A committee of leading U.S. vaccine scientists recommended Thursday that the Food and Drug Administration authorize the first COVID-19 vaccine for Americans.
The endorsement paves the way for a final decision by the FDA and mass vaccinations to begin within days in thousands of front-line heath care workers and nursing home residents.
After an eight-hour public hearing, the independent
Vaccines and Related Biological Products Advisory Committee voted 17 to 4 with 1 abstention to recommend the vaccine made by Pfizer and its partner BioNTech called BNT162b2.
Members found the benefits of the vaccine outweighed the risks for most people 16 years old and older.
"It's a huge milestone," said Dr. Ofer Levy, a pediatric infectious disease expert and head of the precision vaccine program at Boston Children's Hospital.
While some committee members struggled with whether to authorize the vaccine for use in teenagers ages 16 and 17, Levy argued that it was important to include children.
Most vaccines in the world are delivered to children, and their vaccination rates are far higher than adults', he said. To reach the kind of vaccination rates needed to stop widespread transmission of COVID-19 will require minors to be vaccinated he said.
Sixteen and 17 year-olds were added to the study this fall, so there was less long-term safety data available for them than for adults. Levy, who has treated teens with a complex immune problem caused by COVID-19, said he doesn't see any reason why a 17-year-old would be any different than an 18-year-old, and was comfortable with the FDA's recommendation that 16 and 17 year-olds be included in the authorization.
Other committee members expressed more concern, including Dr. Cody Meissner, chief of the division of pediatric infectious disease at Tufts University School of Medicine, who said he supported authorization for adults, but not for minors. He abstained from voting for the measure.
The mixed vote is a good sign because it shows the group’s independence, said Dr. William Schaffner, an infectious disease specialist at the Vanderbilt University School of Medicine in Nashville, Tennessee, who is not on the committee.
“Seventeen to four is not a put-up job, it’s a real committee,” he said.
“My general response to the vote is ‘Bravo!’” he added. “Now the hard part starts – we have to get the job done.”
National distribution of the vaccine, which will start almost immediately if the FDA gives the go-ahead, will be far more complicated than developing the vaccine, Schaffner said.
Pfizer/BioNTech are requesting an “emergency use authorization,” a more rapid review just shy of a full vaccine approval. While the companies have compiled as much short-term safety and effectiveness data as is typical with any vaccine, the process has been compressed, and it's not clear how long the vaccine will continue to be effective.
Committee members also brought up other knowledge gaps they hope are filled in coming months, including how safe and effective the vaccine will be in pregnant and nursing women, in people with severe allergies, and in those who are immunocompromised from conditions such as HIV.
With the vote made, the committee’s recommendation now goes to the FDA, which could authorize the vaccine for emergency use as early as Friday. Once it's authorized, vials of the vaccine will begin shipping to all 50 states.
One last important meeting will take place Sunday, when an advisory committee to the Centers for Disease Control and Prevention meets to make a final recommendation on who should get the vaccine first when it is in very short supply.
While the Advisory Committee on Immunization Practices doesn’t have regulatory power, providers receiving COVID-19 vaccine sign agreements to comply with committee guidelines. If that committee gives its thumbs up, mass vaccination could start as early as Monday.
Thursday’s meeting of VRBPAC (pronounced verb-pack) came a day after the U.S. set a new daily record for COVID-19 deaths, topping 3,000 – nearly as many as died on 9/11.
Overall, the committee was satisfied with the safety and effectiveness data provided by Pfizer/BioNTech.
But Dr. Paul Offit, director of the Vaccine Education Center at Children's Hospital of Philadelphia, raised concerns about the
allergic reactions in two British people who got the vaccine when it first became available there on Tuesday.
He said he is not personally concerned about the safety of the vaccine and supports authorization but wants the companies to run a separate study of people with egg or peanut allergies to reassure them that the vaccine is safe. “This issue is not going to die until we have better data,” Offit said.
He also pointed out that it will be difficult for people with severe allergies to know if they are allergic to the ingredients in the vaccine. People who are allergic to any of its ingredients have been told to avoid vaccination, he said, but “if you look at the components of that vaccine, which has probably the longest chemical name of any vaccine I’ve ever seen, nobody’s going to look at that name and say 'I’m allergic to that.'”
Dr. Arnold Monto, the committee’s chair and an epidemiologist at the University of Michigan’s School of Public Health agreed that more information on allergic reactions is warranted.
“Facts may be important, but perception drives a lot of decisions,” he said.
Layers of monitoring for problems
Watching for any adverse reactions among people who’ve gotten the vaccine is a major concern.
During the morning portion of the meeting, the U.S. Centers for Disease Control and Prevention Dr. Nancy Messonnier outlined the multiple systems that will monitor possible problems.
New to the vaccine world is V-SAFE, a smartphone-based after-vaccination health checker that people who get COVID-19 vaccine can sign up for if they choose.
It will send text messages and web surveys to those who do, and feed information about any health problems directly back to CDC. Anyone who reports a medically significant side effect will get a telephone call from a CDC staffer to find out more.
Another monitoring system is VAERS, the Vaccine Adverse Event Reporting System. This is a joint CDC and FDA system established in 1990. It collects reports about adverse events from vaccines from health care professionals, vaccine manufacturers and the public.
