6 ms·

While randomized trials are certainly the gold-standard for determining if you should give a new drug to treat an arbitrary disease, that process is far too con

While randomized trials are certainly the gold-standard for determining if you should give a new drug to treat an arbitrary disease, that process is far too conservative during a pandemic where a huge majority of the world cannot access proper medical care. Ivermectin is already massively produced, used throughout the world, and cheap to manufacture (compared to new anti-Covid drugs). Even months ago before the benefits were known, the risks of taking the drug were very small, especially when the treatment guidelines were to do practically nothing. Still, the many pieces of non-randomized evidence can still clearly point towards this drugs efficacy. The sudden drop in Covid cases in India as the clearest indicator to me.

jsnell 5y ago
> The sudden drop in Covid cases in India as the clearest indicator to me. What's the alleged connection here? Are you claiming that some non-trivial number of patients in India were treated with this? How many, and at what point after being infected? And just how did the treatment affect the case numbers? Generally you'd expect the vast majority of secondary infections to happen before the diagnosis, not after, so a treatment seems totally irrelevant to the case numbers.
- spadez 5y ago
  >Are you claiming that some non-trivial number of patients in India were treated with this Yes, example from two states. https://indianexpress.com/article/cities/lucknow/uttar-pradesh-government-says-ivermectin-helped-to-keep-deaths-low-7311786/ https://indianexpress.com/article/cities/lucknow/uttar-prade... https://www.news18.com/news/india/mortality-rate-much-lower-goa-govt-defends-use-of-ivermectin-for-covid-19-treatment-3786590.html https://www.news18.com/news/india/mortality-rate-much-lower-... The testimony video in this page cites examples in many other countries https://covid19criticalcare.com/ https://covid19criticalcare.com/
  - jsnell 5y ago
    I see no numbers on how many people were treated on either of the first two links, and certainly don't intend to comb through the dross on the third link. So do you actually have a number? It doesn't need to be exact, just a credible source on the order of magnitude will be enough. Are we talking a thousand, a million, or a billion here? To reduce R by a factor of 2 by the use of a prophylactic drug, you'd need to have half of the population on a regime of the drug. It seems pretty obvious that did not happen if this kind of reporting is the most impactful there is. Just think of the logistics of trying to do that! India has a population of 1.4 billion. On the other hand, if they only gave the snakeoil to e.g. a single digit number of millions of people the reduction in the number of infections would be imperceptible.
    - epicureanideal 5y ago
      This is a great comment, and an example of why discussion of ivermectin should not be CENSORED but instead debated. These would be good questions to ask the creators of any videos on the topic and from what I can see, the most popular creators would probably be open to the discussion.
    - spadez 5y ago
      Its the governments of the two states that are making the claims in the news articles. I think it is safe to suppose they or the associated medical authorities have observed a big enough benefit before making that claim. But no, no concrete numbers, as I think there was not much of tracking the number of patients who were given the drug. May be it is because such numbers are not much of a value in terms of research data due to lack of controls.
- wrycoder 5y ago
  Not a primary source, so FWIW. The article compares states in India using ivermectin against those which are not. Some digging in the sources listed might get what you are looking for. https://www.thedesertreview.com/news/national/ivermectin-obliterates-97-percent-of-delhi-cases/article_6a3be6b2-c31f-11eb-836d-2722d2325a08.html https://www.thedesertreview.com/news/national/ivermectin-obl...
belltaco 5y ago
>The sudden drop in Covid cases in India as the clearest indicator to me. Nah that's just confirmation bias and rumors. It wasn't effective at all, otherwise India wouldn't have taken it off the recommended drugs list.
- spadez 5y ago
  >India wouldn't have taken it off the recommended drugs list. Normally authorities are afraid to go against W.H.O recommendations, because if it didn't work out, it would be hard to justify it on the basis of local observations alone, at least on paper. But the important thing is that some states still did it, which might indicate there was very observable benefit.
- flenserboy 5y ago
  That's rather credulous.
  - ceejayoz 5y ago
    So's the idea that ivermectin must be the explanation for India's COVID spike abating. Spikes abated all over the world, more than once in most countries, without ivermectin.
- known 5y ago
  Numbers (China = 1.01 Billion, India = 270.91 Million) do not lie https://ourworldindata.org/covid-vaccinations https://ourworldindata.org/covid-vaccinations
janoc 5y ago
