Even to know (in the double-blind trials "gold standard" sense) whether a medicine works, you need to diagnose reliably what it is supposed to treat.
But the DSM is full of illnesses that are really a half dozen completely different conditions with the same (or just similar) apparent symptoms, each with its own cause, and no reliable way to distinguish it from the others except that maybe drug X helps one, and drugs Y, Z, W, and V are useless for it. Likewise, the one that Y helps, and the one that responds to Z, and the rest where nothing seems to work. In double-blind trials, V, W, X, Y, and Z are all "shown" to be equally useless.
That does NOT mean V, W, X, Y, and Z don't work. The "gold standard" is as subject to GIGO as everything else. You simply cannot tell anything about what it means without looking at underlying facts.
Yeah. When evaluating a drug we should not only be looking overall, but if there is a subset of the test population for which it behaves differently. This is especially true for any diagnosis of exclusion.
Such a drug should be approved but with a big warning that it only works in some cases.
1. Drug candidates seeking approval must show non-inferiority to gold standard, meaning they are not worse than the top choice for the same treatment. This non-inferiority is quite easy to game, as we all know statistics are fungible and may be manipulated. If all I have to show is no significant difference, and I can use one of 10 different outcomes or surrogates, well my job got a LOT easier than showing superiority on the primary outcome of interest.
2. Before approval, drugs are tested in non-representative samples, either because they are too small in sample size, the disease is too rare, or because there needs to be a VERY large (post-market) population to tease out rare side effects.
3. Doctors and geneticists should come together and provide genetic testing to ensure that patients and their drugs are appropriately matched. This could be done in cancer, for instance, as you can genotype the cancer and provide a drug cocktail specifically for it. Another instance would be depression, as some drugs do not work for people with certain neurotransmitter genotypes. Physically, this means that each of us may have slightly differently shaped receptors that different drugs bind to differently. This explains a lot of the difference in drug responses, whether it be SSRIs or alcohol or cannabinoids, people simply have different receptors/biochem.
4. Medicine has always been a battle between doing nothing, providing the placebo effect, providing beneficial treatment, and avoiding/minimizing harm. In medieval times, exposure to medicine was tantamount towards increased risk of death and complication (see leeching, blood letting, terrible hygiene in surgery/childbirth, etc). Even now in modern times, going into a hospital is risky: hospital-associated infection is a massive killer, never mind acute psychological stress leading to delirium. We demand improvements in healthcare, new drugs, innovations, and extending life, and yet that is a very complex and challenging process that we will work on for centuries to come.
Simply put, doing medicine well has always been very hard. We have many legacy treatments and practices which probably should be put on the back shelf, but as with coding practices and legacy code, it is very hard to stop practices with momentum and inertia, whether the field is energy (fossils dominate), medicine, coding, or anything.
I think a big part of this is that statistical significance is taken as a surrogate for clinical significance. They are not the same. Antidepressants for instance may be statistically significant in meta-analyses, but the average gain is less than 3 points on the Hamilton scale which is not even detectable by most people or doctors. The same goes with these other measures such as slight tumor shrinkage, ect. Its a difference that doesn't make a difference clinically.
Yet, for millions of people, the antidepressant they take makes the difference between a productive, engaged life and miserable penury or suicide.
How can that be?
The answer is GIGO. Feed garbage to your Hamilton scale, get garbage out. The "gold standard" is no better than your diagnoses, and depression is the diagnostic counterpart to a "wastebasket taxon", polyphyletic. The only way we know to distinguish one "depression" from the next is which med fixes it. Now, design a "gold-standard" protocol to evaluate those meds.
The effect size of xanax is .3, antidepressants .3, and morphine .4. So if the effect size of antidepressants aren't clinically significant than neither are xanax and morphine.
Can you explain what you mean by "clinical significance"? Is it a case of "we're confident the treatment shrank the tumour by 10%, but the patient is still going to die in a week?"
This study doesn't mention "number needed to treat" - if we give X people this medication we'd expect to prevent Y occurances of this condition. Sometimes X can be surprisingly high and Y worryingly low.
It also doesn't mention the drug company funding provided to some patient campaign groups. It's pretty cynical: you know your medication is not effective enough for the cost, so you give money to dying people and their families to campign to get your med provided by single payer systems and insurance companies.
This is obviously a hard and serious problem to address. That said, I little part of me smiled a bit at 5 withdrawals out of 93 drugs. It's bizarrely close to what blindly applying 95% confidence intervals get you. I'm both terrified and impressed that it's that close enough.
