VRBPAC evaluation of Pfizer vaccine - Printable Version
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VRBPAC evaluation of Pfizer vaccine - BostonCard - 12-08-2020
Here's the report:
https://www.fda.gov/media/144245/download
Here's the efficacy analysis:
Quote:In a mid-Novemberanalysis of 36,621 participants randomized 1:1 to vaccine or placebo who were included in the per-protocol efficacy analysis population of participants without evidence of SARS-CoV-2 infection prior to 7 days after completion of the vaccination regimen, efficacy in preventing confirmed COVID-19 occurring at least 7 days after the second dose of vaccine was 95.0%, with 8 COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates across age groups, genders, racial and ethnic groups, and participants with medical comorbidities associated with high risk of severe COVID-19. Secondary efficacy analyses suggested benefit of the vaccine in preventing severe COVID-19, in preventing COVID-19 following the first dose, and in preventing COVID-19 in individuals with prior SARS-CoV-2 infection, although available data for these outcomes did not allow for firm conclusions.
More in Table 6 (overall) and Table 8 (important subgroups). One really cool thing is figure 2 (page 30). The curves between the placebo and vaccinated group start diverging 14 days after the first dose. This suggests that although two doses may be needed to generate lasting immunity, one dose is adequate to start giving people enough immunity to prevent infection. This is great news! It means that the vaccines will start having an effect earlier (and that probably if the booster dose is delayed that will be ok). As the review notes, "Based on the number of cases accumulated after Dose 1 and before Dose 2, there does seem to be some protection against COVID-19 disease following one dose; however, these data do not provide information about longer term protection beyond 21 days after a single dose." They also note that "The efficacy observed after Dose 1 and before Dose 2, from a post-hoc analysis, cannot support a conclusion on the efficacy of a single dose of the vaccine, because the time of observation is limited by the fact that most of the participants received a second dose after three weeks. The trial did not have a single-dose arm to make an adequate comparison." So you would never approve the vaccine for one dose, but it means that if someone doesn't get their second dose (or it is delayed), they will probably still have some (maybe substantial) immunity.
The data on severe cases is on page 31; it suggests about 90% efficacy, but we are dealing with small numbers.
Here's the safety analysis:
Quote:Safety data from approximately 38,000 participants≥16 years of agerandomized 1:1 to vaccine or placebo with a median of 2 months of follow up after the second dose suggest a favorable safety profile, with no specific safety concerns identified that would preclude issuance of an EUA. Available safety data from all participants enrolled through the November 14, 2020 data cut-off ( N=43,252, which includes late enrollment of additional adolescent and adultparticipants), was consistent with the safety profile for the approximately 38,000 participantswith median follow-up of 2 months and also did not raise specific safety concerns. The most common solicited adverse reactions were injection site reactions (84.1%), fatigue (62.9%),headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), fever (14.2%); severe adverse reactions occurred in 0.0% to 4.6% of participants, were more frequent afterDose 2 than after Dose 1, and were generally less frequent in participants≥55 years of age (≤2.8%) as compared to younger participants (≤4.6%). The frequency of serious adverse events was low (<0.5%), without meaningful imbalances between study arms. Among non-serious unsolicited adverse events, there was a numerical imbalance of four cases of Bell’s palsy in the vaccine group compared with no cases in the placebo group, though the four cases in the vaccine group do not represent a frequency above that expected in the general population. Otherwise, there were no notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events (including other neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to BNT162b2 vaccine. With the exception of more frequent, generally mild to moderate reactogenicity in participants <55 years of age, the safety profile of BNT162b2 was generally similar across age groups, genders, ethnic and racial groups, participants with or without medical comorbidities, and participants with or without evidence of prior SARS-CoV-2 infection at enrollment.
Looking at the data, about 1/3 of volunteers developed moderate or severe fatigue after the second dose and a quarter had moderate or severe headache. A substantial number of placebo recipients also had these symptoms, which goes to show how strong the placebo effect is.
