Why is one dose Johnson and Johnson better than 1 dose of Pfizer/Moderna
May 28, 2021 8:34 AM Subscribe
Why is one dose of Pfizer at 80% effectiveness worse than one dose of Johnson and Johnson at 60% effectiveness?
I'm trying to understand the recommendations- for me I have heart inflammation and have two family members with cardiovascular reactions to the moderna/pfizer; but only on the second dose. I'm wondering why it's worse to get one moderna or pfizer than one johnson and johnson when even one dose of the first two offers better protection?
Is one dose of moderna/pfizer really less effective than one dose of johnson and johnson? I find it confusing they they say one dose of moderna is unacceptable but one dose of johnson and johnson is considered fully and acceptably vaccinated when my untrained understanding is it looks like you'll still have worse protection with the j&j.
I'm trying to understand the recommendations- for me I have heart inflammation and have two family members with cardiovascular reactions to the moderna/pfizer; but only on the second dose. I'm wondering why it's worse to get one moderna or pfizer than one johnson and johnson when even one dose of the first two offers better protection?
Is one dose of moderna/pfizer really less effective than one dose of johnson and johnson? I find it confusing they they say one dose of moderna is unacceptable but one dose of johnson and johnson is considered fully and acceptably vaccinated when my untrained understanding is it looks like you'll still have worse protection with the j&j.
It's not necessarily less effective, I don't think? But a single dose of Moderna isn't authorized in the US, because it hasn't gone through the rigorous testing that the two-dose regimen has, or the one-dose regiment of J&J. It does seem unlikely, as a layperson, that one dose would be somehow problematic, but the scenario doesn't seem to have been studied the way we want scenarios to be studied, even for an EUA.
posted by chesty_a_arthur at 8:51 AM on May 28, 2021 [1 favorite]
posted by chesty_a_arthur at 8:51 AM on May 28, 2021 [1 favorite]
Best answer: Nobody in public health wants to say anything, understandably, because (presumably) they don't want to discourage anyone from getting a shot. As someone noted on Twitter, we beat polio with a vaccine that isn't even as effective as Johnson and Johnson. It's still quite protective. But it is pretty clear to me that one dose of Pfizer (I haven't seen one dose Moderna studies) is 80-85% effective at 2 weeks and J&J is 65-70%. I don't think you'd find a single doctor who would recommend that a vulnerable person who's gotten J&J should go get another shot, but I bet that you'll see that recommended once the flow of folks who have gotten zero shots slows down.
posted by wnissen at 8:55 AM on May 28, 2021 [6 favorites]
posted by wnissen at 8:55 AM on May 28, 2021 [6 favorites]
Best answer: Non-immunologist here, but from a research perspective, post hoc analyses (redefining your research question) are not really cool.
The null hypothesis for all these trials was "[Vaccine] has no impact on covid infection/hospitalization/death." That is the default position until proven otherwise. Then you run the trial in a blinded fashion, and at the end you determine whether you can reject the null hypothesis based on your data.
Post-hoc analyses are like peeking under the blind. They can be useful in designing a follow-up trial, like "Hey, maybe one dose of Moderna/Pfizer really is enough" but you can't state that with any certainty until you actually do that trial.
I have no idea why Moderna and Pfizer designed their trials as two-dose, but given that two-dose trials are harder than one-dose trials, I assume it was for good reason based on their understanding of mRNA vaccinology.
posted by basalganglia at 8:56 AM on May 28, 2021 [14 favorites]
The null hypothesis for all these trials was "[Vaccine] has no impact on covid infection/hospitalization/death." That is the default position until proven otherwise. Then you run the trial in a blinded fashion, and at the end you determine whether you can reject the null hypothesis based on your data.
Post-hoc analyses are like peeking under the blind. They can be useful in designing a follow-up trial, like "Hey, maybe one dose of Moderna/Pfizer really is enough" but you can't state that with any certainty until you actually do that trial.
I have no idea why Moderna and Pfizer designed their trials as two-dose, but given that two-dose trials are harder than one-dose trials, I assume it was for good reason based on their understanding of mRNA vaccinology.
posted by basalganglia at 8:56 AM on May 28, 2021 [14 favorites]
PS these trials were telescoped, meaning that Phase 1 (safety testing), Phase 2 (efficacy and/or dose finding), and Phase 3 (large population, the money trial) all happened in parallel. That is really unusual and was done for reasons of speed.
It's possible that if it had been done traditionally, we would have discovered in Phase 2 that a single dose of Moderna/Pfizer is as effective as 2 doses, so Phase 3 would have been just a single dose. But no one wanted to wait the 2-3 years that would have taken.
posted by basalganglia at 9:03 AM on May 28, 2021 [10 favorites]
It's possible that if it had been done traditionally, we would have discovered in Phase 2 that a single dose of Moderna/Pfizer is as effective as 2 doses, so Phase 3 would have been just a single dose. But no one wanted to wait the 2-3 years that would have taken.
posted by basalganglia at 9:03 AM on May 28, 2021 [10 favorites]
First, as others have said, the numbers you have seen are not good for comparing against each other. You'd need a head-to-head trial, basically.
As to some of the background, during the initial planning (and IIRC based on some early human data) Pfizer and Moderna thought their protection would fade with only one dose, so they set up the trial for two doses. Which is now the only thing we know works, because that's all we've studied.
