4 ms·

Long-term studies of Covid vaccines hurt by placebo recipients getting immunized

57 points by g42gregory 5y ago

hprotagonist 5y ago
truly, a problem you want to have.
- NonContro 5y ago
  Not really, because if there are long-term side effects, we need to have a control group. For example, the vaccine used for the 2009 Swine Flu: https://en.wikipedia.org/wiki/Pandemrix https://en.wikipedia.org/wiki/Pandemrix "Pandemrix was found to be associated with narcolepsy from observational studies, increasing the risk of narcolepsy by 5-14 times in children and 2-7 times in adults. The increased risk of narcolepsy due to vaccination in children and adolescents was around 1 incident per 18,400 doses." If you don't have a large section of the population unvaccinated, you can't conclusively prove that the vaccine was the cause.
  - hprotagonist 5y ago
    “Problems you want to have“ are still problems, after all. It’s just, which would you rather have: a perfectly run trial because your vaccine efficacy is so low that your control group doesn’t feel incentivized to get vaccinated? Or a vaccine that works well enough to quell a pandemic, causing your control group to jump ship and potentially lessen your statistical power?
    - deleted 5y ago
      [deleted]
    - H8crilA 5y ago
      There was a comment here that got deleted. It had something cool I haven't seen before: a risk calculator/estimator for Covid (both death and hospital admission), for the UK: https://qcovid.org/Calculation https://qcovid.org/Calculation
      - chiefalchemist 5y ago
        Interesting. Especially that it uses a number of different "properties" (e.g., post code) to "fine tune" the calculation.
    - guscost 5y ago
      Either way, the higher-order effects will continue and cascade in perpetuity. The world is not a well-controlled experiment, and if you think there is an obvious “better” choice here which can be separated from all the context, then you have no idea how the world works.
      - hprotagonist 5y ago
        and if you think all choices are obviously bad (because there's no discernable 'better'), then i don't want you running a public health office. (disclaimer: i've run experiments with patients, i'm well aware of how messy the world is)
        guscost 5y ago
        > i'm well aware of how messy the world is No, you are not. Not even close.
  - jdavis703 5y ago
    In this case, there is a suspected autoimmune link between the similarity of the inactivated viral protein and a brain protein that is associated with sleep regulation. The real question to ask isn’t whether the placebo group was better off, but whether people infected with Swine Flu had a lower risk of narcolepsy than vaccine recipients.
  - markus92 5y ago
    Not necessarily true. The incidence rates of those are well-known. Rarer side effects are impossible to find by comparing vaccinated/unvaccinated in a phase 3 and need larger groups to be found. That’s routine, though. Look at the VITT for the Adenoviral vector vaccines, no strict control group was necessary to identify that.
deleted 5y ago
[deleted]
AuthorizedCust 5y ago
This is old news, from February. A Google search on pfizer moderna studies placebo doesn’t turn up much of anything beyond similar articles. I wonder if the close scrutiny of the vaccines in the months following have been enough to allay concerns?
- kaczordon 5y ago
  The problem is that now we can’t do it even if we wanted to. The Big Corpos effectively blew up the control arm to protect their bottom line.
  - RcouF1uZ4gsC 5y ago
    >The Big Corpos effectively blew up the control arm to protect their bottom line. Knowing what I know, if I was in the control arm, I would take the vaccine as soon as it was available. It would be highly unethical to keep people from being vaccinated who were in the control arm. Those “Big Corpos” literally saved millions of lives and trillions of dollars.
    - kaczordon 5y ago
      We do this all the time with cancer drugs. The ethical thing to do is to do the trial first and collect the data. You will benefit an order of magnitude more people and you will be able to answer future questions in a timely fashion.
      - epmaybe 5y ago
        No, we definitely don’t. If the treatment arm is seen as largely effective, the data safety and monitoring board will most definitely recommend unblinding participants and publishing the results as is. Please educate me with trials that do what you say if this is not true.
        pbak 5y ago
        If all was well in the land of milk and honey, yes. However, if unlike me, and like most professionals, you didn't spent an unhealthy amount of time researching the details, you wouldn't know they didn't : https://www.bmj.com/content/371/bmj.m4956 https://www.bmj.com/content/371/bmj.m4956 "And even before the FDA advisory committee meeting on Moderna’s vaccine on 17 December, the company notified volunteers that they could learn their status if they chose to receive the vaccine. Pfizer also sent a letter to its trial participants one week after its vaccine was authorised on 10 December." Or you could go the Israeli way, and do the Pharma's job for them, keeping a 290K people with matched control group since December 2020 : https://www.cnbc.com/2021/07/23/delta-variant-pfizer-covid-vaccine-39percent-effective-in-israel-prevents-severe-illness.html https://www.cnbc.com/2021/07/23/delta-variant-pfizer-covid-v... That's what you get when go "warp speed" and doubt anything was done correctly under Trump, to suddenly forget and somehow believe everything was done AOK beforehand now that Biden is in...
devit 5y ago
Why not use unvaccinated people from the general population? There would be some selection bias, but it's going to be irrelevant for most things.
- Exmoor 5y ago
  Based on what we know about the demographics of those actively choosing to avoid COVID vaccination make me think that they would differ pretty significantly from those who would volunteer to participate in a phase 3 trial.
- loonster 5y ago
  Will never be a blind study. Unvaxed do not want to be vexed. They would never consent to a 50% chance of getting g vaxxed.
realreality 5y ago
> Perhaps in a year or two the existing vaccines will have proven so effective that COVID-19 becomes not much more than a nuisance. This sentence won't age well.
- halfjoking 5y ago
  We don't have to wait for it to age - Gibraltar, one of the only places in the world with 99% vaccination rate is seeing a spike in cases: https://www.worldometers.info/coronavirus/country/gibraltar/ https://www.worldometers.info/coronavirus/country/gibraltar/ https://www.express.co.uk/travel/articles/1469353/Gibraltar-green-list-restrictions-tighten-covid-cases-events-nightclubs https://www.express.co.uk/travel/articles/1469353/Gibraltar-...
  - CarelessExpert 5y ago
    You mean the spike that's already subsiding, during which there was 1 death of a person who was unvaccinated? https://graphics.reuters.com/world-coronavirus-tracker-and-maps/countries-and-territories/gibraltar/ https://graphics.reuters.com/world-coronavirus-tracker-and-m... https://www.euroweeklynews.com/2021/08/05/gibraltar-resident-who-died-from-covid-19-was-unvaccinated/ https://www.euroweeklynews.com/2021/08/05/gibraltar-resident... Let's not get hysterical. Breakthrough cases will happen. That they cluster is no great surprise at all. Is covid a nuisance for Gibraltar? No. But it's far from the threat it was pre-vaccine.
    - yokaze 5y ago
      To add to that: Gibraltar isn't isolated, but has a lot of people coming and going from neighbouring Spain. Vaccination rate raising, but still far from 99%
  - 8note 5y ago
    300 cases for 30k population? With 99% vaccinated, that's 10% of the unvaccinated population
strstr 5y ago
A lot of the early study members were physicians and health care workers, so this doesn’t come as a huge surprise. A pulmonologist I know that was in the Moderna study was offered a vaccine from their employer back in December. They tried to get urgently deblinded (this was after the primary study was done but before deblinding) so they could ensure the doses didn’t go to waste. This ended up being a bit of a bureaucratic nightmare, and they weren’t able to find out the answer until a few hours before their scheduled appointment. They had in fact been in the treatment group, so the dose was fortunately redirected to another healthcare worker.

