5 ms·

I dont understand the combative and critical tone and direction of the article. Nothing mentioned in the article justifies it. When piecing together a story fro

I dont understand the combative and critical tone and direction of the article. Nothing mentioned in the article justifies it. When piecing together a story from second hand or off the cuff remarks of course people will say different things because their own knowledge is incomplete. It seems like the author threw her hands up in the air and just dumped everything she had gathered into a heap. I guess that's what a wire service is supposed to do tho?

dannyw 6y ago
You have a dosing error that resulted in some participants getting half the dose initially, and this group turned out to have substantially better resistance (~90%) than the one receiving the full dose (~60%). This is completely mysterious, in the opposite direction of every other vaccine candidate, and should we be following normal safeguards, there is zero chance this vaccine would be approved. It also raises concerns of rushedness/negligence. When you get two conflicting measurements of the dosages, the correct response is to test it a third time, not assume the second is correct. This failure mechanism was the same in Boeing. Not that we need to be: we already have Pfizer and Moderna, that did their trials properly and showed proper results.
- deleted 6y ago
  [deleted]
- Exmoor 6y ago
  I disagree with your general conclusion that the vaccine should not be approved as-is. The efficacy results are certainly disappointing compared to the near-miraculous results with the two mRNA vaccines, but 60%+ efficacy is still enough to save many, many lives and bring the world back to normalcy. Remember, the 60% number doesn't mean 60% see improvement, it means of the people who would've gotten COVID without the vaccine, 60% didn't get it at all and 40% got it with significantly less negative effects. In all likelihood it will also greatly reduce the ability to spread the virus. They have already begun testing the half-full dose as another trial, so if that works better than full-full we may see the approval modified down the line. > we already have Pfizer and Moderna Unfortunately production constraints are going to mean that it will take a long time for those two vaccines to be produced in enough quantity to vaccinate most of the rich world. The cost for them and temperature requirements mean that they'd be impractical for most countries even in a few years.
  - apendleton 6y ago
    > 60% didn't get it at all and 40% got it with significantly less negative effects We don't know that. As with the Pfizer and Moderna trials, the endpoint was incidence of disease, and only people with disease symptoms were tested. 60% fewer people experienced symptoms in the treatment group than the control group, but some of those may well still have "gotten it." There were very likely asymptomatic infected people in both groups, and we have no idea how many there were, or how the numbers different between groups. For all we know, just as many people in the treatment group were infected as in the control group, they were capable of spreading infection the whole time, and all the vaccine did was suppress their symptoms. (Again: possibly true of any of the vaccine candidates.)
    - Exmoor 6y ago
      When the broadest studies indicate that symptomatic cases are ~25x more likely to transmit the virus to people in their household[0] I would say that converting a lot of symptomatic cases to asymptomatic cases is likely pretty consequential. [0]https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2774102 https://jamanetwork.com/journals/jamanetworkopen/fullarticle...
    - btbuilder 6y ago
      Are you sure Oxford and AstraZeneca did not test for asymptomatic participants? My understanding is they tested a proportion weekly. Edit: Nature mentions they did: https://www.nature.com/articles/d41586-020-03504-w https://www.nature.com/articles/d41586-020-03504-w
      - Exmoor 6y ago
        My understanding is that they did test a subset of participants, but that the 62% figure doesn't figure in the asymptomatic cases. They've made it very confusing though, much like how they've explained the half-full dose results.
      - Closi 6y ago
        Relevant section: The Oxford–AstraZeneca team is the only one of the three leading vaccine developers that monitored for asymptomatic infections, by collecting weekly swabs from some participants to determine whether they had the coronavirus but did not become ill.
- angry_octet 6y ago
