Tens of thousands of Americans have volunteered to test COVID-19 vaccines, but only about half of them got the real deal during trials.
Now, with the initial rollout of vaccines and an increase in coronavirus infections, experts are debating what to do about half who received a fake shot.
Should everyone be offered a vaccine now? Or should the two groups in the Pfizer and Moderna studies remain intact to collect long-term data on how well the vaccines work?
“There’s a real tension here,” said Dr. Jesse Goodman, an infectious disease specialist and former chief scientist at the US Food and Drug Administration. “There is no easy answer.”
HOW VACCINE STUDIES WORK
New drugs, vaccines, or treatments usually undergo rigorous testing and evaluation before reaching regulators for approval.
For vaccines, researchers compare what happens when a large group of volunteers are given the shot with what happens to another large group that doesn’t. They compare side effects in each group. And they measure the effectiveness of the vaccine by looking at how many infections in each group.
To do this fairly, researchers randomly assign participants to receive a vaccine or a dummy injection, usually a dose of salt water.
Volunteers know there is a 50-50 chance that they could be placed in either group – and they are not told which group they ended up in. Often the researchers or others involved in the testing are also “blinded” and don’t know.
SHOULD TEST VOLUNTEERS BE TOLD?
About 17,000 of the participants in Moderna’s study received a placebo, as well as about 22,000 people in Pfizer’s study.
With the ongoing coronavirus crisis, health experts worry that they will leave them in the dark and unprotected. They believe they should now receive a vaccine in recognition of their willingness to participate in the trials during the pandemic.
“Volunteers have played a huge role,” said Moncef Slaoui, chief scientist for the government’s Operation Warp Speed program. “They should be rewarded for it.”
The companies would have to ‘unblind’ or ‘unmask’ the studies to reveal whether the participants received the vaccine or the dummy injection.
Exposure usually occurs at the end of testing. However, Moderna and Pfizer designed their studies to be two years long for long-term follow-up.
“I don’t think anyone would find it reasonable or feasible to keep people blinded for two years,” said Susan Ellenberg, an expert on clinical trials at the University of Pennsylvania.
“Since we have a pandemic, people are willing to settle for the short-term results.”
PROS AND CONS OF “UNMASKATION”
With the rollout of vaccines and uncertainty about their status, volunteers may decide to lose weight as soon as they become eligible to get one. They can stay in the study if told what they have, said Dr. Ana Iltis, a bioethicist at Wake Forest University.
“The participants were able to leave en masse. They might say, ‘If you don’t tell me what I have, I’ll be out of here,’ ”said Iltis. “You can’t force people to stay.”
In an ideal world, participants could wait to find out if they got the dummy shot or the vaccine. But experts agree that the current conditions are extraordinary.
Still, unmasking participants would undoubtedly affect the scope and results of the studies.
For example, if someone learns that they have already been vaccinated, they can stop socializing or wear masks, increasing their potential exposure to the virus and potentially spreading it. It is not yet known whether vaccinated people can still carry and transmit the virus.
On the other hand, if a person finds out that they only got the dummy shot, they can take precautions that they otherwise wouldn’t.
Both outcomes, Goodman said, “means that the process is in fact over.”
Before granting emergency use approval, the FDA required Pfizer and Moderna to provide two-month follow-up data. When studies are cut short, it becomes more difficult to get long-term effects, including how long immunity lasts.
“There is a reason why we do clinical research in a certain way,” said Iltis. “We must not give up our standards and our principles. Are we going to be happy with short-term evidence in a year? “
WHAT THE COMPANIES SAY
Pfizer plans to eventually vaccinate all study participants. It opts for a more gradual, voluntary process. The company will offer that option to those who have received sham injections as soon as they have access to the vaccine outside of the study.
Moderna is considering immediately offering the vaccine to anyone who has received sham injections. More than a quarter of them are health professionals and are first in line for the vaccine anyway, the company said.
“Many have already left. Unfortunately it is not a small number, ”says Dr. Lindsey Baden, who is involved in testing Moderna’s vaccine at Brigham and Women’s Hospital in Boston. “This is not theoretical. It’s happening.”
British pharmaceutical company AstraZeneca, which has so far enrolled at least 23,000 in its ongoing US study, recently decided to allow individual participants to be exposed as soon as they become eligible for the approved vaccines.
“You never really want to eliminate the blindness,” said Dr. William Hartman, a researcher for the AstraZeneca study at the University of Wisconsin-Madison.
However, he added that the pandemic has complicated things.
“A lot of people are nervous and scared,” said Hartman. “And everyone comes to court hoping to get the vaccine.”
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The Associated Press Department of Health and Science is supported by the Science Education Department of the Howard Hughes Medical Institute. The AP is solely responsible for all content.