Interesting ... it's presented in the context of drugs for curing infections.
I wonder if this is being used for other drugs. My curiosity stems from personal experience: I had Migraine headaches from age 17 to about 35. I was put on ancient seizure medication that's common prescribed for Bipolar[0] because this doctor had three other patients that it nearly eliminated Migraine from. It was fall, a time when I'd get about one a week. After five days of taking it, I had my first Migraine ... if you could call it that -- I could only identify that it was a Migraine by the aura; the pain was about 10% what I'm used to).
Searching through the web, I found a forum that was filled with Migraine sufferers. Sure enough, there were a handful of people who swore by it. There were also a handful of people who it didn't work for. Looking at the more official sources, there was no indication that this drug could have any effect on Migraine; they listed all of the other off-label uses[1], but Migraine was not among them.
This medication had been in the news several times (and on the front page, here[2]) over the last few years and a year ago (or so), I looked it up on the "official sources", again. It now indicated that it was prescribed for Migraine.
It made me wonder ... how are things like that figured out/communicated down-stream? Is it entirely informally amongst doctors? I went to four different specialists before I found one who suggested this drug -- and he did so in a "half-hearted manner" not truly expecting it would work. It'd be nice if this was centrally tracked/managed as it might surface both "new uses for old drugs" and "new problems with old drugs."
[0] Which I do not have.
[1] It's rarely, if ever, prescribed for what it was originally approved for.
[2] It's Depakote, I'm not being cagey for nefarious purposes, I just didn't want this to be a drug advertisement.
Once drugs lose patent protection, it's difficult for them to gain approval for new indications, because drug approval procedures are extremely expensive and there's no patent holder left for whom it would make economic sense to spend all that money.
So in cases like valproate for migraine, those drugs usually stay off-label long term. That makes them unattractive for doctors to prescribe, since they assume more liability if something goes wrong, and insurance companies are less likely to cover the drugs.
The way information about off-label uses gets communicated is basically the same way as elsewhere in science: through scientific papers, conferences, textbooks, and the like. A doctor who discovers that their migraine patient does well on valproate might publish this as a case report. If there are many such reports, someone might do a randomized trial. Once there are many randomized trials, meta-analyses can be performed, and eventually, the information will end up in textbooks and medical school curricula.
It takes a certain amount of agency for a doctor to stay up to date on the latest research; while medical boards tend to have certification requirements for CME (continuing medical education), these are usually quite lax, and a truly lazy doctor can probably just live their years without really learning anything new.
At the same time, reading all new research that comes out is basically impossible, and even just trying to do this would risk always following the latest fads that later evidence might show to, in fact, be harmful. Every doctor needs to find their own middle ground here, and you as a patient must find a doctor that suits your own preferences.
> Once drugs lose patent protection, it's difficult for them to gain approval for new indications, because drug approval procedures are extremely expensive and there's no patent holder left for whom it would make economic sense to spend all that money.
This is precisely why I think a gov't run research effort is the right way to handle this. You don't want to grant a new patent on the existing drug just because of new use of it. That would prevent the generics being used for the original purpose. So if the bigPharma company that created it for original purposes does not want to spend money researching alternate uses, then allow the gov't direct the research in the name of keeping its citizens healthy.
Unfortunately, that doesn't really stand up as a great solution with using the current administration as an example of what happens when you get anti-science mindsets in charge of things. It also helps to have a gov't that is empathetic for its citizens which does not always happen.
Yes, in fact, most of the types of research I mentioned, where random people at hospitals do small trials on existing medications, is going to be partially government funded.
But care must be taken to avoid the tulip subsidies problem [1]: the barriers to drug approval are regulatory, not natural. If a drug regulatory agency sets high requirements for approval and another governmental agency must do expensive work to satisfy these requirements, there is a risk that costs go out of control without any real benefit.
Instead, my favoured solution would be to significantly relax regulatory requirements in cases like this where a drug has already been proven to be safe both in the original approval trials and in years of real-world use, such that when trials and meta-analyses exist that suffice to convince the medical establishment of a drug's safety and efficacy for a new indication, these would also be enough for the drug to gain approval for that indication.
