6 ms·

I originally thought the Oxford/AstraZeneca vaccine was significantly behind the mRNA vaccines in efficacy. But then I learned that the Oxford trials PCR-tested

by m12k 6y ago

I originally thought the Oxford/AstraZeneca vaccine was significantly behind the mRNA vaccines in efficacy. But then I learned that the Oxford trials PCR-tested every participant regularly, while the Pfizer and Moderna trials only tested participants that were showing symptoms. So there's a very real chance that behind that ~95% number the mRNA vaccines also had asymptomatic cases that were never discovered during trials, and the actual protection is nearly the same as the Oxford one. The mRNA vaccines still seem like a great leap forward, and they don't come with the potential complications of resistance to the vector virus that adenovirus-based vaccines do - but I'm less sure now that they actually offer better protection overall.

tpmx 6y ago
> But then I learned that the Oxford trials PCR-tested every participant regularly, while the Pfizer and Moderna trials only tested participants that were showing symptoms. That seems substantial, weird and important. Source?
- m-ee 6y ago
  They did do more PCR but that isn’t reflected in the efficacy numbers. The end point for all trials has been prevention of symptomatic disease.
  - tpmx 6y ago
    And where is your source for that?
    - m-ee 6y ago
      It's quite literally one of the first things mentioned in the trial protocols and journal articles https://clinicaltrials.gov/ct2/show/NCT04516746 https://clinicaltrials.gov/ct2/show/NCT04516746 "The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19 in adults ≥ 18 years of age [ Time Frame: 1 year ] A binary response, whereby a participant is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs ≥ 15 days post second dose of study intervention. Otherwise, a participant is not defined as a COVID-19 case." https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... "The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. "
      - m12k 6y ago
        I think you're right, now that I know what to look for. The AZ/Oxford vaccine has lower symptomatic efficacy than the mRNA ones, and it's asymptomatic efficacy is lower still. We don't know what the asymptomatic efficacy of the mRNA vaccines is yet, but since their symptomatic efficacy is higher, it would be reasonable to expect their asymptomatic efficacy to also be higher. So at the end of the day, the main question regarding the AZ/Oxford vaccine is whether a half-dose starter shot regimen, or longer time between doses can bring its efficacy more consistently up around 90%, which would make it only slightly less effective than the mRNA ones, or if it's efficacy is actually just lower.
        m-ee 6y ago
        The half dose and longer time efficacy numbers have confidence intervals around 50-60% wide, definitely need to do more testing on that. I agree its the biggest question to answer for them (aside from just getting cleaner data through the US trial that will hopefully report soon). I believe they were also doing a study with mixed doses of Oxford/Sputnik.
      - kelnos 6y ago
        The links you provided seem to be for AstraZenica's vaccine, though, not for Moderna's or Pfizer's (which is what 'm12k was originally talking about). That seems to suggest that Oxford/AZN were only testing symptomatic trial participants, no? And says nothing about what Moderna or Pfizer were doing?
        m-ee 6y ago
        Moderna and Pfizer/Biontech did not do regular screening to check for asymptomatic cases, aside from some samples taken in between the shots. Oxford/AZ did regularly screen some participants, but the primary efficacy analysis only looked at symptomatic cases similar to the mRNA vaccines.
        kelnos 6y ago
        Ok, but the question in the thread was about sources showing that Moderna & Pfizer did not do regular screening; seems like no one had found that info earlier, but I now see someone downthread has posted more about this.
- M2Ys4U 6y ago
  "Unlike other vaccines being trialled, the Oxford team had been taking weekly swabs from all volunteers to check whether they were infected but showing no symptoms." https://www.bbc.co.uk/news/health-55308216 https://www.bbc.co.uk/news/health-55308216
