Human challenge studies to speed development of a COVID-19 vaccine are unethical

LONDON, ONT.—The COVID-19 pandemic is a once-in-a-century global health crisis. In Canada, a coordinated public health response, involving physical distancing, testing, contact tracing, and isolation of cases and contacts, has largely been successful in “flattening the curve.” Yet, many European countries are now in the midst of a second wave that Canada may not be able to avoid. It seems clear that a return to normal life will not occur until a safe and effective vaccine is widely available. How can we speed the development of a vaccine for COVID-19? Some have suggested that human challenge studies, in which healthy volunteers are intentionally exposed to the novel coronavirus, are the answer. Traditional vaccine studies are stepwise and laborious. Establishing that a vaccine prevents disease requires large trials in the community in which some people receive the vaccine and others are given a placebo. But epidemics are capricious; infection rates wax and wane, and epicentres of infection may shift away from communities in the trial. Because exposure to the infectious agent is uncontrolled, vaccine trials in the community require tens of thousands of participants. Human challenge studies are more efficient than traditional vaccine trials because they control for exposure. Healthy volunteers are given either vaccine or placebo and then all are exposed to the infectious agent. If less people who received the vaccine become sick, this is evidence that the vaccine prevents disease. Because exposure is assured in a challenge study, only a few hundred participants are needed. But is it ethically permissible for scientists to intentionally expose healthy volunteers to the novel coronavirus? Earlier this year, I served on the World Health Organization’s Working Group for Guidance on Human Challenge Studies in COVID-19 that examined this question. In May 2020, WHO issued ethical guidelines for COVID-19 challenge studies. Because the guidelines did not rule out COVID-19 challenge studies tout court, some interpreted our report as giving them a “green light.” The Guardian reported that “WHO has said could possibly go ahead using healthy, young volunteers.” Nir Eyal, a bioethicist at Rutgers University, was quoted in the same article saying the acceptability of challenge studies reflects an “emerging consensus among everyone who has thought about this seriously.” Having thought about this seriously, I do not believe that COVID-19 challenge studies can, at present, satisfy the WHO ethical guidelines. Three criteria present obstacles to challenge studies. First, the WHO guidelines require that a challenge study be scientifically justified. Scientists must provide evidence that “similar results could not feasibly be obtained as efficiently or expediently in other study designs involving less risk to human participants.” The considerable progress observed in traditional vaccine development since May 2020 has largely undercut the case for challenge studies. According to an article in Nature Reviews Drug Discovery (Sept. 4, 2020), of 321 vaccine candidates, 32 are currently being evaluated in clinical trials “with plans to enrol more than 280,000 participants … in 34 different countries.” We are told that “data to support licensure are anticipated to be available later this year.” As challenge studies take months to set up, we are likely to have a vaccine in hand before such studies can even begin. Second, the risks and potential benefits of a challenge study must be rigorously assessed. In challenge studies, “risks to participants should … be carefully controlled and minimized.” But too many uncertainties remain about the long-term effects of COVID-19 to view intentional infection as plausibly “controlled” or posing minimal risk. While the effects of COVID-19 on the lungs is widely known, it has emerged that the virus can infect the heart, major blood vessels, and the brain resulting in myocarditis, strokes, and other neurological sequelae. Even more worrisome, are the increasing numbers of people reporting symptoms that persist months after acute illness, so-called coronavirus “long haulers.” Third, procedures for selecting participants must be fair. One possible way of reducing the risks of participation in a challenge study is to include people who are at higher risk of infection in the community—the incremental risks of study participation are discounted by their background risk. But the WHO guidelines are clear that “those whose background risk is high as a result of social injustice should be excluded from participation because their inclusion could be considered unethical exploitation.” It has become clear that some social groups are at higher risk of COVID-19 because of structural injustice. Health providers are at higher risk of COVID-19 when access to personal protective equipment is lacking. Black people and indigenous people have higher rates infection and death from COVID-19 when living conditions are crowded and access to healthcare is poor. If COVID-19 challenge studies are not ethical at present, do they have a future role in vaccine development? I believe they may. Work should continue on the development of an attenuated strain of the novel coronavirus that causes only mild disease and poses no risk of severe disease. The development of an attenuated strain may take one or two years, but it could prove useful in the efficient identification of second-generation vaccines for COVID-19, particularly as rates of infection decline. Charles Weijer is a professor of medicine, epidemiology & biostatistics, and philosophy at Western University. He was a member of the WHO Working Group for Guidance on Human Challenge Studies in COVID-19. The Hill Times