5 ms·

> The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians. OK, so weak evidence. > Prior to 2020, basically ev

by mlyle 5y ago

> The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians. OK, so weak evidence. > Prior to 2020, basically everyone on earth agreed (including the WHO, who STILL agrees) that front-line clinicians and observational studies are excellent signals that can lead to scientific investigations that can lead to medical breakthroughs. Sure-- weak/crappy evidence and practitioner intuition can definitely point at worthwhile things to study rigorously, even if most of what they generate is trash. > The evidence for IVM as a treatment for covid (and many other viruses) is quite strong. ??? Quite a leap you made there.

sjwalter 5y ago
Calling the investigatory and experiential evidence of thousands of highly-trained doctors (some of whom pioneered the standard of care for covid) as "weak evidence" is something that only somebody carrying water for large pharmaceutical companies would say. Doctors in my area are prescribing IVM to treat covid because in their experience and that of their peers IT WORKS. They have fewer deaths, fewer complications. But it's "weak" evidence just because Pfizer didn't sponsor a gigantic RCT to "prove" it. "The only science is real is expensive science done by large corporations!"
- dionian 5y ago
  Agreed, retract all the meta-analyses you want, but never dismiss actual front line results by physicians. If you have a regimen with zero deaths for a disease, I don't think we should be suppressing their clinical data. What a world...
  - ashtonkem 5y ago
    “Zero deaths” should have set off your alarm bells. That’s way too neat of a number for the real world; you only get that kind of result with small sample sizes or fraud. Even the vaccines, which are very effective, do not have a 0% death rate from infection.
    - chana_masala 5y ago
      Officially the FDA and CDC say there have been 0 deaths from adverse events. I agree, that's way too neat of a number for the real world.
      - lamontcg 5y ago
        https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-Shimabukuro-508.pdf https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-... 3 deaths from TTS following J&J as of May 7th where there were 8.73 million doses of J&J administered.
      - mlyle 5y ago
        You're saying re: vaccines? There's been several deaths believed to be caused by the vaccines and attributed as such by the FDA/CDC. And, you know, a few hundred thousand lives saved.
        pigeonhole123 5y ago
        Not a troll: how do you know that number? Pfizer’s own RCT showed no difference in all cause mortality after six months
        jjeaff 5y ago
        That was the trial that only had 40k participants. Adverse effects are so rare, it had to be administered to tens of millions of people to the public at large before just a few showed up.
        mlyle 5y ago
        Which number? The few hundred thousand saved? There's possible confounds, but none can explain vaccinated people being fewer than 6% of deaths (my MLE: about 2% of deaths) and more than 50% of the population. Especially since the vaccinated are, overall, a sicker and older population than the country at large. The vaccine RCTs were not powered sufficiently to show a reduction in COVID death, given that they had no or basically no COVID death in either group. They did show a huge reduction in illness and severe illness, and now we're observing a commensurate reduction in death in the population.
- koboll 5y ago
  It's weak evidence because COVID-19 observational studies are riddled with confounders due to COVID patients generally throwing everything at it they can to try and stay alive. The exact same pattern occurred with hydroxychloroquine. Lots of small observational studies showed promise. Then it repeatedly failed large RCTs. It turns out that the people with the resources to use HCQ also had the resources to use other things, things that were actually effective.
  - chana_masala 5y ago
    So what were those other things, then?
    - ashtonkem 5y ago
      Dexamethasone, Remdesivir, and monoclonal antibodies are part of the go to treatments for severe Covid cases. They’re the major exotic bits of what they gave trump when he got sick, along with a bunch of over the counter stuff (zinc, vitamin D, melatonin, etc.) My understanding is that the monoclonal antibodies are the really expensive treatments. The Dexamethasone one is an interesting story. It started out as a more controversial “throw everything at the wall and see what sticks” solution by a specialist who knew steroids well. Later studies have shown a strong effect on survival, so it’s become a fairly uncontroversial part of the tool kit for severe Covid.