  - m-ee 6y ago
    This does not mean that this is reflected in the efficacy numbers. Read the paper and protocols they very clearly specify symptomatic disease confirmed with PCR.
- m12k 6y ago
  Oxford: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... "To test for asymptomatic infections, participants in COV002 in the UK were asked to provide a weekly self-administered nose and throat swab for NAAT testing from 1 week after first vaccination using kits provided by the UK Department of Health and Social Care (DHSC)" Moderna: https://www.nih.gov/news-events/news-releases/phase-3-clinical-trial-investigational-vaccine-covid-19-begins https://www.nih.gov/news-events/news-releases/phase-3-clinic... "Investigators will closely monitor participant safety. They will call participants after each vaccination to discuss any symptoms and will provide participants with a diary to record symptoms and a thermometer for temperature readings. If a participant is suspected to have COVID-19, the participant will be asked to provide a nasal swab for testing within 72 hours." https://www.nejm.org/doi/10.1056/NEJMoa2035389 https://www.nejm.org/doi/10.1056/NEJMoa2035389 "although our trial showed that mRNA-1273 reduces the incidence of symptomatic SARS-CoV-2 infection, the data were not sufficient to assess asymptomatic infection, although our results from a preliminary exploratory analysis suggest that some degree of prevention may be afforded after the first dose" Pfizer: https://www.sciencemediacentre.org/expert-reaction-to-phase-3-results-for-the-pfizer-biontech-bnt162b2-mrna-covid-19-vaccine/ https://www.sciencemediacentre.org/expert-reaction-to-phase-... "The Pfizer study did not report studies of the impact of its vaccine on asymptomatic infection. The Oxford study reported that efficacy for “asymptomatic or symptoms unknown infection” based on weekly self-swabbing was 3·8% (−72·4 to 46·3%) following standard dose and 58·9% (95% CI 1·0 to 82·9) following low dose regimen." https://www.nejm.org/doi/10.1056/NEJMoa2034577 https://www.nejm.org/doi/10.1056/NEJMoa2034577 "These data do not address whether vaccination prevents asymptomatic infection; a serologic end point that can detect a history of infection regardless of whether symptoms were present (SARS-CoV-2 N-binding antibody) will be reported later" PS: Sorry, but it took a little while to dig up original sources to random news articles I'd read months earlier
  - deleted 6y ago
    [deleted]
  - tpmx 6y ago
    I owe you an excuse (I'm sorry), I think you are indeed correct - there seems to be a marked difference between the protocols.
- jepler 6y ago
  I found this document https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222-oxford-phase-iii-trials-interim-analysis-results-published-in-the-lancet.html https://www.astrazeneca.com/media-centre/press-releases/2020... which stated about the phase I/II trial that "Weekly COVID-19 PCR testing is performed". However, the phase II/III and phase III trials state "Suspected cases presenting with compatible symptoms were tested for virological confirmation by COVID-19 PCR" (slightly different wording in the two cases)
deleted 6y ago
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deleted 6y ago
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mlyle 6y ago
No. AstraZeneca also tested with weekly PCR surveillance. But the efficacy numbers we're comparing between AstraZeneca and the mRNA vaccines are measures of how often they prevents symptomatic illness-- a very similar standard to that used in the Moderna and Pfizer trials (but not absolutely, directly comparable). Unfortunately, the AZ trial is a mess. One way it was a mess is that the error bars on how much they prevent all illness (not just symptomatic illness) go all the way down to 1%.
benrapscallion 6y ago
One must also take into account the fact that when the Moderna and Pfizer vaccines were tested, the South African, U.K., and Brazilian variants didn’t exist. In the J&J trial they were dominant. As a result they are not comparable. The J&J vaccine had 0 cases of severe disease in the treatment arm and that really is the statistic one is looking for.[1] [1] https://twitter.com/chrislhayes/status/1355352505987854340 https://twitter.com/chrislhayes/status/1355352505987854340

