Dr. Susan Ellenberg is a Professor of Biostatistics, Medical Ethics and Health Policy, in the Perelman School of Medicine at the University of Pennsylvania, Her research interests have focused on issues in the design and analysis of clinical trials, and on assessment of medical product safety. She is an associate editor of Clinical Trials as well as of the Journal of the National Cancer Institute.
Episode Description
Last week the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention announced a pause on the distribution and use of Johnson and Johnson’s COVID vaccine. The pause amid reports that 6 women who had received the vaccine had developed rare blood clots. The concern this has brought up around J&J’s vaccine mirrors earlier concerns raised in relation to the vaccine produced by AstraZeneca. Vaccine safety is a focus of this episode of Stats and Stories.
You can check out more of Susan’s work on Vaccine Safety here.
+Full Transcript
Rosemary Pennington: Last week the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention announced a pause on the distribution and use of Johnson and Johnson’s COVID vaccine. The pause amid reports that 6 women who had received the vaccine had developed rare blood clots. The concern this has brought up around J&J’s vaccine mirrors earlier concerns raised in relation to the vaccine produced by AstraZeneca. Vaccine safety is a focus of this episode of Stats and Stories where we explore the statistics behind the stories and the stories behind the statistics, I'm Rosemary Pennington, Stats and Stories is a production of Miami University's Department of Statistics and media journalism and film, as well as the American Statistical Association. Joining me are panelists, John Bailer, chair of Miami’s Statistics department and Richard Campbell, professor emeritus of Media Journalism and Film. Our guest today is Dr. Susan Ellenberg is a professor of biostatistics, medical ethics and health policy in the Perelman School of Medicine at the University of Pennsylvania. Her research has focused on issues in the design and analysis of clinical trials, and on the assessment of medical product safety. She's an associate editor of clinical trials as well as the Journal of the National Cancer Institute, Susan, thank you so much for being here today.
Susan Ellenberg: I'm glad to be with you,
John Bailer: Susan, I'm just delighted to have you back on the program. I mean, you're like the early 30s In terms of an episode so it's wonderful to have you have you back again. But but it's certainly an incredible time to be thinking about, about vaccine safety, and, and what an amazing development to see a vaccine developed in less than a year, and be put in a production and use, but but we're still starting to think a little bit about the fact that even post release, there's a whole system that's available to think about vaccine safety, and so can you talk a little bit about what's done kind of post, post release of vaccines to the monitoring what goes on in terms of the safety of these vaccines.
Ellenberg: Sure, I should say that there's also a system to look at safety of drugs after they're on the market, any medical product that's released, we worry about safety because the clinical trials that we do to evaluate the safety and efficacy before something can be put on the market are even when they're large are not large enough to be able to detect rare adverse events that people would want to know about. And that's particularly the case for vaccines. Why is that? When you take a drug, you take it to relieve a symptom or to treat a disease, you're, you're tend to be willing to accept some level of risk, in order for the benefit that you might immediately gain, but vaccines are given to people with no particular immediate health problem that a vaccine is intended to fix. It's a preventive and so it's given to basically Healthy People, you're particularly concerned. Then, about safety issues about any kind of risks that people might be taking, if they took the vaccine, and so we have systems in place, and those systems have become more elaborate and better over the years, certainly since the time that I was overseeing those systems when I was at the FDA. There's a reporting system called a passive surveillance system that VAERS (Vaccine adverse event reporting system). Anybody who experiences, something bad, some kind of adverse event after they get a vaccine can report that to that system, or they report it to their doctor, their doctor might report it, or if they report it to their doctor and their doctor calls the pharmaceutical company and says, Hey, have you ever heard anything like this, the pharmaceutical company then is required by law to report that, if you yourself experience it. You're not required by law to report it, but if it gets to the attention of the company they're required to report it so we have this enormous database, consisting of all manner of reports from all different kinds of people,
Richard Campbell: Susan, what you just described. The general public doesn't know anything about these systems right. So, you know, the New York Times had an article you probably saw this week, just a couple days ago why the vaccine safety numbers are still fuzzy. So we're looking at this, and I actually my son's girlfriend was supposed to get a job at Johnson and Johnson vaccine this she's in her early 20s supposed to get a vaccine, this week, and couldn't be canceled. So, I'm looking at this article and it says that this halt has happened because of these six cases. But there were 6.9 million vaccines given to me as a general public person as I play that role on this podcast. That seems, this seems like a really low risk. So why, why is this a good thing that this got stopped.