My favorite example of this was when the feds essentially replaced pseudoephedrine (which works brilliantly, but now you're treated like a criminal if you need to buy it) with phenylephrine (which, quite frankly, doesn't do a damned thing: https://www.jwatch.org/na39054/2015/09/17/phenylephrine-no-m... - it's worse than a placebo in that it has side-effects AND doesn't do anything for what it's supposed to treat!)
Anecdotally, I find phenylephrine to be definitely effective as a topical decongestant (nasal spray); especially more so than its alternative (oxymetazoline), so it's not a placebo effect. But I agree that it doesn't do a thing as an oral drug.
Statins are very notorious in this regard. While they do indeed affect cholesterol, for most members of the population it does nothing to change all cause mortality.
When I had a case of Man Flu I used to walk right past the OTC PE crap and ask the pharmacist for the pseudoephedrine ones from behind the counter. Had to show ID and put my name on a list so they could see I wasn't Walter White. It was like once or twice a year max so not an issue.
But then the war on opiates happened and they removed all OTC codeine. I understand the evidence on codeine's efficacy as an antitussive in the amounts used was mixed but the tablets seemed to work for me. Alternatives like dextromethorphan probably work as well or better but the pseudoephedrine containing cold and flu meds seem to have disappeared instead of being reformulated. I am guessing the market was getting too small and higher volume OTC placebos make more money.
Phenylephrine's efficacy as a decongestant when taken orally is dubious. Still, it doesn't mean it's a useless drug. IV phenylephrine is a standard drug used during anesthesia to counteract the hypotensive effects of opioids and sedatives.
Slightly off topic, but one medicine that really does work is Accutane (Isotretinoin) for cystic acne, and I'm super grateful for it. If you still have acne, I highly recommend trying it.
I came across it on reddit a while back and it's basically solved my acne problem. You get a super dry face and chapped lips, but there are lots of products to help mitigate that.
Accutain is some heavy chemistry and you need to be careful. It slows cell growth at a fundamental level. That is why it has pregnancy warnings, and there are concerns about brain growth. It is a reasonably effective anti cancer agent, you can find some of the clinical trial data if you look hard.
I went on Accutane after a decade of tetracycline kept persistent mild acne under control but never got rid of it.
Accutane worked amazingly, and very fast. Acne gone in a week, and never returned. I stayed on Accutane til I hit the target dose (maybe 3 months, I forget exactly). Twenty years later, I'm still acne free.
Though without a doubt, Accutane is the strongest drug I've ever taken. I needed a liver function test before starting, and monthly during the treatment. My nasal lining and lips were unbelievably dry. I carried lip moisturiser and creams with me everywhere, used them several times an hour. I remember my dermatologist telling me to avoid the sun, and treatment was over the winter months.
To anyone on long-term courses of tetracycline, I suggest trying Accutane. Be prepared for the side effects. And only do it under medical supervision.
I approached my GP after suffering with acne who put me on tetracycline which has some horrible side-effects such as staining your teeth and it didn't work for me at all.
I bypassed my GP and bought accutane online. The side-effects are some of the worst I've had from a medicine, dry skin and eyes, regular nose bleeds, sensitivity to the sun etc. Nothing mental though. That said. It works.
Before I used accutane I had several acne spots turn into keloid scars which I have been treating over the last decade with corticosteroid injections.
Yep. Only thing that worked for me to get rid of my acne. My original dermatologist wouldn't prescribe it, so we moved to one who we knew would. Worked really quickly (within a year, it was mostly all gone), and haven't had issues since.
We need to end off label use. Saying a drug is approved for one diagnosis and then allowing it for any other diagnosis is, in the modern age, simply crazy. One might as well not have fda approval.
The problem of tainted and ineffective generics confounds the analysis. A recent investigation shows the fda's proceedure of unannounced inspections only in the us means that 75 percent of indian and Chinese generics makers failed inspections during the few years when unannounced inspections were done. Now they have moved back to announcing. It is not sure that each failure meant there are bad drugs out there, but a majority of failures were 100 percent faked test data regarding the chemicals inside the drugs.
As somebody that benefits from using a drug 'off-label' I strongly disagree.
There are many cases where off-label drug use gives a minority of people tremendous benefit. Take a look at the people with various brain disorders using Ambien off-label. It can literally bring people out of coma-like states temporarily.
Other examples off-label use:
* Propranolol for anxiety.
* Guanfacine for blood pressure issues, now used on label for ADHD.
For less common diseases, sometimes all medications are off-label, because the market is small enough that nobody will fund studies to get a new indication approved. There are approximately 100,000 human diseases known to science. Who is going to pay for new approvals (costing tens of millions each) for every single one? Should every patient with one of these diseases be yanked off their existing medication indefinitely, even if it works for them?
