As Millions Get Shots, F.D.A. Struggles to Get Safety Monitoring System Running

More than 34 million Americans have received Covid vaccines, but the much-touted system the government designed to monitor any dangerous reactions won’t be capable of analyzing safety data for weeks or months, according to numerous federal health officials.

For now, federal regulators are counting on a patchwork of existing programs that they acknowledge are inadequate because of their small sample size, missing critical data or other problems.

Clinical trials have shown both of the vaccines authorized in the United States — one from Pfizer-BioNTech and the other from Moderna — to be highly protective and safe against the coronavirus.

But even the best trials have limited ability to detect adverse reactions that are rare, those that only occur in certain population groups, or which happen beyond the three-month period studied in the trials. Tracking adverse events once the vaccines are administered to the public at large is essential not just to detect problems but to build confidence in the safety of vaccines.

In interviews, F.D.A. officials acknowledged that a promised monitoring system, known as BEST, is still in its developmental stages. They expect it to start analyzing vaccine safety data sometime soon — but likely not until after the Biden administration reaches its goal of vaccinating 100 million people.

“I’m concerned about this disjointed tracking system,” said Dr. Ashish K. Jha, dean of the Brown University School of Public Health. “We knew these vaccines were coming for at least several months before they got authorized, so we really should have had a well-developed system.”

Dr. Jha and others believe that with all the public attention on the vaccines, any serious adverse reactions will likely be reported somewhere. But, they say, a more systematic approach is crucial.

“It’s critical to track, because it will help build confidence,” Dr. Jha said.

Monitoring is all the more important because the vaccines were developed and approved in record time, with the goal of inoculating most of the U.S. population as quickly as possible.

“It’s the right thing to do, but the fact of the matter is we don’t have enough information and we’re desperately in need of post-market information and monitoring,” said a high-ranking F.D.A. official, who asked not to be named because he was not authorized to discuss the matter publicly.

The government is now relying most on a 30-year-old safety monitoring system that the F.D.A. shares with the Centers for Disease Control and Prevention, and a new smartphone app that people who get vaccinated can download and use to report problems if they wish. The C.D.C. also runs the Vaccine Safety Datalink, a collaboration between the agency and nine health systems that collects vaccine data and electronic medical records of roughly 12 million patients. Although it is well-regarded, it is of limited use because of its small size.

ImageBoxes of the Pfizer-BioNTech vaccine were prepared for shipment at a facility in Portage, Miich., in December.
Credit…Pool photo by Morry Gash

“It’s great for routine stuff, but when it comes to safety surveillance, it’s all about size,” said Dr. Daniel Salmon, director of the Institute for Vaccine Safety at Johns Hopkins University, and a former federal vaccine official. “The bigger it is, the faster you get an answer. Eventually the VSD will get a really good answer — probably one of the best answers of anybody out there because they are so good at doing it. But in a pandemic, time isn’t on our side.”

So far, few serious problems have been reported through these channels and no deaths have conclusively been linked to the vaccines. The 30-year-old initiative, known as the Vaccine Adverse Event Reporting System, or VAERS, relies on self-reported cases from patients and health care providers.

Health officials say that so far, the two vaccines already authorized for use appear to be quite safe. There have been a few severe allergic reactions, including anaphylaxis, but they are treatable and considered rare. The rate at which anaphylaxis has occurred so far — 4.7 cases in every million doses of the vaccine by Pfizer and BioNTech, and 2.5 cases per million for the vaccine by Moderna — are in line with what happens with other widely used vaccines.

Bruising and bleeding caused by lowered platelet counts have also been reported, though it is not known if they are linked to the vaccines, or coincidental. In total, 9,000 adverse events were reported, with 979 serious and the rest classified as nonserious, according to the most recent C.D.C. report available.

In interviews, public health experts, including current and former officials at the F.D.A. and the C.D.C., expressed a need to improve upon old “passive” surveillance, which depends on self-reporting. They said that funding shortages, turf wars and bureaucratic hurdles had slowed preparing BEST, formally called the Biologics Evaluation Safety Initiative, to monitor the Covid vaccines.

An earlier version of BEST was started in 2017, to improve the F.D.A.’s tracking of new blood products and vaccines, but the agency has only used it on a limited basis. It is considered an “active” surveillance system because scientists can use data collected from clinical care to hunt for safety problems, rather than rely on individuals to report health problems that they believe — but often without proof — were caused by the vaccine. BEST is part of the agency’s move toward using more real-world evidence to vet new products or monitor them after approval. The F.D.A. has done some preliminary studies using BEST to evaluate the safety of shingles and flu vaccines.

