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The FDA Weighs Its First Coronavirus Vaccine

Pfizer and BioNTech have a date on Thursday in front of an FDA advisory committee to review their vaccine data, and the briefing document is available for all to read (here’s the FDA’s own document as well). It’s very interesting stuff, and far more information than we’ve had so far.

First off, safety. There continue to be no serious concerns that I can see. There were two deaths in the vaccinated group, and 3 in the placebo group (both about 19,000 people). More people withdrew from the study in the placebo group. There were 18 adverse events characterized as “life-threatening” in the vaccine group after one month of follow-up, but there were 19 of those in the placebo group, and so on (for two months of follow-up, those numbers were 10 in the vaccine group and 11 in the placebo). There were four incidents of Bell’s palsy (temporary facial nerve problems) across the total participants, all four of those in the vaccine group. That’s worth keeping an eye on, but it’s about the number of people you’d expect to show it in a population that size (Bell’s palsy is not extremely rare), and thus can’t really be associated with the vaccine with that number of incidents. The events that were clearly associated with the vaccine were reactogenic ones (injection site pain, soreness, stiffness, fever, headaches, etc.) Older patients tended to have fewer of these, having overall less active immune systems. Word has come this morning that two severe immune reactions have been seen in the UK, both in National Health Service workers with long personal histories of severe immune reactions, but in general, such people are at higher risk with any vaccine. I have not gone through every line of the safety material, but so far I do not see anything in there that would be a problem for Emergency Use Authorization or later full approval.

We also have a great deal of fresh data on the immunogenicity of the vaccine, both antibody response and T-cell responses. I’m not going to try to summarize those for now because (1) everyone mostly cares about the efficacy and (2) once we have more data of this kind with other vaccines we can try to make some sort of head-to-head comparison. In the Phase I studies, this vaccine showed robust neutralizing antibody levels and T-cell responses, and those numbers look to have continued in the larger Phase 2/3 study, as expected.

Now to efficacy. As we know, “overwhelming efficacy” was declared at the first (and only!) interim analysis, with 94 total cases split 90/4 between the placebo group and the vaccinated group. The final analysis shows 170 cases, split 162/8 (confirmed coronavirus infection at least 7 days after the second dose). That’s a VE (vaccine efficacy) of 95%, with the 95% confidence interval on that number running from 90.3% to 97.6%. A new and interesting data set cover what happened after the first dose and before the second. There were 50 cases of coronavirus in the one-dose treatment group, versus 275 in the placebo group. But look at how those 50 cases came on:

What you can see is that the great majority of those 50 cases happened in the first ten to fourteen days or so after the first shot. At that point, the vaccinated group and the controls diverge sharply, and that’s because ten to fourteen days is the time it takes to raise an antibody response after a vaccination. You can see it kicking in, right there in the chart. This vaccine, in fact, already meets the FDA’s threshold of 50% efficacy with just one shot (but has much greater efficacy, of course, with the two-shot regimen). It’s worth noting that 10 cases of severe infection developed in the treatment group after just one shot, versus only 1 such case after two shots.

Table 8 in the FDA’s document has a good look at the various subgroups in the vaccinated population, and it’s hard to see any real differences in there. Age, gender, body mass index, ethnicity, risk factors – to my eyes, there’s not much to choose from, and that’s a good thing.

So it looks like the vaccine has a very strong protective effect, and that’s the first thing you’d want to know. But there are many other things we don’t know yet. What, for example, is its effect on transmission of the disease? We should be seeing more on that early next year, but based on these figures, it seems very likely that this vaccination would cut down the transmission rate sharply. But that has to be proven; there are plenty of things that have seemed very likely over the years in drug development that haven’t worked out. Even at this point in the pandemic, we don’t have solid numbers about the correlation between just what sort of viral load a person is carrying and their infectiousness to others. Think about how you’d try to design such a study and you can see why the data are lacking! We also don’t know the effectiveness of the vaccine in preventing asymptomatic infections, because this trial was based on symptoms, not on constant PCR testing of its participants, which is the only way you’d accumulate such data. The stronger knockdown of severe cases makes one think that asymptomatic cases might be similarly decreased, but you could also imagine that you would take what would be “normal” symptomatic cases and knock them back to being real-but-asymptomatic ones. A priori, you can’t be sure what the real situation is. That question is tied up with the transmission one, of course. We also don’t know what the duration of protection is, for the very simple reason that time just has to keep on tickin’, tickin’, into the future, (S. Miller et al.) for us to have any data on that. There’s no other way; we can’t estimate these things. That we will certainly have data on – eventually.

The data that Pfizer and BioNTech have presented look like far more than would be needed for an Emergency Use Authorization. I expect the FDA to grant that, and very soon. All the concerns about the effect of one or more EUAs that I wrote about here are still real. But some of them are less troublesome now that both this vaccine and Moderna’s have read out with such high efficacies – I was most worried about the first vaccine candidate showing decent-but-not-great effects, and that fortunately has not happened. But questions about (for example) the Pfizer placebo group switching over to vaccine, about the effects of these EUAs on other vaccine trials, and so on are still with us, and are yet to be resolved.

