Tens of thousands of Americans offered to test COVID-19 vaccines, but only half of them got the right thing during trials.
Now, with the first explosion of vaccines and an increase in coronavirus infections, experts are thinking about what to do about the half who got a 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,” said Dr. Jesse Goodman, an infectious disease specialist and former chief scientist at the U.S. Food and Drug Administration. “There is no easy answer.”
HOW WORK STUDIES WORK
New medicines, vaccines or treatments usually go through rigorous tests and evaluations before regulators are reached for approval.
For vaccines, researchers compare what happens when a large group of volunteers gets the shots, versus what happens to another large group that does not happen. They compare side effects in each group. And they measure the effectiveness of the vaccine by looking at how many infections are in each group.
To do this fairly, researchers randomly assign participants to receive a vaccine or a shot, usually a dose of saline.
Volunteers know that there is a 50-50 chance that they could be placed in one of the two groups – and they are not told in which group they ended up. Often the researchers or others involved in the test are also “blinded” and do not know either.
SHOULD VOLUNTEERS BE TESTED?
About 17,000 of Moderna’s study participants received a placebo, as well as about 22,000 people in the Pfizer trial.
With the ongoing coronavirus crisis, health experts are worried about leaving them in the dark and unprotected. They argue that they should now get a vaccine in recognition of their willingness to be part of the trials during the pandemic.
“Volunteers were instrumental,” said Moncef Slaoui, chief scientist of the government’s Operation Warp Speed program. “They should be rewarded for it.”
The companies will need to “unblind” or “unmask” the studies to show whether participants are getting the vaccine or the shot.
Unmasking is usually done at the end of the test. However, Moderna and Pfizer designed their studies to take two years to do long-term follow-up.
“I do not think there is anyone who thinks it is reasonable or feasible to keep people blind for two years,” said Susan Ellenberg, an expert in clinical trials at the University of Pennsylvania.
“Since we have a pandemic, people are willing to be content with the short-term results.”
ADVANTAGES AND DISADVANTAGES OF “UNMASK”
With the deployment of vaccines and the uncertainty about their status, volunteers may decide to drop out as soon as they are eligible to get one. They will possibly stay in the study if they are told what they got, says dr. Ana Iltis, a bioethicist at Wake Forest University.
‘Participants could leave in large numbers. They can say, ‘If you do not tell me what I got, I’m out of here,’ ‘Iltis said. “You can not force people to stay.”
In an ideal world, participants could hold out to find out if they had received the dummy shot or the vaccine. But experts agree that the current circumstances are extraordinary.
Yet the unmasking of participants will undoubtedly affect the scope and results of the trials.
For example, if someone notices that they have already been vaccinated, they may stop taking social distribution or wearing masks, which increases and potentially spreads their potential exposure to the virus. It is not yet known whether people who have been vaccinated can still carry and transmit the virus.
On the other hand, if someone notices that he has just received the dummy recording, they can take precautions if they would not do otherwise.
Both outcomes, Goodman says, “mean that the trial basically came to an end.”
Before the FDA granted permission for emergency use, the FDA required Pfizer and Moderna to provide two months of follow-up data. If studies are cut short, it becomes more difficult to get long-term effects, including how long immunity lasts.
“There’s a reason we do clinical research in a certain way,” Iltis said. “We must not abandon our norms and our principles. Are we going to be content with short-term evidence in a year’s time? ‘
WHAT THE COMPANIES SAY
Pfizer plans to eventually vaccinate all of its study participants. It opts for a more gradual, voluntary process. The company offers the option to those who get a shot as soon as they have access to the vaccine outside of the study.
Moderna is considering offering the vaccine immediately to anyone who has received chips. More than a quarter of them are health workers and are in any case the first in line for the vaccine, the company noted.
‘Many have already left. Unfortunately, this 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. “It’s not theoretical. It happens.”
The British pharmaceutical company AstraZeneca, which has so far enrolled at least 23,000 for its ongoing US study, recently decided to offer individual participants the opportunity to be unmasked as they are eligible for the approved vaccines.
“You never really want to go blind,” said Dr. William Hartman, a researcher at AstraZeneca’s trial at the University of Wisconsin-Madison, said.
However, he added that the pandemic is complicating matters.
“A lot of people are nervous and scared,” Hartman said. “And everyone comes to the trial hoping to get the vaccine.”
___
The Associated Press Health and Science Division receives support from the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.