Six volunteers in the study died, but four of them were in the placebo group, which goes to show the role of chance distribution in safety events. They note that more patients in the vaccine group had appendicitis than placebo (8 to 4). These are things to keep track of when the vaccine is given to millions of people, but likely represent a chance imbalance. From the report: "The cases were considered unrelated to vaccination by the study investigators and occurred no more frequently than expected in the given age groups. FDA agrees that there is no clear basis upon which to suspect that this imbalance represents a vaccine-related risk."
Section 8, starting on page 46 has a nice breakdown of the benefits, risks, and unknowns, and is worth reading if you want a deep dive into the vaccine. That will be the basis for the EUA. I expect it will be granted as I didn't see anything in the report that would be a red flag (or even a yellow flag) for this. The benefits are pretty clear and would be considered a home run, though I'll be interested in seeing things like long-term protection. The potential benefit seven days after the first dose is an unexpected bonus (caveats I mentioned aside). The risks are basically a decent chance (1/4 to 1/3) that you will feel like crap for a day, which seems similar to the shingles vaccine. Compared to the risk of developing COVID-19, even if "mild", I'll take the vaccine any day and twice on Sunday.
BC
RE: VRBPAC evaluation of Pfizer vaccine - BostonCard - 12-08-2020
Here's the figure I was referring to:
[tweet]https://twitter.com/florian_krammer/status/1336362836688297992?s=20[/tweet]
BC
RE: VRBPAC evaluation of Pfizer vaccine - BostonCard - 12-10-2020
Pfizer/BioNTech published their results in the New England Journal:
https://www.nejm.org/doi/full/10.1056/NEJMoa2034577?query=RP
It comes with a short video summarizing the results:
https://www.nejm.org/do/10.1056/NEJMdo005933/full/?requestType=popUp&relatedArticle=10.1056%2FNEJMoa2034577
And here is a nicer version of the figure that I linked earlier
![[Image: nejmoa2034577_f3.jpeg]](https://www.nejm.org/na101/home/literatum/publisher/mms/journals/content/nejm/0/nejm.ahead-of-print/nejmoa2034577/20201210-01/images/img_xlarge/nejmoa2034577_f3.jpeg)
BC
RE: VRBPAC evaluation of Pfizer vaccine - dabigv13 - 12-10-2020
A single dose arm would have been interesting. Seems highly effective after one dose. Given the supply constraints, a highly effective single dose would be much better at saving lives/ending pandemic even if efficacy is more like 80-85% compared to 90-95%.
Doubt Pfizer would go along with that sort of study now that they are on brink of approval. And very unlikely FDA would approve that dose regimen without a study. Will have to wait for retrospective data on people who only got one dose for whatever reason to tease out more fully.
RE: VRBPAC evaluation of Pfizer vaccine - BostonCard - 12-10-2020
(12-10-2020, 10:00 AM)dabigv13 Wrote: A single dose arm would have been interesting. Seems highly effective after one dose. Given the supply constraints, a highly effective single dose would be much better at saving lives/ending pandemic even if efficacy is more like 80-85% compared to 90-95%.
Doubt Pfizer would go along with that sort of study now that they are on brink of approval. And very unlikely FDA would approve that dose regimen without a study. Will have to wait for retrospective data on people who only got one dose for whatever reason to tease out more fully.
See this tweet thread, arguing more or less the same:
[tweet]https://twitter.com/zeynep/status/1337047714341785605?s=20[/tweet]
Interestingly Scott Gottlieb is disagreeing with the government's distribution plans.
![[Image: Eo4xypTXIAELnH8?format=jpg&name=large]](https://pbs.twimg.com/media/Eo4xypTXIAELnH8?format=jpg&name=large)
I agree with Gottlieb here. Get the first dose into as many arms as possible as quickly as possible, and worry about the second dose as it becomes available.
