Quit Your Jibber Jabber

at

The first patient enrolled in Pfizer’s COVID-19 coronavirus vaccine clinical trial at the University of Maryland School of Medicine in Baltimore, Maryland, USA

This afternoon

Pfizer Inc had on Monday disclosed that its experimental vaccine which it is jointly developing with BioNTech was more than 90% effective in preventing COVID-19 based on initial data from a large study, in the ongoing phase 3 trials.

This disclosure was made in a statement by the Chairman and Chief Executive Officer of Pfizer, Albert Bourla, on Monday, November 9, 2020.

Pfizer and German partner BioNTech SE are the first drugmakers to show successful data from a large-scale clinical trial of a coronavirus vaccine. The companies said they have so far found no serious safety concerns and expect to seek U.S. emergency use authorization later this month.

Meanwhile…

Um.

Meanwhile…

After you.

Meanwhile…

Covid-19 vaccine candidate is 90% effective, says Pfizer (The Guardian)

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72 thoughts on “Quit Your Jibber Jabber

  1. ACI Question

    Worth listening to the full clip as Cuomo explains his thinking in some detail and it’s only a few minutes long.

    Also, let’s all laugh at anti-vaxxers, idiots that they are.

    1. alickdouglas

      +1, the comments by the tweeter completely misrepresent what Cuomo says in the clip

      Cuomo’s comments focus on ensuring that the vaccine is made accessible by the federally sponsored vaccination program. Assuming he is correct that the Trump administration’s plan is to distribute via private healthcare, that’s a recipe for uneven access, and it makes sense to prevent it from being initiated. A badly implemented plan is very difficult to rectify later.

      1. scottser

        A good plan violently executed now is better than a perfect plan executed next week.
        Or something.

    2. Micko

      Great news – nice to hopefully get our lives back to normal.

      But, honestly would anyone here want to be in the first round of getting this?

      I think I’ll wait… a good while… like, a really good while.

    3. Cui Bono?

      If I’m 100% for safe and effective vaccines, does that make me anti-vax or pro-vax?

      Let’s not forget that survival rates for under 70s is 99.95% and overall average is 99.77% so I really don’t see much need for a vaccine with 90% effectiveness except for some vulnerable groups. Long covid is minuscule too so not much need for it there either.

      1. Cian

        So vaccinate the old and weak; and if they die, well they had underlying conditions…just say they died with the vaccine not from the vaccine.

        win-win.

  2. SOQ

    How can giving a meningitis vaccine instead, be a placebo?

    Are they using the now questionable PCR test to determine if someone has become infected?

    Are the particularly strong immune reactions those of anti-bodies or T cells?

    How many were first tested for cross immunity before been given this vaccine?

    1. alickdouglas

      Don’t think we’re reading the same things.

      The Pfizer/BioNTech trial was done with placebo, not meningitis vaccine (incidentally, it has become fashionable to provide active control–like meningitis vaccine–rather than saline placebo in clinical trials; many physicians are reluctant to inject placebo saline, as there is no chance of benefit, and hence it might be considered unethical).

      The Pfizer protocol from what I can read doesn’t have a particularly strict definition of a COVID case, deferring to the definition used in the territory where each subject lives. It does seem to require both an onset and a convalescent follow up though, so it seems likely to be fairly robust. This makes sense operationally as it would be a nightmare for a trial sponsor to specify a strict case definition defining such-and-such an assay in a fast-moving trial like this. Pre-vaccination exposure testing wasn’t strictly defined per protocol. Again, the protocol says that all subjects had to have not had COVID, and was somewhat broad about how that was determined. It could be clinical or lab-confirmed. I’ve not gone through everything in depth, but presumably this is tackled more in depth in the ‘final analysis’ (Pfizer are righly clear that this was an interim analysis, and hence less in depth).

      The Pfizer PR I have access to doesn’t mention strength of immune response; the data that Pfizer are highlighting is ‘efficacy against clinical disease’ which is the most interesting measure for an interim analysis under these circumstances.

    2. SOQ

      How can a vaccine for both viral and bacterial meningitis- of which there is over 50- be considered a placebo for SARS-Cov-2?

