Adverse Consequences of Rushing a SARS-Cov-2 Vaccine Implications for Public Trust

Opinion

COVID-19: BEYOND TOMORROW VIEWPOINT Adverse Consequences of Rushing a SARS-CoV-2 Vaccine Implications for Public Trust

Brit Trogen, MD, MS As the SARS-CoV-2 (severe acute respiratory syn- activated polio vaccine developed by Jonas Salk was de- NYU Langone Health, drome coronavirus 2) pandemic persists across the US clared “safe, potent, and effective” following the largest New York, New York. and the world, the spotlight on vaccine science has never public health experiment in the nation’s history, involv- been more intense. Researchers across the globe are ing more than a million schoolchildren.5 Within weeks, David Oshinsky, PhD workingrapidlytoproduceapotentialvaccine,and7can- however, the miracle vaccine intended to end the NYU Langone Health, 1 New York, New York. didates are already in clinical trials. Operation Warp scourge of polio stood accused of causing it. Years in de- Speed, the vaccine development project announced by velopment, the Salk vaccine had been rigorously tested Arthur Caplan, PhD President Trump, has advocated for a vaccine to be made in preparation for the massive trials. But the very suc- NYU Langone Health, available in the US by the beginning of 2021.1 But for sci- cess of these trials led to an understandable outcry for New York, New York. entists and physicians, the term “warp speed” should the immediate, but premature, public release of the vac- trigger concern. Good science requires rigor, discipline, cine. Five pharmaceutical companies were given Salk’s and deliberate caution. Any medical therapy approved formula and left to produce the vaccine without signifi- for public use in the absence of extensive safeguards has cant oversight. As speed took precedence over cau- Viewpoint 5 pages 2462, 2458, the potential to cause harm, not only for COVID-19 pre- tion, serious mistakes went unreported. One com- and 2455 vention efforts and vaccine recipients, but also for pub- pany, Cutter Laboratories, distributed a vaccine so lic trust in vaccination efforts worldwide. contaminated with live poliovirus that 70 000 chil- Long before coronavirus disease 2019 (COVID-19), dren who received that vaccine developed muscle weak- vaccine hesitancy and refusal were increasing.2 In 2019, ness,164werepermanentlyparalyzed,and10died.6 Not the World Health Organization listed vaccine refusal as surprisingly, that incident forced the federal govern- one of the top 10 global health threats.3 Pediatricians, ment to directly intervene. The legacy of this event is a in particular, frequently encounter resistance to child- regulatory landscape in which vaccines undergo thou- hood vaccinations, and as a result, outbreaks of measles sands of tests to ensure their safety and effectiveness.6 Yet on rare occasions, this vital evidence-based process of vaccine de- What cannot and must not be allowed velopment and testing has still been ignored. In 1976, concerns about the is for desperation to result in the emergence of a new swine flu strain suspension of scientific principles reminiscent of the lethal 1918 version led President Gerald Ford to convene a and ethical research values. panel that recommended a government- backed mass vaccination program.7 and other vaccine-preventable illnesses, such as pertus- Poorly conceived, the attempt to vaccinate the US popu- sis and influenza, have increased in recent decades.4 lation at breakneck speed failed in virtually every re- Much of the distrust of vaccines (and, by extension, spect. Safety standards deteriorated as one manufac- thephysiciansandscientistswhopromotethem)isdriven turer produced the incorrect strain. The vaccine tested by widespread misinformation from both online sources poorly on children who, depending on the form of vac- and skeptical communities.2,4 The belief that vaccines cinetested,eitherdevelopedadversereactionswithhigh causeharmfuladverseeffectslikeautismhaspersistedde- fevers and sore arms or did not mount an immune re- spitecarefullydesignedresearchstudiesthathaverefuted sponse at all. Reports emerged that the vaccine ap- such claims. When physicians promote vaccines, they do peared to cause Guillain-Barré syndrome in a very small so knowing that the benefits far outweigh the minimal number of cases, a finding that remains controversial, risks, and that each vaccine has been studied extensively but added to the early momentum of the antivaccine to establish its safety profile. Yet vaccine opponents fre- movement.7 Once again, the pressure to rapidly distrib- quentlyaccusephysiciansandresearchersoffailinginthis ute a vaccine undermined the scientific integrity of the respect,citingfinancialorpoliticalinterestsasthemotiva- process and damaged public trust. tionforpromotingvaccines.AsthesearchforaSARS-CoV-2 COVID-19 has created intense concern and uncer-

Corresponding vaccineaccelerates,physiciansandscientistswhowishto tainty in the US and throughout the world. There are im- Author: Brit Trogen, maintainthepublic’strustmustnotpromoteavaccinethat mense public and political pressures to develop a new MD, MS, 15J-1510 haseitherbypassedestablishedsafetystandardsorisopen vaccine, a process that typically takes years, not months. Lexington Ave, to a serious charge of having done so. But as history warns, these pressures must not sup- New York, NY 10029 (brit.trogen@ There is grim historical precedent for allowing ex- plant rigorous scientific practice. Proceeding stepwise nyulangone.org). pediency to rule vaccine development. In 1955, the in- through the phases of clinical trials is the ethical standard