I wonder if some sort of coalition of compounding pharmacists might be up for making and retaining a repository. They at least make some money by helping would-be patients take these drugs, right? So even if it's nothing like Big Pharma money, I can't really think of anybody who'd have a better chance to benefit from promoting off-label use cases for out of patent drugs than them.
Real world, sometimes a doctor will think up a novel use of the effect of a drug. And sometimes they'll throw stuff at the wall and see what sticks. When you don't have a good answer this can be sane medical practice. But there should be a requirement of reporting it to something like this database.
It's not even about the doctors trying things themselves. Enough people have more than one issue at the time that they will notice "you prescribed this for A, but B went away as well".
I'm in the same boat with propanalol - my doctor told me it was "the worst blood pressure medication available, but surprisingly effective at preventing migraine symptoms (as well as physical symptoms of anxiety)".
There are so many interesting, off-label novel uses for drugs that have already been developed. Recently my wife & I adopted a kitten that developed FIP, a disease caused by a feline coronavirus that was nearly 100% fatal up until just a few years ago.
Turns out, a drug developed by Gilead Sciences (GS-441524) which is the active metabolite of remdesivir, is remarkably effective at treating the disease. It's a nucleoside analog, so it essentially is a slightly modified adenosine molecule which disrupts the virus RNA replication process.
Within 12 hours of the first dose our cat went from dying to making a full turnaround and complete recovery following treatment. For us it was truly a miracle drug, and it only gained awareness recently due to the COVID-19 pandemic [1]. It still isn't technically "approved" for this use case, but is prescribed off-label by vets as of 2024 once the FDA relaxed its position [2]. Folks needed to seek it out on the black market (and still do in some areas).
NCATS and other NIH data resource teams were heavily affected or completely dismantled during the latest reductions in force (RIFs). Getting data from certain areas inside HHS will be difficult to impossible for the foreseeable future.
Your concerns may be justified. The site says: "This repository is under review for potential modification in compliance with Administration directives."
I wonder how this is going (started 2013), because I have a hunch it will be chasing ghosts, mostly. Placebo affect is a factor here. I also wonder how many fake leads from "propaganda physicians" they get.
You don't know you're chasing ghosts until you start running.
There's not much wrong with the system so long as it's used as a place to get ideas for clinical studies or absolute last-ditch attempts at saving lives. On occasion (like the Milwaukee Protocol for rabies), those last-ditch attempts do work.
It's when people pretend there's no real investigation to be done that we get problems.
The real thing is can we (perhaps with new advances in statistics?) find places where doctors at the end of all known treatment try things at random and see if anything works. For rare symptoms it often isn't possible to run a proper controlled study (note that I said symptoms and not disease - often we are not really sure what is going on). So if we can give doctors a list "here is what someone else tried and or treatment Y seems to make things worse that is a clue. Eventually we can say that we don't know why, but X seems like your best shot even if it we can never get to real statistical significance.
Doctors already have case studies which they (at least should) publish anytime they get someone who for whatever reason doesn't respond to standard treatment, or has something unknown. However it is hard for the next doctor to find any that might be relevant.
It became apparent really fast that ivermectin was effective... against a superinfection with parasites, which the reported success cases all had.
But by the time it became apparent, the correction didn't spread nearly as fast nor wide as the original information.
The problem is, most people lack the scientific literacy to understand how science works, and many newspapers have long since gutted their expert journalists.
HCQ combined with Zinc was a valid treatment for Covid. The drugs peddled by the people profiting from Covid were essentially HCQ and Ivermectin clones. Both are considered essential medicines by WHO, or at least, they were at the time.
As someone who had Covid multiple times, CQ+quercetin+zinc was a valid treatment, but it required very cautious dosing. As for ivermectin, it did not help at all, but if someone has worms, perhaps it would help them. And no, the other drugs are not clones, as their mechanisms of action are completely different. Facts matter.