At any rate, any EUA is going to be accompanied by a large monitoring requirement. We’re going to be collecting a lot more data on this vaccine and others as they move into larger populations, data on both safety and efficacy. Vaccine work has its unique challenges because of its unique situation of dosing huge numbers of people who aren’t sick yet, and because of its targeting of the wildly complicated, wildly variable immune system. If there is some nasty side effect that is literally at the one-in-a-million level, which given immunology is absolutely possible, we certainly would not expect to see it in a 38,000-person trial (huge though that is by clinical trial standards). But we certainly would see it after dosing a few hundred million people.

Remember, though, what an EUA is for. That word “emergency” is there for a reason: this authorization is for something extremely serious for which there is no available alternative. That’s exactly the situation we find ourselves in, on both counts, and I think that the risk/benefit ratio is clearly, overwhelmingly in favor. Let’s do it.

77 comments on “The FDA Weighs Its First Coronavirus Vaccine”

  1. Jay says:

    Please correct your article: Bell’s palsy isn’t always temporary. It can be irreversible and permanent.

    1. David E. Young, MD says:

      That’s true, but to some extent that depends upon how rapidly someone is put on treatment. The most important treatment, by far, is corticosteroids, 60 to 80 mg of prednisone daily for 5 to 7 days or so.

      1. Jay says:

        Agreed. But some cases are refractory to treatment.

  2. Derek, great write-up, thank you!
    Maybe you can clarify something that continues to confuse me. That wonderful plot seems to show essentially the *entire* trial population, but is labeled (and discussed) as though only one dose of vaccine (or placebo) was given.
    Was not a second dose given, at or around day 21?
    Now, day 21 is after the “knee” in the blue curve, i.e. 1 dose does seem to be protective. (Some have calculated 1-dose efficacy at ~82%.) But I think Pfizer cautioned against making that interpretation, due to paucity of data (I would assume because ~everyone then got that 2nd dose).
    Please clarify if you can, Thanks,

    1. Patrick says:

      I am also curious about this; I’m kinda confused. The graph *seems* like it just includes everyone, including those who (as intended) got the second dose. I also can’t – in a partial read/scan of the FDA doc; the Pfizer one is too detailed for me – find any reference to an intentional single dose population.

      There is a gap between the total number in the study and the two dose population; are these people who didn’t get the second dose for some reason? I can’t find any reference to this being deliberate.

      1. closer read says:

        Yes, Derek has misinterpreted the single-dose efficacy.

        From the bottom of page 32 of FDA document (just read the last sentence to get the main takeaway):

        “Among all participants (regardless of evidence of infection before or during the vaccination
        regimen), 50 cases of COVID-19 occurred after Dose 1 in the BNT162b2 group compared with 275 cases in the placebo group, indicating an estimated VE of 82% (95% CI: 75.6%, 86.9%) against confirmed COVID-19 occurring after Dose 1, with VE of 52.4% (95% CI: 29.5%, 68.4%) between Dose 1 and Dose 2. 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.”

  3. wst says:

    There is a risk of placebo groups thinning out , would it be possible to share placebo groups between the trials ?

    1. Michael says:

      No, not well. The study populations do not have exactly the same characteristics and don’t have the exact same rates of community spread, and you lose the benefits of randomization. Those that choose to remain unvaccinated will probably not be exactly to identical to those who leave the placebo group, too.

  4. APAJ says:

    Fascinating to see the sharp divergence in the graph after only one shot. It begs the question: would it already be sufficient to dose twice as many people with lower efficacy to significantly decrease the current epidemic? Might that not have a bigger impact, given the respectable but limited supply of vaccines?

    1. Valdis Andersons says:

      There is no phase 1 trial with just the one dose so we’d be running blind in terms of how long the protective effect would last. With the phase 1 trial of two doses still ongoing we have a lead of a few months to let us know when things are starting to get too low for comfort.

      1. Philip says:

        Valdis, not blind. Look at figure 13. It shows that a single dose is protective for at least 3 months. The numbers are small and I am not a statistician, so I am not sure it is significant, but it sure looks good to me.

        1. JS says:

          That is not how I read it. The majority of the people used for that plot received a second dose at 21 days. As such you can only conclude that one dose is efficient until day 21.

          That is also what is stated in the FDA document. Search for “single”. Specifically:
          “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.”

          Having said that, it could well be that a single dose would give a very good protection and that we would be better off vaccinating twice as many people. But a trial was not done. Same for two smaller doses.

          1. Tony M says:

            For interest sake, the treatment group seems to diverge from the placebo group after day 11. Using the incidences of Covid-19 recorded at the bottom of Fig 2 in the FDA document you get the following incidences and apparent efficacy occurring in the various periods as follows:

            Period Placebo Treatment Apparent Efficiency
            Days No No %

            1-7 25 21 16.2%
            8-11 17 14 17.9%
            12-14 13 2 84.7%
            15-21 18 2 88.9%
            22-28 24 2 91.7%
            29-105 178 9 95.0%

            Total 275 50 82.0%


    2. Philip says:

      Along the same lines, how close to 3 weeks does the second dose need to be given to be effective? If the second dose could be delayed by months and still provide the same boost, that would be great. If not, the issue is much thornier.

  5. Marko says:

    “…We also don’t know the effectiveness of the vaccine in preventing asymptomatic infections, because this trial was based on symptoms, not on constant PCR testing of its participants, which is the only way you’d accumulate such data.”

    No , not the only way. Antibody testing ( non-spike-based ) could detect most of those asymptomatic infections, and would only have to be done every few months or so. Oxford/AstraZeneca has done these studies and presumably we’ll be seeing the results before too long. If this hasn’t been done in the other trials , it would seem a bit odd to me.

