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Thread: covid-19

  1. #2491
    It's not about charts it's about doing what's best. The evidence is that more people is far, far superior to two doses for half as many people.

    But it wouldn't affect the charts anyway. The charts are reporting total doses given, they're not segregated into total people. If double doses were given to half as many people that would be no difference whatsoever in the charts since total doses would be identical.

    So does that put your mind at ease at all?
    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. #2492
    I'm not sure it does. It -should- be about doing what's best and not the charts, I agree. But this is Boris Johnson.

    Which evidence are you referring to?

    Given that the BMA express reservations, the WHO say 4 weeks, very few other countries are doing what we're doing, and I believe that it's essential for Johnson to beat the EU in terms of raw vaccination doses, you'll understand why I have my concerns. Everyone should, tbh.

  3. #2493
    Grant Shapps faces fury over mass Covid outbreak at DVLA

    Minister under fire for ‘shameful’ virus spread as staff told to work on with more than 500 cases at agency in Swansea

    Ministers are at the centre of an explosive row over their failure to protect workers from Covid-19 as the Observer reveals the largest workplace outbreak of the virus has taken place at a top government organisation.

    More than 500 cases have been recorded at the Driver and Vehicle Licensing Agency’s offices in Swansea, where employees claim people with symptoms were encouraged to return to work while vulnerable workers have had requests to work from home turned down.

    The revelation places the transport secretary, Grant Shapps, under pressure to explain how such an outbreak could have happened in an agency where the strictest workplace rules are supposed to apply.

    A complaint received by Public Health Wales’s outbreak control team claims DVLA workers were asked to turn off their test-and-trace apps “so that their phones do not ping”.

    It also says absences relating to Covid have been counted against workers’ sick leave, with anything over 10 days triggering a warning.

    About 1,800 staff are being asked to come into the DVLA to process driving licence applications and vehicle tax renewals, even though there have been 535 Covid cases since September – by far the most infections linked to a single employer in a local area.

    The DVLA insisted safety was a priority: “Staff in roles that enable them to work from home are doing so and have throughout, in line with current government advice. However, in view of the essential nature of the public services we provide, some operational staff are required to be in the office where their role means they cannot work from home.”

    The Department for Transport said it was confident in the “rigorous processes” the DVLA has in place. During the first national lockdown only 250 workers were needed onsite.

    The Hazards Campaign, a workplace safety network, which has been monitoring in-work outbreaks, said it was shameful that a government agency was responsible for the largest known employee outbreak of coronavirus infection in the UK.

    “It is absolutely shocking that the DVLA has overseen the biggest reported workplace outbreak. These workers should have been working remotely, not being packed into offices. They have been put at risk of death and long-term ill health – and the outbreak is still going on,” said Janet Newsham from the campaign. “The DVLA’s actions may also have spread the virus in Swansea.”

    The Public and Commercial Services Union, which represents DVLA staff, said many workers were scared to enter the agency’s three offices in the city. The union’s general secretary, Mark Serwotka, called on Shapps to step in.

    “It is a scandal that DVLA are not doing more to reduce numbers,” he said. “Ministers must intervene and ensure DVLA are doing their utmost to enable staff to work from home and temporarily cease non-critical services.” Just before the DVLA outbreak began in September, Shapps encouraged workers to return to offices, insisting “it is now safe to go back to work”.

    Sian Hughes, who works in the 16-storey DVLA head office, said most people wanted to work at home. “We are all worried. We are all scared,” she said. “Lots and lots of people have been ill. We have had staff in hospital. We are just waiting for the first death. It’s that bad.”

    Hughes, who asked not to use her real name as she fears repercussions, said there were about 120 people on every floor of the building. “On each floor there are only two sets of toilets: ladies and gents. There are four kitchens on each floor too. All the teams are sharing the facilities – it’s high risk,” she said. “There are cases on every floor now.”

    The scale of the outbreak has made people wary of DVLA staff, who sometimes have to catch three of four buses to get into work from across south Wales. “People will not go into local shops if DVLA staff are there because they are scared of catching it from us,” Hughes said. Workers have also been forced to stay away from their extended families. “I have family I have been unable to visit because I work in DVLA,” Hughes said.

    Lots of staff are off sick with stress, with many scared they will lose their jobs if they don’t come back. “There are so many suffering with extreme stress,” she added. “But they know they are going to get a warning because they have been off so long.”

    The DVLA contact centre, where hundreds of workers deal with thousands of calls from motorists every day, has been hit hard by the outbreak, with about 160 cases identified.

    Jim Lewis – also a pseudonym – said the virus had ripped through the centre after the first cases emerged in September. “It actually started in my zone,” he said. “It just spread like wildfire. Loads have tested positive. More than I can count.”

    Lewis, who has had to self-isolate six times, said contact centre staff were not able to wear masks and were sitting close together. “We sit back-to-back, just one metre apart,” he said. “They say ‘the two-metre rule only applies if you’re face to face’.”

    The initial results of a survey of more than 700 Swansea DVLA workers by Prof Phil Taylor of the University of Strathclyde reveals nearly 70% are less than two metres from those seated in front of them and just over 20% are less than two metres from colleagues seated next to them.