BC
RE: VRBPAC evaluation of Pfizer vaccine - Goose - 12-10-2020
(12-10-2020, 11:49 AM)BostonCard Wrote: I agree with Gottlieb here. Get the first dose into as many arms as possible as quickly as possible, and worry about the second dose as it becomes available.Me too, with the added caveat that lots of effort should be expended at the Government level to ensure the second dose will be available. By this I mean actually helping (not interfering in the production) by expediting any supply chain difficulties that may arise.
BC
RE: VRBPAC evaluation of Pfizer vaccine - M T - 12-10-2020
I also agree, and presumed that's what they'd do if there wasn't some critical aspect of the 3 and 4 week intervals before the 2nd dose.
But note, that with a fixed number of doses, this doesn't increase the number of people who get vaccinated, it only accelerates the schedule of first doses. You'd end December with 20M more people having had a first dose; By the end of January, 10M more people would have had first doses; (End of Feb. No additional people). However, with the number of people dying daily, I'd say this is a safe bet to dampen R and save even more lives than those who get the first round early.
Month of distribution of first dose:
2nd dose in-hand plan: 20M in Dec; 30M in Jan; 50M in Feb
Prospective 2nd dose plan: 40M in Dec; 20M in Jan; 40M in Feb.
RE: VRBPAC evaluation of Pfizer vaccine - dabigv13 - 12-10-2020
It seems pretty safe to say that 40m shots will not be delivered to states by December. None of the figures the governors are giving aligns with that number. Seems ~20m is more realistic. I dont think this is related to holding back 2nd doses, but we are reading tea leaves.
RE: VRBPAC evaluation of Pfizer vaccine - M T - 12-10-2020
(12-10-2020, 12:55 PM)dabigv13 Wrote: It seems pretty safe to say that 40m shots will not be delivered to states by December. None of the figures the governors are giving aligns with that number. Seems ~20m is more realistic. I dont think this is related to holding back 2nd doses, but we are reading tea leaves.
I expect if VRBPAC recommends that the 40m be delivered this month and used as first doses (depending on January's expected 60M doses to cover the required 2nd shots), then Operation Warp Speed would try to accommodate that.
RE: VRBPAC evaluation of Pfizer vaccine - dabigv13 - 12-10-2020
They can't deliver the doses if Pfizer has not made the doses. I suspect this is more of the hold up, but again I can only go based off the tea leaves.
To me the numbers of doses that have been delivered, and the numbers the states are saying they are getting in the near term, are more relevant than the predictions by any of the OWS people, which have been repeatedly too optimistic.
Remember when we were supposed to get the AZ vaccine in October?
https://www.hhs.gov/about/news/2020/05/21/trump-administration-accelerates-astrazeneca-covid-19-vaccine-to-be-available-beginning-in-october.html
RE: VRBPAC evaluation of Pfizer vaccine - OutsiderFan - 12-10-2020
Can one of you medical experts answer the reason for concern for people with these conditions receiving the vaccine? I have blood injury phobia that results in anaphylactic shock if it activates. Or is the concern that getting the vaccine can cause these reactions in some people?
[tweet]https://twitter.com/Laurie_Garrett/status/1337130398778798087[/tweet]
RE: VRBPAC evaluation of Pfizer vaccine - BostonCard - 12-10-2020
Right now the answer is we don't know. They've just observed anaphylactic reaction in a few cases in the UK in patients with history of anaphylaxis. So, if you have a history, you might be at increased risk. Or not.
BC
RE: VRBPAC evaluation of Pfizer vaccine - M T - 12-10-2020
(12-10-2020, 01:44 PM)dabigv13 Wrote: To me the numbers of doses that have been delivered, and the numbers the states are saying they are getting in the near term, are more relevant than the predictions by any of the OWS people, which have been repeatedly too optimistic.