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for investigations involving human research participants. Adher- concerns, these and other safeguards should be clearly communi- ence to the scientific method is the only way to safeguard against a cated to the public during the vaccine development process. SARS-CoV-2 vaccine that is ineffective, or worse, carries unaccept- Both the public and the scientific community want an effec- able adverse effects. tive and safe intervention to prevent COVID-19. The morbidity,mor- Failing to abide by standards of safety and scientific rigor dur- tality, and societal and financial devastation that SARS-CoV-2 has ing the COVID-19 crisis will fuel the argument that physicians and sci- caused throughout the world will have wide-reaching conse- entists cannot be trusted. Vaccination rates, which are declining due quences for almost every aspect of life for years to come. Nothing to widespread concern about visiting clinicians’ offices, could fur- should dampen the ardor of researchers worldwide in the aggres- ther decrease. The US could see resurgences of many vaccine- sive search for effective treatments. In this unprecedented crisis, preventable illnesses, and inevitably, massive increases in avoid- novel trial designs, such as those that include challenge studies, able deaths and irreversible outcomes. should be carefully considered.8 But what cannot and must not be There are, however, reasons to hope that these scenarios will allowedisfordesperationtoresultinthesuspensionofscientificprin- not come to pass. In response to past failures, vaccine develop- ciples and ethical research values. Physicians should not adminis- ment in the US is subject to increased regulatory oversight de- ter inadequately vetted vaccines; researchers should not endorse signed to protect against substandard practices. Technological ad- them without sufficient data. The scientific community has only one vances permit the rapid communication of adverse events in clinical chance at winning public acceptance of a SARS-CoV-2 vaccine. The trials, and the understanding of the genetic factors influencing im- likelihood of achieving that goal will depend on convincing evi- munologic responses has increased. To proactively address safety dence of vaccine safety and efficacy.

ARTICLE INFORMATION Boehringer, Sanofi, Novartis (all compassionate use, Accessed May 4, 2020. https://www.who.int/news- Published Online: May 26, 2020. unpaid), FNIH (unpaid), CSL, Glaxo, Fox Chase room/feature-stories/ten-threats-to-global-health- doi:10.1001/jama.2020.8917 Cancer Center, Abeona, Genae/Cardialen-DSMB, in-2019 Parker Waichman LLP, Nelson Mullins Riley & Conflict of Interest Disclosures: Dr Caplan 4. Hotez P. America and Europe’s new normal: Scarborough LLP, UroGen Pharma Inc, Otsuka, and the return of vaccine-preventable diseases. Pediatr reported serving as the unpaid chair of the Cabaletta Bio. No other disclosures were reported. Compassionate Use Advisory Committees Res. 2019;85(7):912-914. doi:10.1038/s41390- 019-0354-3 (CompAC), independent panels of internationally REFERENCES recognized medical experts, bioethicists, and 5. Oshinsky D. Polio: An American Story. Oxford patient representatives formed by NYU School of 1. Sanger DE, Kirkpatrick DD, Zimmer C, Thomas K, University Press; 2005. Wee SL. Profits and pride at stake, the race for a Medicine in collaboration with Janssen. CompAC 6. Offit P. The Cutter Incident: How America’s First advises Janssen about requests for compassionate vaccine intensifies. New York Times. Published May 2, 2020. Accessed May 19, 2020. https://www. Polio Vaccine Led to the Growing Vaccine Crisis. Yale use of its investigational medicines. NYU receives University Press; 2005. administrative funding from Janssen to facilitate nytimes.com/2020/05/02/us/politics/vaccines- the CompAC committees. Dr Caplan reports coronavirus-research.html 7. Sencer DJ, Millar JD. Reflections on the 1976 discussing emerging issues in research ethics 2. Dubé E, Vivion M, MacDonald NE. Vaccine swine flu vaccination program. Emerg Infect Dis. with Western IRB Inc/WIRB-Copernicus Group hesitancy, vaccine refusal and the anti-vaccine 2006;12(1):29-33. doi:10.3201/eid1201.051007 (WIRB/WCG) leadership, giving lectures on research movement: influence, impact and implications. 8. Plotkin SA, Caplan A. Extraordinary diseases ethics topics to WIRB/WCG staff and fellows, and Expert Rev Vaccines. 2015;14(1):99-117. doi:10.1586/ require extraordinary solutions. Vaccine. 2020;38 that the Division of Medical Ethics has a grant from 14760584.2015.964212 (24):3987-3988. doi:10.1016/j.vaccine.2020.04.039 WIRB/WCG to provide education as part of an 3. World Health Organization. Ten threats to global annual international research ethics fellows health in 2019. Published September 2019. educational program held at NYU. Dr Caplan also reports consulting in 2017-2019 for Sangamo,

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