U.K. human challenge trial questioned
U of T bioethicist says COVID-19 poses different set of potential dangers
Volunteers in the U.K. will soon get an intentional dose of COVID-19 in a trial that will deliberately expose them to the virus, and some Canadian ethics and infectious disease experts are wondering if that’s worth the risk.
Studies like the one approved last week in Britain — called human challenge trials — involve exposing volunteers to a specific pathogen to give researchers insight into how infection spreads or which treatments and vaccines work best against it.
Britain’s trial, the first to be authorized by regulators, is expected to start within a month and will feature up to 90 healthy volunteers between the ages of 18 and 30.
While human challenge trials have been used to study other diseases like malaria and cholera, University of Toronto bioethicist Kerry Bowman says COVID-19 poses a different set of potential dangers.
Bowman says challenge trials need to address three issues of consent before they can be considered ethical: participants must be capable of consenting and do so voluntarily, and they need to be informed in their decision. The U.K. study ticks off the first two boxes, he says, but the third is questionable.
“Clearly (consent) is voluntary and it’s quite capable, but what I take issue with is: are volunteers fully informed?” Bowman said. “We’re a year into the pandemic and COVID is still a fairly unpredictable pathogen.
“You cannot definitively say what will happen to a 25-yearold with no pre-existing health problems.”
The U.K. government says volunteers will be exposed to COVID-19 “in a safe and controlled environment,” with participants monitored 24 hours a day.
The study is calling on young people to volunteer because they have the lowest risk of serious illness from COVID-19, but health experts warn that risk isn’t zero.
Dr. Zain Chagla, an infectious disease specialist at St. Joseph’s Healthcare Hamilton, says the U.K. challenge trial will be missing a key safety component: the ability to reverse any damage if things go awry.
“If you want to expose people, it has to be in the context of being able to salvage people,” Chagla said, noting that although some drug treatments exist, they can’t prevent death or significant complications in everyone.
“We know there are young people that die of COVID-19. It’s not a large number, but it’s not predictable who is going to have that outcome.”
So why the risk? Jeff D’Souza, a research associate at McMaster’s Institute on Ethics and Policy for Innovation, says the benefit of a challenge trial — what’s learned from it — needs to outweigh relative danger to volunteers.
The U.K. government says one aim of the study is to determine the smallest amount of virus needed to cause infection. It also hopes to “help support the pandemic response by aiding vaccine and treatment development.”
D’Souza noted that since trial participants will be monitored closely, they’ll be in a safer environment than if they caught the disease naturally.
He adds the study would have needed to pass a stringent review process based on World Health Organization criteria before it gained approval, and that it was “able to demonstrate that such trials are ethically defensible and acceptable.”
While valuable info about infection and transmission can be gleaned from a challenge trial, Chagla says there are safer ways to get those answers.
The pervasiveness of the virus worldwide would make it easy for researchers to study groups of people who were naturally exposed, he said, rather than adding to the COVID burden in a deliberate way.
He also questions whether the trial’s potential findings will be relevant.
“They might matter from an infection control standpoint, but is it going to change how we practise COVID-19 medicine … or change the pathway for vaccines and treatments?” Chagla asked. “It might change infection control a bit, but even that’s not sure.”
At least some Canadians expressed interest in volunteering for a human challenge trial before vaccines were approved. An e-petition with 543 signatures from September to October urged the government to take one on, citing the need for “multiple vaccines to meet global demand.”
The government responded to the petition in December, saying a human challenge trial for COVID-19 would “involve a higher risk” since the virus was still new and long-term effects weren’t fully known.
Bowman thinks it’s unlikely a COVID challenge trial would gain approval in Canada, especially now that multiple vaccines have been approved globally and there’s data from millions who have been inoculated.
“Any kind of contribution to make vaccine (development) faster and more efficacious would be a wonderful thing,” he said. “But my position is I really don’t think a human challenge trial is justifiable.”