The FDA was sued and lost (or at least agreed to a settlement) over those comments, which were consequently deleted. Ivermectin is a human antiparasitic that's even on the WHO List of Essential Medicines. [1] Their comment was akin to saying that amoxicillin is a horse antibacterial drug, which is true, but quite misleading. Off-label usage for pharmaceuticals is extremely common and an important right of doctors. I mean that's pretty much the entire point of this topic!
Ah.. that said, even that wikipedia article points out that multiple research studies were done that demonstrated little to no benefit in the context of covid19 (and the ones that did were eventually proven faulty or fraudulent) - I agree that Ivermectin is an important drug, just not in the context of covid19
The fact that people were obtaining it from sources intended for horses is mostly unrelated to the fact that it is not effective as a Covid treatment for people who don’t have some other parasite in addition to Covid.
I don’t think calling it a horse dewormer is helpful, despite the fact that people were obtaining it from people who were selling it for the treatment of horses. People who (wrongly) think it works as treatment for covid will probably be aware that it is not exclusively a treatment for horses, so I don’t think calling it a horse dewormer will change any of their minds.
Even if it did, I am uncomfortable relying on misleading people in order to convince them of something true. (If someone believes X, and X is false, and you want to convince them of a true statement Z, then it is fine to say “X is false, but, I know you believe that X. Y is true, and X and Y together clearly imply Z. Therefore you should conclude Z.” (Assuming Y is true.) That’s not misleading someone. It is something different.)
It seems like allowing oneself to mislead, even if only when the misleading statements are sorta true in a sense, just not in the way they will be interpreted, in order to convince someone of something that is true, is rather dangerous. If such behavior were universalized, I think it would be rather bad for collective understanding. (What if someone U is trying to convince someone V of some statement P which U only believe is true because someone W misled U in to believe P in order to convince U of some other statement Q that is true, and then U says something misleading to V (leading V to believe a false statement R) in order to convince V that P ? Not good.)
This irrational belief isn't going away either. It seems to be spreading, in fact. A relative of mine recently was diagnosed with cancer and a "friend" of hers suggested she try ivermectin.
The tl;dr, as I recall it: it seems ivermectin really did work in some populations, in reducing COVID mortality. However, those populations were ones where one was much more likely to have worms, so the hypothesis is that indeed did work, but only because it worked as a dewormer and not having worms concurrently with COVID decreased the likelihood of mortality.
Interesting ... it's presented in the context of drugs for curing infections.
I wonder if this is being used for other drugs. My curiosity stems from personal experience: I had Migraine headaches from age 17 to about 35. I was put on ancient seizure medication that's common prescribed for Bipolar[0] because this doctor had three other patients that it nearly eliminated Migraine from. It was fall, a time when I'd get about one a week. After five days of taking it, I had my first Migraine ... if you could call it that -- I could only identify that it was a Migraine by the aura; the pain was about 10% what I'm used to).
Searching through the web, I found a forum that was filled with Migraine sufferers. Sure enough, there were a handful of people who swore by it. There were also a handful of people who it didn't work for. Looking at the more official sources, there was no indication that this drug could have any effect on Migraine; they listed all of the other off-label uses[1], but Migraine was not among them.
This medication had been in the news several times (and on the front page, here[2]) over the last few years and a year ago (or so), I looked it up on the "official sources", again. It now indicated that it was prescribed for Migraine.
It made me wonder ... how are things like that figured out/communicated down-stream? Is it entirely informally amongst doctors? I went to four different specialists before I found one who suggested this drug -- and he did so in a "half-hearted manner" not truly expecting it would work. It'd be nice if this was centrally tracked/managed as it might surface both "new uses for old drugs" and "new problems with old drugs."
[0] Which I do not have.
[1] It's rarely, if ever, prescribed for what it was originally approved for.
[2] It's Depakote, I'm not being cagey for nefarious purposes, I just didn't want this to be a drug advertisement.
