Coronavirus: Experts propose human challenge, ask healthy volunteers to get infected for speedy vaccine trial
As people across the world are avoiding social contact to check disease spread, scientists have come up with a radical and controversial proposal: a human challenge that asks healthy volunteers to get infected with the new coronavirus. The reason behind such a challenge is to speed up the testing of a vaccine by months, offering quick evidence if a shot works or does not.
The experts argue that such controlled studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related deaths and disease. They say multiple measures would be put in place to ensure that before consenting, potential participants fully understand the unusual risks involved in the study.
“A novel strain of coronavirus forces us to consider unconventional approaches. We believe that controlled SARS-CoV-2 vaccine challenge studies may accelerate the time it takes to evaluate and license vaccines and hence could make vaccines available sooner for widespread rollout,” says the scientific trio in a pre-print version of the proposal.
The research team includes Nir Eyal from the Center for Population-Level Bioethics and Department of Philosophy, Rutgers University, US and Department of Health Behavior, Society and Policy, Rutgers School of Public Health, US; Marc Lipsitch from the Department of Epidemiology, and Departments of Immunology and Infectious Diseases at Harvard T.H. Chan School of Public Health, US; and Peter G Smith from the Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, UK.
“Such an approach is not without risks, but every week that vaccine rollout is delayed will be accompanied by many thousands of deaths globally. Importantly, challenge studies are conducted against the background of competent volunteers’ informed consent, minimization of study risks, and high baseline risks of infection for participants. They do not violate participants’ individual rights on the altar of emergency response, but heed both individual rights and the global public health emergency,” says the trio.
Several trials of vaccines and potential drugs are already underway globally. But currently, there is no treatment or vaccine for COVID-19, which has killed 27,762 people globally. Over 598,240 confirmed cases have been reported so far. “We need fresh ideas to get out of the #COVID19 dilemma of sacrificing the economy, health care system, or both. Here Nir Eyal @RutgersU Peter Smith @LSHTM & I propose an ethical way to use controlled human challenge in volunteers to speed vaccine trials,” tweeted Lipsitch.
The World Health Organization (WHO) describes human challenge trials are trials in which participants are intentionally challenged (whether or not they have been vaccinated) with an infectious disease organism.
“Human challenge studies have been conducted over hundreds of years and have contributed vital scientific knowledge that has led to advances in the development of drugs and vaccines. Nevertheless, such research can appear to be in conflict with the guiding principle in medicine to do no harm,” says the WHO.
Explaining their current proposal, the researchers say that volunteers for human challenge studies would be drawn from previously non-infected individuals at relatively low risk of complications or death from COVID-19 infection -- such as young adults without chronic health conditions and not otherwise sick -- and who are at substantial risk of natural exposure to COVID-19 (for example, resident in areas with high transmission rates). The authors say that such a target group might comprise non-infected persons aged 20-45 years, an age range in which the risk of death or serious complications following infection is substantially lower than in older age groups.
“Controlled human challenge trials of SARS-CoV-2 vaccine candidates could accelerate the testing and potential rollout of efficacious vaccines. By replacing conventional Phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly,” says the study.
An article in the MIT Technology Review explains that the problem with vaccines is that it typically takes at least 18 months to test them and get supplies ready. “And a big chunk of the R&D time is given to a phase 3 trial, the main event, in which hundreds or thousands would get the vaccine and others would not, in an attempt to prove that those who are vaccinated don’t get the disease or have fewer symptoms if they do.”
In the current proposal, the experts say after the controlled human challenge model has been set up, vaccines could be evaluated. Following the challenge, the participants would be carefully followed to monitor whether those vaccinated had a different response to viral challenge. The researchers say that any volunteer in whom infection was confirmed, would receive “excellent care” for COVID-19, including priority for any scarce life-saving resources, in state-of-the-art facilities. Throughout the trial and until infectiousness was ruled out, all participants would remain isolated in a “secure and comfortable setting.”
The required size of such studies would depend upon the endpoints chosen, but they might require of the order of 100 volunteers, says the team.
Ethical concerns
The researchers write that deliberate exposure of study participants to COVID-19 clearly raises ethical concerns.
“It may seem impermissible to ask people to take on the risk of severe illness or death, even for an important collective gain. But we actually ask people to take such risks for others’ direct gain every time we ask volunteer firefighters to rush into burning buildings; relatives to donate a live organ to loved ones; healthy volunteers to participate in drug and vaccine toxicity trials with no prospect of improving their health (and some risk of undermining it),” argues the team.
They say a major reason why it is acceptable to risk medical harm to volunteers in medical studies, even when their personal healthcare does not require that risk, is that these volunteers will have “autonomously consented” to take on these risks.
“It might seem as though anybody volunteering to participate in such a study lacks the capacity for rational decision-making or must have misunderstood the informed-consent form. However, human beings do many important things out of altruism. We also let humans volunteer to do risky things all the time,” says study author Eyal in an interview to Nature. He explains that people, for example, volunteer to be emergency medical services during this period. “That significantly elevates their risk of getting infected. But it’s also very important,” says Eyal.
According to the experts, the proposed challenge will contain the risk to participants in multiple ways. “We do human-challenge studies for less deadly diseases quite frequently. For example, for influenza, typhoid, cholera, and malaria. There are some historical precedents for exposure to very deadly viruses. The thing that demarcates the design that we propose from some of these historical instances is that we feel there is a way to make these trials surprisingly safe,” Eyal tells Nature.
The measures to minimize the risk includes recruiting only healthy patients from age groups in which the risk of severe disease, death are low, and monitoring them carefully and frequently. There is the possibility that the vaccine candidate will protect at least some of those who are vaccinated, says the team.
“In the absence of an effective vaccine, a high proportion of the general population is likely to be naturally infected with COVID-19 at some point. This includes those who might participate in a challenge study. By volunteering to be artificially infected, they may be hastening an event that is likely to occur in later months anyhow,” the authors write.
An expert in challenge trials, Myron Levine from the University of Maryland tells MIT Technology Review that he does not believe the idea is merited yet. “Is this something you would allow your loved one to participate in? Ask yourself that,” says Levine.