Scores of academics call for ‘human challenge’ trials of coronavirus vaccine

Dr. Francis Collins (left), director of the National Institutes of Health, and Dr. Robert Redfield, director of the Centers for Disease Control and Prevention, testified during a Senate subcommittee hearing on the plan to research, manufacture, and distribute a coronavirus vaccine.SAUL LOEB/AFP via Getty Images

Scores of academics and prominent figures, including several Nobel laureates from Massachusetts, have signed an open letter calling for consideration of human challenge trials of coronavirus vaccines, saying such trials might be able to speed up development of the shots desperately needed to stop the pandemic.

The letter, addressed to National Institutes of Health Director Dr. Francis Collins, urged the US government, its allies, the World Health Organization, and international funders “to undertake immediate preparations for human challenge trials” that “can greatly accelerate the development of a COVID-19 vaccine.”

In a human challenge trial, a small number of people would get the vaccine and then be intentionally infected with the virus to see if the vaccine works. In a normal clinical trial, thousands of people get the vaccine and researchers wait to see if the vaccine protects them as they go about their daily lives.

“I think we need to prepare for human challenge trials and for the possibility that we will need to do them,” said Marc Lipsitch, a professor of epidemiology at the Harvard T.H. Chan School of Public Health and director of its Center for Communicable Disease Dynamics. “We should be preparing the plans, the protocols, the virus strains, the facilities, and other prerequisites to do them.”

Tens of thousands of people have already indicated their interest, by offering to participate on a website. The idea also caught the eye of Congress earlier this year. Thirty-five House members, including Massachusetts Representatives Stephen Lynch and Seth Moulton, signed a letter in April asking regulators to consider using such trials.

Moulton, a Salem Democrat, said in a statement Thursday night that “tightening the timeline by even a week means thousands of lives saved.”

“We need to act as aggressively as possible to find a vaccine or treatment for this virus,” Moulton continued.

The potential for severe illness, or even death, of the subjects in the human challenge trial raises serious ethical questions. There is no cure for COVID-19, the disease caused by the coronavirus. But some researchers believe there is a way to conduct the trials, with one key safeguard being the use of young, healthy volunteers who are less likely to be harmed by the virus.

“If done properly, live Coronavirus human challenge trials can be an important way to accelerate vaccine development and, ideally, to save the lives of millions around the world as well as help rescue global economies,” the letter said.

The letter, which was posted to the Internet Wednesday, has 125 signers including experts in everything from epidemiology to philosophy and law.

A number of Massachusetts academics are on the list. Nobel Prize winners from Harvard, the University of Massachusetts, and Brandeis were among 15 laureates who signed the letter.

The signatures were rounded up by 1Day Sooner, an organization that has signed up more than 30,000 volunteers from 140 countries for human challenge trials, said cofounder and executive director Josh Morrison. More than 2,000 of the study volunteers signed the open letter.

Lipsitch, who signed the letter and has been an informal adviser to 1Day Sooner, was a coauthor of an influential article in The Journal of Infectious Diseases earlier this year proposing human vaccine trials that, Morrison said, inspired the formation of 1Day Sooner.

Lipsitch said the number of volunteers who have stepped forward says “there are a lot of people out there in the world who feel that it’s worth taking some risk to help humanity by helping develop a vaccine faster.”

“I think we have to be very sober about it,” he said. “This is a serious undertaking, like joining the military or signing up for a dangerous mission, if you’re in some profession that has dangerous missions, or deciding to go climb Mount Everest.”

Noting that the World Health Organization has issued guidance for ethically conducting human challenge trials, the letter laid out a list of protections that “should be clearly in place” for such studies, including:

• Participants should be relatively young and in good health. The letter noted that the mortality risk of the coronavirus to 20- to 29-year-olds, healthy and unhealthy, is similar to that of living kidney donors.
• Participants should be provided the highest quality medical care with frequent monitoring.
• Participants must give their informed consent through a “robust” process.
• The trials must undergo scrutiny, including ethical and scientific reviews of the highest quality, and public discussion.

Skeptics of the idea include Jeffrey Kahn, director of the Johns Hopkins Berman Institute of Bioethics, who said he’s doubtful that a human challenge trial for coronavirus could be conducted while satisfying all the ethical obligations.

Too much remains unknown about the long-term health consequences of the virus for researchers to provide volunteers with full information about the potential risks of infection, Kahn said.

“Voluntary agreement isn’t enough for recruiting people into research,” he said in an e-mail to the Globe. “For me there’s too much uncertainty, making this premature and problematic.”

Kahn added that isolating study participants would add further stress to heavily burdened medical systems, and said a challenge trial doesn’t guarantee that a vaccine will be available sooner.

“It will take months, maybe many months, for a challenge strain to be developed, assessed, and eventually approved by regulators,” he said.

Some, including members of the WHO advisory panel that developed the guidelines, have also raised other questions, including whether a vaccine that prevents the coronavirus in young, healthy people would work in older or high-risk people and whether such trials would really speed vaccine development, The New York Times reported. Questions have also been raised about whether a small challenge study would miss rare side effects that would become a problem when the vaccine is given to billions of people.

Morrison said it’s possible that human challenge trials could save months in the development of a vaccine for the virus, which has killed more than 588,000 people around the world, including more than 138,000 in the United States.

He said a human challenge trial for a vaccine could potentially be set up by the end of the year, and the answer to whether the potential vaccine worked would be available in “about a month.”

But he also noted that some current regular clinical trials, such as those by researchers at Cambridge-based Moderna Therapeutics and Oxford University, could come up with results sooner.

Moderna is poised to enter the final stage of testing on July 27. It will enroll up to 30,000 adults at high risk of contracting the coronavirus, giving half of them a placebo and half the vaccine. Oxford is also already conducting final tests of its vaccine.

Problems can arise for a regular clinical trial if the amount of infected people in the population drops so low that vaccinated people in the trial’s final stage don’t have much chance of running into people who will infect them. That situation does not apply currently in the United States, where cases are surging in many states. But if it did at some point in the future, human challenge trials could step in, Lipsitch said.

Once the first vaccines have been approved, human challenge trials could be used to test new vaccines that might be better or to probe further into the details of how approved vaccines actually work, he said.

“I think it’s something that should be developed because we don’t know how long the pandemic will be raging,” he said. “It’s a tool we might need.”

Jeremiah Manion of the Globe staff and Globe correspondent Jeremy C. Fox contributed to this report.