

    Nobel Laureates

  19. Mario Capecchi, Distinguished Professor in the Department of Human Genetics, University of Utah School of Medicine

  20. Carol Greider, Professor of Molecular Biology and Genetics, Johns Hopkins University School of Medicine

  21. Oliver Hart, Lewis P. and Linda L. Geyser University Professor, Harvard University

  22. Lou Ignarro, Professor Emeritus, UCLA School of Medicine

  23. William G. Kaelin, Jr., Professor of Medicine, Howard Hughes Medical Institute, Harvard Medical School

  24. Barry Marshall, Clinical Professor and UWA Brand Ambassador, The University of Western Australia

  25. Craig Mello, Distinguished Professor in RNA Therapeutics, University of Massachusetts Medical School

  26. Paul Modrich, James B. Duke Professor of Biochemistry, Duke University

  27. Edvard Moser, Professor of Neuroscience, Kavli Institute for Systems Neuroscience, Norwegian University of Technology and Science

  28. May-Britt Moser, Professor of Neuroscience, Kavli Institute for Systems Neuroscience, Norwegian University of Technology and Science

  29. Sir Richard Roberts, Chief Scientific Officer, New England Biolabs

  30. Michael Rosbash, Professor of Biology and Investigator, Howard Hughes Medical Institute, Brandeis University

  31. Alvin Roth, The Craig and Susan McCaw Professor of Economics, Stanford University

  32. Jack Szostak, Alex Rich Distinguished Investigator, Massachusetts General Hospital

  33. Arieh Warshel, Dana and David Dornsife Chair in Chemistry, Distinguished Professor of Chemistry and Biochemistry, University of Southern California

    Experts and Academics

  34. Bolaji Akinyemi, Professor of Political Science, Nigerian Foreign Minister, 1985-1987

  35. Inder Anand, Professor of Medicine, University of Minnesota,

  36. Ralf Bader, Professor of Philosophy, University of Fribourg

  37. Sayantan Banerjee, Lead Volunteer, Infectious Disease, PUBhealth

  38. David Barnett, Assistant Professor of Philosophy, University of Toronto

  39. Christian Barry, Professor of Philosophy, Australian National University

  40. Daniel Batson, Professor Emeritus of Psychology, University of Kansas

  41. Andy Bazar, Professor Emeritus, Mechanical Engineering, California State University

  42. Matthew Bedke, Head of Philosophy Department, University of British Columbia

  43. Karen Bennett, Professor of Philosophy and Department Chair, Rutgers University

  44. Alcino Bonella, Professor of Bioethics, Federal University of Uberlândia, Brazil

  45. Marcel Boyer, Professor Emeritus of Economics, University of Montreal

  46. Michael Bratman, Durfee Professor of Philosophy, Stanford University

  47. John Broome, Emeritus White’s Professor of Moral Philosophy, University of Oxford

  48. Allen Buchanan, Research Professor of Philosophy and Center for Philosophy of Freedom, University of Arizona; Emeritus Professor of Philosophy and Law, Duke University

  49. Eric Budish, Steven G. Rothmeier Professor of Economics, University of Chicago Booth School of Business

  50. Tyler Burge, Flint Professor of Philosophy, University of California, Los Angeles

  51. Jim Buttery, Head, infection and Immunity, Monash Children’s Hospital; Professor of Paediatric Epidemiology, Monash University

  52. Bryan Caplan, Professor of Economics, George Mason University

  53. David Chalmers, University Professor of Philosophy, New York University

  54. Carolyn Riley Chapman, Faculty Affiliate, NYU Division of Medical Ethics

  55. Richard Chappell, Assistant Professor of Philosophy, University of Miami

  56. Andrew Charman, Lecturer in Physics, University of California, Berkeley

  57. Catherine Constable, Assistant Professor, Department of Medicine at NYU Grossman School of Medicine

  58. Lewis Conway, Campaign Strategist, American Civil Liberties Union

  59. Philip Cook, Sanford Professor Emeritus of Public Policy, Duke University

  60. Stephen Darwall, Andrew Downey Orrick Professor of Philosophy, Yale University

  61. Ara Darzi, Professor the Lord Darzi of Denham, OM, KBE, PC, FRS; Director of the Institute of Global Health Innovation, Imperial College London

