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Thread: covid-19

  1. #2521
    Quote Originally Posted by LittleFuzzy View Post
    Rand, have you considered what the effect it can have on the effectiveness of the 2nd dose, once it finally does get administered? Because we don't know that either but informed speculation and what little clinical data there is also tells us that the effect will be weaker. You may be ensuring that in the long-run, 100% of those vaccinated under your strategy might as well have been given a placebo.
    Yes. The JCVI, MHRA and others have said they expect the effect of the booster to be STRONGER after a 12 week gap. Not weaker.

    Both data from the AZN trial and a general understanding of how booster shots work and the historical body of evidence with booster shots in general leads them to have confidence in that.

    What informed speculation or clinical data do you have that it will be weaker?
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  2. #2522
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  3. #2523
    Quote Originally Posted by wiggin View Post
    Can you please direct me to this evidence you keep mentioning?
    I've seen a lot of reports and data but don't have it to hand sorry. If I come across it again I'll share it here.
    Yes, to verify something like this works, I want a placebo controlled RCT. That's the gold standard, and that's what was used to provide the EUA in the first place. If a company thought that a less stringent dosing schedule (or just one dose) would do a good job, they would have included that as an arm in a trial. And in fact that's precisely what JNJ (and, belatedly, AZN) are doing.
    Fine for a study, this isn't a study. This is real life.
    I believe your friend was referring to 'off label' use; generally the manufacturers of a drug or device get them approved under a specific indication - to treat specific diseases in specific ways, up to and including dosing regimens. Certainly physicians are generally allowed to use an approved device or drug in a manner not explicitly on the label provided that their expert judgment determines that to be the best approach for that patient. It is not the same logic being used here, however. No one is claiming that this changing of dosing regimens will be better for the patient being withheld the second dose; at best, they will not be harmed, but at worst they will suffer substantial harm from reduced protection. The logic here has to do with public health policy, arguing that overall outcomes would be better if second doses were withheld at least temporarily. Generally doctors are not allowed to use items off-label if they think it will help someone else but not their patient.
    Yes thanks, that was it. Off label makes more sense than off book.

    Well in this case the JCVI aren't treating a solitary patient, they're explicitly seeking the best protection for across the community. If millions more are protected via this regimen following the logic and numbers I posted before, and if tens of thousands of lives are potentially saved as a result (given we face losing over a thousand a day currently some days that's not an exaggeration), then that seems reasonable to me. Does it seem absolutely unreasonable to you?

    It is only by having this regimen that they will be able to offer at least one dose of vaccine protection to everyone in the most clinically vulnerable groups by the middle of February, if a different regimen were followed then it would potentially be the end of March before the same people were getting a dose - which would include for instance all those under 65 on chemotherapy (priority group 4).
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  4. #2524
    Meanwhile, in the Netherlands ...

    Covid: Dutch curfew riots rage for third night

    Protesters defying a curfew in the Netherlands have again clashed with riot police, after a weekend of unrest.

    More than 150 people were arrested in several cities. In Rotterdam, the police fired warning shots and tear gas, after an emergency order issued by the mayor failed to move demonstrators.

    Unrest started over the weekend as protesters kicked back against newly imposed coronavirus restrictions.

    Prime Minister Mark Rutte has condemned what he called "criminal violence".

    The Netherlands has had nearly one million confirmed Covid cases since the start of the outbreak, with more than 13,500 deaths, according to Johns Hopkins University in the US, which is tracking the pandemic.

    There were further violent scenes in several cities across the country on Monday night. Riot police clashed with protesters in Amsterdam as well as Rotterdam, Amersfoort and Geleen. Police in Rotterdam said a number of officers were hurt.

    Fires were lit on the streets of The Hague, where police on bicycles attempted to move small clusters of men who threw rocks and fireworks, the BBC's Anna Holligan reports from the city. There were also reports of looting in a supermarket in

    There was violence in the southern city of Den Bosch, where rioters set off fireworks, broke windows, looted a supermarket and overturned cars.

    A woman living near the train station told Dutch radio that masked youths had left a trail of destruction in the city centre. "I saw windows smashed and fireworks going off. Really crazy, just like a war zone," the woman said. Roads into the city were closed to stop people joining the rioters.

    A number of arrests were made in Amsterdam and the mayor appealed to parents to keep young people indoors.

    In Rotterdam, police used water cannon during clashes with rioters and Mayor Ahmed Aboutaleb signed an emergency decree, giving police broader powers of arrest.

    He reacted furiously to reports of looting, condemning "shameless thieves, I can't call it anything else."

    Football fans of the Willem II club took to the streets of Tilburg to "protect their city" against rioters, news site Brabants Dagblad reports.

    The violence on Sunday was described by Dutch police as the worst unrest in four decades.

    A Covid-19 testing centre was also set alight on Saturday evening in the northern village of Urk, local authorities said.

    Police arrested a 39-year-old man in Almere on Saturday for posting threatening messages about journalists online, Dutch news agency ANP reported.

    Mayors in several cities have vowed to introduce emergency measures in an effort to prevent more disturbances.

    "It's unacceptable. All normal people will regard this with horror," the prime minister told reporters.

    "What motivated these people has nothing to do with protesting, it's criminal violence and we will treat it as such."

    The Dutch government has introduced its toughest measures since the start of the pandemic - including a night-time curfew which runs from 21:00 (20:00 GMT) to 04:30. It is the first in the Netherlands since World War Two.

    Anyone caught violating it faces a €95 (£84) fine.

    The country's bars and restaurants have been shut since October, while schools and non-essential shops closed last month.







    Are the protesters/rioters from across the spectrum of society, or are they generally disaffected youths ... or ?

    Setting fire to a covid-testing centre
    Quote Originally Posted by Steely Glint View Post
    It's actually the original French billion, which is bi-million, which is a million to the power of 2. We adopted the word, and then they changed it, presumably as revenge for Crecy and Agincourt, and then the treasonous Americans adopted the new French usage and spread it all over the world. And now we have to use it.

    And that's Why I'm Voting Leave.

  5. #2525
    Senior Member Flixy's Avatar
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    Mostly bored/disaffected youth who felt like destroying stuff, as far as I can tell. To be honest the majority of rioters probably isn't even protesting anything. At least, it'd be stupid to say the least to protest against the measures.. by throwing in the windows of some shops and bars who are already suffering by being closed.

    That bottom picture is 10 minute walk from my house I think I smelled the tear gas at home, but not sure because I don't really know what it smells like as I've bever been at a riot
    Keep on keepin' the beat alive!

  6. #2526
    Terrible. Also shocking sharing of antivax fake news by some elements of the German media last night. Papers really ought to do a basic of due dilligence fact checking before sharing fake news antivax stories.

    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  7. #2527
    I don't normally like Peston but he has an excellent summary here. This is the consequence of months being wasted by delaying signing the agreement. If you waste months by not signing the agreement you waste time to sort out issues.

    Last edited by RandBlade; 01-26-2021 at 10:38 AM.
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  8. #2528
    Senior Member Flixy's Avatar
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    Keep on keepin' the beat alive!

  9. #2529


    Self-entitled shitbags.
    Quote Originally Posted by Steely Glint View Post
    It's actually the original French billion, which is bi-million, which is a million to the power of 2. We adopted the word, and then they changed it, presumably as revenge for Crecy and Agincourt, and then the treasonous Americans adopted the new French usage and spread it all over the world. And now we have to use it.

    And that's Why I'm Voting Leave.