Ivermectin has been trialed also and has been available on experimental basis even in Europe - and it was found ineffective and is not recommended anymore. See: https://jamanetwork.com/journals/jama/fullarticle/2777389 https://jamanetwork.com/journals/jama/fullarticle/2777389 Also similar non-randomized evidence was strongly suggesting that hydroxychloroquine was very effective (e.g. Raoult in France) - until proper randomized trials found it was not effective at all. So you really can't rely on such evidence. That someone gets better after they got some drug doesn't automatically mean they got better because of the drug. In the absence of controls for other factors (other drugs, spontaneous recovery on their own, etc.) it only means that the drug didn't make their affliction worse. Not everything has to be immediately a conspiracy of big pharma (or worse).
- shaicoleman 5y ago
  The López-Medina trial was one of the biggest RCTs for Ivermectin. Out of the 60 trials for Ivermectin, it was one of the few that didn't show statistical significance. It was also seriously flawed - a large percentage of the placebo group was self-medicating using Ivermectin, they mixed up the treatment and placebo group, and they switched the primary outcome in the middle of the trial. That trial still showed improvement, but it didn't reach statistical significance. "[López-Medina] has many issues. The primary outcome was changed mid-trial from clinical deterioration to complete resolution of symptoms including "not hospitalized and no limitation of activities" as a negative outcome. Critically, temporary side effects of a successful treatment may be considered as a negative outcome, which could result in falsely concluding that the treatment is not effective. Such an outcome is also not very meaningful in terms of assessing how treatment affects the incidence of serious outcomes. With the low risk patient population in this study, there is also little room for improvement - 58% recovered within the first 2 days to "not hospitalized and no limitation of activities" or better. There was only one death (in the control arm). This study also gave ivermectin to the control arm for 38 patients and it is unknown if the full extent of the error was identified, or if there were additional undiscovered errors. The side effect data reported in this trial raises major concerns, with more side effects reported in the placebo arm, suggesting that more placebo patients may have received treatment. Ivermectin was widely used in the population and available OTC at the time of the study. The study protocol allows other treatments but does not report on usage. The name of the study drug was concealed by refering to it as "D11AX22". The presentation of this study also appears to be significantly biased. While all outcomes show a benefit for ivermectin, the abstract fails to mention that much larger benefits are seen for serious outcomes, including the original primary outcome, and that the reason for not reaching statistical signficance is the low number of events in a low risk population where most recover quickly without treatment." https://ivmmeta.com/#exc https://ivmmeta.com/#exc This prompted an open letter from over 170 physicians concluding that the study is fatally flawed. https://jamaletter.com/ https://jamaletter.com/ This also highlights the risk of only relying on a small number of large RCTs, instead of looking at the totality of evidence.
_dark_matter_ 5y ago
I had the same opinion until my friend convinced me otherwise. The scientific community is taking a long-term approach here. If they were to recommend a drug based without a scientific trial, they risk losing the trust of the world (either from people who want them to only follow the science, and the risk that it is incorrect). The anti-science block is growing, and they are loud. If they continue to grow it could be an even greater threat to humanity than COVID-19. Science is attempting to fight against it by retreating to a science-only corner, for better or for worse.
- emn13 5y ago
  It would be nice if we somehow found a way as society to get the message out that scientists often just don't know. Because too often stories like this are interpreted by quite a few people as "science says ivermectin doesn't work". And perhaps that conclusion will turn out to be right, but the point is the jury is still out - and often enough it turns out wrong, and when such a false statement turns out to be wrong, people lose faith in science regardless, even though a reasonable interpretation of the science actually said "don't know" not "doesn't work". This is kind of a corollary to the issues with rejecting conspiracies - when we reject a supposed conspiracy, due to lack of evidence, that can easily come across as claiming the conspiratorial claim is outright false - but in a sea of such claims, some then turn out to have at least a kernel of truth, which then turns into a big gotcha moment: "see, they're repressing us, we were right all along!" So while I understand the idea of maintaining trust by not backing anything uncertain, I'm not sure it's the right call. Maybe communicating that uncertainty is better, and even communicating hints and possibilities - instead of trying to control the narrative but thereby ceding the ground to nutjobs until certainty arrives, often granting them considerable prestige if they guess sort of correctly ahead of time.
- thu2111 5y ago
  If they were to recommend a drug based without a scientific trial, they risk losing the trust of the world But that's already happened with vaccines. A bit late to worry about that now.