57 points by g42gregory 5y ago

hprotagonist 5y ago

truly, a problem you want to have.

NonContro 5y ago
Not really, because if there are long-term side effects, we need to have a control group. For example, the vaccine used for the 2009 Swine Flu: https://en.wikipedia.org/wiki/Pandemrix https://en.wikipedia.org/wiki/Pandemrix "Pandemrix was found to be associated with narcolepsy from observational studies, increasing the risk of narcolepsy by 5-14 times in children and 2-7 times in adults. The increased risk of narcolepsy due to vaccination in children and adolescents was around 1 incident per 18,400 doses." If you don't have a large section of the population unvaccinated, you can't conclusively prove that the vaccine was the cause.
- hprotagonist 5y ago
  “Problems you want to have“ are still problems, after all. It’s just, which would you rather have: a perfectly run trial because your vaccine efficacy is so low that your control group doesn’t feel incentivized to get vaccinated? Or a vaccine that works well enough to quell a pandemic, causing your control group to jump ship and potentially lessen your statistical power?
  - deleted 5y ago
    [deleted]
  - H8crilA 5y ago
    There was a comment here that got deleted. It had something cool I haven't seen before: a risk calculator/estimator for Covid (both death and hospital admission), for the UK: https://qcovid.org/Calculation https://qcovid.org/Calculation
    - chiefalchemist 5y ago
      Interesting. Especially that it uses a number of different "properties" (e.g., post code) to "fine tune" the calculation.
  - guscost 5y ago
    Either way, the higher-order effects will continue and cascade in perpetuity. The world is not a well-controlled experiment, and if you think there is an obvious “better” choice here which can be separated from all the context, then you have no idea how the world works.
    - hprotagonist 5y ago
      and if you think all choices are obviously bad (because there's no discernable 'better'), then i don't want you running a public health office. (disclaimer: i've run experiments with patients, i'm well aware of how messy the world is)
      - guscost 5y ago
        > i'm well aware of how messy the world is No, you are not. Not even close.
- jdavis703 5y ago
  In this case, there is a suspected autoimmune link between the similarity of the inactivated viral protein and a brain protein that is associated with sleep regulation. The real question to ask isn’t whether the placebo group was better off, but whether people infected with Swine Flu had a lower risk of narcolepsy than vaccine recipients.
- markus92 5y ago
  Not necessarily true. The incidence rates of those are well-known. Rarer side effects are impossible to find by comparing vaccinated/unvaccinated in a phase 3 and need larger groups to be found. That’s routine, though. Look at the VITT for the Adenoviral vector vaccines, no strict control group was necessary to identify that.