Ellenberg: You know, there's a variety of opinions about whether it's a good thing, opinions from knowledgeable people. I'm not going to tell you there's a right or wrong answer to that. But there's a lot of things that they're doing this week. One thing that they're doing is to see whether there's any basis for saying this risk is limited to us, a smaller subset of the population. Right now, we know that there are there six premenopausal women who had this experience I think since then, there's been identified, there's a young man that's also had, you know, had this, but if, if they could identify particular risk factors, so that within that group, maybe the risk isn't one in a million. Maybe it's one in 10,000, which is a lot bigger still very small. But it, it, it would say well maybe these people should not get that vaccine but everybody else, the risk is so small as to be as to be negligible. You know, everything that we do has risks. And so you have to, you know, you have to be able to balance these things. So that's one thing that they're doing another thing that I'm sure they're doing is trying to understand the biology of what happened to understand whether there really is a plausible basis to connect these events with a vaccine after all these, these kinds of things do happen without people being vaccinated, on a very rare basis now people have said well this is a very particular kind of cloth, you know, and that's, that's even more unusual than clots in general. Okay, but there's probably multiple different kinds of clots that are also much more rare. So, you can't get away from the, you know from the probability issue and how, you know, we were always surprised at coincidences but as Persi Diaconis and Fred Mosteller said many years ago, there's, you know way more coincidences, than you then you might imagine we're living with coincidences all the time. But I think, from what I understand, and I'm not a biologist or an immunologist or virologist but from what I understand people do think that there is some biological plausibility, that this vaccine might be associated with this, this rare adverse effect. And if they, if they can, if they can't identify a population and say okay this is just, you know, one in a million kind of thing. My guess is that they'll go ahead and release it after all we're subject to risks many times greater than that. And we know that the disease itself can cause clotting and it can be very, very serious. So we're looking at this, we know about this risk because we're looking so carefully in ways that we don't always look, you know, at other kinds of things that we might, that we might experience.
Campbell: One of the things that you just said was mentioned actually in the Times article where, I think one of the experts on this said, it's much more likely to get a blood clot from COVID, then it is to get it from the vaccine, which I thought was really interesting.
Ellenberg: Well that's, that's, that's true. But then, you know you have somebody, you know, like me, who is not a premenopausal woman but I'm staying home, you know, so I'm at very low risk of getting COVID, no matter what. And, you know, people could decide well they're just gonna stay home and avoid other kinds of contacts, and then they'll be at a very low risk of COVID and then an even lower risk of, of having that having the blood clots, and you know everybody has, has a different concept of risk there are many people who are not yet vaccinated who are out, mixing unmasked with other people. They're willing to take that risk, which is much, much higher than any adverse effect associated with vaccines.
Bailer: You know, you were talking about the idea that potentially risk factors would be identified sort of subgroups that maybe you wouldn't give this vaccine, but it also I think I was reading another article they're talking about this also helps to identify maybe how to prepare treat you know, have treatments available, knowing if someone were to exhibit this rare outcome, what you would do kind of quickly in response to it so, so this kind of alerting system not only helps you with kind of maybe stratifying who gets what, but also preparing for the worst thing that might happen.
Ellenberg: That's exactly right. We've already learned, for example, a natural thing to give people who have a blood clot is Heparin, but we have found that heparin itself is associated with exactly this kind of clotting problem and so, you know, after the first few cases when people started to dig into this they've learned. No, we're not going to give Heparin, we're going to give other kinds of anti clotting therapy and and warning people in advance, you know, will alert them that they start to have the symptoms to get treated quickly. And if you can get treated quickly, you will probably get through this episode without any, any long term sequelae so that's really important. One of the things I worried about when, when this first came up, and people were saying, oh well you know a headache or, you know, something like that. I said, My God, you know, you know anybody with a headache is rushing to the emergency room, but I think they have narrowed it down somewhat.