  10. #2530
    Quote Originally Posted by RandBlade View Post
    I've seen a lot of reports and data but don't have it to hand sorry. If I come across it again I'll share it here.
    You asked for my data for the range of efficacy I quoted; I referenced specific studies. I'm asking you for supposedly voluminous evidence of >50% reduction in viral load and hospitalizations after 1 dose. It's kinda central to your argument.

    Fine for a study, this isn't a study. This is real life.
    I recognize that the UK's strategy does not lend itself to a random assignment, blinded, placebo controlled trial. That was what I was lamenting. You think that because it's an EUA it's somehow okay to go ahead with a huge dosing change without data. But those EUAs weren't granted in the first place without a large placebo controlled RCT precisely because you can't just make an educated guess about whether the vaccine will work in a given formulation/dose/etc.

    I asked it earlier, but I'll pull it out here: In the absence of solid data, how do you know that this change to the dosing will result in a net improvement as opposed to some other change in dosing that is not being contemplated here? There are many ways to skin this cat: reduce the quantity dosed at each dosage but give the same number/timing of doses. Or you could just stick with 1 dose and skip the second entirely - certainly you can get even MORE people vaccinated quickly. Or you could mix and match vaccines to reduce the administrative burden. So how do you know this will work better than the method that is known to work... and that other changes aren't better? Which untested change do you embrace?


    Well in this case the JCVI aren't treating a solitary patient, they're explicitly seeking the best protection for across the community. If millions more are protected via this regimen following the logic and numbers I posted before, and if tens of thousands of lives are potentially saved as a result (given we face losing over a thousand a day currently some days that's not an exaggeration), then that seems reasonable to me. Does it seem absolutely unreasonable to you?
    I have no issue with this basic theory from a public health perspective. My issue is arguing that this falls under off-label use provisions, which are generally related to individual patients, not broader public health.
    "When I meet God, I am going to ask him two questions: Why relativity? And why turbulence? I really believe he will have an answer for the first." - Werner Heisenberg (maybe)

  11. #2531
    Quote Originally Posted by RandBlade View Post
    Yes and all that is being modelled by the JCVI and other relevant bodies
    I spent a lot of time and effort trying—in vain—to find any data on these models you say exist. If you have access to reports modeling the different alternatives, feel free to share.

    Should we cease to consider this to be an emergency and cease to operate on a basis of emergency usage?
    I believe you should use each vial to vaccinate 100 people. This is, after all, an emergency.

    Or should we cease to follow the scientific advice given by the independent scientists that make up the JCVI?
    You should, at the very least, require them to make public their data, models, assumptions and reasoning, so that it can be subjected to scientific scrutiny.

    I do appreciate that but we are operating in a real world emergency and need to operate with the real world body of evidence that we have. I don't know if you listened to the JCVI Professor in that audio clip I posted above but he explains that this is being monitored and evidence is coming in and being evaluated as it is.
    I'm saying that the evidence you have at the moment is not evidence that answers the questions at hand.

    In one sense it was a good thing for the world that Sweden tried a different model for dealing with the pandemic - it didn't work, but they tried and now we know it didn't work. If it did then more countries would have followed Sweden's lead.
    The evidence gained from Sweden—or, indeed, from most countries in Europe—is not sufficient to answer any questions scientifically.

    Quote Originally Posted by RandBlade View Post
    [...]

    Well in this case the JCVI aren't treating a solitary patient, they're explicitly seeking the best protection for across the community. If millions more are protected via this regimen following the logic and numbers I posted before, and if tens of thousands of lives are potentially saved as a result (given we face losing over a thousand a day currently some days that's not an exaggeration), then that seems reasonable to me.

    [...]

    PS anecdotal but one of my friends is a doctor - lifelong Labour/Lib Dem supporter, hates Brexit, hates the Tories, hates Boris. Normally votes Labour, voted Lib Dem in 2019 as he didn't like Corbyn either.

    He has been interesting to hear from through the pandemic as what he has seen is horrible and I wouldn't wish upon anyone. Both he and his wife have caught the virus but thankfully weren't too seriously affected. He dislikes the government but is 100% behind the vaccination policy - he says (and I agree) that they are really struggling to cope and we need to break the back of this virus as fast as possible, with the lockdown and with the vaccine. He says that since it has been shown the vaccine is safe for people to take then it is far from unusual for a medicine approved for usage in one method to be granted an "emergency" authorisation to be used in a different method or for different reasons instead. Sometimes clinical need comes before scientific testing and that is what emergency authorisation is for - and this is an emergency. I am paraphrasing what he said from memory, I think the phrase he used was "off book" but I'm not sure if that's right or not?

    I can't disagree with any of that. As a doctor, do you?
    If you have given an accurate account of his position, I disagree with part of his analysis. 1. The present situation is more or less unprecedented—for the simple reason that pandemics are uncommon, and ones involving novel viruses even more so. 2. Emergency authorization is itself relatively uncommon—and unprecedented for substances being used at such a massive scale. 3. Following emergency authorization, the substances or devices in question are typically used carefully, with adherence to protocols supported by the evidence forming the basis for the authorization. 4. To the extent that he may be thinking of compassionate use practices, the considerations are completely different from vaccinating individuals who are not themselves severely ill. 5. To the extent that he may be thinking of off-label use, I refer you back to my earlier comment on that perspective:

    For example, re. off-label use, it is rare to use a substance off-label—on a large scale, at that—unless there is substantial experience with using it in that manner, often from studies conducted after approval; in this case, we're talking about new vaccines—indeed, new types of vaccines—against a novel illness, so nobody can be said to have any substantial experience with the equivalent of off-label use.
    And 6. It's not just a question of short-term safety for individuals but also a question of medium-to-long-term safety of the strategy from an epidemic control perspective. Depending on parameters such as the ones I have mentioned in earlier posts, the strategy you're currently using can result in a higher or lower overall attack-rate. That's why the decision should be based on thorough modeling and detailed analyses that can be subjected to scientific scrutiny by external experts.

    Quote Originally Posted by RandBlade View Post
    Not really. Pro rata for population and the UK's 5 million delayed is equivalent to 33 million delayed in the EU.
    Except that that is a silly way to look at it. The challenges of producing and handling 5 million doses are different from doing the same with 50 million doses.

    Apparently like Pfizer in November it seems an AZN batch has had to be thrown away. That happens and wouldn't have been known months ago, though it was always known to be a potential issue and should have been understood by everyone. The UK didn't cry over the fact Pfizer had that issue in November because it is part of the process and happens.
    We're talking about a deficit of nearly 50 million doses for the EU order, so I suspect this note about a bad batch at the Welsh facility is not even a little relevant.

    It is entirely relevant.
    It's not even a little relevant for the present discussion. If you believe otherwise, feel free to construct an argument showing how it is relevant.

    Except it pretty much does. See the UK and USA scaling almost exactly linearly - and see the EU doses real world doses currently scaling almost exactly linearly with the difference in spending. Funny that.

    Seriously? The UK has rolled out over 10 doses per 100 capita, the EU fewer than 2 doses per 100 capita and you think that "there is no indication that the rollout has been delayed by lower investment in vaccine development; it is clear that one important cause for a later start is the slower approval, and another important cause is likely to be that AZN bit off more than they could chew"?

    If not the fact that the UK has spent nearly £6 for every £1 per person on building up manufacturing capacity etc in the UK to procure vaccines swiftly then how do you explain the UK rolling out 5-6 doses per capita that the EU have right now? Or is it all a remarkable coincidence?
    If your data appears to show a relationship that is nonsensical, that should prompt you to be more cautious in your interpretation. There are many spurious correlations. What I want to know is, why have the US and the UK chosen to spend so much per capita on vaccine-related matters when it is absolutely clear that greater spending is leading to more deaths per capita? It's unconscionable. They should be spending that extra money on bringing back old-school piracy, as we have compelling data showing that pirates can prevent global warming.