    Many of the workers travel into the offices from Swansea’s commuter belt. Tonia Antoniazzi, MP for Gower, said she had been inundated with messages from desperate DVLA staff. “I’m being bombarded by people telling me how awful it is,” she said. “But there is a culture of fear. People are scared to speak out.”

    She added the DVLA’s IT system was so out of date that people couldn’t work from home. “The system is archaic,” she said. “Lack of investment from the government has caused this problem.”

    The outbreak may have led to more infections in the Swansea Bay area, where there have been in excess of 26,000 cases and 828 Covid deaths during the pandemic. “DVLA is a massive employer and Swansea is densely populated,” said Antoniazzi. “It is a major contributing factor to the spread of Covid.”

    ...
    Pretty shocked to read this.

    Pathetic.
    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.

  4. #2494
    . . . why are people in a call-center not clear examples of who should be working from home?

    Nvm, they have an "outdated" system and couldn't be arsed to work out alternatives the way the private sector was required to. Next question: why does a driving-licensing/registration agency need a 16-story main office? Are they the center for all of Wales? Because their space and manpower requirements seem kinda high for just the greater Swansea area.
    Last night as I lay in bed, looking up at the stars, I thought, “Where the hell is my ceiling?"

  5. #2495
    It's for the whole UK.
    So may your dreams be monumental when your spirit guides the way
    Within in the flicker of a candle, I will heal your soul's decay
    We share a fate, trapped on a page, by the author of our world's demise

  6. #2496
    Yep all car registrations and administration thereof, and all driving licence applications and administration thereof, for the whole of the UK, are all undertaken by the DVLA's offices in Swansea. A sizeable operation.
    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.

  7. #2497
    Ok, that makes sense. But then it seems, again, that the vast majority of the work being done there is something that should be possible to do remotely. Maybe I'm being American here, with a different sense of scale, but most face-to-face interactions would be taking place at satellite offices throughout the UK, right? Drivers in the UK would rarely have to go to Swansea to take care of things on their end?
    Last night as I lay in bed, looking up at the stars, I thought, “Where the hell is my ceiling?"

  8. #2498
    Yeah we have Post Offices for face to face stuff. Nobody actually goes to the DVLA. It's just this mythical place in Swansea you hope you never get a letter from.

  9. #2499
    Unless you lost your driving license and need a replacement. Then you want a letter from Swansea, but in all other circumstances a letter from Swansea is bad.
    So may your dreams be monumental when your spirit guides the way
    Within in the flicker of a candle, I will heal your soul's decay
    We share a fate, trapped on a page, by the author of our world's demise

  10. #2500
    Quote Originally Posted by LittleFuzzy View Post
    Ok, that makes sense. But then it seems, again, that the vast majority of the work being done there is something that should be possible to do remotely. Maybe I'm being American here, with a different sense of scale, but most face-to-face interactions would be taking place at satellite offices throughout the UK, right? Drivers in the UK would rarely have to go to Swansea to take care of things on their end?
    Not impossible but possibly extremely difficult to set wfh-arrangements up for so many people while maintaining security and adequate performance for all the interacting systems—esp. under budget & IT personnel constraints. Sure, some sort of compromise could probably have been cobbled together for many employees, but not a trivial challenge. For comparison, my wife's been wfh for the past few months, and she still has to go in from time to time because some aspects of her job requires physically taking paper from one place to another; and much of what she works with has to be physically scanned in by someone else.
    “Humanity's greatest advances are not in its discoveries, but in how those discoveries are applied to reduce inequity.”
    — Bill Gates

  11. #2501
    Quote Originally Posted by Timbuk2 View Post
    Pretty shocked to read this.

    Pathetic.
    A local council in southern Sweden has banned the use of face masks in schools because they believe it's important that people feel safe.
    “Humanity's greatest advances are not in its discoveries, but in how those discoveries are applied to reduce inequity.”
    — Bill Gates

  12. #2502
    Expect this will be one of the biggest stories of the week:

    https://www.reuters.com/article/us-h...-idUSKBN29R2I9

    AZN released a statement on Friday saying they wouldn't be able to deliver the contractually stipulated number of doses of their vaccine for the first period. A senior EU official has indicated that the shortfall is around 60%. Under the agreement that was concluded last year, AZN was to reserve production capacity for the EU's order, to ensure there would be a certain number of doses ready to be shipped as soon as the vaccine was approved. A shortfall of tens of millions of doses mere weeks before they're due to be delivered suggests either fuckery or an extraordinary—and deadly—fuckup.
    “Humanity's greatest advances are not in its discoveries, but in how those discoveries are applied to reduce inequity.”
    — Bill Gates

  13. #2503
    Not sure what fuckery you're seeing Aimless. All companies have had the same issues, it's a difficult thing to produce. Pfizer had the exact same issue too and the UK's own supplies have been limited as a result too.

    All countries signing deals have reserved production capacity as a result that is the entire point, but if the capacity isn't there due to production limitations then it just isn't there. A problem the EU has is that other countries production reserves can be coming before your production reserves due to the agreements signed. Hopefully production capacity will be at 100% ASAP.



