Opinion

COVID-19 vaccine race is a long way from over, and human challenge trials still have a role to play

The lack of a rescue therapy should not be a deal-breaker for properly conducted challenge trials aimed at thoroughly evaluating COVID-19 vaccines, write Nir Eyal and Bastian Steuwer.

Why the lack of a rescue therapy shouldn't prevent human challenge trials for coronavirus vaccines

A syringe containing a COVID-19 vaccine being developed by the National Institutes of Health and Moderna Inc., in Binghamton, N.Y. Pfizer and BioNTech, Moderna and AstraZeneca have all recently reported field trial results showing promising results for their vaccines. (Hans Pennink/The Associated Press)

This column is an opinion by Nir Eyal and Bastian Steuwer. Eyal is the Henry Rutgers Professor of Bioethics and director of the Center for Population-Level Bioethics at Rutgers University, and a member of the advisory board at 1Day Sooner, which advocates on behalf of COVID-19 human challenge trial volunteers. Steuwer is a Post-Doctoral Associate at the Center for Population-Level Bioethics at Rutgers University. For more information about CBC's Opinion section, please see the FAQ.

The past several weeks have brought good news about vaccines to fight COVID-19. Pfizer and BioNTech, Moderna and AstraZeneca have reported results (preliminary in the case of the latter two) from their field trials, showing high efficacy for their vaccines. This unreservedly good news does not, however, mean that the race for coronavirus vaccines will be over soon.

For one thing, the bulk of preliminary results speak about efficacy in preventing disease, but not about efficacy in preventing infection.

Stopping the spread of the virus would require a vaccine that protects us against contracting and/or spreading the virus. We will need to continue to test the vaccines that are now close to being approved on that front, and new vaccine candidates to see if they are superior to approved vaccines.

A recent petition to the House of Commons urges the federal government to approve human challenge trials to test vaccines against COVID-19. Scientifically, challenge trials are particularly good at assessing protection against getting and transmitting infections, and for checking superiority to alternative vaccines. They could also reveal how long and by what immune system changes a vaccine provides protection, and much else about the virus.

In a human challenge trial, consenting volunteers receive one of the candidate vaccines being investigated, or the control — a proven vaccine, another experimental vaccine, or a placebo — just as participants might in a regular field trial. The difference is that rather than simply going about their daily lives while being monitored to see if they become infected or not, challenge trial participants are deliberately exposed to the virus in order to figure out whether the investigated vaccine protects against infection better than the control.

Results can be obtained fast and with near-certainty in a human challenge trial, as opposed to vaccine field trials in which researchers must wait for a sufficient number of volunteers in the control arm to be naturally infected in the field.

Recruitment for large field trials will also now be complicated by the potential availability of proven alternatives. Such field trials would usually need to deny or postpone access to proven alternatives to thousands of participants, jeopardizing communities at high risk of infection. Challenge trials require only a few dozen volunteers, who can come from any community.

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Human challenge trials could make finding a COVID-19 vaccine faster, but the controversial approach involves exposing volunteers to the virus to see if a potential vaccine works. The National’s Andrew Chang finds out more about this process and the people volunteering to be test subjects. 9:01

Some bioethicists and scientists oppose coronavirus challenge trials while there is no tried and tested cure. They argue that traditionally, challenge trials have been performed either for relatively mild diseases like seasonal flu, or for diseases like malaria or cholera for which there already exist reliable and effective treatment options, a so-called rescue therapy.

Currently, trial teams would only be able to do so much with therapeutics in the highly unlikely event that a participant deliberately infected with COVID-19 deteriorates. However, the lack of such a rescue therapy should not be a deal-breaker for properly conducted challenge trials.

First, the contrast between diseases like seasonal flu, malaria, cholera, and dengue — for which challenge trials have been used recently — and COVID-19 is less stark than it is made out to be. As the WHO points out in discussing coronavirus challenge trials, even seasonal flu challenge trials can in rare cases lead to severe complications, and the treatments for these diseases are never foolproof.

A patient enrolled in Pfizer's COVID-19 coronavirus vaccine clinical trial receives an injection at the University of Maryland School of Medicine in Baltimore. (University of Maryland School of Medicine/File/The Associated Press)

And malaria challenge trials have enrolled approximately 2,000 participants in recent decades without any fatalities or other serious harms, not because a rescue therapy for malaria would work in all cases, but because it sufficiently reduces the risk.

Coronavirus challenge trials are likewise unlikely to create serious harms for the participants. This is not only because some partially effective medications already exist. The main reason is that coronavirus challenge trials mobilize a powerful additional buffer for safety: participant selection.

Let us assume, as do critics of challenge trials, that the risks to challenge trial participants are roughly equivalent to the infection-fatality rate of people of similar age and health status. By restricting study volunteers to young, healthy adults, the risk of death in a challenge trial is predicted to be less than 0.007 per cent — that's far less than one-fourth the risk of dying from living kidney donation (0.03 per cent).

Still, a group of senior researchers who object to challenge trials without a rescue therapy has written that the risk of those trials is unacceptable since it "is not zero." However, rejecting challenge trials because risks of severe adverse effects to volunteers are "not zero" sets an impossibly high standard. The conventional vaccine efficacy human trials already taking place could also have induced severe complications.

Dr. Peter Lin talks about human challenge trials for a COVID-19 vaccine and the ethical questions they raise. 8:07

The WHO guidance has this right: "Although treatment is one important way of reducing risk, the existence of specific, curative treatments is not a necessary condition for the ethical acceptability of challenge studies."

The lack of a rescue therapy should therefore not stand in the way of properly managed efforts to find new vaccines to protect us against not just disease, but also infection with SARS-CoV-2.

Any volunteer for a challenge trial would need to give fully informed consent to take up the risks involved. The consent process would ensure that volunteers understand the risks and uncertainties involved, and still desire to take them.

One may reasonably ask whether there would be enough volunteers. A challenge trial needs only a few dozen participants, yet more than 38,000 volunteers from 166 countries, including 1,788 from Canada, have already declared themselves to be willing. It is prejudiced to declare without checking that all fail to comprehend the risks and uncertainties involved.

With appropriate participant selection, we don't need to wait for a rescue therapy for coronavirus challenge trials to begin. Challenge trials would help us learn faster whether new vaccines protect us against infection as well as disease, a key to stopping the spread of SARS-CoV-2.


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