    You do realise that the AZN delay is going to be forthcoming now and doesn't explain why you're so far behind already - and part of the reason there's been little urgency in the EU authorising the vaccines is because you weren't due to get them as quickly anyway even in the best case scenario without any disruption?
    There is no evidence to support the notion that the delay in authorization was caused by an expected delay in shipments; if anything, the converse is more likely to be true—an expected delay in authorization may have caused AZN in particular to prioritize other orders, while hoping to be able to "catch up" once the authorization was given.

    Incidentally the "early approval" idea has no evidence behind it.

    [ tweet ]
    I can understand how you might think that's a slam dunk, due to your chronic refusal to read things properly. Let me remind you of what you said:

    Congratulations for getting the vaccines at 1/6th of the price of the UK and USA (once you include all investments in developments) but later rollout is a result
    To which I replied,

    it is clear that one important cause for a later start is the slower approval
    The tweet you've posted does not concern that particular issue—it concerns vaccination rate.

    How are the supply requirements far lower than the EU's? Do we have fewer old people per capita? Fewer care homes? Fewer doctors, nurses, over 65s per capita? Or do you mean fewer gross? In which case the response is to scale up investment - linearly if required.
    Yes, your demands are lower in absolute terms than the EU's, which makes them far more manageable. For example, AZN expected to be able to give you 4 million doses using excess capacity at their continental facilities; it's much easier to make up for a shortfall that is small in absolute terms than to make up for a shortfall that is 10 times as large in absolute terms. If I need £5 I can probably get 5 people to give me £1 each. If I need £50, it will be considerably more difficult for me to get 5 people to give me £10 each—I might have to ask 50 people, which presents a greater and completely different challenge than asking 5 people, esp. if I'm working under time constraints.

    If additional expenditure was not required then where is the supply today? Why have you only got <2 doses per 100 people today. Not in the future, not months from now, today.
    You seem to have difficulties keeping track of what you're discussing. If you're wondering about supply, many countries are using their supply very slowly, opting to prioritize people in eg. care homes. The distribution of doses to each member state is a matter between that member state and the company in question, and the distribution within each member state is, of course, a national or regional matter for each state and/or region. Unfortunately, we have no good way to track percentage of distributed doses that have been administered. If you're wondering about administered doses, which is what the chart you tweeted actually shows, that reflects national issues, and most nations have not been constrained by supply; their rollouts have been slow for a variety of reasons, eg. because they're focusing on fully vaccinating care home residents rather than racing to partially vaccinate the entire population, or due to administrative and IT issues. All of these member-state-specific issues are for member states to address—with policies and with spending as required and as they see fit; those things will not be accounted for in any comparison that only looks at the EU's institutional expenditures. I understand that your severe simplism requires black-and-white answers devoid of nuance, but reality won't oblige.

    Yes and so the EU should have had more Pfizer vaccine stockpiled because of the tardy rollout if that was all there was to it, rather than supply constraints, so you should have been able to hit the ground running - which Denmark and Italy did, but then they ran out of supply. Where is the sustained liftoff in doses that the UK, USA etc that spent 6x as much per capita have achieved?
    You're losing track of your own arguments. How do you expect the EU or Pfizer to stockpile something that doesn't exist? If the stock doesn't exist, the stock doesn't exist; it's a complicated procedure to generate it and all companies are struggling with that. The UK's acceleration so far is easily explained by its decision to prioritize broad coverage over fully vaccinating people, and by its earlier deployment of the AZN vaccine.

    Quote Originally Posted by RandBlade View Post
    Yes. The JCVI, MHRA and others have said they expect the effect of the booster to be STRONGER after a 12 week gap. Not weaker.

    Both data from the AZN trial and a general understanding of how booster shots work and the historical body of evidence with booster shots in general leads them to have confidence in that.
    This is a dubious argument. It's not simply that they expect a "stronger" response—it's that they hope, with some justification, for a response that is qualitatively better, eg. wrt affinity to the targeted protein. However, it fails to take into account risk of exposure & illness during the interval between doses, which is 1. higher in eg. the UK and Israel now than when the phase 3 trials were conducted, and 2. changing over time. The reasoning they're using wrt this specific question is appropriate when discussing pre-pandemic vaccination or vaccination for illnesses that are unlikely to result in a pandemic of this kind—situations when risk of infection between doses is virtually zero.

    It is only by having this regimen that they will be able to offer at least one dose of vaccine protection to everyone in the most clinically vulnerable groups by the middle of February, if a different regimen were followed then it would potentially be the end of March before the same people were getting a dose - which would include for instance all those under 65 on chemotherapy (priority group 4).
    Priority groups can be changed as needed; it is a matter of public health policy, not a strict scientific matter. The utility of partially vaccinating at-risk groups is something that should be argued on the basis of data and modeling subjected to outside scrutiny, not simply through an unsystematic discussion of principles.
    “Humanity's greatest advances are not in its discoveries, but in how those discoveries are applied to reduce inequity.”
    — Bill Gates

  12. #2532
    Quote Originally Posted by RandBlade View Post
    I don't normally like Peston but he has an excellent summary here. This is the consequence of months being wasted by delaying signing the agreement. If you waste months by not signing the agreement you waste time to sort out issues.

    [ Tweet ]

    It's worth noting that AZN had originally aimed to produce 30 million doses for the UK by October. They actually delivered 4 million by January. Pfizer promised 10m doses in December and delivered just 1.5m. The US were promised 50m doses by Pfizer in December and received 10m. None of those countries threw temper tantrums.

    This happens with a new product being manufactured in scale for the first time and why early investment which the UK and USA offered and the EU did not is key to success.
    It's worth noting that the official explanation for AZN's initial shortfall in the UK is not that it was due to any sort of manufacturing issue but, rather, that it was due to a regulatory issue:

    https://www.channel4.com/news/factch...ine-do-we-have

    Instead, a spokesman said that the MHRA, the regulator which recently approved the AstraZeneca vaccine, “set out conditions with their authorisation on 30 December and batch testing is taking place to ensure the vaccines consistently meet these strict requirements”.

    “This could not be done before the conditions were outlined by the MHRA.”
    Peston's thread also contains a questionable claim re. pricing. According to a recently leaked document, the EU is paying around $2.2 per dose, while the BBC has reported that the UK is paying around $4.1. Either the AZN source has provided Peston with inaccurate information, or the BBC has reported the wrong price.
    “Humanity's greatest advances are not in its discoveries, but in how those discoveries are applied to reduce inequity.”
    — Bill Gates

  13. #2533
    Quote Originally Posted by wiggin View Post
    You asked for my data for the range of efficacy I quoted; I referenced specific studies. I'm asking you for supposedly voluminous evidence of >50% reduction in viral load and hospitalizations after 1 dose. It's kinda central to your argument.
    https://assets.publishing.service.go...ter_14a_v6.pdf
    I recognize that the UK's strategy does not lend itself to a random assignment, blinded, placebo controlled trial. That was what I was lamenting. You think that because it's an EUA it's somehow okay to go ahead with a huge dosing change without data. But those EUAs weren't granted in the first place without a large placebo controlled RCT precisely because you can't just make an educated guess about whether the vaccine will work in a given formulation/dose/etc.
    We aren't operating with no data, we're operating with limited data. There's a difference.