    UK passed doses equivalent to 10% of the population. Again for the benefit of Gogo all charts report doses not people so this is first and second doses combined it doesn't alter the chart doing one or the other - and the UK is still doing some second doses every day for various clinical or operational reasons.
    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. #2504
    Quote Originally Posted by RandBlade View Post
    Not sure what fuckery you're seeing Aimless. All companies have had the same issues, it's a difficult thing to produce. Pfizer had the exact same issue too and the UK's own supplies have been limited as a result too.

    All countries signing deals have reserved production capacity as a result that is the entire point, but if the capacity isn't there due to production limitations then it just isn't there. A problem the EU has is that other countries production reserves can be coming before your production reserves due to the agreements signed. Hopefully production capacity will be at 100% ASAP.
    If you're supposed to be able to deliver 80 million vaccines over the course of two months, and then announce a week before that period begins that you'll be delivering less than half of that, you've probably fucked up. They must've—or should've—known they would not meet that target months ago—it can't be the result of a recent and unforeseen hickup. Pfizer's delay is different—they're in the process of greatly boosting capacity, whereas AZN is ascribing their shortfall to "reduced" yields. This is politically fraught because, in early December, AZN claimed they would use excess capacity at their continental manufacturing facilities to fulfill their UK orders—to the tune of at least 4 million doses—until their UK facilities were up and running.
    Last edited by Aimless; 01-25-2021 at 11:21 AM.
    “Humanity's greatest advances are not in its discoveries, but in how those discoveries are applied to reduce inequity.”
    — Bill Gates

  15. #2505
    You're wrong. Pfizer have repeatedly delayed, not just the current announcement but back in November or December they announced a major delay in output too. The manufacturing comes with a very complex supply chain and a very rigorous clinical testing - and if anything in that chain goes wrong then that will set back supplies. Pfizer have repeatedly announced reduced yields too, you probably just didn't notice it because it was before the EU gave approval to the Pfizer vaccine.

    The EU still haven't even approved the AZN vaccine anyway. Many vaccine companies said all along they'd send vaccines to the countries they were authorised for, because that saves lives and there's no lives saved by the vaccine sat idle awaiting approval. If the EU wants to start using the AZN vaccine the first step would be to grant emergency authorisation.

    In related news an interesting article.
    https://www.ft.com/content/c9bbc753-...6-dd97a7c4b807

    Stunning chart.


    As I've said before saving pennies on a vaccine during a pandemic is an absolute false economy and the EU is reaping what it sowed in not investing in vaccines properly. 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. Which will economically cost much, much more.

    The UK government, Rishi Sunak, the US government etc have invested in vaccine procurement and development and now it is paying off. The UK has spent nearly 6x the price all-in than the EU but has now rolled out more than 10 doses per 100 population, the EU have saved money and spent about 1/6th the total cost but have rolled fewer than 2 doses per 100 population.
    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. #2506
    Quote Originally Posted by RandBlade View Post
    You're wrong. Pfizer have repeatedly delayed, not just the current announcement but back in November or December they announced a major delay in output too. The manufacturing comes with a very complex supply chain and a very rigorous clinical testing - and if anything in that chain goes wrong then that will set back supplies. Pfizer have repeatedly announced reduced yields too, you probably just didn't notice it because it was before the EU gave approval to the Pfizer vaccine.
    I don't believe Pfizer has announced anything remotely comparable to a 50-million-dose deficit that should've been on their radar for months, but you're welcome to provide an example.

    The EU still haven't even approved the AZN vaccine anyway. Many vaccine companies said all along they'd send vaccines to the countries they were authorised for, because that saves lives and there's no lives saved by the vaccine sat idle awaiting approval. If the EU wants to start using the AZN vaccine the first step would be to grant emergency authorisation.
    They are nevertheless contractually obliged to have a certain number of doses stocked and ready to ship upon arrival. This is essential to ensuring a steady, reliable supply throughout the deployment. A much larger deployment such as the EU's will require a much larger stock, which will require more time to build up. Failing to meet that requirement will disrupt vaccination in many countries, risking the lives of their citizens.

    In related news an interesting article.
    https://www.ft.com/content/c9bbc753-...6-dd97a7c4b807

    Stunning chart.
    Stunningly misleading chart. Drug development costs don't scale linearly with the number of end users, and the same goes for procurement and production. If I'm developing a hypertension drug, do you believe it would cost me 10 times as much per dose to develop and produce that drug for an expected market of 100 million users than it would cost me to develop that same drug for an expected market of 10 million users? The EU has a much larger population than the UK; I would expect their per capita development and production costs to be much lower, all else being equal. The US is a much more interesting comparator, but I expect their numbers are somewhat skewed by higher negotiated cost per dose for those companies that have participated in Operation Warp Speed.

    As I've said before saving pennies on a vaccine during a pandemic is an absolute false economy and the EU is reaping what it sowed in not investing in vaccines properly. 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. Which will economically cost much, much more.
    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.