      - makomk 5y ago
        Of course, what made Dexamethasone such a breakthrough wasn't really the drug itself; I think there's some evidence now that other steroids might actually work better. The big breakthrough was that some UK researchers managed to use the fact that the country got hit hard early on in the pandemic to immediately run a bunch of large randomized controlled trials on all the most promising throw-things-at-the-wall treatments to get evidence on which actually worked as soon as possible.
- PaulDavisThe1st 5y ago
  > "The only science is real is expensive science done by large corporations!" The only science that's real when it comes to public health is the science done across large enough populations and with enough methodology to rule out many confounding issues. That tends to cost money, indeed.
  - sjwalter 5y ago
    This is a neutered philosophy. You surrender you're ability to actually know things outside the purview of large pharma corps. Hey, I guess my view is never gonna get approved: Eat healthy meat, exercise, and get plenty of sunlight. Since that's never gonna get a big Pfizer RCT, you should wait. Don't exercise. Don't get sunlight. Just wait until a big pharmacorp tells you what is healthy.
    - deleted 5y ago
      [deleted]
    - ashtonkem 5y ago
      Come on, that’s clearly a bad faith interpretation of what GP said. You’ve been here long enough to know that that’s a no no.
    - PaulDavisThe1st 5y ago
      I considered adding on a coda noting that "costing money" doesn't imply big pharma. But I didn't because I considered it sort of self-evident. Neverthless, you went there anyway.
    - shapefrog 5y ago
      > I guess my view is never gonna get approved: Eat healthy meat, exercise, and get plenty of sunlight. Study has been approved 1,000s of times and been done 1,000s of times. Eating shit, sitting inside on your sofa all day is less healthy. The jury is out on your so called controversial view, has been for a long time.
- mlyle 5y ago
  > Calling the investigatory and experiential evidence of thousands of highly-trained doctors (some of whom pioneered the standard of care for covid) as "weak evidence" is something that only somebody carrying water for large pharmaceutical companies would say. Keep in mind that bleeding with leeches was once the standard of care-- based on clinical intuition and observational evidence. People-- even very smart, well-educated people-- are easily fooled. There is a reason why the RCT is the gold standard.
  - nradov 5y ago
    The RCT is the gold standard, but observational studies can be sufficient to establish causality when the effect size is large enough with a clear dose response curve. No one has ever conducted an RCT to prove that cigarette smoking causes lung cancer, but we're pretty sure that it does.
    - mlyle 5y ago
      > to establish causality when the effect size is large enough with a clear dose response curve. And when there's some plausible underlying mechanism that can be studied by more rigorous means. Otherwise, observational studies can find correlation, not causation-- and they're not even very robust at that.
      - nradov 5y ago
        No the dose response curve alone can be sufficient. Remember that the FDA has approved multiple SSRI drugs for treating clinical depression despite a lack of understanding on the actual mechanism of action. There are several plausible hypotheses but we really don't know why they work.
        mlyle 5y ago
        A dose response curve in an observational study is irrelevant for establishing causation. There is a dose-response relationship between umbrellas outside and rainfall., but umbrellas do not cause rainfall. And the SSRI point is tangential: they were approved based on RCT evidence. Observing umbrella use and concluding it causes rainfall, even though we don't know of a reason why umbrella use would cause rainfall, is quite different.
- jacquesm 5y ago
  > is something that only somebody carrying water for large pharmaceutical companies would say This is directly against the HN guidelines.
- 8note 5y ago
  I'd consider it weak because covid mostly has non-severe symptoms. A sugar pill could also get the same observational results because the number of severe cases is very low.
dionian 5y ago
Given the recent fall from grace of prestigious journals like the Lancet on the Coronavirus evidence, I think it is useful for all of us to remain skeptical and purely science-based. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31958-9/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