  62. Sir Partha Dasgupta FBA FRS, Frank Ramsey Professor Emeritus of Economics, University of Cambridge

  63. Daniel Dennett, Austin B. Fletcher Professor of Philosophy, Tufts University

  64. Pedro Rosa Dias, Associate Professor of Health Economics, Imperial College Business School, Imperial College London

  65. Thomas Douglas, Senior Research Fellow, University of Oxford

  66. Frances Egan, Professor of Philosophy, Rutgers University

  67. Tom Ellis, Professor of Synthetic Genome Engineering, Imperial College London

  68. Gareth Evans, Former Australian Foreign Minister and President Emeritus of the International Crisis Group

  69. Nita Farahany, Robinson O. Everett Professor of Law & Philosophy, Duke University School of Law

  70. Kyle Ferguson, Postdoctoral Fellow, Division of Medical Ethics, NYU Grossman School of Medicine

  71. Kit Fine, University Professor and Silver Professor of Philosophy and Mathematics, New York University

  72. Stephen Finlay, Director and Professor of the Dianoia Institute of Philosophy, Australian Catholic University; Professor of Philosophy, University of Southern California

  73. Stuart Firestein, Professor of Biological Sciences, Columbia University

  74. Johann Frick, Assistant Professor of Philosophy and Human Values, Princeton University

  75. Matteo M. Galizzi, Associate Professor of Behavioural Science, London School of Economics

  76. Daniel Garber, A. Watson J. Armour III University Professor of Philosophy, Princeton University

  77. Tobias Gerhard, Associate Professor of Pharmacy and Epidemiology, Director, Center for Pharmacoepidemiology and Treatment Science, Rutgers Biomedical and Health Sciences

  78. Daniel Gilbert, Edgar Pierce Professor of Psychology, Harvard University

  79. Rebecca Newberger Goldstein, Author; Research Associate, Harvard University

  80. Robert Goodin, Distinguished Professor of Philosophy, Australian National University

  81. Kenneth Goodman, Professor of Medicine and Philosophy, University of Miami

  82. Joshua Greene, Professor of Psychology, Harvard University

  83. Lori Gruen, William Griffin Professor of Philosophy, Wesleyan University

  84. Alexander Guerrero, Associate Professor of Philosophy, Rutgers University

  85. Saarthak Gupta, Research Fellow, Open Philanthropy

  86. Jonathan Haidt, Professor of Ethical Leadership, New York University – Stern School of Business

  87. Edward Hall, Norman E. Vuilleumier Professor of Philosophy, Harvard University

  88. Hans Halvorson, Stuart Professor of Philosophy, Princeton University

  89. Elizabeth Harman, Laurance S. Rockefeller Professor of Philosophy and Human Values, Princeton University

  90. Stephan Hartmann, Alexander von Humboldt Professor and Director, Munich Center for Mathematical Philosophy, LMU Munich, Germany

  91. Sally Haslanger, Ford Professor of Philosophy and Women’s Gender Studies, Massachusetts Institute of Technology

  92. Dan Haybron, Theodore R. Vitali C.P. Chair in Philosophy, Saint Louis University

  93. Fatemeh Heidary, Director, International Virtual Ophthalmic Research Center

  94. Adrian Hill, Lakshmi Mittal and Family Professor of Vaccinology & Director of the Jenner Institute, University of Oxford

