By: Steve E. Bishop, M.D. on October 27th, 2021
COVID-19 Update 10/27: Pfizer Vaccine Data for Kids
This week, the FDA approved an emergency use authorization for Pfizer's vaccine for children ages 5 to 11. The CDC will meet next week to officially vote on their use in the United States.
Ahead of the FDA meeting, Pfizer released a large amount of data from their trials. On this week's COVID-19 update, Dr. Bishop analyzed that data, including:
- How did they decide the size of the dose?
- Does the vaccine appear safe? What were the reported side effects?
- What was the reported antibody response?
- What was the efficacy rate?
- What about the myocarditis risk?
Watch the full video below or read on for our recap.
The Resource Materials
Here are links to a couple of items we are going to review. One is the FDA data packet, which is 82 pages long. And one is an article on STAT News, which is a highly reliable source that reviewed the whole meeting, including the data, some of the key elements that were discussed during the meeting, and the pros and cons of making the approval, and then summarized the whole thing.
It's a longish read, but you can get it done in probably 15 minutes. It's a good article. I highly, highly recommend you check it out if you don't want to spend the time to read through 82 pages of data on the Pfizer vaccine.
I'm going to hit some of the highlights from the vaccine data packet, and we'll talk a little bit about my interpretations of that as we go through, and then you guys can read the STAT News article.
- FDA Briefing Document: Pfizer Vaccine for Children 5-11
- STAT News: Tracking the FDA advisory panel meeting on Covid-19 vaccines for kids
Then, next week, the CDC's ACIP — Advisory Committee on Immunization Practices — will take up the question about whether to recommend these vaccines officially to the five to 11-year-old kids.
This first step is the FDA saying: is this safe enough to be on the market and does it work? And then the second step is whether it should actually be recommended or not for that age group.
With that, let's go ahead and dive right in. I'm going to start on page 30 of this data packet. In the first 30 pages, there's a lot of data. There's some background information, some rationale for why we're doing this.
Why should we even bother with this? And a lot of it is boilerplate stuff that you are familiar with at this point. It's not that different from some of the other introductory comments we've seen in the data packets.
We're going to go through the phase two and three data, which is the trial where they had about 2,200 kids in the trial.
How did they decide what dose to use?
What they used in this trial was a couple of different doses. They were trying to figure out which one to use. They used a 10-microgram and a 30-microgram dose. They ultimately opted for the 10-microgram dose based on the fact that it seemed to work just as well and had probably a slight reduction in side effects.
If you look at page 30 on the packet, if you're following along in there, you'll see the graph of local reactions and side effects within seven days after dose one and after dose two.
And you can see there, it talks about local reactions, so redness, swelling, pain at the injection site, that sort of thing.
In the 10 microgram dose, you had a slightly less report of things like pain at the injection site. And it was similar in terms of swelling and redness. They ultimately basically said, "Okay, the 10 microgram really is probably a little bit better than the 30. So we're going to go with that one."
Again, lots of data in here, so don't feel bad if you can't digest this all in one sitting. I've had a couple of days to look through it.
If you look at page 31, figure five, you're looking at the vaccine doses at 10 and 30 versus placebo. And what I always find super fascinating about these. These are systemic events. So, did you get a fever? Were you fatigued? Did you have a headache? Did you have chills, muscle aches, pain, all that sort of stuff, after the vaccine?
What I always find super interesting about these studies is if you look at the placebo response, 38% of the kids, or 30% of the kids depending on the dose, had the side effect of fatigue. 25 to 37% of them had the side effect of a headache. And 15% of them had diarrhea or muscle pain or what have you. And all they got was a placebo. It's just saline. It just goes to show you how strong the placebo effect can be, meaning, "Oh, I got something. So, therefore, I need to have a reaction to it." That placebo effect can be quite strong.
If you look at the first set of data there, a majority of the patients got fatigue and headache after the 30-microgram dose, but only about a third for the 10-microgram. And the same thing for chills. Muscle pain was less common in the 10 micrograms. Again, that supports the fact that the 10 microgram has fewer side effects. And so that's why they went with that one.
If you go down to page 32 and look at figure six, kind of the same story. This is after dose two. A little bit higher side effect rate for fever, fatigue, headache, chills, that sort of thing, after dose two compared to dose one, which is pretty consistent with what we've seen in adults for all of these vaccines.
Is the Pfizer vaccine safe for children?
The bottom line is after they did the trials, they found that, in general, these vaccines appear to be relatively safe.
Any kind of negative event — and that could be, "my arm hurts after the injection" — about 10% of the patients had that in in the phase two-three trial. Again, relatively safe.
There were no life-threatening reactions to the vaccines at either dose and no one withdrew from the study due to severe reactions. And there were no documented severe adverse reactions in the vaccine group. That's all really good news.