    1. Valdis Andersons says:

      That’s covered in their Lancet publication (table 2):

      The CIs for the asymptomatic cases are huge, but for the LD/SD group the lower bound does just about creep above 0 with a point estimate at 58.9%.

      1. Marko says:

        That seems to be swab-based data. My understanding was that they also had antibody survey data that they would reveal shortly , but I may be mistaken , it may actually be Pfizer that will have that data. Here’s a quote from Pfizer :

        “In the coming months we will test participants’ blood samples for antibodies that recognize a part of the virus that is not in the vaccine. If fewer participants in the vaccine group than in the placebo group develop such antibodies, we will have evidence that the vaccine can prevent infection as well as disease….We do not yet have those data.”

    2. debinski says:

      Pfizer is doing antibody testing at baseline,1, 6, 12 and 24 months for this:
      S1-binding IgG levels and/or
      RBD-binding IgG levels
      SARS-CoV-2 neutralizing titers
      N-binding antibody

  6. TPO says:

    I used to worry that offering the vaccine to placebo recipients would undermine learning about the durability of the vaccine, but I’m no longer sure that with this spectacular efficacy that this is true. There are other reasons it may be hard to measure vaccine durability using strictly accumulation of disease cases, but I don’t think lack of a placebo group is one of them. I expect we’ll have to go on lab assay correlates (e.g. neutralization titers) when we make decisions about future boosting schedules.

  7. Pedant says:

    The 95% interval from 90.3% to 97.6% is a CREDIBLE interval, not a CONFIDENCE interval. What an enormous blunder by Derek! (Just kidding — in real terms, there is no significant difference in this case.)

    1. Mike says:

      Were they using Baysian analysis?

      1. Pedant says:

        For that particular endpoint, yes. They used both frequentist and bayesian analysis in the paper. Some more detail is available here:

  8. Yehosef says:

    Do we know what is the “placebo” in these studies.

    1. Michael says:

      In the protocol: “Normal saline (0.9% sodium chloride solution for injection)”, supplied from a vial, injected intramuscularly.

  9. Jason P says:

    Hey Derek – Thanks for this!

    I think you need to examine and dicuss in more depth the 2 adverse event cases that happened in the UK. This is all over the news because sensationalism sells as well as it seems our “Cancel Culture” benefits* from beating down the front runner. I foresee a clamoring of Chicken Littles pointing to that to prop up the Anti-Vaxers.

    Also I’d like someone to expand on the FDA process. I assume the data was available to the EU and UK at the same time as the USA and yet others approved the vaccine sooner! Also I see the Moderna vaccine isn’t scheduled for review by the FDA until a week hence? If this is really a serious pandemic, why the heck aren’t those people working day & night, burning the midnight oil reviewing data and getting these vaccines approved? What gives?

    1. Michael says:

      Rushing approval doesn’t really change the picture too much– you have the same number of people vaccinated by, say, Jan 15 even if you save a few days now. The process is far abbreviated and I think these last few steps of careful review are important: the potential for lives saved by careful process (and people trusting this process was careful choosing to get vaccinated) is potentially far more than the ~100 lives you could save if you shaved a week off the process.

    2. Jason P says:

      Also, I’d be interested in understanding the process to remove the EUA designation from one of these vaccines and make them just plain “approved” for use going forward. What does that entail? Will the drug companies have that data? When?

    3. Patrick says:

      They are – The FDA has multiple teams working in shifts to review all the data; even if it takes another two weeks, I’m pretty sure this will be *by far* a record for time since trial analysis

      Also, when the UK approved the vaccine, several major figures and institutions criticized them for going faster than was reasonably possible. Anthony Fauci had fairly negative words about it, and the European Medicines Authority (their FDA) had harsh words (in a public letter) for what they felt was a rushed process.

      Taking more time doesn’t mean they’re not going absolutely as fast as they think is sane. Even if the other agencies all eventually come to the conclusion the vaccine is excellent and should be rolled out without reservation, it doesn’t mean the UK didn’t cut corners. It may just mean they got lucky and their rushed process worked out this time.

      Also, I don’t know too much about the UK regulatory regime, but my understanding is they’ve long relied on the EMA for a lot of the regulatory stuff. I may be wrong here, but it seems a bit of a stretch to think that they’ve suddenly become *more* capable than the (much larger) FDA or EMA in doing these sort of reviews.

      1. ElginFeccles says:

        Dr Anthony Fauci, the top US infectious disease expert, has apologised for remarks that seemed to criticise the UK’s vaccine approval process.

        “I have a great deal of confidence in what the UK does both scientifically and from a regulator standpoint,” Dr Fauci told the BBC on Thursday.

        1. Charles H. says:

          My interpretation of that was that when Dr. Fauci thought it over he decided that that was not a politically correct thing to say, and so issued a politically corrected statement. But this isn’t something that one should feel certain about, as the evidence for *why* he made the statement is … politically adjusted.

          If he were not very careful to be politically correct most of the time, he would have been fired the first time he disagreed with Mr. T.

        2. Bill says:

          [Dr Anthony Fauci, the top US infectious disease expert, has apologised for remarks that seemed to criticise the UK’s vaccine approval process.]

          Dr. Fauci is between a rock and a hard place. When two organizations receive simultaneous start on a safety review and one takes twice as long as the other…either one was rushing it or the other foot-dragging. They can’t both be “right”. Dr. Fauci should have somehow just put off answering because there is no making everyone happy here. And he’s at a “make-happy” level of the bureaucracy.