No doses have been delivered and we've been told none will be until EUA happens. The sets of numbers (6.4M (initial Pfizer allocation), 12.5M (initial Moderna allocation), 40M (December doses (allocation?)), 60M (January doses (allocation?)), 100M (February doses (allocation?))) are all being told to the states by OWS, so they ARE the predictions of the OWS people, presumably based on what Pfizer and Moderna are telling them.
"Allocation" is being used for where both doses (the allocation) are in hand before shipping out the first dose. The 2nd dose is held in storage for 3 or 4 weeks before it is shipped.
In the OWS briefing yesterday, I noted a slippage. They are still predicting enough doses by end of December to vaccinate 20M people (ie, 40M doses), a total of 50M by end of January (ie, 60M in January), and 100M by the end of THE FIRST QUARTER (ie, March instead of February).
636 sites will receive the first round. Syringes, wipes, dilutants are already being delivered, completion by Friday.
Moderna initial allocations were locked in within the last few days.
Of the 6.4M doses estimated 2 weeks ago, 500K are being held as a safety reserve. Of the remainder, 2.9M (2.95, I presume) will be shipped initially; 2.9M three weeks later.
In the video, from 43:00-50:00 is the question & response re shipping first doses, relying on manufacturing to get 2nd dose. Maybe that will happen in latter half of January, but not now, due to concerns that all the manufacturing is all new. (Dr. Slaoui had said that it is preferred to have a longer time between shots for better immunization, but the risk is that the patient gets the illness in the meantime.)
(12-10-2020, 01:52 PM)OutsiderFan Wrote: Can one of you medical experts answer the reason for concern for people with these conditions receiving the vaccine? I have blood injury phobia that results in anaphylactic shock if it activates. Or is the concern that getting the vaccine can cause these reactions in some people?
I'm not a medical expert and this is not a direct answer to your question, but Dr. Slaoui (in yesterday's briefing at 18:30) noted that in the trials subjects with severe allergic reaction were excluded, and that they should not be taking the vaccine until this is better understood.
RE: VRBPAC evaluation of Pfizer vaccine - BostonCard - 12-10-2020
VRBPAC votes to recommend an EUA.
https://www.wsj.com/articles/fda-advisory-panel-takes-up-pfizer-biontech-covid-19-vaccine-11607596201
Interesting that 4 members voted against the recommendation.
BC
RE: VRBPAC evaluation of Pfizer vaccine - Snorlax94 - 12-10-2020
(12-10-2020, 04:00 PM)BostonCard Wrote: VRBPAC votes to recommend an EUA.
https://www.wsj.com/articles/fda-advisory-panel-takes-up-pfizer-biontech-covid-19-vaccine-11607596201
Interesting that 4 members voted against the recommendation.
BC
Yeah it’d be interesting to hear why 4 voted against, but the 2nd graf states:
“In its vote to approve, the panel said the benefits of the vaccine outweigh the risks for people 16 years of age and older. Not all panelists had a chance to explain their votes, but some had expressed the view that the recommendation should be for people at 18 years of age and older.”
So potentially the disagreement was about 16 and 17-year-olds, which would be relevant for some college frosh.
RE: VRBPAC evaluation of Pfizer vaccine - dabigv13 - 12-10-2020
Great news.
MT, I hope the 40m doses in December happens. But I am almost certain it will not. Like I mentioned yesterday, if there were 40m doses, California should get a lot more than the 2ish million Newsom is expecting by the end of the month. If they deliver ~20m as seems more likely, hopefully the other 20m come in January along with the planned 60m for a total of 80m.
But let's see what happens. OWS has to this point overpromised and underdelivered.
RE: VRBPAC evaluation of Pfizer vaccine - Goose - 12-10-2020
(12-10-2020, 04:18 PM)dabigv13 Wrote: But let's see what happens. OWS has to this point overpromised and underdelivered.This is pretty typical of most first time projects, especially one of this magnitude. I expect it will continue for a while until various levels in the chain start inserting "fudge factors", which will also be wrong but will skew the promises towards worse performance. Only after this process becomes routine will the estimates be anywhere close to accurate.