deleted 5y ago

[deleted]

AuthorizedCust 5y ago

This is old news, from February. A Google search on pfizer moderna studies placebo doesn’t turn up much of anything beyond similar articles. I wonder if the close scrutiny of the vaccines in the months following have been enough to allay concerns?

kaczordon 5y ago
The problem is that now we can’t do it even if we wanted to. The Big Corpos effectively blew up the control arm to protect their bottom line.
- RcouF1uZ4gsC 5y ago
  >The Big Corpos effectively blew up the control arm to protect their bottom line. Knowing what I know, if I was in the control arm, I would take the vaccine as soon as it was available. It would be highly unethical to keep people from being vaccinated who were in the control arm. Those “Big Corpos” literally saved millions of lives and trillions of dollars.
  - kaczordon 5y ago
    We do this all the time with cancer drugs. The ethical thing to do is to do the trial first and collect the data. You will benefit an order of magnitude more people and you will be able to answer future questions in a timely fashion.
    - epmaybe 5y ago
      No, we definitely don’t. If the treatment arm is seen as largely effective, the data safety and monitoring board will most definitely recommend unblinding participants and publishing the results as is. Please educate me with trials that do what you say if this is not true.
      - pbak 5y ago
        If all was well in the land of milk and honey, yes. However, if unlike me, and like most professionals, you didn't spent an unhealthy amount of time researching the details, you wouldn't know they didn't : https://www.bmj.com/content/371/bmj.m4956 https://www.bmj.com/content/371/bmj.m4956 "And even before the FDA advisory committee meeting on Moderna’s vaccine on 17 December, the company notified volunteers that they could learn their status if they chose to receive the vaccine. Pfizer also sent a letter to its trial participants one week after its vaccine was authorised on 10 December." Or you could go the Israeli way, and do the Pharma's job for them, keeping a 290K people with matched control group since December 2020 : https://www.cnbc.com/2021/07/23/delta-variant-pfizer-covid-vaccine-39percent-effective-in-israel-prevents-severe-illness.html https://www.cnbc.com/2021/07/23/delta-variant-pfizer-covid-v... That's what you get when go "warp speed" and doubt anything was done correctly under Trump, to suddenly forget and somehow believe everything was done AOK beforehand now that Biden is in...

devit 5y ago

Why not use unvaccinated people from the general population? There would be some selection bias, but it's going to be irrelevant for most things.

Exmoor 5y ago
Based on what we know about the demographics of those actively choosing to avoid COVID vaccination make me think that they would differ pretty significantly from those who would volunteer to participate in a phase 3 trial.
loonster 5y ago
Will never be a blind study. Unvaxed do not want to be vexed. They would never consent to a 50% chance of getting g vaxxed.

realreality 5y ago

> Perhaps in a year or two the existing vaccines will have proven so effective that COVID-19 becomes not much more than a nuisance. This sentence won't age well.

halfjoking 5y ago
We don't have to wait for it to age - Gibraltar, one of the only places in the world with 99% vaccination rate is seeing a spike in cases: https://www.worldometers.info/coronavirus/country/gibraltar/ https://www.worldometers.info/coronavirus/country/gibraltar/ https://www.express.co.uk/travel/articles/1469353/Gibraltar-green-list-restrictions-tighten-covid-cases-events-nightclubs https://www.express.co.uk/travel/articles/1469353/Gibraltar-...
- CarelessExpert 5y ago
  You mean the spike that's already subsiding, during which there was 1 death of a person who was unvaccinated? https://graphics.reuters.com/world-coronavirus-tracker-and-maps/countries-and-territories/gibraltar/ https://graphics.reuters.com/world-coronavirus-tracker-and-m... https://www.euroweeklynews.com/2021/08/05/gibraltar-resident-who-died-from-covid-19-was-unvaccinated/ https://www.euroweeklynews.com/2021/08/05/gibraltar-resident... Let's not get hysterical. Breakthrough cases will happen. That they cluster is no great surprise at all. Is covid a nuisance for Gibraltar? No. But it's far from the threat it was pre-vaccine.
  - yokaze 5y ago
    To add to that: Gibraltar isn't isolated, but has a lot of people coming and going from neighbouring Spain. Vaccination rate raising, but still far from 99%
- 8note 5y ago
  300 cases for 30k population? With 99% vaccinated, that's 10% of the unvaccinated population

strstr 5y ago

A lot of the early study members were physicians and health care workers, so this doesn’t come as a huge surprise. A pulmonologist I know that was in the Moderna study was offered a vaccine from their employer back in December. They tried to get urgently deblinded (this was after the primary study was done but before deblinding) so they could ensure the doses didn’t go to waste. This ended up being a bit of a bureaucratic nightmare, and they weren’t able to find out the answer until a few hours before their scheduled appointment. They had in fact been in the treatment group, so the dose was fortunately redirected to another healthcare worker.