      2. johnnyboy says:

        Yes, the UK’s drug approval scheme was (and is, until dec 31st) determined in large part by the EMA, although each european country has its own internal regulatory agency (taking care of audits and such). The UK’s MHRA gave a ‘temporary’ approval to the vaccine under a new emergency provision that allows countries to give temporary approval for a year without waiting for final EMA approval. The MHRA credit the quickness of their approval to a rolling review of the data, but I doubt that the FDA or EMA wouldn’t have had a similar rolling review. It’s pretty obvious that this was rushed through for political reasons. The current UK government is a collection of incompetent clowns, who are absolutely desperate to present some source of good news, amid the brexit negotiation disaster and the worst Covid response in Europe. This was apparent this morning, with the Health Secretary going on morning TV and saying that the ‘first vaccinations in the world’ were in the UK (somehow the tens of thousands vaccinated in the clinical trials don’t count), and that makes him ‘so proud to be british’, even though britain had zero to do with this vaccine. It’s just part and parcel of this government’s moronic nationalism – the tories are basically trumpians with better verbal skills.

        1. Carl says:

          No idea if your from the UK, but as someone who is, here’s my hot take as they say, on the UK situation, i’ll include some notes for what i imagine is a mostly US based audience around here.

          Whilst i agree it was probably rushed it’s not for the reasons i think most are attributing, and it may even be why Dr Anthony Fauci walked back his comments if he was briefed on any of this. The issue the UK has had is that the Prime Minister and his cabinet, (roughly the equivalent of the white house for those in the US, but with much less actual power), have since the Brexit referendum results came in been fighting parliament, (Not sure which of the senate and the house of representatives is closest in equivalency in the US, don’t really understand the difference myself), to get anything done.

          In the first wave that wasn’t a huge issue, (though it’s been creating 5 kinds of hell with brexit), but with the second wave the Prime Minster has been fighting Parliament every step of the way. It’s obvious sometime in the next couple of months Parliament is going to force a near total lift of the restrictions. The UK government, (when we say government in the UK where generally talking about the Prime Minster and his cabinet), needs to get things sorted by then or it’s going to get a lot worse a lot faster.

          So i do think they rushed the approval for political reasons, (and are pushing the vaccine as hard as possibble to get as many people dosed before they’re forced to open up), but nationalism and incompetence have little if anything to do with it. I’m also confident they gave the data enough of a once over to come to the conclusion Mr Lowe did when we first got data on it a few weeks, (it’s highly efficient and reasonably safe), even if they didn’t look at precisely how good or safe the efficiency was.

          1. Vyctor Meldreugh says:

            I DO NOT BELIEVE IT! An apologist for the clown government led by the clown prince has posted on the Pipeline. Load of non-sequiters written in slack english, so might even be clown prince himself IN PERSON!

            De Pfeffel MUST FALL.

          2. Carl says:

            @Vyctor Meldreugh almost took you seriously for a second till i saw the username. Nicely done.

            For anyone who doesn’t get it, look up the TV series “One Foot In The Grave” oldish British comedy, (older than me i think).

          3. Businesslamb says:

            You are being wilfully disingenuous when you say “with the second wave the Prime Minster has been fighting Parliament every step of the way”, the opposition within parliament to the introduction of a lockdown in the autumn came from a small but noisy minority within his own party. Indeed the opposition labour party leader had called for lockdown sometime earlier in the autumn as cases started to rise and as we discovered this had been the scientific advice in September which the government chose to ignore.

            As for your contention that “sometime in the next couple of months Parliament is going to force a near total lift of the restrictions” this is palpable nonsense. The prime minister has relaxed the rules over Christmas, principally to garner favourable media coverage for “saving Christmas”. In the new year restrictions will almost certainly be tightened, with the support of Parliament to cope with the inevitable surge in cases but as with so much our buffoon of a leader does he is only interested in todays headlines rather than sorting out tomorrows problems.

          4. Vyctor says:

            Buffoon of a leader is being overly GENEROUS to British government by BABOONERY. Virus, Brexit – will only take one more crisis to get fouled up by this right FRED KARNO’S ARMY of a government and the royal THEY (otherwise known as WE…) will all be DOOMED, unless somebody DOES SOMETHING about it.

            I repeat – The Clown Prince MUST FALL.


            …Frederick John Westcott (26 March 1866 – 18 September 1941), best known by his stage name Fred Karno, was an English theatre impresario of the British music hall. As a comedian of slapstick he is credited with popularizing the custard-pie-in-the-face gag.

            Among the music hall comedians who worked for him were Charlie Chaplin and his understudy, Arthur Jefferson, who later adopted the name of Stan Laurel. These were part of what was known as “FRED KARNO’S ARMY,” a phrase still occasionally used in the UK to refer to a CHAOTIC GROUP or ORGANISATION.

            Film producer Hal Roach stated: “Fred Karno is not only a genius, he is the man who originated slapstick comedy. We in Hollywood owe much to him.”

