7 ms·

Which makes me wonder why it takes so long this time?

by vimy 5y ago

data_dan_ 5y ago
Testing and clinical trials!
- vimy 5y ago
  We don’t do clinical trials for the yearly flu vaccine update, do we?
  - s1artibartfast 5y ago
    We also have 80 years of experience with the flu vaccine opposed to 8 months
    - SECProto 5y ago
      > We also have 80 years of experience with the flu vaccine opposed to 8 months 8 months is incorrect. Here's[1] an article from 17 months ago about results from Moderna's covid-19 trials for vaccinations dating back to mar16 2020. So it's been 21 months, not 8 (and that's ignoring trials of mRNA vaccines years earlier as they weren't for this specific virus) [1] https://www.cidrap.umn.edu/news-perspective/2020/07/hopeful-results-phase-1-moderna-covid-vaccine-trial https://www.cidrap.umn.edu/news-perspective/2020/07/hopeful-...
      - s1artibartfast 5y ago
        We can split hairs on what constitutes experience, or when it starts. but the point still stands: We have a lot more experience with the flu vaccine. This is the answer for why not all annual flu vaccines need clinical trials.
        ashildr 5y ago
        „the flu vaccine“? Which one?
        s1artibartfast 5y ago
        The first vaccines in 1933 were against A type influenzas, followed by vaccines against against B type influenzas in 1942. Here is a pretty good summary of the history of vaccine development. https://www.medscape.com/viewarticle/812621_1 https://www.medscape.com/viewarticle/812621_1 While nearly all influenza vaccines generate similar antibodies, Covid and influenza vaccines generate significantly different antibodies Influenza vaccines generate antibodies against influenza Hemagglutinin proteins targeting sialic acid receptors Covid vaccines generate antibodies for (S) glycoproteins targeting ACE-2 receptors. In short, we have 80+ years of experience generating antibodies for hemagglutinin, and much less for (S) glycoproteins. https://en.wikipedia.org/wiki/Coronavirus_spike_protein https://en.wikipedia.org/wiki/Coronavirus_spike_protein https://en.wikipedia.org/wiki/Hemagglutinin_(influenza) https://en.wikipedia.org/wiki/Hemagglutinin_(influenza)
  - heavyset_go 5y ago
    > We don’t do clinical trials for the yearly flu vaccine update, do we? Yes, we do[1][2]. [1] https://www.cdc.gov/flu/vaccines-work/effectivenessqa.htm https://www.cdc.gov/flu/vaccines-work/effectivenessqa.htm [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947948/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947948/
  - GeekyBear 5y ago
    Yes, but it's a greatly abbreviated process for each year's new version of the Flu vaccine. Going forward, the FDA has already said that a reformulation of the mRNA Covid vaccine would face a similarly shortened approval process. >FDA says Covid vaccines that target new variants won’t need large clinical trials to win approval https://www.cnbc.com/2021/02/22/covid-vaccine-fda-says-shots-that-target-new-variants-wont-need-large-clinical-trials-to-win-approval.html https://www.cnbc.com/2021/02/22/covid-vaccine-fda-says-shots...
    - spurgu 5y ago
      This reminds me of the 737 MAX.
- legutierr 5y ago
  It would have been much faster if regulators and ethicists hadn’t been so squeamish about challenge trials. In order to save dozens of lives that might have been lost in challenge trials, we sacrificed hundreds of thousands of lives so that we could wait for more ethically-sound vaccine trials to complete.
  - ajsnigrutin 5y ago
    The problem are the vaccine mandates. If you (soft or hard) mandate a vaccine, and you kill someone with it, that's a lot of responsibility to take, if the vaccine didn't go through a full trial. If the vaccines were as optional as eg. flu vaccines are, then a simple waiver would solve most of the issues. (a 20yo girl died in slovenia due to jannsen vaccine not that long ago, and she got vaccinated, becase she was soft-forced by the government mandates (48 hour testing, far away from home, but unable to use the bus without a test, to go to the testing site, 12eur/test,...).
    - ericb 5y ago
      Your reply is totally off-topic for the parent you replied to.
      - dfabulich 5y ago
        I see why you're saying that, but I think you missed their point. Challenge trials might well allow us to make a safe vaccine available sooner to those who want it, but if we mandate a vaccine that has only undergone challenge trials and then that vaccine kills someone, it would certainly be politically disastrous for challenge trials.
        Wowfunhappy 5y ago
        Challenge trials are dangerous for the people who participate in the trials, but they aren’t any less rigorous.
        5y ago
dredmorbius 5y ago
Drug assessment goes through three stages of human testing, after other models, to assess safety, efficacy, and finally, dosing. If possible, basic efficacy testing is done on non-human models, either in vitro or animal models. For species-specific viruses, this is difficult and may be impossible. I'm not sure what if any such testing was done with the SARS-COV-2 vaccine candidates. A basic safety test with dosages thought to be low enough not to present any risks. The goal here is simply to see what if any side effects occur. Any comorbidities, no matter how unrelated, are reported. Note that these may occur in a control / nontreated population, so the key isn't "individual was treated, had condition", but "there is a statistically robust difference in rates of co-morbidities between treatment and control populations" In normal circumstances, such safety testing may take a year or more, and data reporting are ongoing through drug development and use. Efficacy is determined, where groups treated are assessed for whether or not the drug provides any measureable effect. Note that this can range anywhere from "provides 100% immunity from infection" to "cancer patient dies a horrible painful death 2 weeks after control group". (If you're familiar with cancer research, it is rife with very marginal "positive responses" to therapy. Yes, with some spectacularly better instances.) Finally, dosing is dialed in to find out how much and how often to deliver the drug. That's how we're ending up with single vs. double innoculation recommendations, and/or boosters, and wait times between dosing. Again, multiple groups followed over time. All of this takes time. Since COVID-19 has a course of about 1--2 months from exposure to resolution (you get better or you die), and vaccinations have a lead time of about 2 weeks after second dose to full efficacy, that's about four momths just to get baseline measurements. A typical drug study might have as few as 30--60 patients, though many have more. In the case of the SARS-COV-2 vaccines, trials were much larger as I understand (I don't have data or reports in front of me, so don't take my comments here as significant.) If there's earlier research to build off of (e.g., mRNA base models of solutions and methods) then some of this process can be based on earlier research, which helps. But you're still looking at 6--9 months before a vaccine can be recommended with strong assurances even under highly expedited conditions. Given circumstances, health authorities might be willing to operate more quickly and with less data, but those decisions would have to be considered preliminary and subject to revision. Revised understanding around COVID-19 has been highly problematic around the world, leading to trust issues and opportunists spreading disinformation. And once you have a candidate treatment, you've still got to produce and supply that, with manufacturing and logistics considerations, all of which were evident in the rollout of existing SARS-COV-2 vaccines (e.g., production issues, patent licensing, quality control, storage and refrigeration, cold-chain management, patient contact, scheduling, and follow-up, etc.). It's complicated. Source: Some ancillary PHARMA related work in the past, eccelctic interests.