Once drugs lose patent protection, it's difficult for them to gain approval for new indications, because drug approval procedures are extremely expensive and there's no patent holder left for whom it would make economic sense to spend all that money.
So in cases like valproate for migraine, those drugs usually stay off-label long term. That makes them unattractive for doctors to prescribe, since they assume more liability if something goes wrong, and insurance companies are less likely to cover the drugs.
The way information about off-label uses gets communicated is basically the same way as elsewhere in science: through scientific papers, conferences, textbooks, and the like. A doctor who discovers that their migraine patient does well on valproate might publish this as a case report. If there are many such reports, someone might do a randomized trial. Once there are many randomized trials, meta-analyses can be performed, and eventually, the information will end up in textbooks and medical school curricula.
It takes a certain amount of agency for a doctor to stay up to date on the latest research; while medical boards tend to have certification requirements for CME (continuing medical education), these are usually quite lax, and a truly lazy doctor can probably just live their years without really learning anything new.
At the same time, reading all new research that comes out is basically impossible, and even just trying to do this would risk always following the latest fads that later evidence might show to, in fact, be harmful. Every doctor needs to find their own middle ground here, and you as a patient must find a doctor that suits your own preferences.
> Once drugs lose patent protection, it's difficult for them to gain approval for new indications, because drug approval procedures are extremely expensive and there's no patent holder left for whom it would make economic sense to spend all that money.
This is precisely why I think a gov't run research effort is the right way to handle this. You don't want to grant a new patent on the existing drug just because of new use of it. That would prevent the generics being used for the original purpose. So if the bigPharma company that created it for original purposes does not want to spend money researching alternate uses, then allow the gov't direct the research in the name of keeping its citizens healthy.
Unfortunately, that doesn't really stand up as a great solution with using the current administration as an example of what happens when you get anti-science mindsets in charge of things. It also helps to have a gov't that is empathetic for its citizens which does not always happen.
Yes, in fact, most of the types of research I mentioned, where random people at hospitals do small trials on existing medications, is going to be partially government funded.
But care must be taken to avoid the tulip subsidies problem [1]: the barriers to drug approval are regulatory, not natural. If a drug regulatory agency sets high requirements for approval and another governmental agency must do expensive work to satisfy these requirements, there is a risk that costs go out of control without any real benefit.
Instead, my favoured solution would be to significantly relax regulatory requirements in cases like this where a drug has already been proven to be safe both in the original approval trials and in years of real-world use, such that when trials and meta-analyses exist that suffice to convince the medical establishment of a drug's safety and efficacy for a new indication, these would also be enough for the drug to gain approval for that indication.
[1] https://slatestarcodex.com/2015/06/06/against-tulip-subsidie...
I wonder if some sort of coalition of compounding pharmacists might be up for making and retaining a repository. They at least make some money by helping would-be patients take these drugs, right? So even if it's nothing like Big Pharma money, I can't really think of anybody who'd have a better chance to benefit from promoting off-label use cases for out of patent drugs than them.
Yes, but why be the one to set it up? Why not be the pharmacist who waits for others to do it, and then sell it anyway?
...sell ads on it? Maybe for the docs who are willing to prescribe off-label? Maybe for other pharmacies?
I don't know. Maybe it's not a viable business model, but there are certainly weirder things that make money.
Yeah, sounds like they got something right.
Real world, sometimes a doctor will think up a novel use of the effect of a drug. And sometimes they'll throw stuff at the wall and see what sticks. When you don't have a good answer this can be sane medical practice. But there should be a requirement of reporting it to something like this database.
It's not even about the doctors trying things themselves. Enough people have more than one issue at the time that they will notice "you prescribed this for A, but B went away as well".
I'm in the same boat with propanalol - my doctor told me it was "the worst blood pressure medication available, but surprisingly effective at preventing migraine symptoms (as well as physical symptoms of anxiety)".
Physicians are a priestly profession, and they communicate in mysterious ways known only yo Aesclepias, Hermes, and Hippocrates and Toth...
