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Kevin Kavanagh, MD: “Infection preventionists will need to make sure that they still have access to adequate PPE, even if the vaccine comes out [and they] really need to look at the experimental group that was used for the EUA.”
Infection preventionists and other healthcare professionals need to be aware of the many obstacles to the production of a vaccine for coronavirus disease 2019 (COVID-19) that will be sufficiently effective and that the majority of the American people (including healthcare workers) will be willing to take. Kevin Kavanagh, MD, is a member of Infection Control Today®’s Editorial Advisory Board. He recently attended a meeting of the Vaccines and Related Biological Products Advisory Committee, a panel that advises the US Food and Drug Administration (FDA) about the efficacy and safety of new treatments. Kavanagh wrote about that meeting for ICT®. Kavanagh worries that the FDA’s granting of an emergency use authorization (EUA) for any COVID-19 vaccine can go wrong in many ways. “For example, even the definition of what’s a severe COVID-19 infection was a Pa02 of less than 93, which many asymptomatic patients can have,” says Kavanagh. “Some people can have that just resting at night if they’re not breathing real readily. It [the advisory committee meeting] was very deflating.”
Infection Control Today®: Okay, let’s dive in. What did you find out about the coming COVID-19 vaccine at the FDA meeting that you attended?
Kevin Kavanagh, MD: Well, first of all, I think it was very important to understand that the vaccine isn’t going for FDA approval, it’s going for an emergency use authorization by the FDA. And this type of authorization doesn’t require the rigor in the data, or the evaluation for the vaccine. And so, because of this, there were questions regarding efficacy and safety of the vaccine, if it was approved through EUA.
ICT®: Now, the advisory committee is just that, right? It’s a group of experts that advises the FDA about what they see might be problems coming up.
Kavanagh: That’s correct. But I think the advisory committee has an awful lot of weight with the medical establishment, and even your local doctor. If the advisory committee does not OK the vaccine, even if it’s OK’d by the administration, I don’t think it would be very likely that you would see healthcare professionals jump on board and start distribution. I really do believe the healthcare industry is striving for a very effective vaccine. And they’re going to wait until the data show that it has acceptable effectiveness and safety to start distribution. But again, remember, an EUA a isn’t the same process as an approval from the FDA.
ICT®: It sounds like we’re splitting hairs just a little bit. I mean, if an EUA is granted by the FDA, isn’t that sort of an approval?
Kavanagh: Well, it’s granted, however, on a trial period of two months, or a minimum of two months, as opposed to six months or greater. And it’s granted on data from 3000 subjects which are divided into an experimental and control group, as opposed to tens of thousands of subjects. It’s not nearly as rigorous of a process. There are also concerns, for example, about what the endpoint will be for the vaccine effectiveness. On the current trial, this endpoint is looking at whether or not it prevents COVID-19. And of course, on the surface, that sounds good, but that could be prevention of a cough, or of a fever, as opposed to preventing hospitalizations and deaths. And then the effectiveness goal is set at 50%. Error margins could be as low as 30%. You combine all of that, the vaccine may not be highly effective. That doesn’t mean it won’t provide some benefit to the healthcare worker. But it does mean that at least initially on a vaccine that comes out on EUA one should not abandoned public health strategies. That’s very important. The second aspect has to do with safety. Now, a minimum of two months follow-up is good from the standpoint that the vast majority of vaccine adverse events occur within six weeks after the vaccine has been given. However, there are two caveats. One is there can still be some very delayed adverse events which happen, especially as immunity wanes. There can be very rare events of, for example, enhancement of disease if you get infected. And what’s even more problematic is that when you only have 1500 people in that control group and in that
experimental group, that means all sorts of different types of patients may not be represented to a large extent. For example, if you have rheumatoid arthritis, if you had AIDS, if you’re pregnant, some of the minorities. All of these groups may not have a large enough N to detect adverse events which may occur in that group. If you’re a white male like myself, then it’s not a bad group. But unfortunately, not everybody is going to have that type of representation. So that’s the reason why a larger full-scale trial is needed. The worst-case scenario which could happen is that if a vaccine is approved, and it has minimal effectiveness, and people that get it decide to abandon public health measures, it is possible you could see actually a resurgence of COVID-19. And so that is concerning. You want to make sure that you have proper messaging. That, yes, here’s the vaccine. Frontline workers, people at high risk, you really need to consider getting this, but don’t abandon public health measures. Finally, if you are low risk, you would probably want to have more data regarding effectiveness and quality. But this vaccine is not going to be available to you anyway, until probably mid or the latter part of next year. And by that time, that data should be available. The vaccine is a very good stopgap measure. If it’s granted on an EUA, its effectiveness and quality, however, cannot be assured. You still need to have post-market monitoring, and above all, do not abandon your public health strategies. And let’s all hope that when a vaccine does become available for approval, that it has excellent efficacy and safety data. I mean, that’s something we can all hope for.