    The UK government, Rishi Sunak, the US government etc have invested in vaccine procurement and development and now it is paying off. The UK has spent nearly 6x the price all-in than the EU but has now rolled out more than 10 doses per 100 population, the EU have saved money and spent about 1/6th the total cost but have rolled fewer than 2 doses per 100 population.
    This recalls another recent discussion where you jumped to nonsensical conclusions trying to connect unrelated things. The UK's vaccination rate is almost completely due to their earlier authorization and less demanding supply requirements.
    “Humanity's greatest advances are not in its discoveries, but in how those discoveries are applied to reduce inequity.”
    — Bill Gates

  17. #2507
    Quote Originally Posted by Aimless View Post
    I don't believe Pfizer has announced anything remotely comparable to a 50-million-dose deficit that should've been on their radar for months, but you're welcome to provide an example.
    Pfizer were supposed to delivery 10 million doses to the UK by the end of December 2020. They were still quoting that figure in November.

    In December that suddenly became reduced by half: https://inews.co.uk/news/uk/pfizer-v...plained-782813

    It happens. All companies have experienced similar, AZN are just the most recent to do it.
    They are nevertheless contractually obliged to have a certain number of doses stocked and ready to ship upon arrival. This is essential to ensuring a steady, reliable supply throughout the deployment. A much larger deployment such as the EU's will require a much larger stock, which will require more time to build up. Failing to meet that requirement will disrupt vaccination in many countries, risking the lives of their citizens.
    If the stock doesn't exist, the stock doesn't exist. Its a complicated procedure to generate it and all companies are struggling with that.
    Stunningly misleading chart. Drug development costs don't scale linearly with the number of end users, and the same goes for procurement and production. If I'm developing a hypertension drug, do you believe it would cost me 10 times as much per dose to develop and produce that drug for an expected market of 100 million users than it would cost me to develop that same drug for an expected market of 10 million users? The EU has a much larger population than the UK; I would expect their per capita development and production costs to be much lower, all else being equal. The US is a much more interesting comparator, but I expect their numbers are somewhat skewed by higher negotiated cost per dose for those companies that have participated in Operation Warp Speed.
    That's ridiculous. So you think the EU can free-ride by investing less? Of course during a bloody pandemic when you're trying to go hell for leather to just get it done it costs more - and part of what the UK has spent its money on is investing in domestic manufacturing for the AZN vaccine, as much of AZN's manufacturing capability was previously located in India - and as expected India have put a ban on exporting the vaccine manufactured in India out of the country.

    If you want to build up manufacturing capability for 446 million then yes that will scale with the costs for 67 million, unless you choose to penny pinch or go slower.
    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.
    Yes there is, you're just turning a blind eye to it.
    This recalls another recent discussion where you jumped to nonsensical conclusions trying to connect unrelated things. The UK's vaccination rate is almost completely due to their earlier authorization and less demanding supply requirements.
    Bullshit. The UK has spent roughly 6x the amount per capita, delivered roughly 6x the vaccine doses per capita - but its all because we had earlier authorisation? Bullshit.

    Why didn't the EU authorise too then? Why haven't they been able to catch up? Why have the UK accelerated in vaccine rollout, with a smidgen under 500,000 doses distributed our daily figure yesterday whereas the EU countries that started quickly have had to slow down because they've ran out of supply?
    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. #2508
    Quote Originally Posted by RandBlade View Post
    It's not about charts it's about doing what's best. The evidence is that more people is far, far superior to two doses for half as many people.

    But it wouldn't affect the charts anyway. The charts are reporting total doses given, they're not segregated into total people. If double doses were given to half as many people that would be no difference whatsoever in the charts since total doses would be identical.

    So does that put your mind at ease at all?
    RB, I can't emphasize enough how the evidence doesn't demonstrate that at all. We don't know how 1 dose vs. 2 doses will work because we haven't tested it. And the early data about efficacy in the 14-21 or 14-28 day range for the phase 3 trials was underpowered. In much larger surveillance trials Israel released last week during their rollout, it looks like clinical efficacy is on the order of 50% between the first and second dose - certainly a big improvement, and already reaping results there wrt hospitalizations - but far from the 90% number people were talking about on the basis of low power tightly controlled studies. And we haven't even talked about the many other assumptions that need to be questioned when making declarative statements about 'X is far superior to Y' when there is precious little proof.

    And I don't get your focus on one specific chart here, countries are reporting both doses administered (because there's a fixed cost in time/personnel in dose administration) as well as number of people who are fully vaccinated. Trying to manage one of those numbers without the other seems silly.

    Quote Originally Posted by RandBlade View Post
    You're wrong. Pfizer have repeatedly delayed, not just the current announcement but back in November or December they announced a major delay in output too. The manufacturing comes with a very complex supply chain and a very rigorous clinical testing - and if anything in that chain goes wrong then that will set back supplies. Pfizer have repeatedly announced reduced yields too, you probably just didn't notice it because it was before the EU gave approval to the Pfizer vaccine.
    You're right in some ways, wrong in others. Certainly we should expect there to be challenges with the rapid scaleup of vaccine production; it has actually been surprisingly smooth across the different manufacturers all things considered, and the stated delays for Pfizer (and the much more substantial one for AZN) are not terribly surprising.