  95. Karla FC Holloway, James B. Duke Professor Emerita of English and Law, Duke University

  96. Richard Holton, Professor of Philosophy, University of Cambridge

  97. 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

  98. Thomas Hurka, Professor of Philosophy, University of Toronto

  99. Dale Jamieson, Professor of Environmental Studies and Philosophy, New York University

  100. Robin Jeshion, Professor of Philosophy, University of Southern California

  101. Shelly Kagan, Clark Professor of Philosophy, Yale University

  102. Justin Kalef, Director of Teaching Innovation, Department of Philosophy, Rutgers University

  103. Gregory Keating, Maurice Jones, Jr. – Class of 1925 Professor of Law and Philosophy, Gould School of Law, University of Southern California

  104. Stephen Kennedy, Professor of Reproductive Medicine, University of Oxford

  105. Muhammad Ali Khalidi, Professor of Philosophy, City University of New York

  106. Hadi Kharrazi, Johns Hopkins School of Public Health

  107. David Killoren, Research Fellow in Philosophy at the Dianoia Institute of Philosophy, Australian Catholic University

  108. A. Marm Kilpatrick, Professor of Ecology and Evolutionary Biology, University of California, Santa Cruz

  109. Philip Kitcher, John Dewey Professor of Philosophy, Emeritus, Columbia University

  110. Gary Kobinger, Professor of Infectious Diseases, Université Laval, Qc, Canada

  111. Gene Kopp, Postdoctoral Fellow of Mathematics, University of Bristol

  112. Christine M. Korsgaard, Arthur Kingsley Porter Professor of Philosophy, Harvard University

  113. Colleen Kraft, Associate Professor of Pathology and Laboratory Medicine, Emory University

  114. Zell Kravinsky, Investor and Philanthropist

  115. Yamuna Krishnan, Professor of Chemistry, University of Chicago

  116. Ruipeng Lei, Professor and Executive Director, Center for Bioethics, Huazhong University of Science and Technology; Member, WHO Ethics and COVID-19 Working Group

  117. Béatrice Longuenesse, Silver Professor & Professor of Philosophy, New York University

  118. Mario Macis, Associate Professor of Economics, Johns Hopkins University

  119. Todd May, Class of 1941 Memorial Professor of the Humanities, Clemson University

  120. James McCartney, Associate Professor Emeritus, Department of Philosophy, Villanova University

  121. Trip McCrossin, Assistant Teaching Professor, Department of Philosophy, Rutgers University

  122. Victoria McGeer, Professor of Philosophy at Australian National University; Senior Research Scholar at the University Center for Human Values, Princeton University

  123. Jeff McMahan, White’s Professor of Moral Philosophy, University of Oxford

  124. Aneesh Mehta, Associate Professor of Medicine, Emory University

  125. Marisa Miraldo, Associate Professor in Health Economics, Imperial College London

  126. Jessie Munton, Lecturer in Philosophy, University of Cambridge

  127. Robert Myers, Professor of Philosophy, York University

  128. Kim Nasmyth, Professor of Biochemistry, University of Oxford

  129. Richard Nisbett, Theodore M. Newcomb Distinguished University Professor Emeritus of Psychology, University of Michigan

  130. Akinlolu Ojo, Professor of Medicine and Population Health, University of Kansas School of Medicine

  131. Bishr Omary, Senior Vice Chancellor for Academic Affairs and Research, Henry Rutgers Professor of Biomedical Sciences, Robert Wood Johnson Medical School, Rutgers University

  132. Baroness Onora O’Neill, University of Cambridge, Emerita Professor of Philosophy, winner of Holberg and Berggruen prizes

  133. Steven Pinker, Johnstone Family Professor of Psychology, Harvard University

  134. Philip Pettit, Laurance S. Rockefeller University Professor of University Center for Human Values, Princeton University; Distinguished Professor of Philosophy, Australian National University

  135. Andreas Peichl, Professor of Macroeconomics and Public Finance, University of Munich; Director of the ifo Center for Macroeconomics and Surveys

  136. Michael Potter, Professor of Logic, University of Cambridge

  137. Huw Price, Bertrand Russell Professor of Philosophy, University of Cambridge

  138. Naresh Punjabi, Professor of Medicine and Epidemiology, Johns Hopkins University

  139. 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

  140. Ofer Raban, Professor of Constitutional Law, University of Oregon

  141. Janet Radcliffe-Richards, Professor of Practical Philosophy & Distinguished Research Fellow, Oxford Uehiro Centre for Practical Ethics, University of Oxford