How would you propose doing that? Under the current system, we would simply be redirecting people to on-label prescriptions, which are higher priced but not better.
> Saying a drug is approved for one diagnosis and then allowing it for any other diagnosis is, in the modern age, simply crazy.
That's not what off-label is. Off-label just means that it's not an approved indication for the drug. The approved indications are what the drug companies are allowed to market / recommend.
> One might as well not have fda approval.
This is a fairly absurd comment to make, so I'm not even sure how to respond to it. Surely you are already aware that the FDA approval process requires studying the safety, contraindications, etc for a medication, and that these do not need to be redone from scratch for new applications?
Off-label use is just cutting through a small bit of regulatory box-ticking, box-ticking that doesn't add much value. Off-label use is common and standard of care often involves off-label use.
There are simply not enough resources to research the combination of every drug with every indication, not enough to provide the level of care that we can provide with off-label use.
I work in medical devices and without off label use by doctors it would be really hard and expensive to innovate and explore new indications. Maybe there should be some registry and published information but I don’t see an alternative.
> We need to end off label use. Saying a drug is approved for one diagnosis and then allowing it for any other diagnosis is, in the modern age, simply crazy. One might as well not have fda approval.
Everyday in England 30,000 people with learning disability take a psychotropic medication when they don't have the condition that the medication is licensed for.
This medication is often off-label use of anti-psychotic medication, used for a "sedative" effect.
People with learning disability are at increased risk of constipation (sensory issues around food; reduced range of food being eaten; not much say about what they eat; reduced access to exercise; etc etc), and these meds often have constipation as a side effect.
This combination causes harm. It sometimes kills people.
There's variable awareness of constipation as a side effect of clozapine. Most doctors know about agranularcytosis, and they're aware constipation can be a problem. But there are some doctors who don't know that the constipation side effect kills more people than agranularcytosis.
I agree. It's really important to stop misuse of medication.
> We need to end off label use. Saying a drug is approved for one diagnosis and then allowing it for any other diagnosis is, in the modern age, simply crazy. One might as well not have fda approval.
The approval process itself is what's crazy. Drugs are approved for treating disease X, but drugs don't work that way. They are chemicals that modify processes in the body to produce collections of effects that help treat some medical issue. What does prednisone treat? It's an immunosuppressant, an anti-inflamatory, and it reduces blood calcium levels. That's useful in treating a range of conditions like heart failure, cancer, autoimmune diseases, and many, many others.
One example of the insanity of this regime is the HPV vaccine. What does the drug do? It helps the immune system fight off certain strands of HPV. What was it approved for? Preventing cervical cancer. Since men don't have cervixes, it wasn't FDA-approved for men and any administration of that vaccine was strictly off-label. It took an additional approval and many years to get it approved for men, even though there was no reason to believe the vaccine would work in women but not in men.
Disagree. Yes, I am more libertarian here where I think anyone should have choice to consume ANY drug legal or not.
But even from a more mainstream viewpoint, there are lots of examples of for-profit medicine where a drug company pays for an on-label use via a study where off-label use is cheaper and similarly effective. For example Ketamine and Esketamine. One is very cheap and widely available one is very expensive and not widely available.
I hope we can address the fundamental problems with for profit medicine, I think this is just one negative externality of our crazy system.
> We need to end off label use. Saying a drug is approved for one diagnosis and then allowing it for any other diagnosis is, in the modern age, simply crazy. One might as well not have fda approval.
This is patently ridiculous. The FDA just proved the drug was safe in therapeutic doses and that it treated what it said it treated. They didn't say that the drug wasn't safe to treat other things, and they didn't say the drug was generally unsafe. If doctors are prescribing non-therapeutic doses, yeah, that might be a problem, but there are entire clades of diseases that would otherwise be untreatable without off-label use. (And the frank alternative - labeling all of the drugs as being usable for all of the various conditions - can't keep up with reality. The FDA is slow and meticulous, and if we forced that on off-label used drugs, there'd be a lot more suffering for literally no good reason. And it probably wouldn't do anything for actually stopping off-label usage - doctors would just start lying and overclassifying their patients as having diseases to give them the meds. E.g. there'd be a whole lot of autoimmune patients with various "overlap syndromes" that suddenly have lupus and/or rheumatoid arthritis, despite not meeting the current diagnostic criteria, just so they could keep taking adalimumab, methotrexate and/or hydroxychloroquine. It's just red tape they don't need nor care about.)
We've done actual wonders in the world by simply scanning through approved drug combinations to find treatments for ailments. An example of this is in cancer treatment: it's fairly common one cancer drug will treat multiple classes of cancer, especially in combinations with other drugs (even ones not designed to fight cancer specifically). It's so commonly the case that this is now its own entire enterprise: high throughput scanning of drug combinations to fight tumors. https://www.biorxiv.org/content/10.1101/051698v1.full It's also been done to treat viruses and autoimmune diseases.
