Representative photo: Hakan Nural/Unsplash
While the COVID-19 vaccines currently available in the United States have been proven to be safe and effectiverecent reports of rare adverse events, or side effects, have raised concerns. On July 12, 2021, the Food and Drug Administration approved an update to the Johnson & Johnson COVID-19 vaccine fact sheet to include an increased risk of rare nerve disease Guillain Barre syndrome. This follows previous reports linking the J&J vaccine to a rare blood clot.
Although reports like these can be scary, they are a sign that the vaccine safety reporting system is working. They also point out how the relative risks of rare side effects like these need to be put into context.
As a pharmacist who has managed the operations of the University of Virginia Health System’s COVID-19 immunization program for the past seven months, I have seen how uncertainty and fear of potential side effects can lead to vaccine hesitancy. Understanding how adverse event information is collected and what this means for vaccine safety can help people make informed decisions about their health.
Safety follow-up before, during and after approval
The FDA has rigorous testing and approval processes that manufacturers must go through before a new vaccine can be made available to the public. Whether or not a vaccine is approved by the typical FDA approval process or an emergency use authorization (USA), the steps required to test the safety and efficacy of a new drug are the same. An EUA can get a vaccine to the public faster by streamlining the regulatory process, but no shortcut is used. All measures are taken to ensure that the vaccine is both safe and effective.
Vaccine clinical trials are taking place in four sequential phases. During the first three phases, the study investigators are the ones who identify, quantify and document the safety issues. Phase 1 typically introduces the vaccine to fewer than 100 people over several months under controlled conditions. Typically, the majority of potential adverse events are identified at this stage.
After the FDA reviews the Phase 1 data and deems the vaccine safe enough to study further, the vaccine moves into Phases 2 and 3, where it will be given to more people over longer periods of time. . Here, investigators determine the optimal dosage and screen for rare side effects.
If Phase 2 and 3 data meet FDA approval standards, the vaccine will then move to Phase 4 and be made available to the public. The vaccine is observed in much larger populations and over longer periods of time, and manufacturers are required to regularly check and report potential safety issues to the FDA.
What is different in this final phase is that the public can also contribute to safety reports. The vaccine adverse event reporting system (VAERS) is a national safety monitoring system operated by the FDA and the Centers for Disease Control and Prevention. Although some types of adverse events, such as injuries during vaccine administration and serious complications, are mandatory for health care providers to report, anyone can submit a report. Recent adverse events associated with the COVID-19 vaccine, including Guillain Barre and thrombosis for Johnson & Johnson and myocarditis for Pfizer, were identified through VAERS.
The risk of a vaccine-related serious adverse event is low
A rare adverse event can take months or years to be identified for one simple reason: it is rare. For some less commonly used drugs, the discovery of new safety data takes longer because a relatively small number of patients are using the drug. For example, although the shingles vaccine Shingrix was approved in 2017, it is only March 2021 after more than 3.7 million patients had been vaccinated, the FDA announced a potential increased risk of Guillain-Barré. And it still hasn’t been confirmed that the Shingrix vaccine causes the nerve disease.
For cases like the COVID-19 vaccine, however, millions of people will receive the drug soon after it is released to the public, and new problems or patterns often emerge more quickly.
This can cause two problems.
First, not all the reported adverse event is directly related to the vaccine. For example, many of the tens of millions of people who received the Pfizer vaccine likely had a sunburn. People can report they have had a sunburn to VAERS, but the vaccine has no effect on your skin’s ability to protect itself from the sun. VAERS is very clear that it “is not designed to determine whether a vaccine has caused a health problem, but is particularly useful in detecting unusual or unexpected patterns of adverse event reporting”. Correlation does not mean causation.
Second, a plausibly identified adverse event does not necessarily render the vaccine unsafe. According to the CDC, there have been 100 preliminary reports of Guillain-Barré on 12.5 million doses of J&J, or 0.0008% of people who received the vaccine. Giving a vaccine to a large sample of people can help identify a possible link between the vaccine and a side effect. But that doesn’t mean the risk of getting this side effect is very likely, or that it outweighs the benefits of getting the shot.
These risks, while real and potentially deadly, must be considered in the context of the much greater risk of negative outcomes from the diseases that vaccines protect people against. For example, 1% to 7% of patients who take cholesterol-lowering drugs called statins are at risk of potentially harmful muscle damage. However, these drugs are still taken by millions of people because they are very effective in preventing heart disease and stroke. And in the case of Guillain-Barré, about one in 100,000 people, or 0.001%, develop this disease each year in the United States, regardless of the cause. By comparison, the United States had more than 33 million cases of COVID-19 and more than 600,000 deaths caused by this disease.
COVID-19 a greater risk than vaccine side effects
In times as extraordinary as during a pandemic, it is understandable that people are reluctant to take more risks than they have to. But safety nets are in place to monitor COVID-19 vaccines, and they’re still working as they should.
COVID-19 vaccines have proven to be extremely safe for most people. Over 40,000 patients participated in J&J’s clinical trials before the company applied for emergency use authorization, reflecting Pfizer’s and by Moderna study sample sizes. Some 0.4% of participants in the J&J trial experienced serious adverse events unrelated to COVID-19 infection. In contrast, the trial demonstrated that people who receive the vaccine are 85% less likely contract severe COVID-19 than those who are not vaccinated.
The extremely rare side effects associated with COVID-19 vaccines were discovered because safety reporting tools were used appropriately. Being aware of the risks of treatment, however rare, can help people make health decisions that are best for them. However, these risks must be considered in context. And in the case of COVID-19 vaccines, they must be weighed against the consequences of not being vaccinated and letting the pandemic rage.
Justin Vesser is director of outpatient pharmacy services at the University of Virginia.
This article was originally published by The conversation and has been republished here under a Creative Commons license.