    The EUAs were granted because the placebo controlled RCT showed the vaccines were safe and efficacious. After that it becomes a question of how best to use it.
    I asked it earlier, but I'll pull it out here: In the absence of solid data, how do you know that this change to the dosing will result in a net improvement as opposed to some other change in dosing that is not being contemplated here? There are many ways to skin this cat: reduce the quantity dosed at each dosage but give the same number/timing of doses. Or you could just stick with 1 dose and skip the second entirely - certainly you can get even MORE people vaccinated quickly. Or you could mix and match vaccines to reduce the administrative burden. So how do you know this will work better than the method that is known to work... and that other changes aren't better? Which untested change do you embrace?
    This change is based on evidence that it works.

    We know for a fact that supply is the constraining factor.

    We know for a fact that the choice is 2 doses for half as many people, or single doses for now for twice as many people, since all supply is being used.

    We know from the data that exists that a single dose works after a fortnight with a Confidence Interval over a 50% from one dose which means that twice many people getting one dose provides more community protection than 2 doses for half as many people.

    We don't know that a reduced dosage at each dosage works. We don't know that mix and match vaccines works, which is why its only authorised as a last resort if it is necessary for operation reasons but is not recommended.

    As for a single dose alone, a booster dose probably gives more protection than just one dose so there's no reason to permanently skip the second dose. Given the risk profile too it makes sense to be giving second doses for the eldest and clinically vulnerable before first doses for the youngest. Given the vast majority of the deaths are from the first 4 priority groups, while under 1% of deaths are from the under 45s, a second dose for the first 4 groups makes sense before the first dose for people like me. But a first dose for all the vulnerable, makes sense before a second dose for half of the vulnerable.

    Ultimately there's no guarantee which method is best, we're operating in an imperfect world not a trial. A reasonable best guess is required - and a reasonable best guess that twice as many vulnerable people with 1 dose > half as many vulnerable people with 2 doses is well reasoned.
    I have no issue with this basic theory from a public health perspective. My issue is arguing that this falls under off-label use provisions, which are generally related to individual patients, not broader public health.
    The principle is the same, just its off label based on an overriding public health emergency.

    Since it takes about a fortnight for vaccine protection to take effect, then a week to two weeks to go from infected to hospitalisation, it takes about a month from vaccination to an avoided hospitalisation - so its a bit early to see the vaccines feeding through to hospitalisation figures in the UK. However there's already some early evidence that vaccinations are having an impact on hospitalisation numbers. The age-related hospitalisation figures have gone up and down together to scale, they're starting to go down now thanks to lockdown but there are early signs the over 85s admissions are declining faster than other admissions are.

    Last edited by RandBlade; 01-26-2021 at 06:50 PM.
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  14. #2534
    Quote Originally Posted by Aimless View Post
    It's worth noting that the official explanation for AZN's initial shortfall in the UK is not that it was due to any sort of manufacturing issue but, rather, that it was due to a regulatory issue:

    https://www.channel4.com/news/factch...ine-do-we-have
    No that's the secondary reduction. The initial projection was 30 million by September, that became 10 million by December due to manufacturing issues, which became hundreds of thousands by end of December due to vials (with the rest not taken from the batch to the vial yet).

    As for pricing you've left out the possibility that the leak was wrong. But the UK has paid to get a brand new production plant operation fully operational in the UK so that the vaccine isn't being imported which could have inflated the cost.
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  15. #2535
    Quote Originally Posted by Aimless View Post
    I spent a lot of time and effort trying—in vain—to find any data on these models you say exist. If you have access to reports modeling the different alternatives, feel free to share.

    You should, at the very least, require them to make public their data, models, assumptions and reasoning, so that it can be subjected to scientific scrutiny.
    Its online. With explanations, reasoning and tons of references and citations.
    https://assets.publishing.service.go...ter_14a_v6.pdf
    I believe you should use each vial to vaccinate 100 people. This is, after all, an emergency.
    Have you got a method of making that work? Following the JCVI advice is possible, 100 doses per vial is not.

    However comparably getting 6 doses per vial, when Pfizer only said 5, was possible. So it was done. Same logic. Should the 6th doses be thrown in the bin since it wasn't part of Pfizer's original plan?
    And 6. It's not just a question of short-term safety for individuals but also a question of medium-to-long-term safety of the strategy from an epidemic control perspective. Depending on parameters such as the ones I have mentioned in earlier posts, the strategy you're currently using can result in a higher or lower overall attack-rate. That's why the decision should be based on thorough modeling and detailed analyses that can be subjected to scientific scrutiny by external experts.
    Which is what has been done and the data is online - and more reports going online regularly. The JCVI are external experts like the Professor quoted above and their research is put online so anyone in the world can scrutinise it further every couple of weeks.
    Except that that is a silly way to look at it. The challenges of producing and handling 5 million doses are different from doing the same with 50 million doses.
    Only by scale. If you've invested to scale it isn't. Have you invested to scale?
    We're talking about a deficit of nearly 50 million doses for the EU order, so I suspect this note about a bad batch at the Welsh facility is not even a little relevant.
    And there was a 30 million deficit for the UK's order too. Very similar. Its the sort of problem that all companies have faced - in the UK and USA before the EU. We got ours three months later than planned, which wasn't an issue since we'd ordered three months earlier and the vaccine wasn't authorised when originally planned (September).

    You only put your order in just before ours was originally planned to be completed.
    It's not even a little relevant for the present discussion. If you believe otherwise, feel free to construct an argument showing how it is relevant.
    I have done, read it again.
    If your data appears to show a relationship that is nonsensical, that should prompt you to be more cautious in your interpretation. There are many spurious correlations. What I want to know is, why have the US and the UK chosen to spend so much per capita on vaccine-related matters when it is absolutely clear that greater spending is leading to more deaths per capita? It's unconscionable. They should be spending that extra money on bringing back old-school piracy, as we have compelling data showing that pirates can prevent global warming.

    There is no evidence to support the notion that the delay in authorization was caused by an expected delay in shipments; if anything, the converse is more likely to be true—an expected delay in authorization may have caused AZN in particular to prioritize other orders, while hoping to be able to "catch up" once the authorization was given.
    Except that's bullshit. The orders are coming from different plants. As part of the authorisation the plants producing the vaccine are part of the actual submission to get authorisation and the EU submission and the UK one are different plants. Its not like its all coming from the same plant but has been sent to the UK instead of the EU as some sort of twisted conspiracy - the EU plants were approved months later when the contracts were signed months later and have hit similar problems to what the plants started earlier for the UK faced and already had to overcome too.
    Yes, your demands are lower in absolute terms than the EU's, which makes them far more manageable. For example, AZN expected to be able to give you 4 million doses using excess capacity at their continental facilities; it's much easier to make up for a shortfall that is small in absolute terms than to make up for a shortfall that is 10 times as large in absolute terms. If I need £5 I can probably get 5 people to give me £1 each. If I need £50, it will be considerably more difficult for me to get 5 people to give me £10 each—I might have to ask 50 people, which presents a greater and completely different challenge than asking 5 people, esp. if I'm working under time constraints.
    Except that's not the case. The UK's plants, which were approved three months before the EU ones, faced a slow start but are now operating as planned. The EU plants, with a needless three month delay caused by the EU not signing contracts until three months later, are not doing so.

    The UK isn't "asking for" excess supply from the EU. There is no "excess EU supply" if there was this wouldn't be an issue. The UK is getting supply as the plants its paid for, months sooner, are actually working. The plants the EU dragged their heels on during a pandemic are not.