Now wave that cadaceus around my head another time, Morpheus
Just today I read about this in the book "Who is Government" by Michael Lewis where he presents the case on how it can help find cure for rare diseases. You can read his article at https://www.washingtonpost.com/opinions/interactive/2025/mic....
Also highly recommend the book.
That article has a horrible writing style. So much fluff and so litlle content.
There are so many interesting, off-label novel uses for drugs that have already been developed. Recently my wife & I adopted a kitten that developed FIP, a disease caused by a feline coronavirus that was nearly 100% fatal up until just a few years ago.
Turns out, a drug developed by Gilead Sciences (GS-441524) which is the active metabolite of remdesivir, is remarkably effective at treating the disease. It's a nucleoside analog, so it essentially is a slightly modified adenosine molecule which disrupts the virus RNA replication process.
Within 12 hours of the first dose our cat went from dying to making a full turnaround and complete recovery following treatment. For us it was truly a miracle drug, and it only gained awareness recently due to the COVID-19 pandemic [1]. It still isn't technically "approved" for this use case, but is prescribed off-label by vets as of 2024 once the FDA relaxed its position [2]. Folks needed to seek it out on the black market (and still do in some areas).
[1] https://www.theatlantic.com/science/archive/2020/05/remdesiv...
[2] https://www.fda.gov/animal-veterinary/cvm-updates/fda-announ...
Very cool seeing this show up on HN. FDA has a bunch of interested datasets like this that are full of interesting data points.
During COVID, I actually wrote a small sample app that pulls info from this DB: https://www.covidcureid.com/
And gave a talk on it: https://learn.microsoft.com/en-us/shows/azure-serverless-con...
How viable would it be to mirror the set? Given that the US is having it's ISIS book-burning moment so the original sources are at risk :(
Try emailing the team and see if you can get the data set: https://cure.ncats.io/resources/ehr-resources
Otherwise, my code to extract the data is here: https://github.com/CharlieDigital/covidcureid/blob/main/serv...
NCATS and other NIH data resource teams were heavily affected or completely dismantled during the latest reductions in force (RIFs). Getting data from certain areas inside HHS will be difficult to impossible for the foreseeable future.
Your concerns may be justified. The site says: "This repository is under review for potential modification in compliance with Administration directives."
I wonder how this is going (started 2013), because I have a hunch it will be chasing ghosts, mostly. Placebo affect is a factor here. I also wonder how many fake leads from "propaganda physicians" they get.
You don't know you're chasing ghosts until you start running.
There's not much wrong with the system so long as it's used as a place to get ideas for clinical studies or absolute last-ditch attempts at saving lives. On occasion (like the Milwaukee Protocol for rabies), those last-ditch attempts do work.
It's when people pretend there's no real investigation to be done that we get problems.
The real thing is can we (perhaps with new advances in statistics?) find places where doctors at the end of all known treatment try things at random and see if anything works. For rare symptoms it often isn't possible to run a proper controlled study (note that I said symptoms and not disease - often we are not really sure what is going on). So if we can give doctors a list "here is what someone else tried and or treatment Y seems to make things worse that is a clue. Eventually we can say that we don't know why, but X seems like your best shot even if it we can never get to real statistical significance.
Doctors already have case studies which they (at least should) publish anytime they get someone who for whatever reason doesn't respond to standard treatment, or has something unknown. However it is hard for the next doctor to find any that might be relevant.
Yeah, this seems like a worthwhile service, but I can't stop thinking about ivermectin.
It became apparent really fast that ivermectin was effective... against a superinfection with parasites, which the reported success cases all had.
But by the time it became apparent, the correction didn't spread nearly as fast nor wide as the original information.
The problem is, most people lack the scientific literacy to understand how science works, and many newspapers have long since gutted their expert journalists.
"Content current as of: 06/08/2020"
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I find it amazing that a king can just say that a drug works and then it becomes the absolute truth forever
Sometimes people want to believe in stuff so hard there's no way objetive reality will ever get to them.