    That being said, it does seem like AZN has made multiple key missteps during the development of this vaccine. Most egregious in my mind is how they executed the clinical trials, and their overall clinical trial strategy. They clearly also overpromised and underdelivered for the initial rollout phase; it's still not clear to me exactly what went wrong at Novasep but the question is how early they could have determined a realistic assessment of expected yields and whether they could have provided better forward guidance. Even if they were as upfront as possible with their timing, one might also question if their mfg process has been as carefully managed as possible, there's all sorts of risk analysis that goes into this kind of thing to prevent exactly this kind of scenario. It doesn't always work out, but my confidence in their internal processes has been shaken.

    This doesn't detract from your main point, that much of Europe has not been as aggressive on securing diverse and robust vaccine supplies as early as possible; in the poor world it's entirely understandable for countries to economize and wait a bit, but Europe doesn't have this excuse.



    The more I think about this, the more I think JNJ is going to come out of this looking really good. They realized that speed is not as critical as thoroughness, and they took the time to develop a more temperature stable vaccine that they think will work with one dose (and based on a better understood mechanism), and they're only running about 6 weeks behind the fastest mover. They have large scale mfg lined up *and* have a very solid clinical trial design that allows them to hedge their bets on dosing. The Moderna/Pfizer efforts were amazing and I think that vector strategy is going to be a very important part of our toolbox for future pandemics given the speed with which they can be developed and modified... but they're nightmares for distribution and only work well in the rich, urban world. JNJ has been very, very smart.
    "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. #2509
    Quote Originally Posted by wiggin View Post
    RB, I can't emphasize enough how the evidence doesn't demonstrate that at all. We don't know how 1 dose vs. 2 doses will work because we haven't tested it. And the early data about efficacy in the 14-21 or 14-28 day range for the phase 3 trials was underpowered. In much larger surveillance trials Israel released last week during their rollout, it looks like clinical efficacy is on the order of 50% between the first and second dose - certainly a big improvement, and already reaping results there wrt hospitalizations - but far from the 90% number people were talking about on the basis of low power tightly controlled studies. And we haven't even talked about the many other assumptions that need to be questioned when making declarative statements about 'X is far superior to Y' when there is precious little proof.
    Sorry wiggin I normally respect and agree with almost everything you say but on this one I have to disagree. It isn't 1 dose vs 2 doses, it is 1 dose to twice as many people vs 2 doses to half as many people - and there is an abundance of evidence on that.

    This Professor who sits on the JCVI that made the decision (it was scientists on the JCVI that decided it, not Johnson or the UK Government, which gogo seems to forget) but speaking in a personal capacity put it well on the radio earlier, especially his final remarks.
    Last edited by RandBlade; 01-25-2021 at 04:34 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. #2510
    Quote Originally Posted by RandBlade View Post
    This Professor who sits on the JCVI that made the decision (it was scientists on the JCVI that decided it, not Johnson or the UK Government, which gogo seems to forget)
    I didn't forget. I didn't know.

    But what you're describing seems to contradict the JCVI's code of practice.
    https://assets.publishing.service.go...13_-_final.pdf

    Their ToR states:

    "To advise UK health departments on immunisations for the prevention of infectionsand/or disease following due consideration of the evidence on the burden of disease,on vaccine safety and efficacy and on the impact and cost effectiveness ofimmunisation strategies. To consider and identify factors for the successful andeffective implementation of immunisation strategies. To identify important knowledgegaps relating to immunisations or immunisation programmes where further researchand/or surveillance should be considered."

    It also states:

    "JCVI provides advice and recommendations as described in the terms of reference(see earlier) based on consideration of scientific and other evidence (see later) that isused by Government to inform, develop and make policy. JCVI is not a policy maker inits own right and has no regulatory function"

    Has their ToR changed?

  21. #2511
    Quote Originally Posted by RandBlade View Post
    Sorry wiggin I normally respect and agree with almost everything you say but on this one I have to disagree. It isn't 1 dose vs 2 doses, it is 1 dose to twice as many people vs 2 doses to half as many people - and there is an abundance of evidence on that.

    This Professor who sits on the JCVI that made the decision (it was scientists on the JCVI that decided it, not Johnson or the UK Government, which gogo seems to forget) but speaking in a personal capacity put it well on the radio earlier, especially his final remarks.
    He's speculating, I don't understand why you think this is some sort of slam dunk.

    You're right to say we don't know how much protection one dose alone before the booster gives, some reports suggest that after two weeks after initial vaccination "over 50%" is the level of protection the lowest, while others at the highest report 89%, reality is likely somewhere in-between (and the data from Israel does suggest significantly over 50% more than two weeks after initial vaccination if not 89%). So being conservative and putting a confidence interval of 50% to 89% then one dose to twice as many people gives more community protection than two doses to half as many people. Unless one dose protection is below 50% that is a mathematical truism.
    No, we have data on weeks 3 and 4 that range from about 30% to about 90%, with the lower estimates consistently coming from larger studies in a real life context. We don't know squat about weeks 5-12, nor do I have any confidence that that week 12 won't be fudged a bit as well.

