The Pfizer COVID vaccine is a home run.
There are caveats, of course, and immense hurdles still to climb, but the bottom line here is that this is a gigantic win for society.
A full paper was published in the New England Journal of Medicine and the full 53 page briefing that was given to the FDA was put online as well.
This permits us to look at the data in detail and unpack more information about efficacy and safety. So let’s dive into the data a bit to get some more details.
Trial design matters, and if you don’t get into the weeds a little bit, you may miss important details.
Who was in the trial?
As with any clinical trial, before you can draw any conclusions about who might benefit from a treatment, you need to think about who was studied.
So if the trial population doesn’t reflect the actual population, you can’t just extrapolate to say that things will be the same for everyone.
When I read a paper like this, I always look first at Table 1, the place where the authors of the article describe the patient population in table form.
The group was half female, mostly white (about 80%) and American (about 75%), 34% were obese, and about 40% were over age 55. 28% were Hispanic (which overlaps with the white group). 9% were Black. There were even a small number of people over 75 in the trial.
The patients studied certainly aren’t a perfect representation of the people who are dying the most of this disease - Blacks, Hispanics, those with chronic disease, and the elderly - but these groups were included in the trial.
What is the vaccine regimen?
This vaccine has 2 shots given 21 days apart.
The vaccine needs to be kept at incredibly cold temperatures, basically the temperature of dry ice.
How well does the vaccine work?
Pretty freaking well.
Th type of graph below is called a Kaplan Meier curve. It’s the kind of graphic representation of medical illness that you’ll see in published papers across all domains of medicine - from cardiology to oncology and certainly to COVID.
The horizontal axis of the graph is time and the vertical axis is the proportion of patients who meet the primary endpoint - in this case, the people who developed symptomatic infection with SARS-CoV-2.
Take a look at how different the blue curve - placebo - and the red curve - vaccine - are. They’re wildly different!
Perhaps the part of the curve that’s most exciting here is when the blue line diverges from the red line. That divergence takes place around day 7 - way before the second dose.
That means there’s an impressive degree of vaccine efficacy from a single dose. So the two dose regimen is the way that the vaccine is designed according to preliminary studies on the immune response, but a single dose seems to protect against COVID in the real world.
It’s really big deal in terms of vaccine logistics, tracking, and the concern about losing people to follow up.
Based on the published report, efficacy continues for at least a period of about 4 months, and there’s real optimism that it will last for significantly more than that.
Any caveats with effectiveness?
There’s a huge one - we don’t know anything about this protects against asymptomatic infection. We also don’t know how this impact spread of the virus.
That doesn’t mean that the vaccine provides no protection against asymptomatic infection, it just means that we simply don’t know because it wasn’t tested.
It’s a real gap in our knowledge here.
What are the side effects?
The safety of this vaccine is going to make or break it in the real world.
There are two groups of side effects that we can expect as normal with an vaccine. First is a local reaction, i.e. a reaction to the injection itself. Redness, itching, pain, etc. That happens here, not really with any difference in frequency compared to other vaccines.
The second expected side effect is due to our body mounting an immune response to the vaccine. We would expect a certain proportion of people to get a fever and flu-like symptoms. This should be transient, lasting for about a day, and is not “getting the flu from a flu shot” but instead is a normal part of the process of generating immunity from vaccination.
I’m not going to dwell on the local impacts, not because they don’t matter, but because I don’t think they’re super important.
As far as the fever and brief systemic illness, that seems to happen much more frequently after dose 2 than after dose 1:
Diarrhea and vomiting occurred equally in both the placebo group and the vaccine group.
Headache and fatigue were reported in 40% of the vaccine group and a third of the placebo group.
What about rare but severe side effects?
This is the thing that you care most about when you’re going to be vaccinating millions of people.
There is one note in the FDA briefing that I had to read twice:
“A total of six (2 vaccine, 4 placebo) of 43,448 enrolled participants (0.01%) died during the reporting period from April 29, 2020 (first participant, first visit) to November 14, 2020 (cutoff date). Both vaccine recipients were >55 years of age; one experienced a cardiac arrest 62 days after vaccination #2 and died 3 days later, and the other died from arteriosclerosis 3 days after vaccination #1.”
There’s one unexplained death that occurred in the vaccine group 3 days after getting the first shot.
This might just be bad luck - a heart attack in an adult over age 55 that happened right after getting the first shot. There isn’t a clear report here.
It’s not crazy to think it’s a coincidence. But it’s also not crazy to want to know more here.
The authors of the NEJM paper don’t think this is a big deal:
“Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the vaccine or placebo.”
I don’t mean to be fear mongering here. But as Fred Feit, a cardiologist at NYU said to me once about PCSK9 inhibitors, when a new drug gets tested, “new molecule, new impact. Many unknowns.”
Who wasn’t included in the trial?
A few groups weren’t tested and we need to be cautious before extrapolating.
No pregnant women.
No kids.
No one with a previous COVID infection.
No one with immunosuppressed condition or on immunosuppressive therapy.
And there were a limited number of people over 75 in the trial, so extra caution should be taken with this group.
The final caveat
Rare side effects are going to come up when we’re giving this shot to millions of people.
Paul Offit, perhaps the world’s biggest expert on vaccines and vaccination, suggests that you don’t feel totally confident about safety until about 2-3 million doses are out there and we’ve had time to see the safety impact.
We should expect a few rare side effects to be reported.
Again, this is the expectation. It would be weird if we don’t see anything. But the signal in the patients that have been tested is really encouraging so far.
We don’t know what the future will bring, but don’t be alarmed if you read about some odd side effects occurring with vaccination.
Bottom line: this is amazing news
I’m ready to get vaccinated.
We don’t know what we don’t know, of course. And there will be some revelations as we get more data and more people get the vaccine.
But I’m ready to get in line to get my shot.
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