Like trickle-down economics.
Strong Rabois, "I'm literally saving lives by tweeting about HCQ and Covid" vibes.
HCQ combined with Zinc was a valid treatment for Covid. The drugs peddled by the people profiting from Covid were essentially HCQ and Ivermectin clones. Both are considered essential medicines by WHO, or at least, they were at the time.
> HCQ combined with Zinc was a valid treatment for Covid.
What do you mean by "valid?"
> The drugs peddled by the people profiting from Covid were essentially HCQ and Ivermectin clones
Which specific drugs "peddled" by which people are you talking about?
> Both are considered essential medicines by WHO
Yeah... for things other than COVID.
Your squishy-to-the-point-of-meaningless language should be a red flag. To everyone else for sure, but even to you.
As someone who had Covid multiple times, CQ+quercetin+zinc was a valid treatment, but it required very cautious dosing. As for ivermectin, it did not help at all, but if someone has worms, perhaps it would help them. And no, the other drugs are not clones, as their mechanisms of action are completely different. Facts matter.
No it wasn't. You're buying into some alt-health nonsense.
Which drugs are you referring to?
Presumably something similar to how people (who had to be detached from reality at that point) swore by ivermectin, a horse dewormer as treatment.
The FDA was sued and lost (or at least agreed to a settlement) over those comments, which were consequently deleted. Ivermectin is a human antiparasitic that's even on the WHO List of Essential Medicines. [1] Their comment was akin to saying that amoxicillin is a horse antibacterial drug, which is true, but quite misleading. Off-label usage for pharmaceuticals is extremely common and an important right of doctors. I mean that's pretty much the entire point of this topic!
[1] - https://en.wikipedia.org/wiki/Ivermectin
Ah.. that said, even that wikipedia article points out that multiple research studies were done that demonstrated little to no benefit in the context of covid19 (and the ones that did were eventually proven faulty or fraudulent) - I agree that Ivermectin is an important drug, just not in the context of covid19
This is the truth.
I'm assuming this, like my similar comments, will continue to be downvoted by people who are out of touch with reality.
The fact that people were obtaining it from sources intended for horses is mostly unrelated to the fact that it is not effective as a Covid treatment for people who don’t have some other parasite in addition to Covid.
I don’t think calling it a horse dewormer is helpful, despite the fact that people were obtaining it from people who were selling it for the treatment of horses. People who (wrongly) think it works as treatment for covid will probably be aware that it is not exclusively a treatment for horses, so I don’t think calling it a horse dewormer will change any of their minds.
Even if it did, I am uncomfortable relying on misleading people in order to convince them of something true. (If someone believes X, and X is false, and you want to convince them of a true statement Z, then it is fine to say “X is false, but, I know you believe that X. Y is true, and X and Y together clearly imply Z. Therefore you should conclude Z.” (Assuming Y is true.) That’s not misleading someone. It is something different.)
It seems like allowing oneself to mislead, even if only when the misleading statements are sorta true in a sense, just not in the way they will be interpreted, in order to convince someone of something that is true, is rather dangerous. If such behavior were universalized, I think it would be rather bad for collective understanding. (What if someone U is trying to convince someone V of some statement P which U only believe is true because someone W misled U in to believe P in order to convince U of some other statement Q that is true, and then U says something misleading to V (leading V to believe a false statement R) in order to convince V that P ? Not good.)
This irrational belief isn't going away either. It seems to be spreading, in fact. A relative of mine recently was diagnosed with cancer and a "friend" of hers suggested she try ivermectin.
Not sure how well this article has held up to time but Scott Alexander had a pretty compelling analysis of the situation.
https://www.astralcodexten.com/p/ivermectin-much-more-than-y...
The tl;dr, as I recall it: it seems ivermectin really did work in some populations, in reducing COVID mortality. However, those populations were ones where one was much more likely to have worms, so the hypothesis is that indeed did work, but only because it worked as a dewormer and not having worms concurrently with COVID decreased the likelihood of mortality.
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