One thing that I know everybody wants to know about, and that we'll have to talk through, there were no reports of myocarditis or pericarditis in any of the participants, either the control group or the vaccine group. That is good.
There were some reports of other things like lymphadenopathy, which is swollen lymph nodes, and sore joints and things like that. In other words, they didn't find a whole lot of very concerning side effects.
Again, they followed people for about a month after the second dose and about 2,200 kids. Overall, that's good information.
It's also only 2,200 kids, so it's a fairly small study. I remember the adult studies were on the order of 50,000-60,000 participants, so these are much smaller studies than what we're seeing at the adult level.
What was the antibody response?
So, if we keep going, if you're following along in the document here, I'm going to scroll through some really large blocks of text here. What we get to is a number of tables showing that the antibodies did respond appropriately.
Most people had a four-fold rise in antibodies after the vaccine was given. So just showing, okay, the body does make antibodies to the spike protein after use of this dose, right? That is for the 10-microgram dose and the 30-microgram dose again. We've got evidence showing that both the 30 and the 10 create a pretty strong rise in antibodies.
And with the 10 producing fewer side effects, you would go with the 10 over the 30. If they both give you roughly equivalent increases in antibody levels, but the 10 has fewer side effects, you go with the 10 microgram dose. And so ultimately that's why that dose was the one put forward.
What was the efficacy rate?
Now, if you keep going down, what we really want to see is outcomes data. That's been one of my criticisms and a lot of other people's criticisms about the booster shot data sets. They have not really been showing outcomes data in terms of what happened to the infection rate? What happened to the hospitalization rate? All that sort of stuff.
And to Pfizer's credit, they do have outcome data in here. It is only infections. It's any first occurrence of COVID from seven days after dose two for anybody who had no prior evidence of infection. And they did follow out for 126 days or so for this information.
What they found was, in the vaccine group, there were three cases of symptomatic COVID, and in the placebo group, there were 16.
That's good. There's 90% efficacy is what they're saying, right? 90% reduction, 90% efficacy in the number of cases of COVID after the second dose. And that's very good. That means the vaccine does work essentially as billed. It seems to prevent transmission at least up to that window of time when they stopped following the kids.
And again, that's pretty consistent with what we've seen with the adults, right? It reduces transmission at least for a while. And this was the big area of contention, one of the big areas of contention that was discussed yesterday.
They prevent transmission. We saw that with the adults too, but then it started to break down after a few months. My suspicion is you're going to see the same thing with these vaccines for the children. The transmission reduction is going to last for a few months and then it's going to wane. Just like we saw with the adults. There's no reason to think that that's going to be any different from a mechanistic perspective. We can hope, but I think it will be probably the same outcome.
Does it prevent severe COVID?
Now, what's important to know too, is that there were no cases of severe COVID in either the control group or the treatment group, so they can't really draw any conclusions, any legitimate conclusions, on whether the vaccine prevents severe COVID or not.
You can't say one way or the other because there weren't enough outcomes in the control group to draw a conclusion on that. That's also an area of contention that was discussed yesterday.
And if you roll through the STAT News article, you'll see a lot of this kind of played out, which is to say part of the question is that kids, in general, are quite a low risk for severe outcomes. It's going to be really hard to prove that the vaccines are reducing that outcome because the numbers are so small to start with.
That's an area that's still an open question in my mind and I think a lot of people's minds. I'm far from alone in that interpretation of the data, and this was openly discussed in the committee. I think it's something that still needs to be answered. Does it meaningfully prevent severe COVID in that population?
But clearly, over the 126 days of the follow-up that they did — so what was that? Four or five months or so? — the transmission, the number of cases of symptomatic COVID, was much, much lower in the vaccinated group compared to the unvaccinated group, certainly, but neither group had cases of severe COVID. That is great.
So what decision did they make?
But again, that leaves us with this open question. And if you look on page 61 of this document, you can see all this outcome data plotted nicely. I do want to pull us back to this question of myocarditis because this is one of the key issues that was discussed a number of times during the panel yesterday.
Ultimately, the panel voted to make these vaccines available because they believe, and I agree, that the vaccine should be available for five to 11-year-olds so that parents can make the decision about whether they want their kids to get vaccinated. And I think that kids who have health problems, their parents are probably going to definitely want to get them vaccinated.
That is ultimately where they came down. They are saying, "Okay, looking at all this data, we think they should at least be available." It's going to be up to ACIP and CDC to make a question on whether it's recommended or not formally and for whom.
But again, there was a lot of discussion back and forth during the committee meeting. There were a number of calls to nuance the question down about the approval. Who should we approve it for? Maybe not everyone, maybe a smaller group? But that did not continue, so it was just approved five to 11 under EUA.
What about myocarditis?
Let's go over to the STAT News article and I really want to draw your attention down to the scenarios that the FDA was looking over in terms of the expected side effects and the expected provision of cases and severe disease and all that sort of thing.
