Ethics Expert Says Challenge Trials Are Being ‘Mulled Over’ in the U.S., UK
The University of Oxford and the National Institutes of Health (NIH) are considering launching human challenge trials if enrollment requirements in standard COVID-19 studies can’t be met.
A leading ethics expert who has justified the use of challenge studies says they are being mulled over in the U.S. and UK for COVID-19, using a weaker form of the virus to intentionally infect trial participants.
The University of Oxford is currently preparing a weakened virus agent that researchers may potentially use in a challenge study, said Arthur Caplan, a professor of bioethics at New York University Grossman School of Medicine and the founding director of its medical ethics division, at last week’s WCG Clinical COVID-19 webinar.
“I know that at least there, they’re getting ready if they don’t get enough enrollment on the standard model to move toward the challenge study direction,” he said.
Preparations are also being made in the U.S., including at NIH, “so we could see an argument being made to do the challenge study.”
He contends that challenge studies can provide stronger, faster data and be designed so that participants are monitored closely and given medical care in the case of adverse events. He has argued in the past that in some instances challenge trials can be justified from an ethical perspective (CenterWatch Weekly, May 18). Additionally, trials can be structured to pose less risk, such as by starting with younger subjects who have a lower chance of dying, he said.
On the other hand, critics of challenge studies argue that they violate the “do no harm” principle by deliberately infecting patients, aren’t that much faster, pose too great a risk and are especially immoral without a strong rescue therapy. They also believe that not enough patients will consent to participating.
“Yes, it’s dangerous, but I don’t think the risk is too high,” Caplan said. “And the consequences of not going faster is the world is exposed both to the damage of the virus and the economic consequences.”
He noted that many past studies have been done without a rescue therapy, including other challenge studies on vaccines, and added that 1Day Sooner, an advocacy organization for patients interested in participating in COVID-19 challenge trials, has had thousands of people sign up as volunteers. Currently, the website lists 32,665 patients in 140 countries who have expressed interest in participating.
“A couple places are already building the weakened virus right now to get ready should it come to the point where we decide — a sponsor or government — to do a challenge study model,” he said. “I think the model is worth considering.”
In a July 15 letter to the NIH, more than 125 of the world’s top scientists called on the U.S. government to start conducting human challenge trials to accelerate COVID-19 vaccine development.
Citing the urgency of finding a vaccine for the deadly virus, the scientists — among them 15 Nobel laureates as well as the director of Oxford University’s large COVID-19 vaccine program — say the ethical objections to infecting healthy volunteers with a disease that has no known cure are outweighed by the common good.
In a similar letter sent to the FDA in April, 35 U.S. lawmakers also encouraged the use of challenge trials, saying “justifiable risks may be taken” (CenterWatch Weekly, April 27). The agency responded by suggesting animal testing could be used instead.
NIH Director Francis Collins’ previously stated position on the subject has been that challenge trials are open to discussion, but that the NIH is not yet ready to move forward with a human challenge trial plan.
At the webinar, Caplan also expressed criticism of a lack of peer review of COVID-19 research articles and papers. He says a lack of peer review has become apparent during the pandemic, which has seen research move at lightning pace. According to Caplan, medical journals are not conducting the same amount of peer reviews they did pre-pandemic, and preprint servers “are often throwing the papers out there with very minimal review of what’s there.”
“Journals are speeding up the time they have to review articles in the plague era, from submission to publication. Thousands of papers are also being uploaded on open access preprint servers without really going through the normal peer review process,” he said. “We face a big peer review problem.”
NYU’s Retraction Watch, which has been keeping track of retraction notices and expressions of concern about COVID-19-related research, has seen a sharp rise in retractions, he said, including some in big name journals like the New England Journal of Medicine and the Annals of Internal Medicine. These big journals have had to pull papers either because the authors did not submit raw data for confirmation or had sample sizes that were underestimated, Caplan said.
“A lot of these studies get into social media. The press and the media have an unending appetite for solutions to the COVID pandemic,” he said. “Bad science moves quickly to the public.”
Caplan called for the scientific community to start waiting for confirmation and begin testing promising initial hypotheses in real trials to be sure that “junk” science is not promoted and recommended that more money and resources be put toward peer review overall.
“The system can’t take publication pressures in a plague. It just wasn’t built for that, and it’s getting overwhelmed,” he said.