ICT®: How many people would you like to see how have tried the vaccine for it get emergency use authorization?
Kavanagh: I would like to see 30,000 to 40,000 people being studied for a minimum of six months. In other words, the entire cohort. And within that study group, it’s not only important of the total number, but having different cohorts or different patients at risk being represented in enough numbers, that that study would be beneficial to guiding them in whether or not to get the vaccine.
ICT®: You and I spoke after you attended the advisory board meeting and you sounded a little bit deflated about actually getting a vaccine out to the majority of people and the majority of the people actually accepting that they should take the vaccine. Is that a fair assumption on my part?
Kavanagh: I think it’s very fair. Yes, I was very disappointed. For example, even the definition of what’s a severe COVID-19 infection was a Pa02 of less than 93, which many asymptomatic patients can have. Some people can have that just resting at night if they’re not breathing real readily. It was very deflating. A minimum of five severe cases in a control group again seems far too small and these were items that were being said again for the EUA, not full evaluation, but the emergency use authorization. And this was disappointing. And you have to realize, if you don’t have proper messaging, then you will just fuel the anti-vaccination movement. If indeed this vaccine doesn’t meet expectations. For example, the vaccine could very easily still have COVID-19 infections occurring in patients that get the vaccine. This is to be expected. You want to have the public educated on this. That this may reduce the severity and may reduce the incidence of these infections. You don’t want to have in the news media a number of patients that got COVID-19 [after getting the vaccine] and go out saying the vaccine’s not any good, don’t get it. And this is similar to what we see with the flu vaccine. The flu vaccine’s not 100% effective. Nowhere near. If it’s 50% effective people are very happy with this. But if you do get the flu, it decreases the severity. And it decreases the spread of flu in the community, because more and more people are resistant to it. So overall, it’s very beneficial. This is the type of messaging we need to get out with this COVID-19 vaccine. Remember, this is the first iteration of the vaccine. We will see better and better vaccines coming over the course of years. Similar to the shingles vaccine, where the initial vaccine people got was good, but several years later, a better vaccine came out and people got revaccinated with that better vaccine.
ICT®: Are you against the emergency use authorization for a COVID vaccine?
Kavanagh: Absolutely not. I feel that when it comes out, it will provide some effectiveness, it will provide some protection if done correctly. But people are going to have to weigh the risks versus benefits. If you’re a frontline worker, or if you’re high risk like myself and want to see your grandchildren, I will probably take that vaccine. Because the risks of a chance occurrence of a severe episode from the vaccine is far less in my opinion, to the risks of having a COVID-19 fatality, disability, or death which occurs with myself. So, of course, I would get it but I’m not going to not use a mask and not social distance until we have some better long-term data. For example, it was only a two-month follow-up. You can’t say for sure how long the immunity to that vaccine is going to last. We know from multiple studies now that antibody rates fall rapidly with COVID-19. The same may be true for the vaccine. Now you can have memory B cells. But how effective those are, we don’t know. As I’ve said repeatedly, pray for memory B cells. And I do feel that a vaccine will be worthwhile, people should get it. Especially if you’re high-risk. Of course, you’re going to have to weigh for yourself your risks versus benefits. But above all, you need proper messaging to the public. And you need to not abandon public health measures. This is like adding a layer of armor to your protection. It’s not a replacement suit of armor.