      SARS-Cov-2 which has been found in sewage systems MONTHS before people got sick.

      1. alickdouglas

        I don’t follow; 1) there isn’t a vaccine for both bacterial and viral meningitis. Most ‘meningitis’ vaccines target one or a combination of (bacterial) Neisseria meniningitidis A, B, C, W, Y and/ or (bacterial) Hemophilus influenzae type C. Prevnar which acts against some serotypes of Streptococcus pneumoniae might prevent (bacterial) ‘pneumococcal’ meningitis. Virus/bacteria combos are fairly rare (DPT-IPV types being one of the few). 2) Pfizer didn’t use a meningitis vaccine as a control in their phase 3, they used Saline placebo. 3) ‘Active comparators’ are sometimes used instead of a ‘control’ instead of a placebo where the sponsor believes giving a saline placebo might be unethical. In that case, the sponsor needs to choose an active comparator that cannot impact on endpoints. Neisseria vaccines are used occasionally under such circumstances, but I don’t believe it’s common.

        1. SOQ

          OK thanks alick.

          Well point one is that using a meningitis vaccine as a placebo is not a placebo because they too can have side effects and, meningitis can be either bacterial or viral but you have answered some of what is in them.

          Point 2 is that a sizeable number of people are already immune to SARS-Cov-2 from either cross immunity or previous exposure so what is the point of vaccinating them? Personally, I would like to know my immune status is before proceeding.

          Is there not also the issue of immune response declining with age? That those who need it most will have the weakest response because their immune system is already so compromised.

        1. ce

          Also maybe they’ll throw in a couple of viagra for the elder groups along with the vaccine to make up for lost time

      1. Daisy Chainsaw

        Except the same freedumb ranters will be protesting the vaccine too. The herd doesn’t want that type of immunity.

          1. Daisy Chainsaw

            If it’s offered, I’ll take it. I’ve never had any adverse reactions to vaccines in the past and if it gives further protection from ratlicking, pro disease dimwits, I’ll be in the socially distanced queue.

          2. Pat Mustard

            Yeah typical, screw the many many people who do get adverse reactions.

            As long as you can virtue signal and heil the nazi pharmaceutical companies pumping out the untrialled unnecessary vaccines.

          3. millie

            I would take a vaccine, Micko. Like Daisy, I’ve been very lucky in that I’ve only ever experienced the benefits of vaccination. I have a lot of faith in the EU and their stringent policies regarding safe regulation of vaccines and healthcare.

            I can understand doubts and fears about a vaccine being rushed, but once the usual guidelines are adhered to, I’d be happy enough to take the chance.

          4. Micko

            Well I deffo wouldn’t Millie.

            It’s not worth the risk for a disease that has such a low fatality rate.

            If it was Ebola or similar and there was an outbreak – for sure. But not for this.

            And definitely not for my kids or family.

          5. Daisy Chainsaw

            Typical. The pro disease, anti lockdown cohort want to get back to boozing and shopping but don’t want to do it safely. What’s an acceptable number of dead people?

        1. Cui Bono?

          Not much need for this vaccine because the average survival is 99.77%, and 99.95% for under 70s. Also, long covid is tiny too.

          I’d prefer to get covid rather than take this new type of vaccine and I probably already had it in January anyway.

  3. v AKA Frilly Keane

    Makes you wonder how far along they were into researching and developing this if its already gone through a test trial

    All in less than a year

    as Jimmy would say – Aunty’s Fanny they did

    I could kinda understand if an upstart but brilliant research lab in MIT or somewhere high brow make a discovery

    But Pfizers – nah
    They’d be mangled in set up compliance, budget requests, staffing by their own Corporate Framework and Working Manual
    Feck I’d say it would take three months alone to get the R+D stuff signed off to comply with Tax Relief etc
    And believe me, they did nothing until that was in the back pocket

    1. alickdouglas

      Ah, but don’t forget, they purchased the IP from BioNTech. I’d have a guess that BioNTech already had a MERS program underway, at least in non human primates, and switched over to SARS-CoV early.