    6 P's in operation: Piss Poor Preparation leads to Piss Poor Performance.
    You seem to have difficulties keeping track of what you're discussing. If you're wondering about supply, many countries are using their supply very slowly, opting to prioritize people in eg. care homes. The distribution of doses to each member state is a matter between that member state and the company in question, and the distribution within each member state is, of course, a national or regional matter for each state and/or region. Unfortunately, we have no good way to track percentage of distributed doses that have been administered. If you're wondering about administered doses, which is what the chart you tweeted actually shows, that reflects national issues, and most nations have not been constrained by supply; their rollouts have been slow for a variety of reasons, eg. because they're focusing on fully vaccinating care home residents rather than racing to partially vaccinate the entire population, or due to administrative and IT issues. All of these member-state-specific issues are for member states to address—with policies and with spending as required and as they see fit; those things will not be accounted for in any comparison that only looks at the EU's institutional expenditures. I understand that your severe simplism requires black-and-white answers devoid of nuance, but reality won't oblige.
    They're using supply slowly because they're capped in supply. No member state has been capable of matching the UK's progress, or anything close to it, because no member state has the UK's supply.
    You're losing track of your own arguments. How do you expect the EU or Pfizer to stockpile something that doesn't exist? If the stock doesn't exist, the stock doesn't exist; it's a complicated procedure to generate it and all companies are struggling with that. The UK's acceleration so far is easily explained by its decision to prioritize broad coverage over fully vaccinating people, and by its earlier deployment of the AZN vaccine.
    No. The Pfizer stock did begin when the UK used it, it existed. If the EU had paid for the same proportion of doses as the UK had - at the same delivery schedule as the UK had - then the weeks the UK was using the Pfizer stock and the EU wasn't then the EU's stockpile would have been building. It wasn't because the EU was tardy at ordering the Pfizer one too.
    This is a dubious argument. It's not simply that they expect a "stronger" response—it's that they hope, with some justification, for a response that is qualitatively better, eg. wrt affinity to the targeted protein. However, it fails to take into account risk of exposure & illness during the interval between doses, which is 1. higher in eg. the UK and Israel now than when the phase 3 trials were conducted, and 2. changing over time. The reasoning they're using wrt this specific question is appropriate when discussing pre-pandemic vaccination or vaccination for illnesses that are unlikely to result in a pandemic of this kind—situations when risk of infection between doses is virtually zero.
    I'm glad you acknowledge its with some justification.

    Absolutely there is a risk of exposure between the interval doses, nobody denies that. However the risk of exposure to the unvaccinated are greater too. So all the more reason to ensure all the vulnerable are protected as fast as possible. It is a sprint to save lives.

    The risk of exposure is real for both the vaccinated and unvaccinated so its not a question as to whether to give someone two vaccines with no opportunity cost, if it was then give the 2 vaccines. The question is whether to give the 2 vaccines to the same people or different people and since the majority of protection comes from dose 1 then giving the majority of protection to double the people > giving full protection to half the people.
    Priority groups can be changed as needed; it is a matter of public health policy, not a strict scientific matter. The utility of partially vaccinating at-risk groups is something that should be argued on the basis of data and modeling subjected to outside scrutiny, not simply through an unsystematic discussion of principles.
    Which it is.

    How would you change the priority groups if you were not to take the JCVI's advice to get all done by middle of February for the first dose, then start doing the second doses for all of them within 12 weeks of the first?

    For ease of reference the priority groups are

    1: Residents in a care home for older adults and their carers.
    2a: All those over 80
    2b: All frontline health and social care workers
    3: All those over 75
    4a: All those over 70
    4b: The clinically extremely vulnerable individuals.

    All of them are categorised as clinically extremely vulnerable, the latter category means specifically though eg younger adults suffering from cancer undergoing chemeotherapy etc.

    If you're going to reject the JCVI advice, sacrifice half of those in order to give the booster shot to half of them rather than one shot to all of them, then which half would you choose to sacrifice and why?
    Last edited by RandBlade; 01-26-2021 at 08:02 PM.
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  16. #2536
    The only vaguely relevant information in that link is the phase III results from Pfizer and AZN, which no one is disputing. Those data do not, however, represent comprehensive data on 'lower viral load and lower hospitalizations after 1 dose' by > 50% especially when I have already shared data that disputes that, and the CIs on the Pfizer and AZN data were enormous given the small window for infections. You have yet to share additional data beyond what can be inferred from the original phase III trials.

    The EUAs were granted because the placebo controlled RCT showed the vaccines were safe and efficacious. After that it becomes a question of how best to use it.
    No, a question on 'how best to use it' might be something along the lines of who gets it first rather than 'let's just completely change the dosing regimen that was clinically tested because our gut tells us it'll be fine'.

    This change is based on evidence that it works.
    Evidence that does not exist past 3 or 4 weeks and is thin before then.

    We know for a fact that the choice is 2 doses for half as many people, or single doses for now for twice as many people, since all supply is being used.
    Those are hardly our only choices! Why couldn't we also include 2x half doses for twice as many people? Other doses were used in the phase I/II trials and some showed modest efficacy, albeit underpowered. Why couldn't we push for true herd immunity (albeit shittier than a full regimen) for the entire population by giving everyone one dose and figuring that will provide better overall protection for at risk groups than giving them the second dose before everyone else gets their first? There are perfectly reasonable justifications for any of these strategies, but without testing (or at a bare minimum, really rigorous modeling) we don't know which are awful ideas and which are winners.

    We know from the data that exists that a single dose works after a fortnight with a Confidence Interval over a 50% from one dose which means that twice many people getting one dose provides more community protection than 2 doses for half as many people.
    We also know from data that exists in a bigger and more realistic dataset that a single dose of the Pfizer vaccine works with 33-60% efficacy after 10-14 days until 3 weeks. Which means, well, it's hard to know without a lot more information, but it's certainly not proof for your conclusion.

    The principle is the same, just its off label based on an overriding public health emergency.
    Just don't use the word off-label use, it means something different and has different legal and ethical underpinnings than what you're talking about.
    "When I meet God, I am going to ask him two questions: Why relativity? And why turbulence? I really believe he will have an answer for the first." - Werner Heisenberg (maybe)

  17. #2537
    Quote Originally Posted by wiggin View Post
    The only vaguely relevant information in that link is the phase III results from Pfizer and AZN, which no one is disputing. Those data do not, however, represent comprehensive data on 'lower viral load and lower hospitalizations after 1 dose' by > 50% especially when I have already shared data that disputes that, and the CIs on the Pfizer and AZN data were enormous given the small window for infections. You have yet to share additional data beyond what can be inferred from the original phase III trials.
    That's not the only evidence but it is substantial evidence and what I was able to find from a quick search. As I've said other evidence is out there too but that is significant evidence.
    No, a question on 'how best to use it' might be something along the lines of who gets it first rather than 'let's just completely change the dosing regimen that was clinically tested because our gut tells us it'll be fine'.
    Not just gut, evidence and reason.
    Evidence that does not exist past 3 or 4 weeks and is thin before then.
    Yes it does. Evidence is not proof. If there's evidence that the vaccine provides protection at week 3 and week 4 then given everything we know about how vaccines work that is evidence it will be comparable in weeks five and week six. Immunity does not just magically vanish overnight, it doesn't work that way.

    This seems to be the biggest difference between a few of you guys and any of the scientists in the UK I've heard speak on it. You are acting as if the second the trial data ends that is the end of what we know and the end of any protection then that's it - the great unknown and zero there. Whereas the scientists here are using a well-reasoned understanding of what we know about vaccines to extrapolate past the three week window. The PIII trial revealed that immunity was acquired, it won't be gone overnight after that.