  It isn't actually completely mysterious. If you listen to what immunologists/ & virologists they can explain a number of mechanisms which might be responsible. Obviously I'm not qualified to give a good explanation, but there's plenty of good exposition if you look. https://www.nature.com/articles/d41586-020-03326-w https://www.nature.com/articles/d41586-020-03326-w - Statistical effects, which might decrease the difference as the trial progresses. - A bigger dose causing an over-effective suppression of the carrier adenovirus, suppressing it's ability to make the COVID spike protein, and hence the production of COVID targetting T cells. There is also a huge flaw in the testing of the Pfizer and Moderna vaccines: they didn't test everyone. Only people with symptoms (whatever that means) were tested (PCR). Whereas with the Oxford AZ vax all participants were tested, so we can actually get an idea of asymptomatic infection.
  - estaseuropano 6y ago
    > There is also a huge flaw in the testing of the Pfizer and Moderna vaccines: they didn't test everyone. Only people with symptoms (whatever that means) were tested (PCR). Wow, do you have a source for this? That's quite a stunning difference and really should put the ~~Pfizer~~ BioNTech and Moderna vaccines in doubt if the aim is herd immunity.
    - blueblisters 6y ago
      Have a look at Table 4 here: https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-moderna-vaccine.html#results https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-modern... They seem to have preliminary results for asymptomatic testing: 14/14314 asymptomatic individuals were found in the vaccine group v/s 38/14073 in the control group. At least from the preliminary data, the Moderna vaccine nowhere near as effective in stopping asymptomatic infections.
    - angry_octet 6y ago
      A more detailed overview: https://theconversation.com/covid-19-vaccine-faq-6-things-to-look-for-in-clinical-trial-results-150843 https://theconversation.com/covid-19-vaccine-faq-6-things-to... You'd have to look at the registered study details for the full protocol. See this BMJ article for references: BMJ 2020;371:m4058 | doi: 10.1136/bmj.m4058 It doesn't prevent herd immunity if it only prevents the disease (i.e illness) but it makes it very difficult to achieve strong suppression if there is vaccine hesitancy (a polite grab bag term for science denialism, people who watch Fox, loopy muffin brain people, etc) above 20%. Which there will be in many parts of the US and Europe because of years of uncontested bullshit. (Thanks Facebook.)
refurb 6y ago
The article is mostly based off the 1,000 pages of supporting documents Oxford released with their paper, no?
dbcooper 6y ago
I've worked with nucleic acids (DNA and RNA) in my postdoc, and now in my own lab, and I'm quite shocked that anyone would rely on UV absorption measurements. They're inherently insensitive, and suffer from unreliability and reagent interference. Especially when they were taken over PCR based methods. It's a remarkable f*ck up for a clinical trial. These decisions should have been made with data from gold standard analytical methods.
freeflight 6y ago
I don't really see a tone like that in the article. I'm also pretty convinced if a "mishap" like that came to light about the Russian Sputnik, or one of the Chinese vaccines, then the combative and critical tone would go straight to "How Putin/Xi personally wanted to kill millions of people!" with news outlets all over the planet constantly regurgitating headlines along that line and Hanlon's Razor given zero consideration. While this article ends on the notion of how this is just some kind of "oddity" and yet somehow at the same time allegedly a universal problem of "reporting having slightly nationalistic tone". The article is so muddled up, and long-winded, the result of which is that it barely gains any traction in the online sphere, can't a find a single submission about this on Reddit with more than a dozen upvotes. The few there are the top-comments are very ad-hominemy "Good thing journalists never make mistakes!", which is a reminder that stuff like this [0] is a very real thing. [0] https://theintercept.com/2014/02/24/jtrig-manipulation/ https://theintercept.com/2014/02/24/jtrig-manipulation/
fabian2k 6y ago
The mistake that happened here is the kind of thing you explain to students the first time they're in the lab. It's really obvious and something everyone should know that uses a UV/Vis spectrometer. And of course the method itself is suspect, as the main benefit is that it is cheap and quick, not accurate. And then taking the wrongly performed measurement with the worse method over the qPCR by the manufacturer (who likely has much more robust QC than someone in academia) is just insane.