Pennington: How often do pauses like this happen when a vaccine has been distributed maybe, maybe you don't have a good read on this but I just wonder if because we're also glued in on the COVID vaccines that this may be is caught more of our attention than maybe other moments when a vaccine or a drug has been paused, that we just have not known about.
Ellenberg: Yeah, everything is more visible with these vaccines now. I think I've read that there have been other pauses. I'm not familiar with them once it's out on the market. Both the Johnson and Johnson vaccine, and the AstraZeneca vaccine clinical trials were paused while the trials were ongoing because of a single one or two adverse events that they observed that they wanted to study before reopening. And in fact when the AstraZeneca, clinical trial, clinical trial was paused they. The trial in the United States was paused as well and that pause was not a lot longer than the pause in the UK, so it does happen. Many years ago, there was a vaccine for rotavirus. that was approved and there were adverse events that were detected. Shortly after it went out again through this vaccine adverse event reporting system. And that was a signal and it was studied then in other databases. And I don't know, eventually, and it didn't take too long, that vaccine was withdrawn from the market, whether there was a pause before it was formally withdrawn, I really don't remember.
Pennington: You're listening to Stats and Stories and today we're talking about vaccine safety with the University of Pennsylvania's Susan elenberg. You know, one of the interesting things about this is the sort of media coverage of these issues. And again, I think, you know, as you're talking about like you know, when you saw the news about this coming out and being worried about people with headaches, you know, rushing to the ER, I had a moderna vaccine, and I had a headache long after this and I was like oh no, am I having a, you know it and I did it does feel like we're all very tuned in to the coverage of all these things. What advice would you give to people as they're consuming news about vaccine safety about these pauses. What advice would you give to them as they read these stories to help them keep maybe their sanity a little bit through all of this and maybe not have that moment of panic and rushing to the ER,
Ellenberg: I would first remind them that everything they do, carries some level of risk, and they have to bear that in mind. So far, the risks that have been identified are either not serious, you know, some people are going to feel really rotten for a day or two, or perhaps even a couple even two or three days after the vaccine. Yeah, by my, my daughter and son in law. We're both got a J and J vaccine; they're in the two dose trial, the results of which haven't yet been released and they both were pretty sick. I think one of them ran a fever of 103. The day after they got the vaccine so these, but these things are well known. We know that vaccines cause fevers, they cause headaches, they cause soreness, they cause swelling. Those are the kinds of things we know and we also know that, again, very rarely, they cause a serious allergic or anaphylactic reaction and that's why they make you sit in the place where you got the vaccine for 15 minutes I had to sit for 30 minutes because I have asthma so if you have any kind of any kind of thing like that they make you sit a little bit longer to make sure you're not going to have that kind of reaction with those kinds of reactions. We're not worried about whether the vaccine caused it, we're pretty sure the vaccine caused it because people don't just get anaphylactic reaction walking down the street, you know, mentally, and their arm doesn't usually swell up, you know, with no other, you know, of course they could get bitten by an insect and that could cause it but, you know, without any other obvious cost so those are not the we know about those. Those are, those are rare risks. But what people should take out of what's happened here is that people are looking very closely at the experience that people have had out after they get vaccinated. And this is what they've come up with, something that may be as infrequent as one in a million. That should be very reassuring to people.
Campbell: So I have a question about something you referred to earlier so the pause is about, you know, is this release is this particular kind of clotting, a coincidence or a preexisting condition, how, How much uncertainty can we live with. I mean, when can the paws be lifted how much work has to be done here to sort of reassure, folks.