    We don't know for certain what the level of protection is - but we do have well reasoned evidence. What we do know for certain is the level of protection the unvaccinated get: None whatsoever.
    Those are hardly our only choices! Why couldn't we also include 2x half doses for twice as many people? Other doses were used in the phase I/II trials and some showed modest efficacy, albeit underpowered. Why couldn't we push for true herd immunity (albeit shittier than a full regimen) for the entire population by giving everyone one dose and figuring that will provide better overall protection for at risk groups than giving them the second dose before everyone else gets their first? There are perfectly reasonable justifications for any of these strategies, but without testing (or at a bare minimum, really rigorous modeling) we don't know which are awful ideas and which are winners.
    For what possible reason would we do 2x half doses for twice as many people, when we don't know if half doses work, rather than 2x full doses spaced just a little bit further apart?

    We don't have time to test every strategy. We need to make a decision sometimes. This isn't a scientific endeavour, it is real life. We know what the consequences are for not bothering to vaccinate people.
    We also know from data that exists in a bigger and more realistic dataset that a single dose of the Pfizer vaccine works with 33-60% efficacy after 10-14 days until 3 weeks. Which means, well, it's hard to know without a lot more information, but it's certainly not proof for your conclusion.
    Its not proof but it is evidence.
    Just don't use the word off-label use, it means something different and has different legal and ethical underpinnings than what you're talking about.
    I didn't use off-label, I said off-book originally because I misquoted the person who used it - who was himself using an analogy. I made clear I was quoting someone else, but from memory.
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  18. #2538
    Just curious - where did you learn immunology? Because it must have been somewhere with much more sophisticated understanding and predictive power than where I was taught it.
    "When I meet God, I am going to ask him two questions: Why relativity? And why turbulence? I really believe he will have an answer for the first." - Werner Heisenberg (maybe)

  19. #2539
    I didn't, I have an economics background and nor am I making an appeal to authority - I am making reasoned arguments from studying the details and providing sources - and quoting others who are Professors of immunology but I don't pretend to be one myself or make an appeal to their authority either.

    If you want to have an interesting discussion based on reasoned arguments and facts then that can be interesting. If I say something that is wrong I'm sure you can say so.

    If you just want to pull rank and dismiss everything because of your superior educational background then there won't be anything further to discuss - but that won't convince me that you were right and the Professors of Immunology and others who have made the decisions here and whose reports I've been reading and trying to understand are wrong.

    EDIT: I put this link into the last page but I would be curious what you think of the Professor's response to the question at the 2:10 mark here on the exact subject of how the immune response works going past the three week mark, also perhaps the final remarks at the 5 minute mark: https://soundcloud.com/blacktriangle...ccine-strategy
    Last edited by RandBlade; 01-26-2021 at 10:37 PM.
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  20. #2540
    Fascinating article with the CEO of AstraZenica. Originally in Italian, I used the Google Translate option in Firefox to read it in England and it is entirely readable: https://www.repubblica.it/cronaca/20...eca-284349061/

    Covers everything we have discussed today it seems. Wiggin and Aimless I strongly, strongly urge you to read this article.
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  21. #2541
    Incidentally Wiggin the entire article from the CEO of Astrazeneca there is worth reading but to quote a snippet from the interview he is 100% behind and agrees with the three month rollout policy.

    Quote Originally Posted by Via Google Translate, CEO of Astrazeneca
    The UK has decided to greatly delay the second dose of the vaccine, be it Oxford or Pfizer. A strategy criticized by many parties. Given also the scarcity of doses at the moment, especially in Europe, do you recommend this approach?

    "I think it is absolutely the right way. I cannot comment on Pfizer's vaccine so according to their studies it is recommended not to exceed three weeks between doses. But in our case, in tests in Brazil, the United Kingdom and United States we carried out the second administration even after 2 or 3 months and the results satisfied us, for various reasons. First of all, the first dose protects 100% against serious courses of Covid such as to require hospitalization and provides general protection to 71 -73%. The second dose, on the other hand, provides long-term immunity. But, for the studies we have carried out for the Oxford-AstraZeneca vaccine, paradoxically it seems that more immunity is generated if the second dose is delayed: do it after two or three months is better than one.This is because our technology based on an adenoviral vector differs from Pfizer's vaccine which is based on mRna. Johnson & Johnson's vaccine is also similar to ours and is heading towards a two-month gap between first and second doses. This is why I have no doubt that the UK has made the right choice, thus maximizing the number of people vaccinated, which will reach 28-30 million by March ".
    If the first dose alone gives general protection of 71% - 73% (the MHRA said "over 70%" in comparison so it matches) and it lasts for three months then absolutely rolling out to twice as many people is 100% the correct thing to do.

    Let alone a 100% level of protection against hospitalisations.

    If their science is right and the protection is 71% - 73% and therefore potentially tens of thousands of lives are saved by vaccinating 14 million instead of 7 million twice in the first rollout then are you prepared to accept the right thing was done?
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  22. #2542
    I'm not going to wade into the data but is vaccinating at risk people with two doses vs. vaccinating at risk people with one dose and other people at one dose the more accurate comparison?

  23. #2543
    https://www.nbcnews.com/news/world/c...lands-n1255631

    Netherlands rioting, can't claim to know a lot about them but I wouldn't have assumed they were very riot prone.

  24. #2544
    As the UK stumbles over the dreadful 100,000 people dead mark, the front pages are awash with a shamed Clown.

















    The Guardian has a feature on reasons why the UK has suffered a disproportionately high death rate, and the first European country to pass the 100k mark.
    Last edited by Timbuk2; 01-27-2021 at 06:37 AM.
    Quote Originally Posted by Steely Glint View Post
    It's actually the original French billion, which is bi-million, which is a million to the power of 2. We adopted the word, and then they changed it, presumably as revenge for Crecy and Agincourt, and then the treasonous Americans adopted the new French usage and spread it all over the world. And now we have to use it.

    And that's Why I'm Voting Leave.

  25. #2545
    Quote Originally Posted by Lewkowski View Post
    I'm not going to wade into the data but is vaccinating at risk people with two doses vs. vaccinating at risk people with one dose and other people at one dose the more accurate comparison?
    Only once you've vaccinated all your at risk people.

    Tim, I think the sombre and serious nature that he took the press conference and his remarks regarding the deaths were quite appropriate - and quite appropriately reflected on the front pages. Its not a case of "shame".

    Your link to the Guardian isn't working but the reasons for fatalities are multiple and varied but its not a league sport. Hopefully with the vaccine rollout going smoothly we can be out of this sooner than later, but I still think we should have mandatory hotel quarantines for any foreign travellers (especially holiday makers) especially as we learn more about new variants.
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  26. #2546
    LOL after AZN CEO's excellent and informative interview last night, they've informed the EU Commission they won't be attending the 'please explain' meeting the Commission had demanded.

    Good for AZN for refusing to be bullied and made scapegoats for the Commission's failings. Disgusting way to treat a company that is operating on a not for profit basis to end this pandemic.
    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  27. #2547
    Curious what Khen thinks about Zeit?

    And if he's ready to acknowledge yet that anything has gone wrong with the EU scheme? That was signed three months after Britains?

    Quote Originally Posted by Ominous Gamer View Post
    ℬeing upset is understandable, but be upset at yourself for poor planning, not at the world by acting like a spoiled bitch during an interview.

  28. #2548
    Quote Originally Posted by RandBlade View Post
    No that's the secondary reduction. The initial projection was 30 million by September, that became 10 million by December due to manufacturing issues, which became hundreds of thousands by end of December due to vials (with the rest not taken from the batch to the vial yet).

    As for pricing you've left out the possibility that the leak was wrong. But the UK has paid to get a brand new production plant operation fully operational in the UK so that the vaccine isn't being imported which could have inflated the cost.

    [...]

