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What I still can't wrap my head around is that they vaccinated the control group after less than a year and got away with it. Here we are, with a novel coronavi

What I still can't wrap my head around is that they vaccinated the control group after less than a year and got away with it. Here we are, with a novel coronavirus, a novel vaccine technology and a novel vaccine, and we can't even do a 2 year longterm study. > "During that visit we discussed the options, which included staying in the study without the vaccine," he says, "and amazingly there were people — a couple of people — who chose that." He suspects those individuals got spooked by rumors about the vaccine. But everybody else who had the placebo shot went ahead and got the actual vaccine. So now Fierro has essentially no comparison group left for the ongoing study. https://www.npr.org/sections/health-shots/2021/02/19/969143015/long-term-studies-of-covid-19-vaccines-hurt-by-placebo-recipients-getting-immuni https://www.npr.org/sections/health-shots/2021/02/19/9691430...

dekhn 5y ago
Have you carried out clinical trials before, done any sort of public health research, or worked in any way in science that involves people? When you say "got away with it" it sounds like you think they were intentionally carrying out a conspiracy theory. The reality is far more banal.
- raxxorrax 5y ago
  I did for non-invasive devices that were mostly class I + II. Even for those 1-2 years is very fast. Larger manufacturers might be quicker, but it is the time you should calculate with at minimum. I think the state of emergency allows to cut the time short, because these are very short time frames for clinical trials.
- angelzen 5y ago
  Somebody was kind enough to explain in a fair amount of detail how the process goes. It is an difficult ethical question. Mine is also an unfortunate formulation, perhaps "went under the radar" reflects the sentiment better. Here we are, managing a deadly pandemic with a novel technology and no depth line. All of this to say, given that there is no shortage of people willing to weather covid without a vaccine (17% of adults "definitely not" or "only if required" as of July 2021), perhaps there is a way to ethically design a study of the vaccines that doesn't lose its control group after less than a year. To risk "conspiratorial thinking" charges, what are the odds that in a country with 31% unvaccinated adults, only 2 participants in the control arm of a critical RCT didn't want to take the vaccine as soon as it was offered? https://www.nytimes.com/2021/07/31/us/virus-unvaccinated-americans.html https://www.nytimes.com/2021/07/31/us/virus-unvaccinated-ame... Edit: The study the NYT article references: https://www.kff.org/coronavirus-covid-19/poll-finding/kff-covid-19-vaccine-monitor-july-2021 https://www.kff.org/coronavirus-covid-19/poll-finding/kff-co... Edited the numbers to reflect the original source.
  - dekhn 5y ago
    I recommend that instead of postulating things on hacker news, you go read up some more, and then temper your comments. Really, large numbers of highly educated people who do this for a living have been arguing about this. We want to do better but we're restricted by human ethics and public opinion.
    - angelzen 5y ago
      I would be grateful for a handful of links to the highly educated people arguing about this, if the discussion happens to be public. I did speed read a few top academic Google hits on RCTs, but none of them tackled the particular issue of long term followups. Edit. Really, the only point I want to convey is that perhaps the highly intelligent and educated people could reflect on why RCT population of the covid studies don't seem to reflect the country population for the particular dimension of taking the vaccine as soon as the RCT ended. Perhaps this can be fixed somehow. This is as kind of a suggestion as I can muster. Perhaps they already do, and then all of this is moot.
      - dekhn 5y ago
        3 years isn't enough. People need to spend at least a decade working in human health before they can really contribute significantly towards improvements.
        angelzen 5y ago
        Incidentally, I originally wrote 10, but then I cut it down to 3. More than happy to accept your correction. [This refers to paragraph I ended up editing out because it was not constructive enough, sorry for any confusion. Sometimes I wish HN had DMs.]
throwawaysea 5y ago
That's an alarming detail I didn't realize. Without a control group maintained over some lengthy period (10+) years, is there any other methodology to identify and attribute any potential long-term side effects of a vaccine? I'm not worried about this all that much, as someone who opted for an mRNA vaccine, but I think we should still be rigorous in studying it just in case.
- xyzzy21 5y ago
  This is why "unvaxxed" often call themselves "The Control"; they noticed this long ago. In other news: most anti-vaxxers have advanced degrees and above average IQ.
  - dEnigma 5y ago
    Is your last claim a joke or serious? Because anecdotally I've seen almost the exact opposite in my social circles. But of course that's just personal experience.
    - throwawaysea 5y ago
      I think it is a reference to a study earlier this year that found that vaccine hesitancy was greatest among PhDs: https://www.usnews.com/news/health-news/articles/2021-07-27/whos-most-likely-to-refuse-a-covid-vaccine https://www.usnews.com/news/health-news/articles/2021-07-27/...
  - deleted 5y ago
    [deleted]
  - dTal 5y ago
    >most anti-vaxxers have advanced degrees and above average IQ I find this deeply implausible, both from first principles and personal experience. Can you back this extraordinary claim up? This study shows a negative correlation between IQ and covid vaccine hesitancy: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133799/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133799/