      Pfizer has a relatively small vaccine portfolio, but their Prevnar business generates more cashflow than–for example–GSK’s entire vaccine portfolio. They have been successful in the past because when they smell an opportunity they splash ludicrous amounts of cash on development and manufacturing. Pfizer are just the kind of big pharma company that would be exploring alternative-tech like mRNA (unlike for example someone like Sanofi who are more tech-conservative, and recently got bitten with their Dengue technology). It’s also possible that there was an existing discussion ongoing between BioNTech and Pfizer. Astra and Jenner/Oxford are in the same boat (Astra have 0 vaccine expertise) and J&J the same with their candidate.

      1. SOQ

        How do they measure the efficacy of vaccines without exposing the patients to the actual virus alick?

        1. Micko

          Yeah I always wondered that?

          I guess they test for the presence of antibodies after the vaccine is administered?

          Interestingly as an aside, more people actually get infected by polio now as a result of receiving the vaccine than catch it in the wild.

          But the numbers are tiny still – really small.

          1. alickdouglas

            Yes, they will eventually look at antibodies and t cells and whatnot but they are not reporting those for this particular interim analysis timepoint, I’m assuming all those are done a bit later (I’ve not had time to read every line of their protocol, and life might be too short for that). In theory the idea of an interim analysis is to check for futility, you look at the most important safety paramaters, and the most assessable and clinically relevant disease measures. Unfortunately, it’s also now become a method to drive corporate communications.

            Worth remembering however, there are loads of caveats here. For me the most important are:

            1) all the people included in this analysis received 2 doses of vaccine, and subjects were only assessed 7 days after the second shot (28 days after the first shot). This sounds to me like it might be the peak immune response time. While it is certainly very encouraging to see 90% protection at that timepoint, it will be more relevant to look at impact 6 months after dose 2. Gossip suggests that mRNA based immunity might not be sustainable (but that is gossip). For most vaccines, the observable immune response tanks after a month but without necessarily impacting efficacy. HepB vaccine is extremely effective at really quite low levels of measurable antibodies, as long as you have a few circulating, you are usually fine (this is a major gap in our COVID knowledge, and the only way to test it will be to wait 6 months).

            2) also important to realise: although there are tens of thousands of subjects in the trial, this analysis was done on the first 96 cases. Pfizer are not saying that 90% of however-many-thousand were protected, they are saying that 90% of the 96 cases reported up to the analysis timepoint occurred in recipients of placebo (it’s not quite 90% because I’m slightly misrepresenting the analysis for the sake of keeping this comment a readable length).

        2. alickdouglas

          The ‘hope’ (ahem) during a development program like this is that you do the trial at a time when there is natural transmission. Developers who are currently in development are ‘lucky’ because in many territories transmission is high. This means that the risk of trial participants being exposed is also high. Statisticians attempt to capture this with an estimation of the ‘attack rate’. The greater the attack rate, the quicker a trial can get done.

          It’s important to remember that the Pfizer trial is ‘randomized, double (observer) blind’. This means that the people doing the assessment (and ideally the vaccine candidate recipient also) do not know whether they received treatment or control. The interim analysis for the Pfizer trial was set to be done after 96 cases had been reported. Briefly, you would determine how many of those 96 received placebo and how many received candidate. There’s a bit of statistical magic to it, but the proportion of those who fall ill after getting vaccine compared to those who got placebo is approximately your efficacy.

          This is a neat way to get a quick insight into vaccine impact, and because of the ‘radomization’ element, both placebo and vaccine groups should have an even mix of genders, age and risk of disease. Therefore, to a large (but not complete) extent, the specific definition of what constitutes a COVID case is less important as you are looking at a difference in disease incidence between vaccine and placebo recipients. As long as the definition of a case is the same for both (which it is in this case) then it’s likely that they are observing a true vaccine impact on incidence

          1. Micko

            Cool replies alickdouglas

            I’m guessing you work in “the business” or are you just a science fan?

          2. alickdouglas

            Glad it’s helpful Micko, vaccine assessments are a different beast to drug assessments. Most of the people feeding the media are drug assessors and they don’t get a lot of the subtelties of vaccine development. I’ve grown to realise that a lot of what’s done on vaccine assessments doesn’t appear intuitive to folks who aren’t used to it, and it needs a bit of explanation.