Ellenberg: Well, that they, the people who are looking at this carefully people at the FDA and CDC and their advisors are going to be looking at this from lots of different angles. And, you know, I'll be very comfortable with whatever they come up with, we may never be absolutely sure. But you know this is what we live with in our life. You know, we're never absolutely sure of anything. When you get in your car, you put on your seatbelt, right, because we're all very confident that you're safer if you're in an accident, right, if you're wearing a seatbelt you're safer. However, there are certain types of accidents that you're less safe if you're wearing a seatbelt. That's a lot, that's a small percentage of accidents. But, you know, are you not going to wear a seatbelt because maybe you're going to be in that kind of accident no of course you're going to do, you know, that's going to protect you from what's the greater risk. And that, that, that's the kind of thinking that should, you know, inform people about vaccines, what's the greater risk right now, the greater risk is clearly getting, getting COVID Even people who don't get really sick right away. We've seen that there are people who get seriously ill later, they have symptoms that you know that could be worse for a long time, even people who are basically asymptomatic at the beginning. This is a very scary pandemic. And so, you know, the way we're going to solve this pandemic is for as many people as possible to get vaccinated, then the virus won't be able to transmit, it'll be, it'll be shut back from transmitting and eventually it will ebb and that's what we're all looking forward to. We don't want to protect ourselves by having to stay at our house and not see anybody for the rest of our lives.
Bailer: You know you were talking about these, these risk comparisons and this, this, this is a really hard problem. It's really you know because I think that a lot of people that just, just assume that oh I've got this intervention so risk is zero. I think it's that we all know there's almost this hope this incredible hope that that's it, but it's not. I mean, you know, there's, I was just reading about the cases of people that were fully vaccinated that got the disease. Well, that does happen, it's not, it's not it doesn't push things to zero, it makes it awfully small it may help with, with, you know, suppressing more severe experience with a disease if you do get it, you know, How do you help people understand that zero is not achievable in, in this kind of risk.
Ellenberg: It's an issue, you know when something is approved by the regulatory agency, the word is that it's safe and effective. What does that mean effective never means 100% of that give and save never means 100% safe. It means safe enough for what, what the product does. We have products that we give to people who are seriously ill. Who can kill them? You know you have a child with, with, with cancer. There are very intensive drugs that those children get and some children will not survive the therapy. Now, if you, if you are taking an antihistamine and somebody tells you there's a 10% chance that you'll die from this anti histamine, you're not going to take that antihistamine, you'd rather have a runny nose for the rest of your life than take something that's going to happen. But if, but if you have a 95% chance of dying in the next three months, and there's a medication that can reduce that to 20%, but that medication has a small chance of being so toxic that that's going to kill you, you're going to take it. Right, you're balancing the risks and benefits, all the time for vaccines, the risks have to be very very low. But people don't expect that that's not zero. And, you know, if we, if we don't say safe if we say safe enough, you know, maybe that's gonna scare people, you know, it's safe compared to everything else we do in our, in our daily lives and the risks that we take, you know,
Bailer: you talked about this earlier when you were saying, the thing that's special or different about vaccines is it's typically healthy people that are, that don't have any other symptoms. So the idea that here I, that, that I'm healthy, but yet, yet I'm taking something that might have risk seems somewhat different like than the than the example that you just provided
Ellenberg: right it's true and we have drugs like that. Okay, people, many, many people give zillions of people take a stat. They don't take a stat and to cure something that they have, they take a stat and to prevent a bad cardiovascular outcome and there are clinical trials that have proven that they do that, but they have side effects. And so, you know, people may be more hesitant to start on something like that, which is going to prevent something that they don't know they're ever going to get anyway. Then to take an antihistamine which is going to make their nose stop running, which they will really appreciate. As someone who has allergies, I can I can testify to that. Yeah so, so with a vaccine is, it's, it's even more so, you don't know whether you're going to get the disease, right, and if you do get the disease you don't know if you're going to be one of the ones who gets really sick. And in fact, if you get the vaccine. And don't ever get the disease. You don't know whether you wouldn't have gotten it anyway, right, you can never be sure that you're the one who benefited from that vaccine why you can be sure of is that society is benefiting from you're getting the vaccine because the more people that get the vaccine, the less people there are going to be who are going to get infected and the less transmission there's going to be, and it's going to, it's going to go down, that's how we got rid of the epidemics of measles, that's how we got rid of the epidemics of polio by basically vaccinating everybody. So, that's what you can be sure of that you're, you're helping everybody else, even if you don't know that you personally will have benefited
Campbell: you mentioned there the, you know, the more of us, you know, the more of us that get the vaccine, the better of course so this is a more of a general question on how we deal with the sort of anti Vax vaccine movement that's out there that's the drive in social media. Is there a number that we got to. We got to get to, and how do we how do we fight that mentality. I mean I think this is a problem, big problem.