      3. Druid says:

        UK scientists were established in EMA assessment teams until brexit when this happened: “For EMA, this means that as of 1 February 2020, no one who represents the UK, or is appointed or nominated by the UK can participate in any EMA scientific committee meeting, working party meeting or in the Agency’s Management Board.” So, plenty of UK assessors sitting around at just the right time, leaving the EMA embarrassed and so pointings fingers. Of course, from January 1, the vaccine will have to be airlifted into UK …

      4. A Nonny Mouse says:

        The EMA was in London until 18 months ago when it moved to Amsterdam. Since then, the UK people left were given little to do which is why they had the manpower to take this on and get it done so rapidly before being able to do their own thing from 1st Jan.

        A side effect of Brexit rather than the reason.

    4. DataWatcher says:

      The news reports about the UK incidents I’ve seen have been pretty even-handed — the explanation has been clear that these were allergic reactions, that allergic reactions aren’t terribly uncommon with vaccines, and that people with histories of vaccine allergies should be aware of this (i.e., “ask your doctor”). But of course this is “mainstream” media, not online clickbait sites; no telling what will happen in that world.

      1. Adrian says:

        I would blame the rushed approval for this blunder.
        “Both NHS workers have a history of serious allergies and carry adrenaline pens around with them.”


        Allergic reactions are (as expected) a (usually mild) side effect of the vaccine, chances are people with such serious allergies were not even admitted to studies.

        This does not indicate a general safety problem of the vaccine, but a clear failure in the approval process to define for whom the vaccine might not be safe.

        1. drsnowboard says:

          the entry does indeed exclude people with known allergies in P1 ie
          “History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).” however after that it’s on the PI / physician to decide whether to include the subject. One could argue that as healthcare workers , epi-pen carriers and being administered in a hospital environment, they did everyone a service by being vaccinated and then the reporting system worked quickly to disseminate the information. Yes, the anti-vaxxers may make hay, but P3 trials and the real-world are messy as patients are a completely heterogenous population..

          1. Adrian says:

            Don’t argue against an anti-vaxxer strawman when the real problem is premature vaccine approval for political reasons.

            And please don’t blame the victims or their physician for that, neither is expected to do anything different from the official recommendation.

            After these two incidents the MHRA issued an advice that persons with a history of a significant allergic reaction should not receive this vaccine. There is no excuse that they failed to do so before approval.

            The regulator knew about allergic reactions caused by the vaccine, and failed to issue proper advice for people for whom this might be deadly.

        2. debinski says:

          A “rushed approval” had nothing to do with the allergic reactions. Whomever was administering the vaccines should have asked if the person previously had a severe reaction to a vaccine and if so, they shouldn’t have administered it. They always ask that when you get a flu vaccine, why would this be any different? And as mentioned, people with severe reactions to vaccines were excluded from the study as they should have been.

          1. Druid says:

            … and now everyone knows – the public information machine has worked wonders. I suspect these people knew what they were doing, being in hospital at the time. When this vaccine goes out into the care homes and schools, it is best if everyone is forewarned.

          2. DataWatcher says:

            It will take a lot of careful explanation to “forewarn” people in the right way. Dr. Fauci has said now that “a person [with] an underlying allergic tendency” might want to “be cautious about vaccination, or at least be prepared to respond with some sort of antidote to the allergic reaction . . .” I wonder whether this will scare away a lot of people who actually shouldn’t be scared away. Anyone with seasonal hay fever might say, “Well, I have allergies” and decide not to get vaccinated.

          3. A Nonny Mouse says:

            This is to “Druid”

            Of course they were in hospital at the time as the were heathcare workers!

      2. Alberto J. Villena says:

        About the hyperallergic reactions seen in two UK vaccinated people, it is of interest what the FDA report (page 40) states:
        “ FDA independently conducted standard MedDRA queries (SMQs) using FDA-developed software (MAED) to evaluate for constellations of unsolicited adverse event preferred terms that could represent various diseases and conditions, including but not limited to allergic, neurologic, inflammatory, and autoimmune conditions. The SMQs, conducted on the phase 2/3 all-enrolled safety population, revealed a slight numerical imbalance of adverse events potentially representing allergic reactions, with more participants reporting hypersensitivity-related adverse events in the vaccine group (137 [0.63%]) compared with the placebo group (111 [0.51%]).”

    5. Todd says:

      It’s two separate things. One is that the FDA asks for raw data, then reviews its themselves and makes their own summaries. Two is that the soonest a treatment can be approved under US law is 15 days after the application is filed and published openly, so that the public can question the information, if need be. It’s likely not necessary here, but if something went wrong after a shortcut, the FDA would be in deep legal trouble.

    6. DCSZ says:

      According to Reuters:
      The Medicines and Healthcare Products Regulatory Agency (MHRA) said there had been two reports of anaphylaxis and one report of a possible allergic reaction since rollout began.
      The two staff members – who both carried an adrenaline auto injector and had a history of allergic reactions – developed symptoms of anaphylactoid reaction after receiving the vaccine on Tuesday.
      Pfizer has said people with a history of severe adverse allergic reactions to vaccines or the candidate’s ingredients were excluded from their late stage trials, which is reflected in the MHRA’s emergency approval protocol.
      However, the allergic reactions may have been caused by a component of Pfizer’s vaccine called polyethylene glycol, or PEG, which helps stabilize the shot and is not in other types of vaccines.
      Imperial College London’s Paul Turner, an expert in allergy and immunology, who has been advising the MHRA on their revised guidance, told Reuters: “As we’ve had more information through, the initial concern that maybe it affects everyone with allergies is not true.”
      “The ingredients like PEG which we think might be responsible for the reactions are not related to things which can cause food allergy. Likewise, people with a known allergy to just one medicine should not be at risk,” Turner told Reuters.

