Good news for tens of thousands of volunteers in the COVID-19 vaccine trials: Many of those who received a placebo are now being offered a vaccine—in some cases, earlier than they would otherwise have been eligible.
Participants in Pfizer’s vaccine study—some of whom had mounted a noisy campaign on social media—have been advised that anyone who wants one can receive the first of two shots by March 1. Participants in Moderna’s vaccine trial are already getting immunized.
That wasn’t always the plan, and some experts fear “unblinding” volunteers—that is, letting them know whether they got the vaccine or a placebo—could make it difficult to collect good, long-term data on the experimental vaccines, including how safe they are and when their immunity starts to wear off. But others argue it would be unfair to leave trial participants unprotected from a raging pandemic when an effective vaccine is available.
“Who brought you here?” asked Dr. Larry Corey, a virologist at Fred Hutchinson Cancer Research Center in Seattle and co-leader of the vaccine testing program for the U.S. government’s Operation Warp Speed. “Social justice says you should vaccinate all the placebo recipients as quickly as you can.”
He noted that vaccine lots manufactured and labeled for clinical trials are earmarked exclusively for research: “These vials of vaccine can’t be given to anyone else.”
When they registered for clinical trials, volunteers signed consent forms agreeing to be randomly assigned to receive shots of an experimental vaccine or a placebo—salt water—and to be followed for two years. Nothing was mentioned on those forms about placebo recipients getting the real vaccine if and when it was approved.
But the trials, nearly all supported by Operation Warp Speed, have reportedly been spectacularly successful. In a matter of months, two vaccines—those developed by Moderna and Pfizer/BioNTech—collected enough evidence of safety and efficacy to receive approval for emergency use from the federal Food and Drug Administration, and at least one more—Janssen’s—is believed to be close behind.
An unknown number of volunteers have been offered vaccine shots through their work or their local health department and have dropped out of the trials. The threat of losing study participants to follow-up may have sped up the unblinding process.
“It’s critical, no matter what they got, that we continue to observe these folks, particularly for evidence of waning immunity,” said Dr. Steven Goodman, professor of epidemiology at Stanford School of Medicine. “If too many people feel they’re disadvantaged by being in the trial, you could lose a lot of people to follow-up.”
Michael Tovar of Los Angeles, who owns a postproduction film company with his husband, Brian Levin, is a volunteer in the Pfizer trial. He doesn’t know whether he received a vaccine or placebo and was sorely disappointed when he was told he’d have to wait until his fourth clinic visit—April 6—to find out.
“We all stepped up, and we should be rewarded,” he said. “I started to tweet at Pfizer daily, and so did a ton of others.
“I want all developers—once they get the EUA (emergency use authorization)—to vaccinate the placebo group as soon as possible. They should have people vaccinating 24/7.”
Nevertheless, Tovar said he’s “somewhat OK” with the updated news that he’ll be called back no later than March 1.
Levin, who is in the ongoing Janssen trial, has heard nothing yet. Janssen stopped enrolling new volunteers on Dec. 17 and is expected to release data for its single-dose COVID-19 vaccine later this month.
Dr. Habib Ahsan, leader of the Janssen trial and director of the Institute for Precision and Population Health at UChicago Medicine, said “any participant who will become eligible to receive an approved vaccine should be allowed to decide if they want to be unblinded” and get immunized outside the trial. But, “as of now, only 1a’s are eligible—front-line health care workers and nursing home staff and residents.”
Volunteers who received Janssen’s experimental vaccine (an adenovirus-based vaccine) will be told there is no data about the safety of receiving a different type of vaccine (Pfizer and Moderna are both mRNA vaccines), so they should probably wait at least two weeks (as recommended by the Centers for Disease Control and Prevention). But for those in the placebo arm, “there are no safety concerns.”
Importantly, Janssen trial volunteers who choose to get a different vaccine can remain in the trial and continue to be followed.
“Those persons will still be valuable to the trial,” Ahsan said.
Levin, 37, said he expected that, if the experimental vaccine turned out to be safe and effective, the trials would follow a protocol known as blinded crossover, endorsed by Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, among other experts, in which all volunteers come back for a second round of shots. Those who got the placebo get the vaccine, and those who got the vaccine get the saline solution—but everyone remains blinded.
That is considered the gold standard for clinical trials, but it was not part of the original protocols. Pfizer and Moderna told the FDA it would be too cumbersome to impose now.
Goodman, the Stanford epidemiologist, said unblinding volunteers as they become eligible for an approved vaccine—and as those approved vaccines become available—is a good compromise. “The blinded crossover would have afforded more scientific validity,” he said, “but if they’re getting at least five or six months of data for most participants, that may be as good as they can get—and it might keep people in the trial who would otherwise leave.”
Dr. Jesse Goodman (no relation to Dr. Steven Goodman), professor of medicine and infectious diseases at Georgetown University School of Medicine and a former FDA chief scientist, agreed that volunteers who are eligible “shouldn’t be penalized because they’re in a trial.” But he questioned the Moderna approach, which might let trial participants “go to the front of the line: Does that then become the expectation of everyone in every trial?”
He also pointed out that “as exciting as these vaccines are, they’re not yet approved. We have very strong data, but only a few months’ worth. We need high-quality clinical follow-up and observation. You don’t want them disappearing.”
Source: Read Full Article