Could risky human challenge studies help find a vaccine sooner?

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As researchers around the world race under immense pressure to develop a COVID-19 vaccine, a controversial approach could potentially help get them there faster — but it's incredibly risky.

The process is known as a human challenge study, and it involves intentionally infecting willing volunteers with the coronavirus that causes COVID-19 in order to test the effectiveness of potential vaccines and treatments against it.

"These are very powerful studies that could make a difference, especially since we don't know a lot about the novel coronavirus," said Seema Shah, a medical ethicist at Northwestern University and Lurie Children's Hospital of Chicago. 

"They could clarify what's happening in infections with people who are not symptomatic and people who have more severe disease — even if they don't have underlying conditions that put them at higher risk."

Shah said COVID-19 human challenge studies could also help identify people who have developed immunity to the coronavirus, while also helping to narrow down the growing list of potential vaccines and treatments for patients.

"If there were a couple of vaccine candidates that had gotten through safety testing and there was a question about which one of those vaccines was more likely to work, a human challenge study could be a quick way to pick the best vaccine of the candidates," she said. 

"It could also be useful to study whether the vaccine itself causes different kinds of harm."

The WHO says any potential vaccine is still at least a year away, but human challenge trials could accelerate the process because of the time they save in the clinical trial phase.

Typically, researchers inject thousands of study participants with a vaccine or placebo and wait for symptoms to develop — an approach that can take months or years after vaccine development.

Human challenge studies instead vaccinate a small group of people and then intentionally infect them with the virus, saving critical research time, especially during a global pandemic.

But despite the potential benefits of a controlled human challenge study on COVID-19 patients, experts say the controversial approach is an ethical minefield that could have disastrous consequences if not handled carefully.

Ethical balancing act

Human challenge studies typically recruit young, healthy volunteers in an effort to keep the risk of severe medical complications low. 

Thousands of potential volunteers have already pledged to participate in human challenge trials on a website called 1DaySooner, but no such studies are yet underway.

Yet given what we know and don't know about the different ways in which COVID-19 attacks the human body even in young, healthy people, how do we effectively inform participants who may be unknowingly putting themselves at severe risk? 

"We know that younger people tend to tolerate COVID-19 as an illness better, but what would worry me about that is there's a lot that is still unknown," said Kerry Bowman, a bioethicist and professor of global health at the University of Toronto. 

He said the potential for COVID-19 patients of all ages to face long-term health implications and even death from a virus we still know so little about calls into question how truly informed participants could be on the risks of a human challenge study. 

"Do you truly have an informed decision?" he said. "You have consent, but is it really well-informed? Do people fully understand? Because if we don't understand the virus itself, I wonder about the quality of informed consent that you can ask of people."

'Amount of social value is unprecedented'

In a new paper published in the journal Science Thursday, Shah and a team of international researchers outline an ethical framework for how human challenge studies could be effectively used to combat COVID-19. 

The researchers support developing a "challenge strain" of the coronavirus — a stabilized version of the one that is circulating worldwide — to potentially infect participants, but stopped short of advocating for the work to proceed. 

"The pandemic has affected just about everyone in the world in various ways, so the potential amount of social value is unprecedented here," Shah said. 

"That's why our group concluded it's really important to give challenge studies a hard look and potentially invest in laying the groundwork for doing them.

"But then make that judgment call about whether and how to do them at a later date when they're ready to go."

The World Health Organization released specific criteria this week outlining its recommended approach to conducting human challenge studies, without advocating for or against them.

Volunteers must know the uncertainties

Among those recommendations is a need for "strong scientific justification" for the studies, ensuring that the potential benefits outweigh risks and that the selection of participants should be done with "rigorous" informed consent.

"The overarching, really important one is to minimize risk to participants as much as possible," said bioethicist Dr. Ross Upshur, of the University of Toronto's Dalla Lana School of Public Health, who helped work on the WHO guidelines. 

"You need to make sure that people understand what's being proposed: what they're going to be doing; how they're going to be managed in this situation; how their safety and their well-being is going to be protected.

"But it's also incumbent on the researchers to outline all of the uncertainties, because we may not be able to actually quantify some of those risks."

Huge implications if studies backfire

Timothy Caulfield, a Canada Research Chair in health law and policy at the University of Alberta who has researched human challenge studies, said those ethical dilemmas have historically plagued this approach. 

"I understand the desire to use human challenge trials, especially in this context, because people are desperate to get a vaccine quickly, not just for clinical reasons, but also for economic and social reasons," he said.

"So the pressure is intense, but the exact reason that we have research ethics guidelines is to protect research participants." 

Caulfield said the damage that could be done if a human challenge trial were to go awry would be devastating. 

He points to the ethics scandal involving Jesse Gelsinger, a teenager who died in a clinical trial for gene therapy in 1999, as an example of a failed human study that set the research ethics field back immensely. 

Gelsinger had a genetic disease called ornithine transcarbamylase (OTC) that he controlled through diet and medication, but after enrolling in the trial he was injected with an experimental therapy and died a few days later. 

"Just imagine the impact that it could have on vaccine research, especially in this environment where there's so much uncertainty," Caulfield said. 

"If it doesn't go well and if we cut corners on research ethics standards, it could end up backfiring and being really problematic."

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