by mlyle 5y ago

sjwalter 5y ago

Calling the investigatory and experiential evidence of thousands of highly-trained doctors (some of whom pioneered the standard of care for covid) as "weak evidence" is something that only somebody carrying water for large pharmaceutical companies would say. Doctors in my area are prescribing IVM to treat covid because in their experience and that of their peers IT WORKS. They have fewer deaths, fewer complications. But it's "weak" evidence just because Pfizer didn't sponsor a gigantic RCT to "prove" it. "The only science is real is expensive science done by large corporations!"

dionian 5y ago
Agreed, retract all the meta-analyses you want, but never dismiss actual front line results by physicians. If you have a regimen with zero deaths for a disease, I don't think we should be suppressing their clinical data. What a world...
- ashtonkem 5y ago
  “Zero deaths” should have set off your alarm bells. That’s way too neat of a number for the real world; you only get that kind of result with small sample sizes or fraud. Even the vaccines, which are very effective, do not have a 0% death rate from infection.
  - chana_masala 5y ago
    Officially the FDA and CDC say there have been 0 deaths from adverse events. I agree, that's way too neat of a number for the real world.
    - lamontcg 5y ago
      https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-Shimabukuro-508.pdf https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-... 3 deaths from TTS following J&J as of May 7th where there were 8.73 million doses of J&J administered.
    - mlyle 5y ago
      You're saying re: vaccines? There's been several deaths believed to be caused by the vaccines and attributed as such by the FDA/CDC. And, you know, a few hundred thousand lives saved.
      - pigeonhole123 5y ago
        Not a troll: how do you know that number? Pfizer’s own RCT showed no difference in all cause mortality after six months
        jjeaff 5y ago
        That was the trial that only had 40k participants. Adverse effects are so rare, it had to be administered to tens of millions of people to the public at large before just a few showed up.
        mlyle 5y ago
        Which number? The few hundred thousand saved? There's possible confounds, but none can explain vaccinated people being fewer than 6% of deaths (my MLE: about 2% of deaths) and more than 50% of the population. Especially since the vaccinated are, overall, a sicker and older population than the country at large. The vaccine RCTs were not powered sufficiently to show a reduction in COVID death, given that they had no or basically no COVID death in either group. They did show a huge reduction in illness and severe illness, and now we're observing a commensurate reduction in death in the population.
koboll 5y ago
It's weak evidence because COVID-19 observational studies are riddled with confounders due to COVID patients generally throwing everything at it they can to try and stay alive. The exact same pattern occurred with hydroxychloroquine. Lots of small observational studies showed promise. Then it repeatedly failed large RCTs. It turns out that the people with the resources to use HCQ also had the resources to use other things, things that were actually effective.
- chana_masala 5y ago
  So what were those other things, then?
  - ashtonkem 5y ago
    Dexamethasone, Remdesivir, and monoclonal antibodies are part of the go to treatments for severe Covid cases. They’re the major exotic bits of what they gave trump when he got sick, along with a bunch of over the counter stuff (zinc, vitamin D, melatonin, etc.) My understanding is that the monoclonal antibodies are the really expensive treatments. The Dexamethasone one is an interesting story. It started out as a more controversial “throw everything at the wall and see what sticks” solution by a specialist who knew steroids well. Later studies have shown a strong effect on survival, so it’s become a fairly uncontroversial part of the tool kit for severe Covid.
    - makomk 5y ago
      Of course, what made Dexamethasone such a breakthrough wasn't really the drug itself; I think there's some evidence now that other steroids might actually work better. The big breakthrough was that some UK researchers managed to use the fact that the country got hit hard early on in the pandemic to immediately run a bunch of large randomized controlled trials on all the most promising throw-things-at-the-wall treatments to get evidence on which actually worked as soon as possible.
PaulDavisThe1st 5y ago
> "The only science is real is expensive science done by large corporations!" The only science that's real when it comes to public health is the science done across large enough populations and with enough methodology to rule out many confounding issues. That tends to cost money, indeed.
- sjwalter 5y ago
  This is a neutered philosophy. You surrender you're ability to actually know things outside the purview of large pharma corps. Hey, I guess my view is never gonna get approved: Eat healthy meat, exercise, and get plenty of sunlight. Since that's never gonna get a big Pfizer RCT, you should wait. Don't exercise. Don't get sunlight. Just wait until a big pharmacorp tells you what is healthy.
  - deleted 5y ago
    [deleted]
  - ashtonkem 5y ago
    Come on, that’s clearly a bad faith interpretation of what GP said. You’ve been here long enough to know that that’s a no no.
  - PaulDavisThe1st 5y ago
    I considered adding on a coda noting that "costing money" doesn't imply big pharma. But I didn't because I considered it sort of self-evident. Neverthless, you went there anyway.
  - shapefrog 5y ago
    > I guess my view is never gonna get approved: Eat healthy meat, exercise, and get plenty of sunlight. Study has been approved 1,000s of times and been done 1,000s of times. Eating shit, sitting inside on your sofa all day is less healthy. The jury is out on your so called controversial view, has been for a long time.
mlyle 5y ago
> Calling the investigatory and experiential evidence of thousands of highly-trained doctors (some of whom pioneered the standard of care for covid) as "weak evidence" is something that only somebody carrying water for large pharmaceutical companies would say. Keep in mind that bleeding with leeches was once the standard of care-- based on clinical intuition and observational evidence. People-- even very smart, well-educated people-- are easily fooled. There is a reason why the RCT is the gold standard.
- nradov 5y ago
  The RCT is the gold standard, but observational studies can be sufficient to establish causality when the effect size is large enough with a clear dose response curve. No one has ever conducted an RCT to prove that cigarette smoking causes lung cancer, but we're pretty sure that it does.
  - mlyle 5y ago
    > to establish causality when the effect size is large enough with a clear dose response curve. And when there's some plausible underlying mechanism that can be studied by more rigorous means. Otherwise, observational studies can find correlation, not causation-- and they're not even very robust at that.
    - nradov 5y ago
      No the dose response curve alone can be sufficient. Remember that the FDA has approved multiple SSRI drugs for treating clinical depression despite a lack of understanding on the actual mechanism of action. There are several plausible hypotheses but we really don't know why they work.
      - mlyle 5y ago
        A dose response curve in an observational study is irrelevant for establishing causation. There is a dose-response relationship between umbrellas outside and rainfall., but umbrellas do not cause rainfall. And the SSRI point is tangential: they were approved based on RCT evidence. Observing umbrella use and concluding it causes rainfall, even though we don't know of a reason why umbrella use would cause rainfall, is quite different.
jacquesm 5y ago
> is something that only somebody carrying water for large pharmaceutical companies would say This is directly against the HN guidelines.
8note 5y ago
I'd consider it weak because covid mostly has non-severe symptoms. A sugar pill could also get the same observational results because the number of severe cases is very low.

dionian 5y ago

Given the recent fall from grace of prestigious journals like the Lancet on the Coronavirus evidence, I think it is useful for all of us to remain skeptical and purely science-based. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31958-9/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...