          3. millie

            Your comments are incredibly helpful alick. They cut through a lot of the speculation and guesswork seen online. I always take the time to read them. Thanks for the input!

    2. george

      You don’t even know the name of the company, Vanessa so forgive me if I don’t trust your expertise on this.

      1. v AKA Frilly Keane

        I’ve never once promoted the notion that I was an expert

        my comment there only deals with the logistics of a roll out to production
        and from a highly regulated and corporate culture controlled multi national

      2. Micko

        Did she not spell it correctly or are you giving out that V didn’t put an apostrophe in?

        Harsh dude

        Also, as far as I know V is an accountanty type and you should always follow “de money” ;-)

        1. v AKA Frilly Keane

          something else to follow

          Leo was tweeting a back slap to Pfizer there not more than a month ago

          Jesus
          that would be a great board to get on all the same

          I’d say their meetings take place in different locations around the World
          Seats 100K plus pa
          Seats + Committees 150K
          Chair 300K easily

          Plus all the goodies

          1. GiggidyGoo

            I think Leo Varadkar has offloaded any notions he may have had of such office. He can’t be trusted. His performance in the Dail last week won’t be part of his CV but will be a reference.

          2. goldenbrown

            +1 V

            sorry Giggidy but this is the reality unfortunately

            you and I might feel differently however Varadkers experience at dark arts would count in spades….whereas honesty, integrity or a semblance of vocational attitude just don’t. the ability to be morally flexible does however and he’s literally made for a gig like that, I have no doubt that it’s where he’s headed eventually

    3. Charger Salmons

      Makes you wonder why they waited until after the POTUS election to announce the news.
      I don’t really care either way but I just want to see if Comical Nigel blows a circuit.

      1. bisted

        …Comical Nigel…Farage?…Broadsheet Nigel is not known for a sense of humour…neither is he a member of Bord Na Rona…so we can’t even call him Chemical Nigel…

        1. Charger Salmons

          You’re wrong about Nigel’s sense of humour.
          He keeps cracking this joke about china dolls with peculiar eyes.
          I’m not sure what he’s on about but in the Dark Web world where fellers sit in their crusty underpants all day checking flight arrivals into Davos Airport I’m told he has ’em rocking in the aisles.

  4. Conski

    you’ve managed to trump the news with the headline – wonderful stuff

    *currently reclaiming parts of the English language from Benito Cartman

  5. johnny

    its a poo show.
    Sec. Ben Carson tested positive for COVID-19 this morning. His deputy chief of staff says he’s “in good spirits & feels fortunate to have access to effective therapeutics which aid and markedly speed his recovery.” Carson attended the election night party at the White House.
    Pfizer declined to take government money for research and development and is actively distancing itself from Operation Warp Speed because it did not want its work politicized by the Trump administration.

  6. SOQ

    A flipped switch is not a herb grown in a chemical soup called hydroponics and then sprayed with synthetic cannabinoids from China- in South Armagh / north Louth?

  7. GiggidyGoo

    So, if they vaccinate, 90% success rate? If they vaccinate, for arguments sake, everyone worldwide, then 90% will be successfully immune (for a short, long, or what, length of time?) The other 10% will catch it? Has 10% of the worlds population got covid at the moment?

    1. alickdouglas

      Well, if you were to interpret the data literally, you would say that 90% of the people who receive 2 shots within 21 days of each other would be protected up to 1 week after the second shot. Beyond 1 week post dose 2, there isn’t any data. You would want to be very mean-spirited however to think that your immunity will drop precipitously, but Pfizer will have to produce more data and 6 m and 12m data will be fundamental (and indeed, they are committed to 24 months of data per subject).

      But your calculation also assumes steady-state viral prevalence. As more people become immune, your attack rate should drop… so… your relative efficacy goes up, and you start straying into herd immunity…

      Also note that it took the smallpox eradication initiative what, about 15 years to vaccinate everyone with a single shot. Now we have 2 billion more people and they need 2 shots… The polio eradication initiative started in 1984 and still hasn’t vaccinated everyone. Pesky birth cohort.

