National Post (National Edition)
The ethics of giving volunteers COVID-19
Scientists endorse petition to hold challenge trials in Canada
Under normal circumstances, the petition to Parliament might seem rather rash: urgently and publicly support a plan allowing scientists to intentionally infect people with a sometimes-deadly virus to more rapidly find an effective vaccine.
“The risk to young healthy volunteers is on par with other acts of public service, such as living kidney donation,” reads in part the e-petition, co-sponsored by Liberal MP Marcus Powlowski, from Thunder Bay, Ont., and several Canadian infectious diseases experts.
The petition, endorsed by just under 600 people, is in support of human challenge trials for COVID-19 in Canada — the same experiments set to get underway in January at the Royal Free Hospital in London, England.
The U.K. government announced this week plans to back human challenge trials led by Imperial College London scientists along with a subsidiary of a Dublin-based medical research company. The first volunteers will enter a 19-bed isolation facility early in the New Year, where, as the Washington Post reports, they will have a purified strain of the live virus squirted into their noses.
Researchers will first try to determine the minimal amount of the SARS-CoV-2 pathogen needed to cause an active infection by administering tiny amounts of virus, and then increasing the dose until the person develops mild symptoms.
Scientists then hope to inject volunteers with test vaccines, and expose them to the challenge dose to determine how well the vaccines protect them.
With no proven rescue therapies, challenge trials are unnerving many. Dalhousie University philosopher Francoise Baylis and bioethicist Landon Getz recently warned of the “twin risks of exploitation and coercion.” Volunteers will be quarantined and compensated, likely around $6,500 (the current remuneration pay for influenza challenge studies in Britain), but possibly higher. “Is `$6,500+' too little or too much for those consenting to a small chance of death or serious disability,” Baylis and Getz wrote. “What is fair compensation for agreeing to be infected with a deadly pathogen and then quarantined?” Baylis tweeted.
Already, nearly 39,000 people from around the globe, including 1,600 Canadians, have expressed a willingness to be human challenge test subjects through the advocacy group, 1Day Sooner.
The young and healthy 18-to-25year-olds, without underlying illnesses, are thought to be at low risk of death from COVID-19.
Challenge trials have a long history, used for decades to create vaccines for flu and other diseases.
In normal vaccine trials, volunteers are vaccinated, or injected with a placebo, and then sent out into the real world to see how many get exposed and infected. But the less virus circulating in a community, the longer it takes to determine whether a vaccine is working. By contrast, “challenge studies take much less time, require fewer volunteers, aren't tethered to natural infection rates and can therefore accelerate progress,” medical ethicists Kyle Ferguson and Arthur Caplan of NYU Grossman School of Medicine wrote in June. Given what is at stake, with properly informed consent, COVID-19 challenge trials can be justified, Caplan has argued.
The University of Ottawa's Amir Attaran agrees. “Good for Britain, doing challenge trials over the all too predictable bleating of some bioethicists,” Attaran, an epidemiologist and professor of law and medicine tweeted this week. “In my view, taking a known risk can be done ethically.”
Nature reports that volunteers will be treated with antiviral drugs, such as remdesivir, as soon as a nose swab tests positive for the SARS-CoV-2 virus. Interim results from a study by the World Health Organization, however, concluded remdesivir appears no better than a placebo at limiting the need for mechanical ventilation or the risk of death in severely ill people with COVID.
The “first, do no harm” principle doesn't necessarily apply here, Attaran said. “Trials are experimentation. They're not intended with the same goal as routine treatment in medicine.”
The better analogy is firefighters, he said. “With firefighters you recruit people who are willing to take the risk to run into a burning building. They know that running into a burning building can kill them, they know there may be no rescue for them. But they nonetheless volunteer to do it, for high stakes, surely, although less high than a global pandemic, which is on its way to killing millions.”
Dr. Michael Silverman said there are groups in Canada who are interested in human challenge trials, and would likely come forward if they knew the federal government was open to it.
“We do feel that political leaders should come forward, because we would like Canada to be part of the solution, rather than waiting for others to do this,” said Silverman, chief of the division of infectious diseases at Western University's Schulich School of Medicine & Dentistry. With proper ethical oversight, safe places for volunteers to stay so they won't spread the virus and selecting only those with the least known risk of developing severe complications, “only then would you then try different vaccines and see if they prevent infection,” Silverman said.
“We do allow people to volunteer for things that carry risk,” Silverman said. “People can join the military during the war because they want to help their country, and we don't say that's unethical because they might get harmed.”
Ten vaccines are currently in latestage human trials. “We don't know how well any of these are going to work — unless were are exploring all options, there is a strong chance that it takes longer and longer before we have a solution,” Silverman said. “That's more deaths, more people getting sick, more people spending more time in ICU, hospitals having to reduce surgeries because we have too many people ill and too many people living in isolation.”
Others aren't so sure there would be much value in Canada conducting human challenge trials, at this stage. We're not a country that normally runs human challenge trials. They involve a significant investment in time and resources — “it takes a LONG time to get these trials going,” Claudia Emerson, a philosopher at McMaster University and a member of a World Health Organization expert group that has developed guidelines for the ethical acceptability of challenge trials, wrote in an email.
The first criterion listed in the WHO guidance is “scientific justification” — which may no longer exist once one or more vaccines are licensed before any Canadian challenge trial could be up and running, she said.
There's also debate about rescue treatment: We don't have one. “As such, are we really justified in intentionally infecting healthy human volunteers — even those that fully appreciate what they are consenting to, and are at low risk for complications and death from COVID-19 — given that we are still discovering much about SARSCoV-2 and its long-term impact?” Emerson asked.
“I just don't think we've hit the bar to justify the risk — we may get there, but I don't think we are there now.”
Health Canada has not received any applications for human challenge trials for any treatments, including for vaccines for COVID-19, the department said in an email. Before considering allowing a COVID-19 human challenge study, “we need to have sufficient information about the potential risks of the virus and how to mitigate them,” the agency said. “Global scientific and clinical knowledge of this new virus, including its impact on people, is still evolving.”
I JUST DON'T THINK WE'VE HIT THE BAR TO JUSTIFY THE RISK.