    You also don't understand the sheer complexity of immunology. Maybe you can make some sort of linear back of the envelope extrapolations that you're making, but chances are that you can't. It's not like you have perfect immunity vs. no immunity, there's a continuum. And maybe a single dose means you have a lower chance of hospitalization than no dosing but a higher chance than 2 doses; maybe a single dose means you are more likely to have higher viral loads even if you're asymptomatic, contributing to community spread. Maybe complex factors associated with the vector and where/when it's displayed means that certain types of immunity are more prevalent than others during altered dosing regimes (e.g. mucosal vs. humoral, different tissues, different cell types). You don't know, and anyone who suggests they do is deceiving themselves.

    I think that one can reasonably speculate that in a supply constrained environment this strategy might work. I'm not disputing the underlying logic might be sound. But one could also reasonably speculate based on lab studies and such that a given vaccine might only need one dose, or that you can lower the dose and get a good result. The reason we have clinical trials is to test specific doses and dose frequencies that seem to be most efficacious (based on our best guesses, bench work, and early phase trials). We might be wrong - there might be a better strategy we haven't tested yet. But it's absolutely certain that there are a lot of also reasonable-sounding strategies that are worse and we haven't tested them either; how to determine which untested strategy is the winner? We only know what we've tested, everything else is at best informed speculation.

    You know the worst part about this? We're probably never going to know the answer to this question because the data out of the UK strategy is going to be a mess and we won't have adequate controls.
    "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)

  22. #2512
    Quote Originally Posted by wiggin View Post
    He's speculating, I don't understand why you think this is some sort of slam dunk.
    Yes it is speculation, but it is very well informed and reasoned speculation that could and should save tens of thousands of lives.
    No, we have data on weeks 3 and 4 that range from about 30% to about 90%, with the lower estimates consistently coming from larger studies in a real life context. We don't know squat about weeks 5-12, nor do I have any confidence that that week 12 won't be fudged a bit as well.
    All evidence I've seen shows in week 3 well over 50%. I'd be curious to see any evidence for as low as 30%. But if it is over 50% then that is a slam dunk.
    You also don't understand the sheer complexity of immunology. Maybe you can make some sort of linear back of the envelope extrapolations that you're making, but chances are that you can't. It's not like you have perfect immunity vs. no immunity, there's a continuum. And maybe a single dose means you have a lower chance of hospitalization than no dosing but a higher chance than 2 doses; maybe a single dose means you are more likely to have higher viral loads even if you're asymptomatic, contributing to community spread. Maybe complex factors associated with the vector and where/when it's displayed means that certain types of immunity are more prevalent than others during altered dosing regimes (e.g. mucosal vs. humoral, different tissues, different cell types). You don't know, and anyone who suggests they do is deceiving themselves.
    All evidence so far shows lower viral load and lower hospitalisations, over 50% lower, from a single dose. So again vaccinating twice as many people should entail more reduction in viral load.
    I think that one can reasonably speculate that in a supply constrained environment this strategy might work. I'm not disputing the underlying logic might be sound. But one could also reasonably speculate based on lab studies and such that a given vaccine might only need one dose, or that you can lower the dose and get a good result. The reason we have clinical trials is to test specific doses and dose frequencies that seem to be most efficacious (based on our best guesses, bench work, and early phase trials). We might be wrong - there might be a better strategy we haven't tested yet. But it's absolutely certain that there are a lot of also reasonable-sounding strategies that are worse and we haven't tested them either; how to determine which untested strategy is the winner? We only know what we've tested, everything else is at best informed speculation.
    Informed speculation is the best we have. This isn't a clinical authorisation it is an emergency authorisation and informed speculation, so long as there is a good enough justification and evidence is sufficient for an emergency use authorisation. That's the difference between clinically approved and EUA and the UK is operating on the principle of EUA.
    You know the worst part about this? We're probably never going to know the answer to this question because the data out of the UK strategy is going to be a mess and we won't have adequate controls.
    What controls do you want? Do you want a placebo for half so half aren't vaccinated? That's precisely what we are seeking to avoid. This isn't a trial, except it might help inform Phase IV data, it is real life.
    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.

  23. #2513
    Quote Originally Posted by RandBlade View Post
    Pfizer were supposed to delivery 10 million doses to the UK by the end of December 2020. They were still quoting that figure in November.

    In December that suddenly became reduced by half: https://inews.co.uk/news/uk/pfizer-v...plained-782813

    It happens. All companies have experienced similar, AZN are just the most recent to do it.
    I thought we'd share a common understanding about 50 million and 5 million differing by an order of magnitude, but apparently not.

    If the stock doesn't exist, the stock doesn't exist. Its a complicated procedure to generate it and all companies are struggling with that.
    The point is that they should've known months ago that they would not meet that target, and they should've notified the EU then—not a mere week before they're supposed to begin shipping.