      So dreams do not equal reality. But on balance yes you are correct. : D

      1. goldenbrown

        alickdouglas
        could I ask a couple of questions as you seem to know a fair bit on the subject?

        1) how do they understand side-effects? doesn’t that take months/years to shake out?
        2) reading the Pfizer blurb it appears to me that their vaccine has to be stored at a very low temperature…..

        “challenges related to our vaccine candidate’s ultra-low temperature formulation and attendant storage, distribution and administration requirements, including risks related to handling after delivery by Pfizer; the risk that we may not be able to successfully develop non-frozen formulations…”

        apparently it’s -90deg F….so not your average GP scenario

        so even assuming it’s safe and effective how is it a practical proposition for mass deployment?

        https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against

        1. alickdouglas

          For the side effects you have three or four categories that need to be monitored a) solicited adverse events b) unsolicited adverse events c) serious adverse events and d) adverse events of special interest. Solicited are events that are almost certainly related to vaccination, and it’s a standard list: local injection site pain, redness, swelling, and then ‘general’ events, fever, fatigue, headache (there’s a bit of leeway for the trial designer). These are typically recorded up to 7 days post vaccination, and if they happen are usually judged ‘related to vaccination’ (by the physician running the trial center, not a company physician). These are analysed statistically simply by comparing the vaccine group to the placebo. Practically always, the vaccinated group have a higher rate of events (if the vaccine works, it elicits an immune response, which is inflammatory, and hurts). The second category, ‘unsols’ are a catch all term for everything else you can imagine; runny nose, accidents, coughs… These are captured up to 28 days post last dose, and again, analysed by comparing one group to the other. In this case you typically don’t want to see a difference, and a proficient analysis team will compare the rate of events to that reported in the county(ies) in which the trial is done. Serious adverse events are basically hospitalisations. Again, you don’t want to see a (statistically significant) higher rate in one group vs the other (or at least not the vaccinees). The emotional issue with serious events (and deaths) is that when you recruit 43000 people into a trial, there is a natural rate of death (strokes, heart attacks, cancer, car crashes). But again, because the trial is randomized you want to see an approximately even rate between the groups (hence some weasly sounding statistical analysis). Finally, you have the ‘special interest’ which in reality is focussed on paralysis (guillain barré syndrome) and narcolepsy. There are a few others too. Once again, you are looking for balance.

          If you see imbalance, especially ‘worse’ events in the vaccine group, it’s a red flag, but you need to also account for statistical significance; i.e. to account for, for example, 5 events in one group and 8 in another: are they really different?

          The reality is that clinical trials are very bad at catching rare events. Everyone’s favourite is narcolepsy. The problem is that narcolepsy is hard to diagnose, and rare. From memory the background rate is about 1/100 000 with geographic variation. Therefore in Pfizer’s clinical trial you’d expect to see between 0 and perhaps 3 cases, just as background. But the reality is that a trial with 50 000 volunteers isn’t big enough to catch a side effect like narcolepsy. So what do you do? Do you require that all trials are minimum 300k people? Back of the envelope, that’s a 60 million dollar trial just there, minimum, with a very high risk of failure. No sponsor, even a well-funded one would do that. So, Phase III trials are designed to build a picture of the risk profile of the vaccine, and to prepare physicians for what the might see. Also worth remembering that licenses are temporary. The original Rota virus vaccine was judged to be safe, and licensed. However, post phase III it was found to be associated with serious adverse events (only became obvious after >1 million vaccinees) and the vaccine was withdrawn. Subsequent Rota vaccines were obliged to do trials in >120 000 subjects and because of that, only ‘big pharma’ were willing to develop them. Indian producers, for example, don’t have the cashflow to cover the cost. risk and indemnity for such a big trial, so the developing world doesn’t get the cheap vaccine it needs.

          1. goldenbrown

            thanks for such a comprehensive reply!

            so are we saying there that (albeit good progress in the right direction in the development cycle of a brand new product)……

            1) it’s not anywhere close yet to being an actual shipping product, in computer terms it’s pre-beta, v0.9?