  10. An Old Chemist says:

    UK Investigates Reports of Allergic Reactions to Pfizer-BioNTech COVID-19 Shot (Biospace, 12-09-2020):

  11. Marko says:

    N.Carolina has had over three times the Covid deaths this year than flu deaths over the last ten years, COMBINED :

    “…Well, just to be sure that she was telling the truth, we also reached out to the CDC and asked their interpretation of North Carolina’s numbers and to cross-check it with numbers that they had from North Carolina.

    And a spokesman for the CDC said Cohen is right. If you look at deaths from flu alone dating back 10 years and then you look at this year’s COVID deaths, then she’s right. We have had three times more coronavirus deaths in one year than we’ve had flu deaths in 10 years.

    That’s why we rated this claim true. Just a straight-up true. “

    1. theasdgamer says:

      Marko, you are such a sheep. We have been trying to get PCR and health statistics numbers out of the county and state health departments for some time and they just stonewall us. So we have excellent reason to be skeptical of the numbers.

      Quit being a sheep and start digging.

      1. Marko says:

        ” We have been trying…”

        So it’s “we”, is it ? You’re part of a larger operation , and not just a solo zone-flooder? If so, I think you should tell your handlers that you’re in desperate need of some professional help over here, because nobody is buying what you’re selling.

    2. Ex Pharma R&D says:

      Re: “N.Carolina has had over three times the Covid deaths this year than flu deaths over the last ten years, COMBINED:”

      High number of deaths in N Carolina relative to historical number looks like what, in the data-rich part of my drug R&D career (around year 2000 onwards), used to be referred to as “an outlier.” Understand outlier and underlying dataset more understood.

      Which assumes a dataset to understand. For Big Pharma’s Data Barons, this meant formatted and curated state of the art database covering compounds and linked biological data, that could be systematically searched and for example, if hypothesised informative, drilled down to get at raw data to look for inconsistencies between different experimentalists or assays. Oh my Oracle, ISAC and IBIS of long ago!

      Depth and range of data often what distinguished Data Barons from start up companies. From occasional discussion with medical practitioners, doubt comparable datasets exist for Public Health. Maybe this is what “theasdgamer” is alluding to in requesting PCR data and health stats from County and State authorities.

      Not disputing fact check kindly linked by Marko. But, to this former R&D scientist, fact check reads as listing of what fact checker Lisa Worf heard from journalist Paul Specht, who’d spoken with a representative of the Dept of Health and Human Services, who’d summarised some sort of collated data obtained from representatives of several health providers and hospitals, that included PCR data and doctors’ diagnoses…

      …When what’s really needed is skilled, insightful and articulate data analyst who can look at properly curated data whatever which way he or she can, and go on to explain the meaning within the numbers. Which may (or may not) boil down to a bleedin’ obvious explosion of SARS 2 in N Carolina, understanding origins of which outlier could still be mighty informative.

      Reminds me of years ago problem in infancy of digital age with slow and variable domestic internet speed. Phone Customer Support who insightfully tell you… there’s a problem witth your internet speed. Get the engineer out, who in half an hour tells you… Nick detected in copper wire up road, cable being rubbed by cherry tree branches, splitter in loft not recommended, wire running under carpet not advised…

      Just occurs to me to wonder how different S Carolina’s stats are from N Carolina’s?

      1. theasdgamer says:

        What you are suggesting is a different way of approaching the data than what I am doing. Maybe you can use statistical techniques to discover garbage in the data. I am trying to prove that hospitals in my county are loading the public health data with garbage.

        The state has told us what the covid PCR limit is–42, but that doesn’t tell us what hospitals are actually running and neither the state nor the county will mandate that hospitals and labs provide data on Ct’s to them. This is very concerning.

        Hospitals are paid a premium for covid patients–a covid patient being defined as anyone who tests positive for covid, whether they have a miniscule amount of SARS-COV-2 RNA in their system or active covid disease with symptoms. Testing all elective patients is a convenient way for hospitals to generate an additional amount of revenue and from my anecdotal sources, this is what they are doing at several hospitals in several states.

        So it looks like garbage is being inserted into the hospitalization data because covid is becoming ubiquitous and lots of people have miniscule amounts of RNA as a result. We aren’t seeing deaths tracking hospitalizations in my state nor in LA. Hospitalizations are tracking cases maybe because more people are going to the hospital for elective procedures/surgeries and covid is incidental. This might explain why deaths aren’t tracking hospitalizations.

        Labs are seeing a nice chunk of change from all the covid PCR testing, too. They won’t be pushing for accurate data nor will hospitals. Ka-ching.

        We KNOW that the state isn’t concerned about false positives because of the extremely high limit it has set on Ct for covid PCR.

        1. Ex Pharma R&D says:

          Kerching! Indeed. Thank you theasdgamer for telling more than enough to be going on with. Not a problem to be tackled any time soon with a formatted, curated and searchable database. The more mundane and venial to be nailed first. Good luck with that.

          Not delved too deeply, but sense of comparable but different issue in UK. GOV.UK contracted out PCR testing to administration by likes of finance and logistics companies. Well known of course for molecular biology wizardry… Reply awaited 10 days now to Freedom of Information request asking for details of SOP, cycle number, false positive rate, etc, etc, etc. Am not holding my breath. Few whistles briefly tooted already.