dannyw 6y ago

You have a dosing error that resulted in some participants getting half the dose initially, and this group turned out to have substantially better resistance (~90%) than the one receiving the full dose (~60%). This is completely mysterious, in the opposite direction of every other vaccine candidate, and should we be following normal safeguards, there is zero chance this vaccine would be approved. It also raises concerns of rushedness/negligence. When you get two conflicting measurements of the dosages, the correct response is to test it a third time, not assume the second is correct. This failure mechanism was the same in Boeing. Not that we need to be: we already have Pfizer and Moderna, that did their trials properly and showed proper results.

deleted 6y ago
[deleted]
Exmoor 6y ago
I disagree with your general conclusion that the vaccine should not be approved as-is. The efficacy results are certainly disappointing compared to the near-miraculous results with the two mRNA vaccines, but 60%+ efficacy is still enough to save many, many lives and bring the world back to normalcy. Remember, the 60% number doesn't mean 60% see improvement, it means of the people who would've gotten COVID without the vaccine, 60% didn't get it at all and 40% got it with significantly less negative effects. In all likelihood it will also greatly reduce the ability to spread the virus. They have already begun testing the half-full dose as another trial, so if that works better than full-full we may see the approval modified down the line. > we already have Pfizer and Moderna Unfortunately production constraints are going to mean that it will take a long time for those two vaccines to be produced in enough quantity to vaccinate most of the rich world. The cost for them and temperature requirements mean that they'd be impractical for most countries even in a few years.
- apendleton 6y ago
  > 60% didn't get it at all and 40% got it with significantly less negative effects We don't know that. As with the Pfizer and Moderna trials, the endpoint was incidence of disease, and only people with disease symptoms were tested. 60% fewer people experienced symptoms in the treatment group than the control group, but some of those may well still have "gotten it." There were very likely asymptomatic infected people in both groups, and we have no idea how many there were, or how the numbers different between groups. For all we know, just as many people in the treatment group were infected as in the control group, they were capable of spreading infection the whole time, and all the vaccine did was suppress their symptoms. (Again: possibly true of any of the vaccine candidates.)
  - Exmoor 6y ago
    When the broadest studies indicate that symptomatic cases are ~25x more likely to transmit the virus to people in their household[0] I would say that converting a lot of symptomatic cases to asymptomatic cases is likely pretty consequential. [0]https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2774102 https://jamanetwork.com/journals/jamanetworkopen/fullarticle...
  - btbuilder 6y ago
    Are you sure Oxford and AstraZeneca did not test for asymptomatic participants? My understanding is they tested a proportion weekly. Edit: Nature mentions they did: https://www.nature.com/articles/d41586-020-03504-w https://www.nature.com/articles/d41586-020-03504-w
    - Exmoor 6y ago
      My understanding is that they did test a subset of participants, but that the 62% figure doesn't figure in the asymptomatic cases. They've made it very confusing though, much like how they've explained the half-full dose results.
    - Closi 6y ago
      Relevant section: The Oxford–AstraZeneca team is the only one of the three leading vaccine developers that monitored for asymptomatic infections, by collecting weekly swabs from some participants to determine whether they had the coronavirus but did not become ill.
angry_octet 6y ago
It isn't actually completely mysterious. If you listen to what immunologists/ & virologists they can explain a number of mechanisms which might be responsible. Obviously I'm not qualified to give a good explanation, but there's plenty of good exposition if you look. https://www.nature.com/articles/d41586-020-03326-w https://www.nature.com/articles/d41586-020-03326-w - Statistical effects, which might decrease the difference as the trial progresses. - A bigger dose causing an over-effective suppression of the carrier adenovirus, suppressing it's ability to make the COVID spike protein, and hence the production of COVID targetting T cells. There is also a huge flaw in the testing of the Pfizer and Moderna vaccines: they didn't test everyone. Only people with symptoms (whatever that means) were tested (PCR). Whereas with the Oxford AZ vax all participants were tested, so we can actually get an idea of asymptomatic infection.
- estaseuropano 6y ago
  > There is also a huge flaw in the testing of the Pfizer and Moderna vaccines: they didn't test everyone. Only people with symptoms (whatever that means) were tested (PCR). Wow, do you have a source for this? That's quite a stunning difference and really should put the ~~Pfizer~~ BioNTech and Moderna vaccines in doubt if the aim is herd immunity.
  - blueblisters 6y ago
    Have a look at Table 4 here: https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-moderna-vaccine.html#results https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-modern... They seem to have preliminary results for asymptomatic testing: 14/14314 asymptomatic individuals were found in the vaccine group v/s 38/14073 in the control group. At least from the preliminary data, the Moderna vaccine nowhere near as effective in stopping asymptomatic infections.
  - angry_octet 6y ago
    A more detailed overview: https://theconversation.com/covid-19-vaccine-faq-6-things-to-look-for-in-clinical-trial-results-150843 https://theconversation.com/covid-19-vaccine-faq-6-things-to... You'd have to look at the registered study details for the full protocol. See this BMJ article for references: BMJ 2020;371:m4058 | doi: 10.1136/bmj.m4058 It doesn't prevent herd immunity if it only prevents the disease (i.e illness) but it makes it very difficult to achieve strong suppression if there is vaccine hesitancy (a polite grab bag term for science denialism, people who watch Fox, loopy muffin brain people, etc) above 20%. Which there will be in many parts of the US and Europe because of years of uncontested bullshit. (Thanks Facebook.)

refurb 6y ago

The article is mostly based off the 1,000 pages of supporting documents Oxford released with their paper, no?

dbcooper 6y ago

I've worked with nucleic acids (DNA and RNA) in my postdoc, and now in my own lab, and I'm quite shocked that anyone would rely on UV absorption measurements. They're inherently insensitive, and suffer from unreliability and reagent interference. Especially when they were taken over PCR based methods. It's a remarkable f*ck up for a clinical trial. These decisions should have been made with data from gold standard analytical methods.

freeflight 6y ago

I don't really see a tone like that in the article. I'm also pretty convinced if a "mishap" like that came to light about the Russian Sputnik, or one of the Chinese vaccines, then the combative and critical tone would go straight to "How Putin/Xi personally wanted to kill millions of people!" with news outlets all over the planet constantly regurgitating headlines along that line and Hanlon's Razor given zero consideration. While this article ends on the notion of how this is just some kind of "oddity" and yet somehow at the same time allegedly a universal problem of "reporting having slightly nationalistic tone". The article is so muddled up, and long-winded, the result of which is that it barely gains any traction in the online sphere, can't a find a single submission about this on Reddit with more than a dozen upvotes. The few there are the top-comments are very ad-hominemy "Good thing journalists never make mistakes!", which is a reminder that stuff like this [0] is a very real thing. [0] https://theintercept.com/2014/02/24/jtrig-manipulation/ https://theintercept.com/2014/02/24/jtrig-manipulation/

fabian2k 6y ago

The mistake that happened here is the kind of thing you explain to students the first time they're in the lab. It's really obvious and something everyone should know that uses a UV/Vis spectrometer. And of course the method itself is suspect, as the main benefit is that it is cheap and quick, not accurate. And then taking the wrongly performed measurement with the worse method over the qPCR by the manufacturer (who likely has much more robust QC than someone in academia) is just insane.