Which makes me wonder why it takes so long this time?

by vimy 5y ago

Which makes me wonder why it takes so long this time?

data_dan_ 5y ago

Testing and clinical trials!

vimy 5y ago
We don’t do clinical trials for the yearly flu vaccine update, do we?
- s1artibartfast 5y ago
  We also have 80 years of experience with the flu vaccine opposed to 8 months
  - SECProto 5y ago
    > We also have 80 years of experience with the flu vaccine opposed to 8 months 8 months is incorrect. Here's[1] an article from 17 months ago about results from Moderna's covid-19 trials for vaccinations dating back to mar16 2020. So it's been 21 months, not 8 (and that's ignoring trials of mRNA vaccines years earlier as they weren't for this specific virus) [1] https://www.cidrap.umn.edu/news-perspective/2020/07/hopeful-results-phase-1-moderna-covid-vaccine-trial https://www.cidrap.umn.edu/news-perspective/2020/07/hopeful-...
    - s1artibartfast 5y ago
      We can split hairs on what constitutes experience, or when it starts. but the point still stands: We have a lot more experience with the flu vaccine. This is the answer for why not all annual flu vaccines need clinical trials.
      - ashildr 5y ago
        „the flu vaccine“? Which one?
        s1artibartfast 5y ago
        The first vaccines in 1933 were against A type influenzas, followed by vaccines against against B type influenzas in 1942. Here is a pretty good summary of the history of vaccine development. https://www.medscape.com/viewarticle/812621_1 https://www.medscape.com/viewarticle/812621_1 While nearly all influenza vaccines generate similar antibodies, Covid and influenza vaccines generate significantly different antibodies Influenza vaccines generate antibodies against influenza Hemagglutinin proteins targeting sialic acid receptors Covid vaccines generate antibodies for (S) glycoproteins targeting ACE-2 receptors. In short, we have 80+ years of experience generating antibodies for hemagglutinin, and much less for (S) glycoproteins. https://en.wikipedia.org/wiki/Coronavirus_spike_protein https://en.wikipedia.org/wiki/Coronavirus_spike_protein https://en.wikipedia.org/wiki/Hemagglutinin_(influenza) https://en.wikipedia.org/wiki/Hemagglutinin_(influenza)
- heavyset_go 5y ago
  > We don’t do clinical trials for the yearly flu vaccine update, do we? Yes, we do[1][2]. [1] https://www.cdc.gov/flu/vaccines-work/effectivenessqa.htm https://www.cdc.gov/flu/vaccines-work/effectivenessqa.htm [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947948/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947948/
- GeekyBear 5y ago
  Yes, but it's a greatly abbreviated process for each year's new version of the Flu vaccine. Going forward, the FDA has already said that a reformulation of the mRNA Covid vaccine would face a similarly shortened approval process. >FDA says Covid vaccines that target new variants won’t need large clinical trials to win approval https://www.cnbc.com/2021/02/22/covid-vaccine-fda-says-shots-that-target-new-variants-wont-need-large-clinical-trials-to-win-approval.html https://www.cnbc.com/2021/02/22/covid-vaccine-fda-says-shots...
  - spurgu 5y ago
    This reminds me of the 737 MAX.
legutierr 5y ago
It would have been much faster if regulators and ethicists hadn’t been so squeamish about challenge trials. In order to save dozens of lives that might have been lost in challenge trials, we sacrificed hundreds of thousands of lives so that we could wait for more ethically-sound vaccine trials to complete.
- ajsnigrutin 5y ago
  The problem are the vaccine mandates. If you (soft or hard) mandate a vaccine, and you kill someone with it, that's a lot of responsibility to take, if the vaccine didn't go through a full trial. If the vaccines were as optional as eg. flu vaccines are, then a simple waiver would solve most of the issues. (a 20yo girl died in slovenia due to jannsen vaccine not that long ago, and she got vaccinated, becase she was soft-forced by the government mandates (48 hour testing, far away from home, but unable to use the bus without a test, to go to the testing site, 12eur/test,...).
  - ericb 5y ago
    Your reply is totally off-topic for the parent you replied to.
    - dfabulich 5y ago
      I see why you're saying that, but I think you missed their point. Challenge trials might well allow us to make a safe vaccine available sooner to those who want it, but if we mandate a vaccine that has only undergone challenge trials and then that vaccine kills someone, it would certainly be politically disastrous for challenge trials.
      - Wowfunhappy 5y ago
        Challenge trials are dangerous for the people who participate in the trials, but they aren’t any less rigorous.
        5y ago

