On Wednesday, federal regulators recommended a pause on the use of Johnson & Johnson’s COVID-19 vaccine after reports of a rare blood-clotting condition following the shots. Called cerebral venous sinus thrombosis, it appeared in six people: All of them women between the ages of 18 and 48 who had received the vaccine, including one who died. To date, more than 6.8 million people have received the single-dose vaccine, which is easier to store and transport than Pfizer and Moderna’s two-shot regimens. While the White House insists the pause will not affect the country’s vaccination effort, the announcement was immediately criticized by people who fear it may undermine the public’s trust in vaccines as the U.S. races to get ahead of the disease.
One person who knows what it’s like to make such a monumental decision is Dr. Margaret Hamburg, who oversaw the Food and Drug Administration from 2009 to 2015. In 2010, she made the decision to recommend pediatricians pause use of a vaccine given to infants and children to prevent severe cases of diarrhea. Intelligencer spoke with Dr. Hamburg about that decision and the risk-benefit calculation FDA officials made this week.
What goes into a decision like this?
When a safety issue emerges there is a pressing need to really try to understand it as quickly as possible. Especially with a vaccine where you’re giving something to people who are basically healthy to protect them from getting disease, you want to put safety as the central priority. You don’t always put a pause or a hold on availability of the product, but you certainly want to dig deeper to understand. Are these symptoms or adverse events related to the vaccine? Are there other cases that we need to look at that might not have been reported? Are there other similar vaccines that we can learn from? I’m sure all of that was in the background as they addressed this emerging concern.
How do you game out whether a pause is worth undermining trust in a vaccine?
It’s a difficult challenge, especially now that we are so eager to expand vaccination and really get out in front of the virus. The important thing is to communicate clearly why this action is being taken and that we’re talking about a very, very rare risk. As the officials have said, they are doing this out of an abundance of caution and a desire to put these adverse events in context and understand them. Stopping the Johnson & Johnson vaccine at this moment in time is unlikely to interfere with overall supply of vaccine because it is not a major component of vaccination in this country. I think people should actually be encouraged. It’s clear that the system is taking safety very seriously and being straightforward and transparent about actions being taken and why. I hope that it will actually boost confidence rather than undermine it.
There is a chance of spooking people, though. How do you justify the pause when so few people have suffered adverse side effects?
Of course it’s a very low risk as we presently understand it, less than one in a million. But it is a complication that is pretty unusual and there is a desire to understand it more deeply. Certainly the FDA could have just issued a clinical alert so that health-care providers would be aware of this possible complication, what to look for and, importantly, how to manage it. Instead, they recommended a pause on its use. Some places may have continued to offer the Johnson & Johnson vaccine. The FDA can make a determination to pull a product from use. Generally, the FDA works closely with the company to decide what the best approach is. As I understand it, shortly after the U.S. FDA, along with CDC, announced this recommendation for a pause, Johnson & Johnson proactively paused the vaccine’s availability in the European Union.
One of the interesting things about this particular clotting syndrome is that it’s accompanied by low blood platelets. Normally when a physician is confronted with a clotting disorder, heparin, or a blood thinner, is a treatment approach. But in this case it would exacerbate the symptoms in the underlying problems. Clearly, there was a sense of urgency from the FDA and the CDC to make clear to clinicians that if they see an individual with this syndrome, they need to take a history, find out if the patient recently received a vaccine, and consider how best to manage them in light of this concern. They should know not to do the sort of routine treatment approach that they would pursue. I think there was a sense of needing to put a spotlight on how to clinically manage these cases, even if they are decidedly rare.
When you were commissioner you put a pause on Rotarix, a vaccine used to prevent diarrheal illness that can cause dehydration in infants and kids. What was it like being in the hot seat and making that very big decision, even when there was no evidence that the vaccine was causing disease?
That was a hard decision. It was an instance where we unexpectedly discovered a contaminant in the vaccine, a pig virus, which was not at all likely to cause disease in people. But it shouldn’t have been there and we didn’t understand how it got there and we decided we needed to pause use of this vaccine while we ascertained the nature of the problem and how best to address it. Again, there were multiple factors that went into the decision making. We might have managed the situation differently if there was a huge burden of disease in this country from rotavirus or if there wasn’t another rotavirus vaccine available for use in place of this vaccine. But we did worry about the message that was being sent and we talked about it carefully and we tried to message our decision in a way that wouldn’t compromise the use of this vaccine in other settings where the risk-benefit calculation might have been quite different.
Looking back, would you have done anything differently?
No, I don’t think so. These are always hard decisions. You have to weigh risks and benefits. If there were no other coronavirus vaccines available, the FDA and CDC might have made a different recommendation, simply alerting these clinicians to this concern and working with health-care providers and vaccinators to really ramp up monitoring for this adverse event and studying it while continuing to allow its use.
Can you put me in the shoes of acting FDA Commissioner Janet Woodcock?
Clearly Commissioner Woodcock is working closely with her team at FDA that work day-in and day-out on vaccine development review and ongoing monitoring and oversight. We are fortunate in this country to have an extraordinarily capable Food and Drug Administration and the team that has been working on coronavirus vaccines are among the best scientists that I’ve had the opportunity to work with over the course of my career. I do feel that we are in good hands.
What kinds of questions is the FDA asking right now?
Right now they’re just taking a pause to try to better understand the nature and scope of the problem. I think they’ll move very quickly, but obviously in Europe and some other places they looked at the risks and determined that the risk of COVID, and serious disease related to COVID, outweighed the potential risk of the vaccine. The more we know about the potential risks of vaccines, the better we can manage those risks and minimize them, even if they do exist.
One important question is whether this is a complication of this class of vaccines, the so-called viral vector vaccines. The AstraZeneca vaccine is in that class and there have been other adenovirus vaccines, such as the Ebola vaccine. It’s important to go back and take a look at the experience with this type of vaccine.
It’s also important to realize that it’s not unexpected, as you go from controlled clinical trials of a vaccine candidate, where you’re studying it in thousands or tens of thousands of individuals, to the actual real-world use of the vaccine with millions of people taking it, that you’re going to see the emergence of rare but perhaps significant safety complications. The fact that we’re having this discussion and looking intensively at this Johnson & Johnson vaccine doesn’t mean anything in terms of whether it was developed too quickly or without robust adherence to scientific standards. It’s simply a fact of life that there are always certain kinds of risks that can emerge, and as more and more people are taking vaccines you start to see them. It’s still a very low level of safety concern when you compare that to driving a car every day.