          FYI, to spice things up am posting In the Pipeline under multiple aliases. Among others, think War of the Worlds, father of Nemesis and same first and last initial as science fiction writer, but with another initial in between, writer who once upon a time said, “People ask me to predict the future, when all I’m trying to do is prevent it.”

  12. Mike in Boston says:

    I was curious about Table 2 on P. 18: Reasons for Exclusion: “Had other important protocol deviations.” 311 excluded in vaccine arm vs. 60 in placebo arm. All the other exclusions are pretty balanced between the vaccine and placebo arms. What could this one be about?

  13. Gary Cornell says:

    The news is clearly good but the confidence intervals for people 65-74 and especially >74 aren’t. Obviously, even if the vaccine is somewhat less effective for people >65 (as one might expect) , they will still likely be pretty darn good. I wrote up a discussion of the numbers here:

  14. DH says:

    “…time just has to keep on tickin’, tickin’, into the future, (S. Miller et al.)”

    I believe that Miller et al. (1973) claimed instead that time keeps on “slippin’, slippin’, slippin'” into the future.

  15. Jonathan says:

    Quick comment from a UK angle, though with no personal inside knowledge (retired academic). My understanding is that while regulatory bodies in many major countries were in constant dialogue with vaccine developers about submission requirements, only the UK actually started looking at data in advance. A lot of regulatory approval is about manufacturing standards, quality assurance and the like (for Pfizer QA about maintaining a supply chain) and if the technical work on these matters had already been done it would allow concentration on the efficacy and safety data.

    Second, the FDA to their credit insist on getting their own team to analyse the raw data from scratch, which inevitably is more time-consuming than the close scrutiny of analysis by the trial team which is the approach by other regulators worldwide.

    But the MHRA do have a reputation for being thorough. My wife (retired pharmaceutical regulator with continuing links to colleagues) reports that Dr June Raine their CEO has a reputation for being a complete hawk when it comes to safety data, so even if efficacy isn’t the highest the vaccine will have been determined to be safe. I will certainly take it if offered.

  16. Marko says:

    In a time of vaccine scarcity , with 2500-3000 people dying per day in the US , nobody who’s been previously infected should get a single dose of vaccine from the early rollouts , much less two doses. For the others , the young and healthy among the supposedly “at risk” cohorts who will be first in line should get one shot only , which will place them in a similarly-protected category as those who’ve been infected previously. The only people who should get the two-dose regimen are the elderly ( >65 or 70 ) or those who have other conditions that make them less responsive to vaccines in general. Once vaccine doses are plentiful , go ahead , jab away to your heart’s content. For myself , I’m inclined to think a single dose of vaccine will be plenty of protection against moderate-severe disease , for the duration , and will continue to be so inclined until I see the data that suggests otherwise.

    Michael Mina expresses some similar sentiments:

  17. DataWatcher says:

    How much time can elapse between the first and second doses, for the second dose to be fully effective? If one of those younger or otherwise less at-risk people takes the first dose but then have to wait several months, will they need to start all over again, or will the second dose still boost their immunity to the full 90 – 96% level? (For the record, Dr. Fauci advises people who have been infected to get vaccinated anyway because it might increase the likelihood of longer-lasting immunity, which along with post-vaccination asymptomatic spread is one of the wild cards in this.)

    1. Marko says:

      ” For the record, Dr. Fauci advises people who have been infected to get vaccinated anyway because it might increase the likelihood of longer-lasting immunity….”

      He has his head up his ass , again. If he’d said they should get vaccinated EVENTUALLY , when we have plenty of vaccine to go around , I’d have no problem with the statement. As it is, in this period of vaccine scarcity , he’s saying someone who already has significant protection should get vaccinated and thus deny someone who has zero protection the opportunity. It makes no sense , and it’s right up there with his early statements on masks for the damage it does to intelligent discourse about this pandemic , this time about the strategy for vaccine distribution.

      1. DataWatcher says:

        Well, with his early statements about the masks, he could plead (legitimately, I’d say) that he was going with the best information available at the time. This time around, of course, he has a lot more data, and he’s had more time to think about things. I’m still curious, though — do we know how long it’s safe for someone to wait between shots? That might come up for any of various reasons (availability, access, etc.) aside from the very practical consideration you raise.

        1. Marko says:

          Fauci has admitted that the main reason for his initially saying we shouldn’t wear masks was to conserve the limited supply for use by HCWs. He knew they were effective then as he does now:

          As to length of time between shots , without studies we’ll never know for sure , but I doubt that there’s a narrow window. With tetanus , you’re supposed to get a booster every ten years or so. With coronavirus common cold strains , reinfection seems to occur after a year or so has passed since previous infection with the same strain , so if you had a vaccine for these strains , you might recommend an annual booster for those who would be high-risk. I wouldn’t take a vaccine for the common cold , even if one was available. For COV2 , our best information from natural infection to date suggests that reinfection is very rare so far , perhaps indicating the same year or so of sterilizing or near-sterilizing protection , and when reinfection does occur , it is most likely that it results in asymptomatic or mild disease. My bet is that the same will occur with vaccination , and thus when everyone has been exposed once by either vaccination or natural infection , COV2 becomes the fifth common cold coronavirus. It still might pose some threat to a fraction of the elderly and otherwise frail (as do all respiratory infections) thus justifying periodic boosters, but for almost of us, it’ll be a nuisance.