angryasian 5y ago
>Pfizer’s vaccine at several sites in Texas during that autumn, speed may have come at the cost of data integrity and patient safety. A regional director who was employed at the research organisation Ventavia Research Group has told The BMJ that the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase III trial While concerning, this was only a few sites in Texas.
- angelzen 5y ago
  I'm not that concerned about the irregularities in the original article, which are reported for some sites in Texas, though they are signs of rot. I am concerned that we promote, even mandate, mass vaccination for a novel coronavirus with a novel vaccine technology and a novel vaccine and no longterm controlled study in place.
  - banku_brougham 5y ago
    Back in the old days of vaccines we made do with a lot less
    - angelzen 5y ago
      Back in the old days we used to do long term vaccine controlled studies. Cursory Google search finds: > A long-term follow-up study on the efficacy of further attenuated live measles vaccine, Biken CAM vaccine, S Isomura & all, 1986 > Antibody persistence was measured in 39 children in an open community 12-13 years after immunization against measles with further attenuated live vaccine, Biken CAM. [...] For evaluation of the protective efficacy of the vaccine, matched controls were studied during the same period. Serological examination revealed that 97.5% of the controls were infected with measles and contracted the disease. https://pubmed.ncbi.nlm.nih.gov/3778422/ https://pubmed.ncbi.nlm.nih.gov/3778422/
  - BizarroLand 5y ago
    A quick glance at your post history and almost everything you post is antivax covid junk. I think you're too biased.
alecst 5y ago
The alternative is to knowingly let people get infected. Almost everyone will get exposed. The vaccine is safer than infection, both in the short and long term. Saying “they got away with it” makes it sound like a conspiracy.
- deleted 5y ago
  [deleted]
- angelzen 5y ago
  "Got away with it" in the sense that it went under the radar of most media and average people. I only found about it recently, and it was quite a bit of surprise, especially in the context of "science" being thrown away so liberally during this pandemic.
  - jatone 5y ago
    they were very up front about it.... 'operation light speed' they were explicitly removing barriers to speed up development and deployment.
  - Tagbert 5y ago
    I recall this being reported in several reports some months ago. It just wasn’t being treated as some failure or conspiracy.
- tata71 5y ago
  The alternative is having the control data originally plotted out.
- peteradio 5y ago
  It's dissonance inducing to say "both in the short and long term" when the point of the trial is to determine long term outcome.
  - Leparamour 5y ago
    As I've been told repeatedly, the science is settled and there is consensus from >99% of scientists that the politically critical Covid vaccine is completely safe. Questioning any of this just means that you're a science denier and blasphemer.
derbOac 5y ago
So, I know people involved in COVID vaccine trials (I can't remember which, I think it was Pfizer or Moderna), and also work with people who have been involved with other sorts of trials involving sensitive populations. Awhile ago, we had a conversation about the issue you're referring to. Basically what was happening was that people in the control group were getting vaccinated, increasingly so, after the trials showed efficacy. It wasn't even so much they were leaving the study, they were just violating the inclusion criteria. They were very aware of this, and discussed all sorts of ways of trying to get around it, too many to note here, including some weird designs with a new sample that at the time didn't really make logical sense to me from an efficacy RCT standpoint, but did from an ethical standpoint. There were at least two things on their mind. First, you can't force participants to remain in the trials long-term. So if they want to go get vaccinated, they're going to get vaccinated. You can't keep them from doing that. So if you lose 95% of your participants to that, and your power goes through the floor, what can you do? Second, there's a strong argument to be made that if you show strong efficacy of an intervention that prevents a world-crippling disease, it is highly unethical to keep the intervention from the control participants. It's not just unethical to encourage them not to get the vaccine, it's unethical to not offer it to them. There are many RCTs my colleagues have been in, of much more inconsequential treatments, where they ended up giving the treatment to controls because of this issue. So what about a COVID vaccine? Yes, long-term findings are necessary and/or desirable, but this can't really be done while circumventing ethical issues about withholding a highly effective intervention. There's lots of scenarios where this happens all the time -- where you'd like to get more and/or any RCT data but doing so raises ethical obstacles that are difficult to overcome. Maybe you could scrounge together enough people across trials but then you run into another issue: are the people who choose to remain in the control group long term really comparable to treatments on average anymore? You lose your randomization in an important sense, so it's all moot anyway. It's a difficult issue.
- peteradio 5y ago
  How do you make sure we don't inadvertently fuck over a huge population in a black swan event? It's like the establishment is using small scale tactics at totality scale which is certainly a critical point to be concerned about.