            2) the side-effect scenario is a bit of a shot in the dark – we don’t really truly know (due to economics etc.) if the vaccine is harmless when it gets deployed, something might only become apparent after some time in the field requiring some rework or even switchover to an alternative product and some damaged people…oh well but like whaddya do (shrug)?

            3) (per below) there’s actually no practical way to deliver this product into the population as it exists presently?

            so (rhetorical) wtf is everyone getting so super-duper-over-excited about today? it’s starting to look like a pile of spin to me anyway

            (btw I’m definitely not an anti-vax type, but I like to think I still have a bit of sanity left, I am highly suspicious of new products of any kind….nevermind anything pharma related given the present understandable stampede for everything to be back to normal lol )

          2. alickdouglas

            no, it pretty much is a shipping product; all the manufacturers have apparently been ‘manufacturing at risk’ and so Pfizer I guess are sitting on a few hundred litres of bulk at this stage, perhaps already in vials (putting into vials sometimes has stability implications, so they may still have it in bulk bags, awaiting regulator’s approval).

            Vaccines are always heavy on logistics, but this mRNA one will be worse. This was the point Gov. Cuomo was making in that original clip. He’s saying that the federal government should not be relying on private practitioners and clinics to deliver the vaccine, rather there should be a ‘mass vaccination’ campaign coordinated by the federal govt, something that the trump administration is refusing to do. Federal mass vaccination doesn’t in itself mean compulsory vaccination: it means that you have a centralised access. That’s what I’d want to see for an atypical vaccine like this. I cannot tell you how many calls I’ve had to deal with with physicians making errors with unfamiliar vaccination routines. The frequency with which physicians and nurses don’t read the package insert is really startling. With a -90F vaccine (and I guess it will therefore be a vial, and not a prefilled syringe, but I could be wrong), the opportunity for error is essentially endless.

          3. alickdouglas

            oh, regarding your point on spotting side effects post-licensure. Yes, this can happen, although if you do see it, it’s rare that a correction can be made. I’m only really aware of one occasion, and that was the ‘cutter incident’ for Salk’s 1954 vaccine. It was realised that Salk’s inactivation protocol wasn’t really clear enough, and the manufacturer’s procedures were written more clearly, but not changed. Cutter went out of business and at least a thousand lives were ruined, but the vaccine manufacturing process itself wasn’t really inherently changed, and hence carried on to be used until about 1970 (the current Salk vaccine uses a very different manufacturing process). For the original Rota vaccine, the problem was inherent to the design of the vaccine and it was withdrawn (although with less dramatic implications for the vaccinees who got the vaccine).

            ‘Post licensure’ data is more useful to look at vaccine impact really, and to inform use. If memory serves, Gardasil was originally licensed due to its demonstrated impact on visible genital warts, with the implication that if it was effective vs. visible warts it was likely effective vs. cervical cancer. It was (I think) only shown post licensure that it was quantifiably impactful vs. cervical cancer.

        2. alickdouglas

          oh, the -90F thing. Nightmare.

          This is one of the many reasons why we need to see other companies coming forward with more robust, easier to administer solutions.

          Delivery solutions, especially for mass vaccination campaigns are a battleground between pharma developers (who want $$ margins) and delivery services (UNICEF, MSF). Awful.

  8. Pat Mustard

    Pfizer set a record for the largest health care fraud settlement and the largest criminal fine of any kind with $2.3 billion in 2009.

    Prempo

    Nearly 10,000 women filed Prempro breast cancer lawsuits against Pfizer. By 2012, Pfizer settled most of the claims for more than $1 billion.

    Chantix

    About 3,000 people filed Chantix lawsuits against Pfizer. They claimed Chantix caused suicidal thoughts and severe psychological disorders. In 2013, the company set aside about $288 million to resolve these cases. One case settled for an undisclosed amount just before trial in 2012.

    Effexor XR

    In 2014, Pfizer recalled two lots of its antidepressant drug Effexor XR. Tikosyn was discovered in an Effexor XR bottle. Tikosyn is one of the company’s heart pills. Pfizer warned that the combination of the two different drugs could be deadly.

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