    And there was a 30 million deficit for the UK's order too. Very similar. Its the sort of problem that all companies have faced - in the UK and USA before the EU. We got ours three months later than planned, which wasn't an issue since we'd ordered three months earlier and the vaccine wasn't authorised when originally planned (September).

    [...]

    Except that's bullshit. The orders are coming from different plants. As part of the authorisation the plants producing the vaccine are part of the actual submission to get authorisation and the EU submission and the UK one are different plants. Its not like its all coming from the same plant but has been sent to the UK instead of the EU as some sort of twisted conspiracy - the EU plants were approved months later when the contracts were signed months later and have hit similar problems to what the plants started earlier for the UK faced and already had to overcome too.

    Except that's not the case. The UK's plants, which were approved three months before the EU ones, faced a slow start but are now operating as planned. The EU plants, with a needless three month delay caused by the EU not signing contracts until three months later, are not doing so.

    You only put your order in just before ours was originally planned to be completed.

    The UK isn't "asking for" excess supply from the EU. There is no "excess EU supply" if there was this wouldn't be an issue. The UK is getting supply as the plants its paid for, months sooner, are actually working. The plants the EU dragged their heels on during a pandemic are not.
    1. It's not even remotely similar, except possibly for AZN—and the government—over-promising. One reason for missing targets for the AZN vaccine deliveries was a delay associated with the final stages of the trial, and another official reason that has been offered is a delay associated with regulatory approval and regulatory requirements. Reading between the lines, the 30 million figure was also predicated on getting the Welsh facility up and running properly very quickly in order to enable a rapid linear scaling up of production. That they might not reach that target is something they hedged against in their initial announcement that it would be only "up to" 30 million by September; I wouldn't call that a shortfall, and they duly notified you of their expected failure to hit that target. EU countries are being told, barely a week before they're supposed begin receiving their shipments, that they'll be getting 60% less.

    2. The FT reported in early December that the 4 million doses that were actually delivered were imported from their facilities in Netherlands and Germany:

    https://www.ft.com/content/651be7e7-...9-b4b7e887f6e8

    The UK government’s vaccines task force acknowledged on Monday that just 4m doses of the vaccine developed by Oxford university and AstraZeneca would be delivered this year, imported from the Netherlands and Germany.

    [...]

    AstraZeneca said it was using a continental facility initially because it had booked capacity there “which we wanted to use rather than waste”, not because of problems at the British sites.
    3. I said "excess capacity" in reference to production capacity at the continental facilities; what on earth made you quote me as saying "excess supply"? Please at least try to read.

    Quote Originally Posted by RandBlade View Post
    Its online. With explanations, reasoning and tons of references and citations.
    https://assets.publishing.service.go...ter_14a_v6.pdf
    This does not contain any modeling relevant to the question at hand, nor does it contain particularly compelling data. Here's an example of the type of modeling that might be useful: https://www.sciencedirect.com/scienc...5543651500064X

    This paper is simplified, and an influenza pandemic like the one being modeled is likely to behave differently from our present epidemic, but it's a useful illustration of how the relevant parameters might interact. Publishing something like that would help everyone get a better idea of the tradeoffs, and of the soundness of their reasoning (eg. if their reasoning appears to lead to more positive outcomes across a very broad range of assumptions about strength and duration of immunity as well as risk of exposure).

    Have you got a method of making that work? Following the JCVI advice is possible, 100 doses per vial is not.
    Of course it's possible—just dilute it a little more and adjust the volume you draw for each dose accordingly.

    However comparably getting 6 doses per vial, when Pfizer only said 5, was possible. So it was done. Same logic. Should the 6th doses be thrown in the bin since it wasn't part of Pfizer's original plan?
    Pfizer's trials were not about the physical dimensions of vials and syringes, and the present discussion is about how to use—or not use—the evidence from the trials.

    Which is what has been done and the data is online - and more reports going online regularly. The JCVI are external experts like the Professor quoted above and their research is put online so anyone in the world can scrutinise it further every couple of weeks.
    RB, saying that the "JCVI are external experts" for the purposes of critically appraising the work of the JCVI is like saying I can be an impartial judge at my own trial. This is at least the second time you've misunderstood this very simple issue. The JCVI's experts are external to govt. but that is not relevant to the matter of letting outside experts scrutinize their scientific work.

    Only by scale. If you've invested to scale it isn't. Have you invested to scale?
    Clearly, the companies in question believed the infrastructure and investments were adequate for delivering the agreed-upon doses. So the answer to your question must be "yes"—according to the companies who signed the contracts.

    I have done, read it again.
    It's barely relevant to what you were trying to argue, and the only way it's relevant to what I wrote is in that it shows one reason why costs per capita don't scale linearly. The facilities in India are not involved with the EU order.

    They're using supply slowly because they're capped in supply. No member state has been capable of matching the UK's progress, or anything close to it, because no member state has the UK's supply.
    Few member states immediately decided to follow the UK's strategy of only partially immunizing high-risk populations.

    No. The Pfizer stock did begin when the UK used it, it existed. If the EU had paid for the same proportion of doses as the UK had - at the same delivery schedule as the UK had - then the weeks the UK was using the Pfizer stock and the EU wasn't then the EU's stockpile would have been building. It wasn't because the EU was tardy at ordering the Pfizer one too.
    I think you're misunderstanding my intent here. My intent was to show the inconsistency that results from your sloppy reasoning wrt stockpiles & supply. Of course, this side discussion concerns the AZN order and not the Pfizer order.

    I'm glad you acknowledge its with some justification.
    It's not an endorsement; it's an acknowledgement that the notion isn't patently absurd. "Not patently absurd" isn't exactly a high bar.

    Absolutely there is a risk of exposure between the interval doses, nobody denies that. However the risk of exposure to the unvaccinated are greater too. So all the more reason to ensure all the vulnerable are protected as fast as possible. It is a sprint to save lives.
    You misunderstand my point. I mentioned the difference in risk of exposure in response to the argument about a delayed second dose leading to a stronger (but not really) response; it means that the marginal utility of a delayed second dose—if we assume there is any utility at all—might be much, much lower than you're banking on. At the individual level, this may pose a particularly great problem for people who are on—or scheduled to begin—treatments that directly affect the immune system in different ways, both wrt the level of protection conferred and wrt the logistic & clinical problems associated with changing timing of those treatments. Whether or not the tradeoff is worthwhile from an epidemic control standpoint is a question that can be looked at through the use of models. It's also relevant to how confident we can be about the efficacy after a single dose in the interval we're discussing. Even without that consideration, our confidence level should be low—for the simple reason that we're extrapolating from a very short period in the trial, with few events, and very few patients in the highest risk groups that are the most relevant from a real world clinical & policy perspective.

    The risk of exposure is real for both the vaccinated and unvaccinated so its not a question as to whether to give someone two vaccines with no opportunity cost, if it was then give the 2 vaccines. The question is whether to give the 2 vaccines to the same people or different people and since the majority of protection comes from dose 1 then giving the majority of protection to double the people > giving full protection to half the people.
    We do not in fact know the things your statement here presupposes that we know.

    Which it is.
    Haven't seen a single model so far that addresses this question. You're welcome to share if you have one.

    How would you change the priority groups if you were not to take the JCVI's advice to get all done by middle of February for the first dose, then start doing the second doses for all of them within 12 weeks of the first?

    For ease of reference the priority groups are

    1: Residents in a care home for older adults and their carers.
    2a: All those over 80
    2b: All frontline health and social care workers
    3: All those over 75
    4a: All those over 70
    4b: The clinically extremely vulnerable individuals.

    All of them are categorised as clinically extremely vulnerable, the latter category means specifically though eg younger adults suffering from cancer undergoing chemeotherapy etc.