dekhn 5y ago

Have you carried out clinical trials before, done any sort of public health research, or worked in any way in science that involves people? When you say "got away with it" it sounds like you think they were intentionally carrying out a conspiracy theory. The reality is far more banal.

raxxorrax 5y ago
I did for non-invasive devices that were mostly class I + II. Even for those 1-2 years is very fast. Larger manufacturers might be quicker, but it is the time you should calculate with at minimum. I think the state of emergency allows to cut the time short, because these are very short time frames for clinical trials.
angelzen 5y ago
Somebody was kind enough to explain in a fair amount of detail how the process goes. It is an difficult ethical question. Mine is also an unfortunate formulation, perhaps "went under the radar" reflects the sentiment better. Here we are, managing a deadly pandemic with a novel technology and no depth line. All of this to say, given that there is no shortage of people willing to weather covid without a vaccine (17% of adults "definitely not" or "only if required" as of July 2021), perhaps there is a way to ethically design a study of the vaccines that doesn't lose its control group after less than a year. To risk "conspiratorial thinking" charges, what are the odds that in a country with 31% unvaccinated adults, only 2 participants in the control arm of a critical RCT didn't want to take the vaccine as soon as it was offered? https://www.nytimes.com/2021/07/31/us/virus-unvaccinated-americans.html https://www.nytimes.com/2021/07/31/us/virus-unvaccinated-ame... Edit: The study the NYT article references: https://www.kff.org/coronavirus-covid-19/poll-finding/kff-covid-19-vaccine-monitor-july-2021 https://www.kff.org/coronavirus-covid-19/poll-finding/kff-co... Edited the numbers to reflect the original source.
- dekhn 5y ago
  I recommend that instead of postulating things on hacker news, you go read up some more, and then temper your comments. Really, large numbers of highly educated people who do this for a living have been arguing about this. We want to do better but we're restricted by human ethics and public opinion.
  - angelzen 5y ago
    I would be grateful for a handful of links to the highly educated people arguing about this, if the discussion happens to be public. I did speed read a few top academic Google hits on RCTs, but none of them tackled the particular issue of long term followups. Edit. Really, the only point I want to convey is that perhaps the highly intelligent and educated people could reflect on why RCT population of the covid studies don't seem to reflect the country population for the particular dimension of taking the vaccine as soon as the RCT ended. Perhaps this can be fixed somehow. This is as kind of a suggestion as I can muster. Perhaps they already do, and then all of this is moot.
    - dekhn 5y ago
      3 years isn't enough. People need to spend at least a decade working in human health before they can really contribute significantly towards improvements.
      - angelzen 5y ago
        Incidentally, I originally wrote 10, but then I cut it down to 3. More than happy to accept your correction. [This refers to paragraph I ended up editing out because it was not constructive enough, sorry for any confusion. Sometimes I wish HN had DMs.]

throwawaysea 5y ago

That's an alarming detail I didn't realize. Without a control group maintained over some lengthy period (10+) years, is there any other methodology to identify and attribute any potential long-term side effects of a vaccine? I'm not worried about this all that much, as someone who opted for an mRNA vaccine, but I think we should still be rigorous in studying it just in case.

xyzzy21 5y ago
This is why "unvaxxed" often call themselves "The Control"; they noticed this long ago. In other news: most anti-vaxxers have advanced degrees and above average IQ.
- dEnigma 5y ago
  Is your last claim a joke or serious? Because anecdotally I've seen almost the exact opposite in my social circles. But of course that's just personal experience.
  - throwawaysea 5y ago
    I think it is a reference to a study earlier this year that found that vaccine hesitancy was greatest among PhDs: https://www.usnews.com/news/health-news/articles/2021-07-27/whos-most-likely-to-refuse-a-covid-vaccine https://www.usnews.com/news/health-news/articles/2021-07-27/...
- deleted 5y ago
  [deleted]
- dTal 5y ago
  >most anti-vaxxers have advanced degrees and above average IQ I find this deeply implausible, both from first principles and personal experience. Can you back this extraordinary claim up? This study shows a negative correlation between IQ and covid vaccine hesitancy: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133799/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133799/

angryasian 5y ago

>Pfizer’s vaccine at several sites in Texas during that autumn, speed may have come at the cost of data integrity and patient safety. A regional director who was employed at the research organisation Ventavia Research Group has told The BMJ that the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase III trial While concerning, this was only a few sites in Texas.