    That's ridiculous. So you think the EU can free-ride by investing less?
    Perhaps you can re-read what I actually said?

    Of course during a bloody pandemic when you're trying to go hell for leather to just get it done it costs more - and part of what the UK has spent its money on is investing in domestic manufacturing for the AZN vaccine, as much of AZN's manufacturing capability was previously located in India - and as expected India have put a ban on exporting the vaccine manufactured in India out of the country.
    This is not particularly relevant to what I wrote.

    If you want to build up manufacturing capability for 446 million then yes that will scale with the costs for 67 million, unless you choose to penny pinch or go slower.
    So I see you're back to doing that stupid thing where you respond without reading. Let's go through what I wrote:

    Drug development costs don't scale linearly with the number of end users, and the same goes for procurement and production.
    Oh, look, there's an important word there that you missed. Now that I have pointed it out to you, perhaps you can try again?

    Yes there is, you're just turning a blind eye to it.
    You're welcome to provide evidence for that connection. You haven't yet. Do you know how to tie cause and effect together using logically sound factual arguments? I ask because you did something similarly stupid during our exchange about the role of the media, so it's beginning to look like a pattern with you.

    Bullshit. The UK has spent roughly 6x the amount per capita, delivered roughly 6x the vaccine doses per capita - but its all because we had earlier authorisation? Bullshit.
    There is no indication that your higher vaccination rates can be ascribed to any meaningful extent to your higher spending. You authorized your vaccines earlier, and started vaccinating before other countries, ramping up quickly. Your supply requirements are, of course, also far lower than the EU's. To the extent that your higher rates can be ascribed to spending, one might argue that your spending on the NHS may have contributed to that. But your vaccine-specific spending has been less relevant. Moving forward, your spending on the facility in Wales—for example—will be critical to sustaining your vaccination rates over time; the EU, fortunately, already has several facilities producing vaccines, so that additional expenditure was not required.

    Why didn't the EU authorise too then? Why haven't they been able to catch up? Why have the UK accelerated in vaccine rollout, with a smidgen under 500,000 doses distributed our daily figure yesterday whereas the EU countries that started quickly have had to slow down because they've ran out of supply?
    The EU's expert authority decided they needed more time and more information. Whatever you may feel about that decision, it is not a political decision. Delays in individual EU countries are attributable to country-specific issues, so you'll need to look at each specifically. Countries like Denmark have had to slow down for a number of reasons, one of which may be supply constraints—but you've already argued quite persuasively that unforeseen supply constraints can arise no matter what—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.
    “Humanity's greatest advances are not in its discoveries, but in how those discoveries are applied to reduce inequity.”
    — Bill Gates

  24. #2514
    Quote Originally Posted by gogobongopop View Post
    I didn't forget. I didn't know.

    But what you're describing seems to contradict the JCVI's code of practice.
    https://assets.publishing.service.go...13_-_final.pdf

    Their ToR states:

    "To advise UK health departments on immunisations for the prevention of infectionsand/or disease following due consideration of the evidence on the burden of disease,on vaccine safety and efficacy and on the impact and cost effectiveness ofimmunisation strategies. To consider and identify factors for the successful andeffective implementation of immunisation strategies. To identify important knowledgegaps relating to immunisations or immunisation programmes where further researchand/or surveillance should be considered."

    It also states:

    "JCVI provides advice and recommendations as described in the terms of reference(see earlier) based on consideration of scientific and other evidence (see later) that isused by Government to inform, develop and make policy. JCVI is not a policy maker inits own right and has no regulatory function"

    Has their ToR changed?
    No. They've informed that the appropriate policy would be to do this strategy. The NHS and the government could accept or reject the JCVI's advice. The 4 nations Chief Medical Officers all unanimously recommended accepting their advice. The four nations governments who are regulatory all did.

    Technically any of the four governments could have rejected the JCVIs advice since it is only advice not regulation. They have not.
    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.

  25. #2515
    Quote Originally Posted by RandBlade View Post
    This Professor who sits on the JCVI that made the decision (it was scientists on the JCVI that decided it, not Johnson or the UK Government, which gogo seems to forget) but speaking in a personal capacity put it well on the radio earlier, especially his final remarks.
    It's not only a question of logic and first principles. This is a complex problem, and ad hoc strategies to deal with it should at least be modeled under a wide range of conservative assumptions—for each vaccine candidate. Whether this strategy is better from a strict epidemic control perspective will depend on the strength and duration of the primary response, size and variability in reproduction numbers in various settings and contexts, the stage of the pandemic at which it's deployed, and—of course—uptake. On top of this, there are theoretical—but not unfounded or trivial—concerns from immunological and virological perspectives, but those are much more difficult to assess—even for the various experts who are giving over-confident assurances. It's possible that the greater transmissibility of the UK lineage shifts the balance in favour of vaccinating more people with a first dose, but, again, that hunch should be modeled—esp. in light of unsurprising evidence of lower efficacy in live deployment.