Any effects of the vaccinethat are unexpected, appear to happen more often than expected or have unusual patterns
will be followed up with specific studies.
The Department of Defense also has its own system for following adverse events among its personnel, as does the Indian Health Service.
Finally, there's the Vaccine Safety Datalink, a network of nine large integrated health care organizations across the United States that conduct active surveillance and research on vaccine side effects. Because these health systems have access to their members’ medical records, they can often see patterns that might not immediately be visible to other networks.
Ethical considerations of ongoing trials
The group also discussed the ethics of how to deal with trial participants who received a placebo rather than an active vaccine.
So far, all the COVID-19 vaccine trials have provided half of their participants an active vaccine and half a placebo or a vaccine against another condition.
When people signed onto the Pfizer trial, they agreed to remain “blinded” for two years, not knowing whether they received the active vaccine or placebo.
But once there is a safe, effective vaccine reaching the public, experts are concerned about the ethics of leaving half the volunteers unprotected. They also are worried that many participants, who believe they got the placebo because they did not react to their shots, will drop out of the trial, compromising its longer-term results.
To avoid that, Dr. Steven Goodman, an associate dean and professor of medicine at the Stanford University School of Medicine, urged the group to consider changing the trial design.
He suggested that companies not tell trial participants whether they received vaccine or placebo earlier in the trial but give them whichever they didn’t get before whenever they would normally become eligible for the vaccine.
That way, they would remain “blinded” to which arm of the study they were in, maintaining the integrity of the scientific study, Goodman said.
He also suggested putting them at the head of the line among their peers, so that a healthy young person, who would typically not be eligible to get a vaccine until April or May, would not jump ahead of an older person at high risk of serious COVID-19 disease. Instead, they would be among the first of the young, healthy people to be offered a vaccine.
That would remove the incentive they would otherwise have to drop out of the trial, Goodman said, and provide them a reward of sorts for volunteering to help with the research.
This “deferred randomization” design, he argued, requires ethical and scientific compromise, but is fair and justifiable.
At a certain point, he said, maybe in about a year when vaccines are widely available, trials will no longer be ethically able to justify including a placebo group but will have to compare vaccines against each other.
Pfizer's Dr. William Gruber appeared to balk at the suggestion of adding to the trial, saying it was unrealistic to expect trial participants to consent to the two additional visits and one extra blood draw that would be required in an expanded trial.
Gruber, who is responsible for global clinical development of vaccines at Pfizer, said it would be better to let the current trial run its course.
Roughly 20% of participants are health care workers and so would be eligible for the vaccine within the next month or two. There will be enough data from the others, he said, to return a scientifically valid result without extending the trial with the crossover design.
Marion Gruber (no relation to William), director of the FDA's Center for Biologics Evaluation and Research, seemed to agree with Pfizer's recommendation and suggested that FDA likely would not require the company to extend its trial.
Public concerns expressed
In the early afternoon, the committee heard from members of the public, including speakers who expressed concern that the trials hadn’t yet included young children, pregnant or nursing women, or large numbers of people with HIV and other immunocompromising conditions – all groups Pfizer has promised to study in the future.
Several questioned the speed of the research and others demanded more African American people and senior citizens be included in the research before the vaccine is authorized. They also asked for continued research after the vaccine is authorized, which the company and the government plan to conduct.
Vaccine hesitancy also came up several times.
Dr. Peter Lurie, president of the Center for Science in the Public Interest, a consumer advocacy organization, told committee members he was impressed by the apparent safety and effectiveness of the vaccine and urged them to sign off on it.
But he said he is worried that not enough public attention has be directed to the vaccine’s side effects, which appear to be extensive, including pain at the injection site, headaches, fever, muscles aches and chills.
“We are already facing significant levels of vaccine hesitancy,” he said, “and if patients are not forewarned about these potential events, word will surely spread rapidly potentially exacerbating that hesitancy problem.”
Evan Fein, a New Yorker who participated in an early trial of the Pfizer/BioNTech vaccine, described his experience with the vaccine, hoping, he said, to reassure people of its safety.
He had passing chills, fever and arm pain, he said, but no lasting effects. “It’s been more than 5 months now since my first shot and I can happily report that there were none,” Fein said.
This vaccine has not been rushed, he said, rather other medical innovations move too slowly. “Pfizer has just set the gold standard for future clinical trials. let’s live up to that,” Fein said.
He urged the panel to recommend authorizing the vaccine.
“The skepticism of some does not justify delay for others who desperately want to take it,” he said. “The burden of proof is on those who don’t want to authorize the vaccine. Absent a compelling reason not to authorize it, it is simple immoral and unethical to deny the vaccine to healthcare workers and first responders who want it.”
After the public presentations, Pfizer and BioNTech executives spent more than an hour presenting data and answering committee members' questions on their vaccine and the FDA followed with its findings.
New England Journal of Medicine Thursday published a peer-reviewed version of the data from the late-stage Pfizer/BioNTech trial. The study confirmed numbers that the companies and the FDA have already made public and found that the vaccine was safe and highly effective.
"The results demonstrate that COVID-19 can be prevented by immunization, provide proof of concept that RNA-based vaccines are a promising new approach for protecting humans against infectious diseases, and demonstrate the speed with which an RNA-based vaccine can be developed with a sufficient investment of resources," the study concluded.