The risk to young, healthy participants, the argument goes, is small to start with and offset by the potentially massive benefit to society
It began as a proposal on the fringes of science: deliberately exposing people to COVID-19 to speed up development of vaccines, even though there’s no sure-fire treatment for the potentially lethal bug.
But the controversial idea of so-called challenge trials to test coronavirus shots seems to be picking up steam, with one huge endorsement pushing the concept ahead in recent days.
Scientists at Oxford University, which published promising early results of its would-be vaccine Monday, say they’re actively planning a challenge study.
The Oxford team is working with an unusual grass-roots group, 1DaySooner, that has recruited more than 32,000 volunteers from around the world willing to risk getting COVID-19 by taking part in such a trial.
And the group said Monday it is in talks with other vaccine developers, too, not yet ready to go public with their intentions.
Last week, the organization released an open letter signed by several Nobel laureates and other academic experts promoting the concept, as a separate survey of residents of Canada and other countries found wide support for it.
“Challenge trials are no longer a thought experiment; they may soon become a reality,” Abie Rohrig, a 1DaySooner spokesman, said Monday. “Support is growing from many scientific fields.”
Underlying the movement is the widespread belief that the world will not be free of the pandemic — and the economic devastation wrought by it — until people can be immunized against SARS-COV-2, the virus that causes COVID-19.
The hope is that challenge trials can get vaccines on the market sooner than conventional Phase 3 studies, which depend on subjects being exposed to a pathogen in everyday life to see if they have immunity to it. That can take months or longer.
The risk to young, healthy participants, the argument goes, is small to start with and offset by the potentially massive benefit to society.
Critics respond that the danger is unacceptable because, unlike challenge trials conducted in the past, COVID-19 can kill and there’s no life-saving “rescue therapy” to treat it. Researchers preparing one of the first human trials of a vaccine in Canada have rejected the idea.
Adrian Hill, head of Oxford’s Jenner Institute, told The Guardian last week that his team developing a COVID-19 shot hopes to begin a challenge trial by the end of the year, in parallel with conventional Phase 3 studies.
Challenge trials are no longer a thought experiment
Using healthy people in their 20s as subjects, “everybody would agree that the risk is extremely low,” Hill told the British newspaper. “It’s so low that it’s very difficult to measure.”
The Oxford vaccine candidate, being developed with pharmaceutical giant AstraZeneca, is one of the furthest advanced in the world. And on Monday, the journal Lancet published results of a combined Phase 1 and 2 trial involving 1,073 people that found it to be safe and to generate an immune response.
Whether it actually prevents infection from the COVID-19 virus is another question, one that the Phase 3 or challenge trials would seek to answer.
A vaccine developed by China’s CanSino, which the Canadian government is now helping test, also published results of a 500-person trial showing general safety and a less-promising immune response.
Rohrig said 1DaySooner is in touch with other vaccine developers about conducting their own challenge trials, but they’re “not at a point where they can make a similar announcement.”
Meanwhile, the group is collaborating with the Oxford team in preparing the “challenge doses” — the live coronavirus to which participants will be exposed. That involves finding facilities where the exposure can occur safely, he said.
Ethicist Nir Eyal, who published the first peer-reviewed journal paper advocating COVID-19 challenge trials with colleagues at Rutgers University, said he too has heard from other scientists in the field.
“Some vaccine production teams have been in touch and expressed keen interest (in challenge trials),” he said. “That sometimes included people who publicly expressed no interest.”
Eyal said the concept can satisfy all the basic requirements of ethical research, such as informing subjects of the risk, limiting that danger and providing a commensurate benefit to society.
Rohrig cited recent French research that suggested the risk of death for COVID-19-infected people between ages 20 and 29 is about one in 14,000, and that includes those with underlying conditions. The risk of dying from donating a kidney — a practice society has long considered acceptable — is about one in 3,300, noted the 1DaySooner spokesman. He donated a kidney himself last year.
But Francoise Baylis, a bioethicist at Dalhousie University, is among those less than keen on the idea. She has advised the Canadian Centre for Vaccinology at Dalhousie that is readying Canadian trials of the CanSino vaccine.
She said challenge trials can only be ethically justified if there is no alternative with a similar risk-benefit equation. In fact, the Dalhousie group is planning to use “adaptive” trial designs, which enable studies to be modified as they move along in response to findings, and which they believe can be just as speedy.
“If you can achieve the same benefit — faster route to a safe and effective vaccine — with less risk to research participants, there is an ethical obligation to take (that) path,” said Baylis.