          The goal today should be to get all high-risk patients one shot ASAP and save as many lives as possible over the next several months , then worry about boosters. The least of our worries should be the young and healthy who are already immune from natural infection.

          1. Oceanus says:

            Re: “…When everyone has been exposed once by either vaccination or natural infection, COV2 becomes the fifth common cold coronavirus. It still might pose some threat to a fraction of the elderly and otherwise frail (as do all respiratory infections) thus justifying periodic boosters, but for almost of us, it’ll be a nuisance.”

            Seems, Marko, you and I might even be converging on the same place..? In case not already seen, you might be interested to please take a look at:


            And, as matter of interest to an ancient mere chemist with little formal biology training, do you give any credence to the hypothesis of partial populace prior immunity due to B and T cell “activation” from previous exposure to SARS 2 related “common cold” coronaviruses:


            …Or do you think SARS 2 descended on virus NAIVE POPULATIONS with NO INNATE IMMUNITY whatsoever? By way of aside, if a mere chemists’s understanding is right, this was the start point for the UK’s Imperial-College-lead epidemiological modelling, “The Science” promoted by the Scientific Advisery Group for Emergencies (SAGE) that the UK government proclaims it was “lead by,” and that lead on 16 March 2020 to published predictions of 510K UK and 2.2M US deaths due to the ravages of SARS 2:

            “Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand”

            Neil M Ferguson et al, WHO Collaborating Centre for Infectious Disease Modelling, MRC Centre for Global Infectious Disease Analysis, Abdul Latif Jameel Institute for Disease and Emergency Analytics, Imperial College London

            Mercifully numbers of dead well short of that (factor of ~10 lower in UK). Prime Ministers, politicos and epidemiological modellers may ascribe “lives saved” to the wonders of National Social Distancism, but this ancient briton scientist more inclined to thank the Prime B and T Cells…

        2. Marko says:

          Speaking of our knucklehead “thought leaders”, here’s two more of them who apparently just realized , minutes ago , that we could save many more lives by not squandering precious vaccine doses on people who are already immune :

          This situation was entirely foreseeable months ago. How can they not have been thinking about this?

          The choice and scale-up of an appropriate rapid Ab test and the logistics of antibody testing of potential vaccinees could’ve been a done deal by now if more of our scientific “leading lights” spent more time working on public health planning and problem-solving and less time on becoming social media sensations.

          1. DataWatcher says:

            Do you think it’s better to not vaccinate previously-infected people at all, or to play Solomon and give them one shot, thus saving at least half the remaining regimens for those at highest risk? (The younger, healthier cohort won’t even be in the running until the final stages of the roll-out, and by then we might well have sufficient vaccines, so they may end up being a moot point in this discussion.)

          2. Marko says:

            I wouldn’t vaccinate the previously-infected even once. The only real, if limited, evidence we have on sterilizing immunity in humans is from those who’ve been naturally infected. Infection in the URT stimulates more of a mucosal immune response than does a shot in the arm, which response , in the end, may be more protective, both in the short and long term. For all we know, vaccinating them will corrupt an existing, potentially ideal immune response. I doubt that would be the case,but we don’t know. We do know that there are many people who have no immunity at all, and every dose we waste on those with immunity is a dose that could be better utilized.

            And , yes , there will indeed be plenty of young and healthy people vaccinated in the first round, if they’re among the front-line HCWs and others that are first in line. One shot would be plenty for them until we have more vaccine supplies.

            It’s all academic at this point. We have a plan and we’re sticking to it, preventable deaths be damned.

  18. DataWatcher says:

    Possible that the Moderna vaccine also brings about sterilizing immunity. Any ideas on what this might portend for the Pfizer/BioNtech vaccine?

    1. Marko says:

      Thanks for the link.

      The numbers are small , but it’s having a positive effect, it appears. Better than a sharp stick in the eye, as they say. Need more and longer-term data to get a good idea of what the practical impact on transmission will be, I think. My WAG is that it will be significant , but not earth-shaking.

      I see no reason to think the Pfizer vaccine wouldn’t show similar results.

  19. Jason P says:

    I just heard the dumbest thing imaginable! Pfizer is filling their 5 dose vials of vaccine with enough material for 7 doses. OK, cool. But those administering the vaccine are throwing away vials with 2 doses worth of material, because they were afraid they would be violating FDA rules by using the extra material? After all the label says 5 doses!

    I mean seriously? We are in a Pandemic! Is the FDA that kind of BIG Heavy Handed force that everyone runs around in fear if them? Why wouldn’t those who administer the vaccine say, I’m going to use the extra 2 doses, expand the supply by 40% and apologize for it later?

    Thankfully it appears that Big Brother has now issued an Okay Dokey to go ahead and use the extra two doses rather than throw them away.

    Wow, just WOW!

    1. Marko says:

      In an Idiocracy , this would all be considered perfectly normal.

    2. DataWatcher says:

      It sounds crazy, but they’re just dotting “i’s” and crossing “ts”, which you have to do when dealing with bureaucracies, and it’s easy to get a little crazy behind it. (Anyone who has ever worked on a project funded by a grant, and then discovered that they were so efficient that they’d actually saved money, and so they had to spend everything left over on paperclips and pencils to avoid having the money cut when the grant was renewed, can attest to what I’m saying). What they should have done, though, rather than throw away those extra doses, would have been to set them aside and wait for official permission to use them. This assumes, of course, that the vaccine can be re-frozen and then re-thawed. Would this be the case?

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