dredmorbius 5y ago

Drug assessment goes through three stages of human testing, after other models, to assess safety, efficacy, and finally, dosing. If possible, basic efficacy testing is done on non-human models, either in vitro or animal models. For species-specific viruses, this is difficult and may be impossible. I'm not sure what if any such testing was done with the SARS-COV-2 vaccine candidates. A basic safety test with dosages thought to be low enough not to present any risks. The goal here is simply to see what if any side effects occur. Any comorbidities, no matter how unrelated, are reported. Note that these may occur in a control / nontreated population, so the key isn't "individual was treated, had condition", but "there is a statistically robust difference in rates of co-morbidities between treatment and control populations" In normal circumstances, such safety testing may take a year or more, and data reporting are ongoing through drug development and use. Efficacy is determined, where groups treated are assessed for whether or not the drug provides any measureable effect. Note that this can range anywhere from "provides 100% immunity from infection" to "cancer patient dies a horrible painful death 2 weeks after control group". (If you're familiar with cancer research, it is rife with very marginal "positive responses" to therapy. Yes, with some spectacularly better instances.) Finally, dosing is dialed in to find out how much and how often to deliver the drug. That's how we're ending up with single vs. double innoculation recommendations, and/or boosters, and wait times between dosing. Again, multiple groups followed over time. All of this takes time. Since COVID-19 has a course of about 1--2 months from exposure to resolution (you get better or you die), and vaccinations have a lead time of about 2 weeks after second dose to full efficacy, that's about four momths just to get baseline measurements. A typical drug study might have as few as 30--60 patients, though many have more. In the case of the SARS-COV-2 vaccines, trials were much larger as I understand (I don't have data or reports in front of me, so don't take my comments here as significant.) If there's earlier research to build off of (e.g., mRNA base models of solutions and methods) then some of this process can be based on earlier research, which helps. But you're still looking at 6--9 months before a vaccine can be recommended with strong assurances even under highly expedited conditions. Given circumstances, health authorities might be willing to operate more quickly and with less data, but those decisions would have to be considered preliminary and subject to revision. Revised understanding around COVID-19 has been highly problematic around the world, leading to trust issues and opportunists spreading disinformation. And once you have a candidate treatment, you've still got to produce and supply that, with manufacturing and logistics considerations, all of which were evident in the rollout of existing SARS-COV-2 vaccines (e.g., production issues, patent licensing, quality control, storage and refrigeration, cold-chain management, patient contact, scheduling, and follow-up, etc.). It's complicated. Source: Some ancillary PHARMA related work in the past, eccelctic interests.