ICT®: As you know, a lot of hospitals make employment contingent on getting the flu. I know just from talking to some sources that hospitals are wrestling with this question right now regarding the COVID vaccine. How do you see that playing out?
Kavanagh: I think it’s going to be something that’s on the table. But until you really know the data of its efficacy and risks, it’s hard to make a statement on whether or not it should be mandatory. For example, if it was as good as measles, where almost everybody is immune for life when you get the vaccine and it prevents a very, very severe disease, then mandatory vaccination of healthcare workers would be something that surely would be considered. But if the vaccine isn’t that effective, and it has a significant amount of complications to it, then it’s up for discussion. One may want to consider another alternative. So definitely that’s going to be on the table. But you really can’t say how you weigh in on the issue until you have the data of what are the benefits, what are the risks. And we don’t have that now.
ICT®: Let me paraphrase what you told me. You are not against the emergency use authorization, but you would like to see a control group of about 40,000 people taking the vaccine and a follow-up six months later before such an EUA is issued? Is that basically what you’re for?
Kavanagh: Not just a control group, you would need a control and experimental group. Well, that would be ideal. Yes. Before mass distribution, so you know exactly what’s going on. Now, if you’re a frontline healthcare worker an EUA coming about should certainly be something that would be beneficial to you. And so, when I say ideally, what I’m saying is six months follow-up is what’s really needed before you start to develop an idea of the safety and effectiveness of the vaccine. Prior to that, there’ll be some increased risks. It may be beneficial. So, it’s a layer of armor, but you shouldn’t be abandoning other strategies. For example, I think it would be a disaster for hospitals to immunize their workers and not give them PPE because they now have the vaccine. I don’t think that’s going to happen. But nevertheless, we need to use this. We need to view this as an added layer of armor, rather than as a substitution especially until we know the effectiveness and the long-term problems that may arise with the vaccine.
ICT®: Doctor Anthony Fauci had a viewpoint in JAMA Network recently saying essentially what you’ve been saying, for months. That when a vaccine comes along, it doesn’t mean to stop wearing a mask, stop the social distancing, stop the hand hygiene. Even with the vaccine. So, that’s kind of where you’re at, right?
Kavanagh: That’s correct. And that’s going to be of utmost importance. And I think, as I said, if you are in a high-risk group, immunologically, for example, rheumatoid arthritis, you have AIDS. And this EUA vaccine comes out, you really are going to want to study that to make a decision whether or not you should take it because again, you’re not in that group of people that was probably studied for the EUA on the safety side of things. And also, they won’t know the effectiveness in that group of people. So, you would still very much want to be relying on public health measures. If you are frontline, you are working with the public, you have a hard time social distancing, then that’s going to make the benefits of this vaccine more pronounced for you, as opposed to someone who can isolate comfortably at home. And of course, during the surge that we’re currently having, it makes those type of decisions of upmost importance. Now, if you’re a frontline health care worker, you're probably really pay praying for any type of added armor that you could have even a vaccine that only has minimal effectiveness, it may well give you enough protection to keep you from dying of COVID-19.
ICT®: Any final words for infection preventionists and how they should handle the vaccine when it comes out?
Kavanagh: Number one is infection preventionists will need to make sure that they still have access to adequate PPE, even if the vaccine comes out. Number two, you really need to look at the experimental group that was used for the EUA. So, if you have people in your hospital that are maybe a high-risk category other than what was studied, they may have to be a carved out on what your hospital policy is. And then you’re going to have to weigh the effectiveness, the risks versus benefits of the vaccine versus not getting the vaccine. And believe me, if I was a frontline healthcare worker at my age, a vaccine would really have to have a lot of complications and concerns before I would not get it. Now that’s just a personal view. Because if it adds any armor to protect me from a highly infectious disease that’s very prevalent in our community, that has a high rate of fatality, and even a higher rate of chronic disability, I would opt for that vaccine. And that’s just my personal opinion.
This interview has been edited for clarity and length.