A research ethics board in the U.K. is in the process of considering whether to approve a first-of-its-kind human challenge trial to test out COVID-19 vaccine candidates. In order to test the potential vaccines, researchers are proposing to infect between 30 and 50 healthy trial participants – between the ages of 18 and 30 – with the virus. If the trial is approved, it is scheduled to begin in January.
Clinical trials are essential for identifying effective drugs and providing understanding about different diseases. But this trial, proposed by a Dublin-based research organization called Open Orphan and its subsidiary hVIVO, raises a few flags for some bioethicists.
While deliberately infecting participants to test a cure is nothing new in clinical trials, doing so when there is no rescue drug is a different matter altogether – even when the trial subjects are at lower risk of long-term suffering as a result of infection.
“You could manage them as best as you could, but the concern is that you could be participating in potentially direct harm to patients,” explains Dr. Kerry Bowman, a bioethicist at the Joint Centre for Bioethics at the University of Toronto. “And that would be problematic.”
For an ethics review board to approve this trial, the researchers will have to have shown a number of things, according to Dr. Francoise Baylis, an ethics professor at the University of Dalhousie faculty of medicine – the same things that must be proven before any clinical trial is given the green light.
The first is weighing the benefit of the trial against the harm. “The complication is often that the harms and benefits devolve onto different people,” Dr. Baylis explains. “So, the research subject is going to be at risk of those harms, but the potential benefits are to a different community – in this case, the population writ large, who would have something that would protect them from harm, including the harm from death.”
The researchers in the proposed vaccine trial may have chosen to infect a younger, generally healthier population in order to minimize the potential harm. But one of the issues that raises concerns for Dr. Bowman is whether consent can truly be informed when there is still so much that isn’t known about the virus.
“We’re going on the assumption that COVID-19 is primarily a respiratory illness and that if you’re young, your chances of becoming sick are lower,” he says. “But what if they have cardiovascular events? What if someone throws a clot? We’re hearing there can even be kidney and neurological involvement. Is that as remote a chance as being hit by lightning? We don’t know, and that is the element of the consent process that I see as so problematic.”
The need for extrapolation in a trial such as this is also a concern – putting one population at risk, even though the risk they face may be smaller, to test a drug that is more essential for a different demographic entirely. “Is it a major benefit or not?” Dr. Bowman says. “How far can you extrapolate between the reaction in people between 18 and 30, and what’s going to happen if you’re 75?”
Walking the fine line between coercion and exploitation of study participants is another ethical challenge in any clinical trial. Typically, trial participants are compensated for stepping out of their lives and taking a risk for the greater good.
But the wrong amount or type of compensation may impact consent. “If I give too little, then I’m clearly exploiting you, but if I give you too much, then it’s coercive,” Dr. Baylis says. “So how do I get to that perfect number? I don’t actually think you can.”
In this and many other regards, bioethics has come a long way since the shocking Tuskegee Syphilis Experiment, which involved 600 poor black men from Alabama and ran from 1932 to 1972. The goal was to study syphilis that was left untreated. The promise was free health care – which none of the participants had ever had. The men were never told they had the disease, and when penicillin was discovered as a treatment in the mid-1940s, they were not given it.
“It’s one of the most disgusting episodes in public health history,” says Dr. Madeleine Mant, a research associate in anthropology at the University of Toronto. “And it’s amazing how recent it is.”
Now, fortunately, every facet of design of a clinical trial has to be rigorously explained. And while researchers in this case would have had no trouble doing so, the question remains of whether the trial is even justified when there are 50 other candidate vaccine trials under way and several more in Phase 3.
“One of the things that’s also worth thinking about is how much acceleration society can tolerate,” Dr. Baylis says. “Everybody wants the vaccine faster, but they want to have confidence that it’s safe and effective, and part of the way you get that robust data about safety and efficacy is [over] time.”