angelzen 5y ago
I'm not that concerned about the irregularities in the original article, which are reported for some sites in Texas, though they are signs of rot. I am concerned that we promote, even mandate, mass vaccination for a novel coronavirus with a novel vaccine technology and a novel vaccine and no longterm controlled study in place.
- banku_brougham 5y ago
  Back in the old days of vaccines we made do with a lot less
  - angelzen 5y ago
    Back in the old days we used to do long term vaccine controlled studies. Cursory Google search finds: > A long-term follow-up study on the efficacy of further attenuated live measles vaccine, Biken CAM vaccine, S Isomura & all, 1986 > Antibody persistence was measured in 39 children in an open community 12-13 years after immunization against measles with further attenuated live vaccine, Biken CAM. [...] For evaluation of the protective efficacy of the vaccine, matched controls were studied during the same period. Serological examination revealed that 97.5% of the controls were infected with measles and contracted the disease. https://pubmed.ncbi.nlm.nih.gov/3778422/ https://pubmed.ncbi.nlm.nih.gov/3778422/
- BizarroLand 5y ago
  A quick glance at your post history and almost everything you post is antivax covid junk. I think you're too biased.

alecst 5y ago

The alternative is to knowingly let people get infected. Almost everyone will get exposed. The vaccine is safer than infection, both in the short and long term. Saying “they got away with it” makes it sound like a conspiracy.

deleted 5y ago
[deleted]
angelzen 5y ago
"Got away with it" in the sense that it went under the radar of most media and average people. I only found about it recently, and it was quite a bit of surprise, especially in the context of "science" being thrown away so liberally during this pandemic.
- jatone 5y ago
  they were very up front about it.... 'operation light speed' they were explicitly removing barriers to speed up development and deployment.
- Tagbert 5y ago
  I recall this being reported in several reports some months ago. It just wasn’t being treated as some failure or conspiracy.
tata71 5y ago
The alternative is having the control data originally plotted out.
peteradio 5y ago
It's dissonance inducing to say "both in the short and long term" when the point of the trial is to determine long term outcome.
- Leparamour 5y ago
  As I've been told repeatedly, the science is settled and there is consensus from >99% of scientists that the politically critical Covid vaccine is completely safe. Questioning any of this just means that you're a science denier and blasphemer.

derbOac 5y ago

So, I know people involved in COVID vaccine trials (I can't remember which, I think it was Pfizer or Moderna), and also work with people who have been involved with other sorts of trials involving sensitive populations. Awhile ago, we had a conversation about the issue you're referring to. Basically what was happening was that people in the control group were getting vaccinated, increasingly so, after the trials showed efficacy. It wasn't even so much they were leaving the study, they were just violating the inclusion criteria. They were very aware of this, and discussed all sorts of ways of trying to get around it, too many to note here, including some weird designs with a new sample that at the time didn't really make logical sense to me from an efficacy RCT standpoint, but did from an ethical standpoint. There were at least two things on their mind. First, you can't force participants to remain in the trials long-term. So if they want to go get vaccinated, they're going to get vaccinated. You can't keep them from doing that. So if you lose 95% of your participants to that, and your power goes through the floor, what can you do? Second, there's a strong argument to be made that if you show strong efficacy of an intervention that prevents a world-crippling disease, it is highly unethical to keep the intervention from the control participants. It's not just unethical to encourage them not to get the vaccine, it's unethical to not offer it to them. There are many RCTs my colleagues have been in, of much more inconsequential treatments, where they ended up giving the treatment to controls because of this issue. So what about a COVID vaccine? Yes, long-term findings are necessary and/or desirable, but this can't really be done while circumventing ethical issues about withholding a highly effective intervention. There's lots of scenarios where this happens all the time -- where you'd like to get more and/or any RCT data but doing so raises ethical obstacles that are difficult to overcome. Maybe you could scrounge together enough people across trials but then you run into another issue: are the people who choose to remain in the control group long term really comparable to treatments on average anymore? You lose your randomization in an important sense, so it's all moot anyway. It's a difficult issue.

peteradio 5y ago
How do you make sure we don't inadvertently fuck over a huge population in a black swan event? It's like the establishment is using small scale tactics at totality scale which is certainly a critical point to be concerned about.