by m12k 6y ago

tpmx 6y ago

> But then I learned that the Oxford trials PCR-tested every participant regularly, while the Pfizer and Moderna trials only tested participants that were showing symptoms. That seems substantial, weird and important. Source?

m-ee 6y ago
They did do more PCR but that isn’t reflected in the efficacy numbers. The end point for all trials has been prevention of symptomatic disease.
- tpmx 6y ago
  And where is your source for that?
  - m-ee 6y ago
    It's quite literally one of the first things mentioned in the trial protocols and journal articles https://clinicaltrials.gov/ct2/show/NCT04516746 https://clinicaltrials.gov/ct2/show/NCT04516746 "The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19 in adults ≥ 18 years of age [ Time Frame: 1 year ] A binary response, whereby a participant is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs ≥ 15 days post second dose of study intervention. Otherwise, a participant is not defined as a COVID-19 case." https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... "The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. "
    - m12k 6y ago
      I think you're right, now that I know what to look for. The AZ/Oxford vaccine has lower symptomatic efficacy than the mRNA ones, and it's asymptomatic efficacy is lower still. We don't know what the asymptomatic efficacy of the mRNA vaccines is yet, but since their symptomatic efficacy is higher, it would be reasonable to expect their asymptomatic efficacy to also be higher. So at the end of the day, the main question regarding the AZ/Oxford vaccine is whether a half-dose starter shot regimen, or longer time between doses can bring its efficacy more consistently up around 90%, which would make it only slightly less effective than the mRNA ones, or if it's efficacy is actually just lower.
      - m-ee 6y ago
        The half dose and longer time efficacy numbers have confidence intervals around 50-60% wide, definitely need to do more testing on that. I agree its the biggest question to answer for them (aside from just getting cleaner data through the US trial that will hopefully report soon). I believe they were also doing a study with mixed doses of Oxford/Sputnik.
    - kelnos 6y ago
      The links you provided seem to be for AstraZenica's vaccine, though, not for Moderna's or Pfizer's (which is what 'm12k was originally talking about). That seems to suggest that Oxford/AZN were only testing symptomatic trial participants, no? And says nothing about what Moderna or Pfizer were doing?
      - m-ee 6y ago
        Moderna and Pfizer/Biontech did not do regular screening to check for asymptomatic cases, aside from some samples taken in between the shots. Oxford/AZ did regularly screen some participants, but the primary efficacy analysis only looked at symptomatic cases similar to the mRNA vaccines.
        kelnos 6y ago
        Ok, but the question in the thread was about sources showing that Moderna & Pfizer did not do regular screening; seems like no one had found that info earlier, but I now see someone downthread has posted more about this.
M2Ys4U 6y ago
"Unlike other vaccines being trialled, the Oxford team had been taking weekly swabs from all volunteers to check whether they were infected but showing no symptoms." https://www.bbc.co.uk/news/health-55308216 https://www.bbc.co.uk/news/health-55308216
- m-ee 6y ago
  This does not mean that this is reflected in the efficacy numbers. Read the paper and protocols they very clearly specify symptomatic disease confirmed with PCR.
m12k 6y ago
Oxford: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... "To test for asymptomatic infections, participants in COV002 in the UK were asked to provide a weekly self-administered nose and throat swab for NAAT testing from 1 week after first vaccination using kits provided by the UK Department of Health and Social Care (DHSC)" Moderna: https://www.nih.gov/news-events/news-releases/phase-3-clinical-trial-investigational-vaccine-covid-19-begins https://www.nih.gov/news-events/news-releases/phase-3-clinic... "Investigators will closely monitor participant safety. They will call participants after each vaccination to discuss any symptoms and will provide participants with a diary to record symptoms and a thermometer for temperature readings. If a participant is suspected to have COVID-19, the participant will be asked to provide a nasal swab for testing within 72 hours." https://www.nejm.org/doi/10.1056/NEJMoa2035389 https://www.nejm.org/doi/10.1056/NEJMoa2035389 "although our trial showed that mRNA-1273 reduces the incidence of symptomatic SARS-CoV-2 infection, the data were not sufficient to assess asymptomatic infection, although our results from a preliminary exploratory analysis suggest that some degree of prevention may be afforded after the first dose" Pfizer: https://www.sciencemediacentre.org/expert-reaction-to-phase-3-results-for-the-pfizer-biontech-bnt162b2-mrna-covid-19-vaccine/ https://www.sciencemediacentre.org/expert-reaction-to-phase-... "The Pfizer study did not report studies of the impact of its vaccine on asymptomatic infection. The Oxford study reported that efficacy for “asymptomatic or symptoms unknown infection” based on weekly self-swabbing was 3·8% (−72·4 to 46·3%) following standard dose and 58·9% (95% CI 1·0 to 82·9) following low dose regimen." https://www.nejm.org/doi/10.1056/NEJMoa2034577 https://www.nejm.org/doi/10.1056/NEJMoa2034577 "These data do not address whether vaccination prevents asymptomatic infection; a serologic end point that can detect a history of infection regardless of whether symptoms were present (SARS-CoV-2 N-binding antibody) will be reported later" PS: Sorry, but it took a little while to dig up original sources to random news articles I'd read months earlier
- deleted 6y ago
  [deleted]
- tpmx 6y ago
  I owe you an excuse (I'm sorry), I think you are indeed correct - there seems to be a marked difference between the protocols.
jepler 6y ago
I found this document https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222-oxford-phase-iii-trials-interim-analysis-results-published-in-the-lancet.html https://www.astrazeneca.com/media-centre/press-releases/2020... which stated about the phase I/II trial that "Weekly COVID-19 PCR testing is performed". However, the phase II/III and phase III trials state "Suspected cases presenting with compatible symptoms were tested for virological confirmation by COVID-19 PCR" (slightly different wording in the two cases)

deleted 6y ago

[deleted]

deleted 6y ago

[deleted]

mlyle 6y ago

No. AstraZeneca also tested with weekly PCR surveillance. But the efficacy numbers we're comparing between AstraZeneca and the mRNA vaccines are measures of how often they prevents symptomatic illness-- a very similar standard to that used in the Moderna and Pfizer trials (but not absolutely, directly comparable). Unfortunately, the AZ trial is a mess. One way it was a mess is that the error bars on how much they prevent all illness (not just symptomatic illness) go all the way down to 1%.

benrapscallion 6y ago

One must also take into account the fact that when the Moderna and Pfizer vaccines were tested, the South African, U.K., and Brazilian variants didn’t exist. In the J&J trial they were dominant. As a result they are not comparable. The J&J vaccine had 0 cases of severe disease in the treatment arm and that really is the statistic one is looking for.[1] [1] https://twitter.com/chrislhayes/status/1355352505987854340 https://twitter.com/chrislhayes/status/1355352505987854340