When the monitoring system is fully up and running, the F.D.A. expects to have access to more than 100 million individual medical records, and will be able to look for signs of safety problems, and then determine whether they are real. But critics say it is folly for the F.D.A. to be launching a new system in the midst of a pandemic. And several C.D.C. officials said the F.D.A. was not giving them a real sense of when the complex system would begin to work.

“It’s been a puzzle to me,” said one C.D.C. official who was not authorized to discuss the issue and asked not to be identified. “F.D.A. talks about this in a way that is really unclear as to what is up and ready to go and what isn’t.”

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Credit…Jim Lo Scalzo/EPA, via Shutterstock

But even BEST will suffer from a data problem that is already hindering existing systems: the dearth of health insurance claims to show who got which vaccine, and when. Typically health care providers and patients submit such claims to insurers, but with the vaccines being given at no charge, often at government-sponsored events, few are bothering to file claims. Critics say that federal health officials should have predicted this glitch and prepared for it.

“The current safety surveillance system in the U.S. is dependent on health insurance claims data and electronic health records,” said Dr. Salmon. “If the vaccine data information doesn’t get into the safety system, then that safety system is unable to function.”

In December, the C.D.C. launched V-safe, a smartphone-based system that checks in with individuals who get the Covid vaccine to monitor for side effects. Roughly two million people who have been vaccinated have enrolled, a small fraction of the total number, and of those, one million have responded to text queries and surveys about their post-vaccine health.

At a recent C.D.C. advisory meeting, Dr. Tom Shimabukuro, who oversees Covid-19 vaccine safety for the agency, said he was pleased that the new app had enrolled so many users, but he also acknowledged problems like errors that indicated men and older women to be listed as pregnant.

It’s also unclear how heartily vaccine providers are promoting V-safe. Some health care providers send post-vaccine emails to patients noting its availability, and others merely put a stack of C.D.C. fact-sheets about V-safe in the vaccination room and hope patients pick it up. Even Dr. Jha said he didn’t sign up for it.

Still, Dr. Shimabukuro said he was confident in the current surveillance system. “For the national Covid-19 vaccination program, we have implemented the most intense safety monitoring in the history of the United States,” he said. “We have multiple systems that are complementary to each other, that are able to rapidly collect information, that are able to rapidly assess the safety of immunizations.”

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Credit…Go Nakamura/Reuters

One factor slowing down BEST is that the F.D.A. has not yet calculated what are called background rates, the levels of certain health problems that normally occur in the non-vaccinated population. These are critical for determining whether the vaccine is actually causing a spike in certain problems, such as heart attacks, strokes, and other issues that the F.D.A. and C.D.C. consider adverse events of special interest, which require close monitoring.

Rather than calculate them on its own, as the C.D.C. does, the F.D.A. sent a proposal out for public comment, in which it detailed how it planned to compute the background rates. They plan to start working on it in the next few weeks. This delay strikes some public health experts as unnecessary.

“It’s a little bit surprising,” said Dr. Peter Lurie, president of the Center for Science in the Public Interest, and a former associate commissioner at the F.D.A. “That doesn’t feel like a mechanism appropriate to the urgency of a pandemic. It seems to me that a few well-placed phone calls to key people in the field would provide as much information as a request for comment.”

Dr. Peter Marks, the director of the F.D.A.’s Center for Biologics Evaluation and Research, which oversees vaccine approval and safety, said the agency needed outside input.

“The background rates are a critical input for our rapid cycle analysis, so we followed a deliberative and transparent process,” he said in an interview. “We needed to develop an approach that could be used in several health care claims data systems and we needed to account for the possibility that health care utilization may have changed during the pandemic.”

Jeffrey Brown, an associate professor at Harvard Medical School and a leader of the F.D.A. program that monitors adverse reactions to drugs, said he is concerned about the lack of insurance claims data and other holes in the vaccine safety surveillance systems.

“It is imperative to have policies that ensure vaccination data are submitted to insurers to enable effective use of the nation’s investment in active safety monitoring,” said Dr. Brown. “It is not only critical to get needles into arms, but also to get data into databases. We still have a chance to get it done well.”

Denise Grady contributed reporting.

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Credit…Jessica Hill/Associated Press

“I’m concerned about this disjointed tracking system,” said Dr. Ashish K. Jha, dean of the Brown University School of Public Health. “We knew these vaccines were coming for at least several months before they got authorized, so we really should have had a well-developed system.”

Dr. Jha and others believe that with all the public attention on the vaccines, any serious adverse reactions will likely be reported somewhere. But, they say, a more systematic approach is crucial.

“It’s critical to track, because it will help build confidence,” Dr. Jha said.

Monitoring is all the more important because the vaccines were developed and approved in record time, with the goal of inoculating most of the U.S. population as quickly as possible.

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