This is the sort of thing that did get compressed on these insanely quick and successful development run: In a normal situation you'd probably spend a lot longer running early tests and working out the best dosing regimen that gives best protection with lowest side effects, possibly with one shot, possibly with two shots further apart, possibly with lower doses, etc. But this is what we have now.
posted by mark k at 9:05 AM on May 28, 2021 [4 favorites]
As to some of the background, during the initial planning (and IIRC based on some early human data) Pfizer and Moderna thought their protection would fade with only one dose, so they set up the trial for two doses. Which is now the only thing we know works, because that's all we've studied.
This is the sort of thing that did get compressed on these insanely quick and successful development run: In a normal situation you'd probably spend a lot longer running early tests and working out the best dosing regimen that gives best protection with lowest side effects, possibly with one shot, possibly with two shots further apart, possibly with lower doses, etc. But this is what we have now.
posted by mark k at 9:05 AM on May 28, 2021 [4 favorites]
From Necessity of 2 Doses of the Pfizer and Moderna COVID-19 Vaccines (from February): "It is known that the immune response to 1 dose of the vaccine is relatively weak, even though people who got their first dose had some protection against symptomatic COVID-19 infection. It is not known what will happen if people get only 1 dose."
So that seems to imply that the real-world efficacy from one dose is larger than would be projected based on the observed immune response. Since they know that the immune response is better with two doses, they're giving two doses, but no one knows what the actual benefits are.
posted by Mr.Know-it-some at 9:12 AM on May 28, 2021 [3 favorites]
So that seems to imply that the real-world efficacy from one dose is larger than would be projected based on the observed immune response. Since they know that the immune response is better with two doses, they're giving two doses, but no one knows what the actual benefits are.
posted by Mr.Know-it-some at 9:12 AM on May 28, 2021 [3 favorites]
Another reason to get both doses is that any recommendation for when to get a booster shot will be based on studies of people who got two shots. And just based on what I've read (as a layperson), there is good reason to assume that the two shots will provide protection for longer.
posted by coffeecat at 10:12 AM on May 28, 2021 [1 favorite]
posted by coffeecat at 10:12 AM on May 28, 2021 [1 favorite]
That is a good and worthwhile question. If you've experienced any sense of having poked about where you don't have any business poking, banish it. The study you refer to (indicating 80% Pfizer effectiveness with one dose) was published by the CDC in March, looking at a population of healthcare workers from mid-December forward. Some of those received only one dose, and demonstrated a somewhat lessened effectiveness. This was not data dredging or other reworking of the extant information. There were speculative concerns expressed about the longevity of the protection.
There are billions of people, many living in circumstances which make 2-dose regimes more difficult and less likely, who need to be vaccinated. Stretching available supplies to stem an epidemic could very well be a reasonable approach. Of course, we are conducting a large scale follow-up study in the US at present; with 165 million doses administered, there is certainly a significant cohort of Pfizer and Moderna first-dose recipients who won't receive the second, for a myriad of reasons.
posted by bullatony at 10:21 AM on May 28, 2021 [2 favorites]
There are billions of people, many living in circumstances which make 2-dose regimes more difficult and less likely, who need to be vaccinated. Stretching available supplies to stem an epidemic could very well be a reasonable approach. Of course, we are conducting a large scale follow-up study in the US at present; with 165 million doses administered, there is certainly a significant cohort of Pfizer and Moderna first-dose recipients who won't receive the second, for a myriad of reasons.
posted by bullatony at 10:21 AM on May 28, 2021 [2 favorites]
You should use vaccines as recommended.
The 80% number is quoted a lot for a single dose of the Pfizer vaccine, but remember that we don't have long-term effectiveness numbers for *any* of the vaccines. We only have short term results. And the people who designed and tested the two MRNA vaccines -- Pfizer and Moderna -- tested and recommended two doses. They did not test and recommend one dose. There has been some follow up analysis, but the designers of the vaccine tested and recommended two doses, and as a layperson that seems important to me.
The Johnson and Johnson vaccine is not an MRNA vaccine. It was developed and tested as a single dose vaccine. It is highly effective.
I don't have time to find and link to explainers, but the effectiveness percentages vaccines are often misunderstood. Don't get discouraged by the 60% number. It's a very effective vaccine.
posted by Winnie the Proust at 1:00 PM on May 28, 2021 [3 favorites]
The 80% number is quoted a lot for a single dose of the Pfizer vaccine, but remember that we don't have long-term effectiveness numbers for *any* of the vaccines. We only have short term results. And the people who designed and tested the two MRNA vaccines -- Pfizer and Moderna -- tested and recommended two doses. They did not test and recommend one dose. There has been some follow up analysis, but the designers of the vaccine tested and recommended two doses, and as a layperson that seems important to me.
The Johnson and Johnson vaccine is not an MRNA vaccine. It was developed and tested as a single dose vaccine. It is highly effective.
I don't have time to find and link to explainers, but the effectiveness percentages vaccines are often misunderstood. Don't get discouraged by the 60% number. It's a very effective vaccine.
posted by Winnie the Proust at 1:00 PM on May 28, 2021 [3 favorites]
Response by poster: By the way, don't worry I'm discussing with doctor as well, just want to do some reading before having the discussion so I have good questions to ask. Thanks so much for the responses!
posted by xarnop at 2:17 PM on May 28, 2021
posted by xarnop at 2:17 PM on May 28, 2021
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posted by pinochiette at 8:50 AM on May 28, 2021 [4 favorites]