    What we need to know is what efficaciousness is from 2-3 weeks onwards from one dose alone and the UK body of evidence so far is at least 70% and upto 89% which puts is in the realm of real net protection of over 3 million to nearly 6 million extra people by following this dosing regime.
    I suspect you're not appreciating just how limited that "body of evidence" as you call it really is.
    “Humanity's greatest advances are not in its discoveries, but in how those discoveries are applied to reduce inequity.”
    — Bill Gates

  26. #2516
    Quote Originally Posted by Aimless View Post
    It's not only a question of logic and first principles. This is a complex problem, and ad hoc strategies to deal with it should at least be modeled under a wide range of conservative assumptions—for each vaccine candidate. Whether this strategy is better from a strict epidemic control perspective will depend on the strength and duration of the primary response, size and variability in reproduction numbers in various settings and contexts, the stage of the pandemic at which it's deployed, and—of course—uptake. On top of this, there are theoretical—but not unfounded or trivial—concerns from immunological and virological perspectives, but those are much more difficult to assess—even for the various experts who are giving over-confident assurances. It's possible that the greater transmissibility of the UK lineage shifts the balance in favour of vaccinating more people with a first dose, but, again, that hunch should be modeled—esp. in light of unsurprising evidence of lower efficacy in live deployment.
    Yes and all that is being modelled by the JCVI and other relevant bodies those scientists are saying to go with this as it provides dramatically more community protection for an emergency use provision which is how we are operating - because it literally is an emergency.

    Should we cease to consider this to be an emergency and cease to operate on a basis of emergency usage?

    Or should we cease to follow the scientific advice given by the independent scientists that make up the JCVI?
    I suspect you're not appreciating just how limited that "body of evidence" as you call it really is.
    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.

    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 UK is doing its own thing in a completely different fashion, following the best scientific brains the country has to offer - in what is frankly a speciality field that the UK scientists are experts on. If it works then that is a good thing not just for the UK but for the rest of the world too - this is akin to a mass real life Phase IV trial in operation - it may not be as "secure" a trial as wiggin might like but it is a real world one. If the UK single dose for as many as possible then booster dose twelve weeks later model works then later in the year when other countries have more vaccine doses then potentially it can be followed saving globally potentially hundreds of thousands of extra lives as a result.
    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. #2517
    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?
    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. #2518
    Quote Originally Posted by Aimless View Post
    I thought we'd share a common understanding about 50 million and 5 million differing by an order of magnitude, but apparently not.
    Not really. Pro rata for population and the UK's 5 million delayed is equivalent to 33 million delayed in the EU.
    The point is that they should've known months ago that they would not meet that target, and they should've notified the EU then—not a mere week before they're supposed to begin shipping.
    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. Should they shortcut clinical testing or override it and use a batch that has failed its safety checks?
    This is not particularly relevant to what I wrote.
    It is entirely relevant.
    Oh, look, there's an important word there that you missed. Now that I have pointed it out to you, perhaps you can try again?
    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.
    You're welcome to provide evidence for that connection. You haven't yet. Do you know how to tie cause and effect together using logically sound factual arguments? I ask because you did something similarly stupid during our exchange about the role of the media, so it's beginning to look like a pattern with you.
    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"? 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?

    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?

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

  29. #2519
    Quote Originally Posted by RandBlade View Post
    What controls do you want? Do you want a placebo for half so half aren't vaccinated? That's precisely what we are seeking to avoid. This isn't a trial, except it might help inform Phase IV data, it is real life.
    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.
    Last night as I lay in bed, looking up at the stars, I thought, “Where the hell is my ceiling?"

  30. #2520
    Quote Originally Posted by RandBlade View Post
    ll evidence I've seen shows in week 3 well over 50%. I'd be curious to see any evidence for as low as 30%. But if it is over 50% then that is a slam dunk.
    Clalit (a major Israeli HMO) released pre-publication data showing a 33% decrease in PCR positivity rate on days 14-18 post first dose, on about 200k patients matched against 200k who had not yet received a dose. Maccabi (another major HMO) looked at days 13-23 post first dose and showed a drop in PCR positivity rate of ~60% by the end of that period (which was 2 days post second dose). This was data on about 50k vaccinated individuals normalized against an age matched cohort of about 400k patients. They also showed a substantial drop in hospitalization.

    Don't get me wrong, this is very good news. There are reasons why these numbers might be lower than the 90-95% numbers we've seen with the phase III trials Pfizer released: there isn't random assignment in who got the vaccine first (which might flatter the numbers for this hypervigilant subpopulation), the endpoint is different (a composite endpoint vs. just symptomatic infection, which make these numbers look worse), the age group is much older (so vaccination might be less effective at producing a robust immune response), etc. But these are simple realities that will happen with other country's vaccine rollouts, too.

    All evidence so far shows lower viral load and lower hospitalisations, over 50% lower, from a single dose. So again vaccinating twice as many people should entail more reduction in viral load.
    Can you please direct me to this evidence you keep mentioning?

    What controls do you want? Do you want a placebo for half so half aren't vaccinated? That's precisely what we are seeking to avoid. This isn't a trial, except it might help inform Phase IV data, it is real life.
    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.

    Quote Originally Posted by RB
    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?
    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.
    "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)

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