Ellenberg: It's a very hard of course, there's the out and out Anti-Vax people and then there's the vaccine hesitant people, and those are different groups, and you can deal with the latter perhaps more easily than the former. Before I went to work at the FDA, I was working in the Division of AIDS in the early days of treatment for HIV, AIDS, and some of you may remember if you're old enough that there was, there was a lot of flack from the AIDS activists community, they thought all of us in the government were murderers we were doing terrible things. You know we weren't doing anything right, we needed to get people more rapid access to drugs, and, and it was pretty, it was pretty scary. But when I saw some of those some of the material that the, that those activists produced, it actually sounded pretty reasonable. You know the kinds of things that they wanted to make clinical trials more acceptable to the community and a lot of suggestions that they had. I remember reading this and thinking to myself, You mean we're not doing it that way, why are not we doing it that way. And, and it started a dialogue which was extremely effective and the AIDS activists actually became the strongest advocates for good rigorous sound research that was going to tell them which drugs were worth having in their medicine cabinet, and which ones were not. They knew it wasn't going to do them any good to have 100 drugs available to them. If they didn't know which ones worked. So that was really important.
So when I went to FDA there was already a very strong anti Vax movement mostly from parents whose children had suffered something after they got a vaccine and they were absolutely 100% certain that the vaccine had caused it. And I thought well I, you know, had some success with the AIDS activists, maybe there's something to be gained from from reaching out and what I what I learned there is that the grief of a parent, when something bad has happened to their child is not something that can be, you know, overcome in many cases by some kind of reasonable discussion, these, these certain many of these people are dealing with a grief about what happened to their child by feeling like they're helping other parents, by making them aware of, of the bad things that can happen if your children are vaccinated, I mean they, they're, they're very sincere.
So talking about coincidences, talking about, you know, all the kinds of things that have happened to try and persuade people that MMR vaccine doesn't cause autism and DTP vaccine doesn't cause SIDS and that Thimerosal, the mercury preservative doesn't cause problems, even the data that have emerged, you know, putting children to sleep on their backs instead of on their stomachs drastically reduced the risk of of SIDS, you know that should have told people that it's not the vaccine, you know, but those kinds of data didn't because I think the grief is too strong. This is what is giving for some of them getting their life some meaning after something that happened to their child, and so it's difficult but the vaccine hesitant people who hear some of these stories, and there's a lot of them out there you know when my, my grandchildren now, are, are all moving into adolescence but when my children were younger and they were first having their children, they would, they would come to me with stories of their colleagues. You know people who were in academia, people with PhDs were saying Didn't your mom do something with Vaccine Safety? Should I worry about giving you know my baby's gonna be born, should I worry about giving them these vaccines. So, you know these stories get to people even highly educated people, they just, they just don't know so it's really important for people to understand something about vaccine safety. The first year of life is the most dangerous year in which bad things happen to little kids and they're vaccinated, multiple times during their first year of life. So you are going to have bad things happen just in the same way as with the COVID vaccines, who are the first people to get COVID vaccines, people in nursing homes, people over the age of 75 What's their risk of death, what's the risk of death of somebody who's 82 years old. So, people see that there are people who died after getting a vaccine. You know, that's expected. We know the vaccine doesn't protect people from anything other than getting COVID doesn't prevent you from having a heart attack, doesn't prevent you from having a stroke, doesn't prevent you from anything else that kills people who are, you know, who are old and have all of these risk factors.
Pennington: Stats and Stories is a partnership between Miami University’s Departments of Statistics, and Media, Journalism and Film, and the American Statistical Association. You can follow us on Twitter, Apple podcasts, or other places you can find podcasts. If you’d like to share your thoughts on the program send your email to statsandstories@miamioh.edu or check us out at statsandstories.net, and be sure to listen for future editions of Stats and Stories, where we discuss the statistics behind the stories and the stories behind the statistics.