    If you're going to reject the JCVI advice, sacrifice half of those in order to give the booster shot to half of them rather than one shot to all of them, then which half would you choose to sacrifice and why?
    Obviously I'd go back in time and order more vaccines and approve them quickly enough to vaccinate everyone, but, barring that, I'd swap out many health- and social-care workers (group 2b) for many people in the clinically extremely vulnerable group.

    Quote Originally Posted by RandBlade View Post
    Yes it does. Evidence is not proof. If there's evidence that the vaccine provides protection at week 3 and week 4 then given everything we know about how vaccines work that is evidence it will be comparable in weeks five and week six. Immunity does not just magically vanish overnight, it doesn't work that way.

    [...]

    We don't know for certain what the level of protection is - but we do have well reasoned evidence. What we do know for certain is the level of protection the unvaccinated get: None whatsoever.
    You're making several mistakes here. 1. For the Pfizer vaccine, the evidence for what the efficacy is at weeks 3 and 4 is weak; we should have very low confidence in any estimates. 2. The evidence for what the efficacy after a single dose is at week 12 is practically non-existent; we should not have any confidence in any estimate of the efficacy. 3. The evidence for what the efficacy is—at any given time but esp. after 12 weeks—for very frail elderly people is weak or non-existent; we should have very low confidence in estimates. 4. Initial immune response is variable, and there is also variation in how that response changes over time. In the 12 week period being discussed, people whose initial immune response was weak may lose much or all of their protection. This is a greater concern among high-risk groups—eg. very frail elderly and younger people who are immunocompromised, for whom we have no meaningful evidence from the studies, and good reason to expect a weaker and less predictable immune response.

    This seems to be the biggest difference between a few of you guys and any of the scientists in the UK I've heard speak on it. You are acting as if the second the trial data ends that is the end of what we know and the end of any protection then that's it - the great unknown and zero there. Whereas the scientists here are using a well-reasoned understanding of what we know about vaccines to extrapolate past the three week window. The PIII trial revealed that immunity was acquired, it won't be gone overnight after that.
    Your characterization is incorrect. Wrt the evidence, I am questioning the soundness of specific arguments and specific interpretations of the Pfizer trial data that underlie their reasoning and extrapolation. My comments on this do not even imply that I believe protection ends the moment you go outside the trial protocol, so your characterization is simply false. It would be fair to say I believe that we cannot have any confidence in estimates of eg. the efficacy when we go so far outside the trial protocol—single dose, 12 weeks, different subjects and a higher risk of exposure & illness. Because the soundness of the strategy being pursued may depend greatly on low-confidence estimates of specific parameters such as efficacy over the period in question, I don't believe you should have a high level of confidence in the soundness of that strategy, absent evidence that estimates of the overall benefit are not particularly sensitive to those key parameters. I am agnostic as to whether or not this strategy will prove to be better from an epidemic control perspective. The AZN trial data is just bad

    We don't have time to test every strategy. We need to make a decision sometimes. This isn't a scientific endeavour, it is real life. We know what the consequences are for not bothering to vaccinate people.[/QUOTE]

    Quote Originally Posted by RandBlade View Post
    Fascinating article with the CEO of AstraZenica. Originally in Italian, I used the Google Translate option in Firefox to read it in England and it is entirely readable: https://www.repubblica.it/cronaca/20...eca-284349061/

    Covers everything we have discussed today it seems.

    [...] to quote a snippet from the interview he is 100% behind and agrees with the three month rollout policy.

    If the first dose alone gives general protection of 71% - 73% (the MHRA said "over 70%" in comparison so it matches) and it lasts for three months then absolutely rolling out to twice as many people is 100% the correct thing to do.

    Let alone a 100% level of protection against hospitalisations.

    If their science is right and the protection is 71% - 73% and therefore potentially tens of thousands of lives are saved by vaccinating 14 million instead of 7 million twice in the first rollout then are you prepared to accept the right thing was done?
    The questions are good but his answers are deeply misleading. You can find the English version here: https://www.repubblica.it/cronaca/20...nes-284349628/

    1. The shortfall is large enough that they should've been able to warn the EU weeks if not months ago. This is irrespective of any "best effort" clause.

    2. The company did ship 4 million doses to the UK in 2020, from their continental facilities—presumably constituting almost all of the doses that were made available to the UK at that stage.

    3. The "no profit" stipulation in their contract only covers the duration of the pandemic, which they may call as early as July. The claim re. costs being $3-4 for pretty much everyone should be viewed with skepticism in light of the leaked info from a Belgian minister whose role should put her in a position to know what they're paying. According to that info, the EU is paying around $2.2, whereas other sources have reported the UK as paying around $4.1. So, if both are at no profit, then costs must vary immensely.

    4. He is being dangerously misleading about the trial evidence and what they say about efficacy in the elderly. Putting aside previously articulated concerns about the haphazard approach to their trials, the interim analysis to which he refers has a very small proportion of subjects in age groups at truly high risk of developing severe illness—the frail elderly. An assertion that delaying a second dose is a good idea because these data show "100%" protection from severe illness is simply meaningless—the vast, overwhelming majority of subjects in those trials have a very low risk of developing severe illness to begin with. Similarly, his overconfident claims about the quantified immune response are not persuasive—lab values don't translate predictably to clinical effect, and there were very few very old subjects in the single dose group. The one thing you can say is that at least they've attempted—however sloppily—to study that regimen, unlike Pfizer, for whose vaccine you do not have similar justification for delaying the second dose by over two months. This is also something I mentioned when we first began discussing the delayed dose strategy for the Pfizer vaccine.

    Quote Originally Posted by RandBlade View Post
    The EUAs were granted because the placebo controlled RCT showed the vaccines were safe and efficacious. After that it becomes a question of how best to use it.
    Efficacy is affected by how it is used. What you're saying here is equivalent to saying, "The EUAs were granted because the placebo controlled RCT showed the vaccines were safe and efficacious. After that it becomes a question of whether or not to use it safely and effectively," because one of the possibilities here is that you'll be using eg. the Pfizer vaccine in a way that is considerably worse than the tested protocol.

    This change is based on evidence that it works.

    We know for a fact that supply is the constraining factor.

    We know for a fact that the choice is 2 doses for half as many people, or single doses for now for twice as many people, since all supply is being used.

    We know from the data that exists that a single dose works after a fortnight with a Confidence Interval over a 50% from one dose which means that twice many people getting one dose provides more community protection than 2 doses for half as many people.

    We don't know that a reduced dosage at each dosage works. We don't know that mix and match vaccines works, which is why its only authorised as a last resort if it is necessary for operation reasons but is not recommended.
    We have more evidence to support a half-dose regimen for the AZN vaccine than to support a 12 week delay for the second dose of the Pfizer vaccine. It's bad quality evidence in both cases, and nearly inapplicable to very old and frail subjects.
    “Humanity's greatest advances are not in its discoveries, but in how those discoveries are applied to reduce inequity.”
    — Bill Gates

  29. #2549
    Would like to commend Aimless and wig for their patience.
    You've been waiting for the truth to come find you
    Are you speaking for yourself or your pain? Do you sleep in the silence to wane the passing shame?
    You are more than what your history made you, let the ghosts of our fathers pass on.
    There's a new dawn to come when the past mistakes are gone

  30. #2550
    Quote Originally Posted by Steely Glint View Post
    Would like to commend Aimless and wig for their patience.
    Tbf RB should be commended for his patience with a discussion that is utterly meaningless but slapped right in the face with a trout for his sloppy reading and also for other reasons.
    “Humanity's greatest advances are not in its discoveries, but in how those discoveries are applied to reduce inequity.”
    — Bill Gates

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