If you scroll down about halfway through the article and see scenarios two, three, and six, they had a number of scenarios they looked through. And this was specifically related to the myocarditis, pericarditis question.
Now, this is a model. Remember. this is not actual data. This is a model based on how many cases of either COVID or myocarditis we would expect to see if rates from other studies hold true in this population once it's released population-wide.
If you look at this data, the bottom line is we are going to probably see, if this model holds true, excess cases of myocarditis, especially in young men and boys. That's fairly undisputed at this point. The vaccines do have that risk. It's small, but it's there. And when you're talking about vaccinating millions of people, you do have to take those models into account.
The risk and benefit of the vaccine in this age group really depends on the transmission prevalence of the virus. If the transmission prevalence of the virus is high, meaning like it was over the summer, or like it was last winter, then the risk-benefit is clearly in favor of the vaccine. More hospitalizations from COVID are going to be prevented than hospitalizations caused by myocarditis and pericarditis. Same thing with cases in general and ICU stays for both COVID and myocarditis from the vaccine.
Again, this is a model. Now, if the transmission rate drops to where we were in, say the spring or where we are now, then the risk-benefit tilts. Then you're causing more cases of myocarditis that result in hospitalization than you're preventing from the prevention of COVID. And that's just what the FDA is modeling out. We have to be transparent about all this and that's okay. We have to take these things into account.
The bottom line is what they were saying is, a lot of the folks on this committee were saying, "Hey, look, this is kind of a toss-up question. Let's go ahead and make the vaccine available because we want people to be able to get it. But there are some questions that we still have unanswered." And I think that that's okay.
At the end of the day, they approved it. We'll see what CDC wants to say about the official recommendation or not. But I want you guys to have all the information as much as possible.
I encourage you to look through this whole STAT News article, read other sources as well, check out the 82-page document, look at the data yourself, and decide what you think. And talk to your doctor about what they think about it too. Again, a lot of good information.
A lot of it is complicated. It's not going to be boiled down to a simple cut and dry with the kids as much as it was for adults. And that's okay. I think that the committee discussion really was transparent about that and I thought it was good. So, take that all for what it's worth, read the information for yourself, make your decisions. I think that being as transparent as we could be about these things, the better off we're all going to be in terms of getting through this, ultimately.
Again, talk to your own physician about this, see what they think about it, and get their recommendation on whether you should vaccinate your kids. Talk to your kid's pediatrician about that. This is just a general discussion about the data that they came out with yesterday and my opinion on it. So, that's that.
"I got the J&J on March I'm planning to get a Moderna shot as my second shot. What do you think?"
Yeah, I think that's totally reasonable if that's what you want to do. The FDA came out and said that was, they believe, probably safe. And I think it probably is safe to mix and match the vaccines in that way. If that's something that you want to do and your doctor is okay with it, I think that's totally reasonable.
"I hear in the news that positivity rate is going down, but certain places like in Richmond are back to requiring mask citing high transmission rates. What does it take to get our status out of that category?"
Yeah, that's a good question. I don't know. I think the Virginia Department of Health, in each locality, has made decisions about what they think high transmission rates are and that's sort of on a locality-by-locality basis. I don't know exactly what thresholds that each place is going to have to get to, but the local authorities, I think, are making these decisions at the local level. So each place is probably a little different in that regard. I would suspect that the Richmond City government may have posted something somewhere on their website about what their target number is. Maybe check there. But it is confusing because it's different everywhere you go.
Myocarditis: The Basics
"Myocarditis — what is it exactly? Is it easy to identify through symptoms? What is the typical treatment and recovery time?"
Yeah, great question. Myocarditis and pericarditis are inflammation either of the heart muscle (myocarditis) or of the sac surrounding the heart muscle (pericarditis)
It is generally easy to identify through symptoms. People generally are going to have chest pain, shortness of breath, and symptoms like that.
Typical treatment is supportive, meaning you get maybe some anti-inflammatories, some rest. And most people recover in days or a few weeks at most. A small percentage of people, as clearly outlined in the FDA documents and other sources, do wind up in the hospital and occasionally in the ICU with myocarditis because it can be quite serious. And it can be fatal in very rare cases, but so can COVID, right? We have to balance these things out a little bit, and that's why you see the FDA comparing the two things. What's worse — getting COVID or getting myocarditis from the vaccine? So that's why they've made those models to compare the two. All right, Diane says,
How Long to Wait Before Testing
"How long after returning from travel should you wait to take a rapid test?"
In general, if you've got exposure, I would wait, around five days. Three to five days. I would wait probably five days, but at least three before you do a test if you're talking about asymptomatic testing after potential exposure.
When is the next update?
The next update will be on Wednesday, November 3 at 1:00 pm on our Facebook page. Dr. David Pong will be filling in for Dr. Bishop. For those without Facebook, we will post our written recap on Thursday morning.