jsnell 5y ago

> The sudden drop in Covid cases in India as the clearest indicator to me. What's the alleged connection here? Are you claiming that some non-trivial number of patients in India were treated with this? How many, and at what point after being infected? And just how did the treatment affect the case numbers? Generally you'd expect the vast majority of secondary infections to happen before the diagnosis, not after, so a treatment seems totally irrelevant to the case numbers.

spadez 5y ago
>Are you claiming that some non-trivial number of patients in India were treated with this Yes, example from two states. https://indianexpress.com/article/cities/lucknow/uttar-pradesh-government-says-ivermectin-helped-to-keep-deaths-low-7311786/ https://indianexpress.com/article/cities/lucknow/uttar-prade... https://www.news18.com/news/india/mortality-rate-much-lower-goa-govt-defends-use-of-ivermectin-for-covid-19-treatment-3786590.html https://www.news18.com/news/india/mortality-rate-much-lower-... The testimony video in this page cites examples in many other countries https://covid19criticalcare.com/ https://covid19criticalcare.com/
- jsnell 5y ago
  I see no numbers on how many people were treated on either of the first two links, and certainly don't intend to comb through the dross on the third link. So do you actually have a number? It doesn't need to be exact, just a credible source on the order of magnitude will be enough. Are we talking a thousand, a million, or a billion here? To reduce R by a factor of 2 by the use of a prophylactic drug, you'd need to have half of the population on a regime of the drug. It seems pretty obvious that did not happen if this kind of reporting is the most impactful there is. Just think of the logistics of trying to do that! India has a population of 1.4 billion. On the other hand, if they only gave the snakeoil to e.g. a single digit number of millions of people the reduction in the number of infections would be imperceptible.
  - epicureanideal 5y ago
    This is a great comment, and an example of why discussion of ivermectin should not be CENSORED but instead debated. These would be good questions to ask the creators of any videos on the topic and from what I can see, the most popular creators would probably be open to the discussion.
  - spadez 5y ago
    Its the governments of the two states that are making the claims in the news articles. I think it is safe to suppose they or the associated medical authorities have observed a big enough benefit before making that claim. But no, no concrete numbers, as I think there was not much of tracking the number of patients who were given the drug. May be it is because such numbers are not much of a value in terms of research data due to lack of controls.
wrycoder 5y ago
Not a primary source, so FWIW. The article compares states in India using ivermectin against those which are not. Some digging in the sources listed might get what you are looking for. https://www.thedesertreview.com/news/national/ivermectin-obliterates-97-percent-of-delhi-cases/article_6a3be6b2-c31f-11eb-836d-2722d2325a08.html https://www.thedesertreview.com/news/national/ivermectin-obl...

belltaco 5y ago

>The sudden drop in Covid cases in India as the clearest indicator to me. Nah that's just confirmation bias and rumors. It wasn't effective at all, otherwise India wouldn't have taken it off the recommended drugs list.

spadez 5y ago
>India wouldn't have taken it off the recommended drugs list. Normally authorities are afraid to go against W.H.O recommendations, because if it didn't work out, it would be hard to justify it on the basis of local observations alone, at least on paper. But the important thing is that some states still did it, which might indicate there was very observable benefit.
flenserboy 5y ago
That's rather credulous.
- ceejayoz 5y ago
  So's the idea that ivermectin must be the explanation for India's COVID spike abating. Spikes abated all over the world, more than once in most countries, without ivermectin.
known 5y ago
Numbers (China = 1.01 Billion, India = 270.91 Million) do not lie https://ourworldindata.org/covid-vaccinations https://ourworldindata.org/covid-vaccinations

janoc 5y ago

Ivermectin has been trialed also and has been available on experimental basis even in Europe - and it was found ineffective and is not recommended anymore. See: https://jamanetwork.com/journals/jama/fullarticle/2777389 https://jamanetwork.com/journals/jama/fullarticle/2777389 Also similar non-randomized evidence was strongly suggesting that hydroxychloroquine was very effective (e.g. Raoult in France) - until proper randomized trials found it was not effective at all. So you really can't rely on such evidence. That someone gets better after they got some drug doesn't automatically mean they got better because of the drug. In the absence of controls for other factors (other drugs, spontaneous recovery on their own, etc.) it only means that the drug didn't make their affliction worse. Not everything has to be immediately a conspiracy of big pharma (or worse).