  142. Martin Rees, Astronomer Royal, University of Cambridge

  143. Ora John Reuter, Associate Professor of Political Science, University of Wisconsin-Milwaukee

  144. Justin Roberts, Director, Rikers Debate Project

  145. Zachary Robinson, Research Fellow, Open Philanthropy

  146. Sherrilyn Roush, Professor of Philosophy, University of California, Los Angeles

  147. Ross Salawitch, Professor of Atmospheric Sciences and Chemistry & Biochemistry, University of Maryland, College Park

  148. Julian Savulescu, Uehiro Chair in Practical Ethics, University of Oxford

  149. Thomas M. Scanlon, Jr., Alford Professor of Natural Religion, Moral Philosophy, and Civil Polity, Emeritus, Harvard University

  150. G. Owen Schaefer, Assistant Professor, Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore

  151. Jonathan Schaffer, Distinguished Professor of Philosophy, Rutgers University

  152. Susanna Schellenberg, Distinguished Professor of Philosophy and Cognitive Science, Rutgers University

  153. Thomas Schmidt, Professor of Philosophy, Humboldt-Universität zu Berlin

  154. Volker H. Schmidt, Professor of Sociology, National University of Singapore

  155. Gina Schouten, Assistant Professor of Philosophy, Harvard University

  156. Michael Schur, Screenwriter and Television Producer, Creator of The Good Place

  157. Jeff Sebo, Clinical Assistant Professor of Environmental Studies, Affiliated Professor of Bioethics, Medical Ethics, and Philosophy, New York University

  158. Andrew Sepielli, Associate Professor of Philosophy, University of Toronto

  159. Michael Smith, McCosh Professor of Philosophy, Princeton University

  160. Peter Smith, Professor of Tropical Epidemiology, London School of Hygiene & Tropical Medicine

  161. Jesse Snedeker, Professor of Psychology, Harvard University

  162. Christopher Snyder, Joel and Susan Hyatt Professor of Economics, Dartmouth College

  163. Scott Soames, Distinguished Professor of Philosophy, University of Southern California

  164. Ernest Sosa, Board of Governors Professor of Philosophy, Rutgers University

  165. Guy-Bart Stan, Professor of BioSystems Engineering and Control, Co-Director of the Imperial College Centre for Synthetic Biology, Imperial College London, U.K.

  166. Stephen Stich, Distinguished Professor of Philosophy and Cognitive Science, Rutgers University

  167. Brian L. Strom, Chancellor, Rutgers Biomedical & Health Sciences; Executive Vice President for Health Affairs; University Professor, Rutgers University

  168. John Sullivan, Professor, Program in Molecular Medicine, University of Massachusetts Medical School

  169. Alex Tabarrok, Bartley J. Madden Chair in Economics and Professor of Economics, George Mason University

  170. Larry Temkin, Distinguished Professor of Moral Philosophy, Rutgers University

  171. Lorna E. Thorpe, Professor and Director in the Division of Epidemiology, NYU Grossman School of Medicine, NYU Langone Health

  172. Benjamin Tolchin, Assistant Professor of Neurology, Yale School of Medicine

  173. Deborah VandenBroek, Principal Consultant, VandenBroek LLC

  174. Alec Walen, Professor of Law and Philosophy, Rutgers University

  175. Dominic Wilkinson, Consultant Neonatologist, John Radcliffe Hospital Oxford; Professor of Medical Ethics, Oxford Uehiro Centre for Practical Ethics, University of Oxford

  176. Alex Wood, Professor of Psychology and Centennial Chair, London School of Economics and Political Science

  177. Ramnik Xavier, Core Institute Member of the Broad Institute & Professor of Medicine, Massachusetts General Hospital & Harvard Medical School

  178. David Zuckerman, Professor of Computer Science, University of Texas at Austin