One hundred days after the first COVID shot was given in the United States, the country continues the largest mass vaccination campaign in history. Currently, more than 2 million shots are administered per day: More vaccines are going in arms every day than in all the clinical trials combined. This means we are now getting more and more real-world data from a larger and more diverse group than any clinical trial could ever hope to produce. And as drug companies continue to apply for full authorization from the U.S. Food and Drug Administration (FDA) on the basis of clinical trials, the real-world data also under scrutiny. According to the Centers for Disease Control and Prevention (CDC), the current vaccine safety monitoring program is one of the most intense in U.S. history. But how does it work — and is it rigorous enough? Aaron Kesselheim, MD, MPH, a professor of medicine at Harvard Medical School and a faculty member at Brigham and Women’s Hospital in Boston joins us on this episode to answer that question. Listen and subscribe on Apple, Stitcher, Spotify, and Google, so you don’t miss the next episode. And if you like what you hear, a five-star rating goes a long way in helping us Track the Vax! Serena Marshall: I want to just start out for those who may not be familiar with how the United States does post-marketing surveillance of vaccines. What happens after the FDA gives approval for a vaccine? Aaron Kesselheim: After the FDA gives approval, the vaccine can be made more widely available and oversight of the vaccine actively shifts to what’s often called post-market surveillance. There are a number of different overlapping systems the United States has in place related to monitoring vaccines on the market to ensure that they are still showing the same activity that we expected them to have in their preapproval trials, and that there aren’t any emerging side effects that we might not have seen in the preapproval studies. Serena Marshall: We sort of saw that play out with anaphylactic shock and reactions that occurred once the mRNAs started to roll out, right? Aaron Kesselheim: Yes. Once the first vaccines rolled out through the emergency use authorizations, there were a couple of reports in the newspaper about people having, as you said, anaphylaxis or some reactions to them that we didn’t necessarily observe in the preapproval studies. That led physicians and other providers to change the way that they administer the vaccines, to ensure that people were being monitored more closely for a certain period of time after the vaccine. Serena Marshall: You mentioned a multilayered system that’s in place. How many reporting systems are there? Aaron Kesselheim: There are three different major systems of post-market surveillance. There’s what’s called VAERS, or the Vaccine Adverse Event Reporting System. This is more of a passive, spontaneous reporting system in which clinicians and manufacturers, and even the public, can voluntarily report adverse events to the government [so we can] learn about them. That’s one major way of identifying safety issues. Another way of identifying safety issues is through post-market studies that the manufacturer agrees to do upon approving the product. And so there might be additional prospective trials potentially in kids or pregnant women or other smaller populations. And then the third major way is through observational data or registries. Serena Marshall: When it comes to the COVID vaccines, we’re seeing all three of those pillars being employed, correct? Aaron Kesselheim: I think that there are a lot of ways that the post-market surveillance of the COVID vaccine could be going better. I think that we are seeing a lot of spontaneous reporting. We haven’t yet had those kinds of formal post-approval studies that have been developed and designed for these trials. So we haven’t really seen that yet. The other major issue is, right now a lot of vaccines are being given outside of healthcare systems, through public, state-government-supported vaccine delivery sites. As a result of that, we’re not getting as much rigorously collected observational data as we might plan to get in the weeks and months that follow when the vaccines become formally approved by the FDA. I think there are ways that the post-market vigilance related to them could be optimized.