shaicoleman 5y ago
The López-Medina trial was one of the biggest RCTs for Ivermectin. Out of the 60 trials for Ivermectin, it was one of the few that didn't show statistical significance. It was also seriously flawed - a large percentage of the placebo group was self-medicating using Ivermectin, they mixed up the treatment and placebo group, and they switched the primary outcome in the middle of the trial. That trial still showed improvement, but it didn't reach statistical significance. "[López-Medina] has many issues. The primary outcome was changed mid-trial from clinical deterioration to complete resolution of symptoms including "not hospitalized and no limitation of activities" as a negative outcome. Critically, temporary side effects of a successful treatment may be considered as a negative outcome, which could result in falsely concluding that the treatment is not effective. Such an outcome is also not very meaningful in terms of assessing how treatment affects the incidence of serious outcomes. With the low risk patient population in this study, there is also little room for improvement - 58% recovered within the first 2 days to "not hospitalized and no limitation of activities" or better. There was only one death (in the control arm). This study also gave ivermectin to the control arm for 38 patients and it is unknown if the full extent of the error was identified, or if there were additional undiscovered errors. The side effect data reported in this trial raises major concerns, with more side effects reported in the placebo arm, suggesting that more placebo patients may have received treatment. Ivermectin was widely used in the population and available OTC at the time of the study. The study protocol allows other treatments but does not report on usage. The name of the study drug was concealed by refering to it as "D11AX22". The presentation of this study also appears to be significantly biased. While all outcomes show a benefit for ivermectin, the abstract fails to mention that much larger benefits are seen for serious outcomes, including the original primary outcome, and that the reason for not reaching statistical signficance is the low number of events in a low risk population where most recover quickly without treatment." https://ivmmeta.com/#exc https://ivmmeta.com/#exc This prompted an open letter from over 170 physicians concluding that the study is fatally flawed. https://jamaletter.com/ https://jamaletter.com/ This also highlights the risk of only relying on a small number of large RCTs, instead of looking at the totality of evidence.

_dark_matter_ 5y ago

I had the same opinion until my friend convinced me otherwise. The scientific community is taking a long-term approach here. If they were to recommend a drug based without a scientific trial, they risk losing the trust of the world (either from people who want them to only follow the science, and the risk that it is incorrect). The anti-science block is growing, and they are loud. If they continue to grow it could be an even greater threat to humanity than COVID-19. Science is attempting to fight against it by retreating to a science-only corner, for better or for worse.

emn13 5y ago
It would be nice if we somehow found a way as society to get the message out that scientists often just don't know. Because too often stories like this are interpreted by quite a few people as "science says ivermectin doesn't work". And perhaps that conclusion will turn out to be right, but the point is the jury is still out - and often enough it turns out wrong, and when such a false statement turns out to be wrong, people lose faith in science regardless, even though a reasonable interpretation of the science actually said "don't know" not "doesn't work". This is kind of a corollary to the issues with rejecting conspiracies - when we reject a supposed conspiracy, due to lack of evidence, that can easily come across as claiming the conspiratorial claim is outright false - but in a sea of such claims, some then turn out to have at least a kernel of truth, which then turns into a big gotcha moment: "see, they're repressing us, we were right all along!" So while I understand the idea of maintaining trust by not backing anything uncertain, I'm not sure it's the right call. Maybe communicating that uncertainty is better, and even communicating hints and possibilities - instead of trying to control the narrative but thereby ceding the ground to nutjobs until certainty arrives, often granting them considerable prestige if they guess sort of correctly ahead of time.
thu2111 5y ago
If they were to recommend a drug based without a scientific trial, they risk losing the trust of the world But that's already happened with vaccines. A bit late to worry about that now.