I'm not a super libertarian or anything, but I believe if a doctor has a reasonable belief that a drug will treat a condition, and therapeutic trial evidence bears it out, there's not a good reason not to prescribe it, whether or not it says on the bottle that that's okay. I've benefited from this in the past and I will continue to in the future.
Especially in the studies they're talking about here, which are about cancer drugs. It's life-and-death stuff, and it's not so simple as "Well, we haven't proven this yet, so you just run off and die while we run a few more studies."
We have a hard enough time keeping desperate people from trying things that we know for a fact are scams. Perhaps doctors could put the studies in clearer context when prescribing, but they are always clear that these drugs aren't perfectly effective and that it's kind of a crapshoot.
When you've got patients who will die anyway, it's no surprise that we end up treating them as a final stage of clinical trials. You need to be honest about that and get consent, but many will give it willingly.
Maybe we should actually be collecting usage and outcomes on all medical things and actually have a process for reviewing the data; even for grandfathered treatments.
That would allow outcome based decisions about keeping that approval or comparing new treatments to the actual efficiency of existing treatments.
"Eschew flamebait. Don't introduce flamewar topics unless you have something genuinely new to say. Avoid unrelated controversies and generic tangents."
[+] [-] ncmncm|6 years ago|reply
But the DSM is full of illnesses that are really a half dozen completely different conditions with the same (or just similar) apparent symptoms, each with its own cause, and no reliable way to distinguish it from the others except that maybe drug X helps one, and drugs Y, Z, W, and V are useless for it. Likewise, the one that Y helps, and the one that responds to Z, and the rest where nothing seems to work. In double-blind trials, V, W, X, Y, and Z are all "shown" to be equally useless.
That does NOT mean V, W, X, Y, and Z don't work. The "gold standard" is as subject to GIGO as everything else. You simply cannot tell anything about what it means without looking at underlying facts.
[+] [-] LorenPechtel|6 years ago|reply
Such a drug should be approved but with a big warning that it only works in some cases.
[+] [-] WhompingWindows|6 years ago|reply
2. Before approval, drugs are tested in non-representative samples, either because they are too small in sample size, the disease is too rare, or because there needs to be a VERY large (post-market) population to tease out rare side effects.
3. Doctors and geneticists should come together and provide genetic testing to ensure that patients and their drugs are appropriately matched. This could be done in cancer, for instance, as you can genotype the cancer and provide a drug cocktail specifically for it. Another instance would be depression, as some drugs do not work for people with certain neurotransmitter genotypes. Physically, this means that each of us may have slightly differently shaped receptors that different drugs bind to differently. This explains a lot of the difference in drug responses, whether it be SSRIs or alcohol or cannabinoids, people simply have different receptors/biochem.
4. Medicine has always been a battle between doing nothing, providing the placebo effect, providing beneficial treatment, and avoiding/minimizing harm. In medieval times, exposure to medicine was tantamount towards increased risk of death and complication (see leeching, blood letting, terrible hygiene in surgery/childbirth, etc). Even now in modern times, going into a hospital is risky: hospital-associated infection is a massive killer, never mind acute psychological stress leading to delirium. We demand improvements in healthcare, new drugs, innovations, and extending life, and yet that is a very complex and challenging process that we will work on for centuries to come.
Simply put, doing medicine well has always been very hard. We have many legacy treatments and practices which probably should be put on the back shelf, but as with coding practices and legacy code, it is very hard to stop practices with momentum and inertia, whether the field is energy (fossils dominate), medicine, coding, or anything.
[+] [-] rjkennedy98|6 years ago|reply
[+] [-] ncmncm|6 years ago|reply
How can that be?
The answer is GIGO. Feed garbage to your Hamilton scale, get garbage out. The "gold standard" is no better than your diagnoses, and depression is the diagnostic counterpart to a "wastebasket taxon", polyphyletic. The only way we know to distinguish one "depression" from the next is which med fixes it. Now, design a "gold-standard" protocol to evaluate those meds.
Checkmate.
[+] [-] JamesBarney|6 years ago|reply
[+] [-] avinium|6 years ago|reply
[+] [-] unknown|6 years ago|reply
[deleted]
[+] [-] BadassFractal|6 years ago|reply
[+] [-] DanBC|6 years ago|reply
It also doesn't mention the drug company funding provided to some patient campaign groups. It's pretty cynical: you know your medication is not effective enough for the cost, so you give money to dying people and their families to campign to get your med provided by single payer systems and insurance companies.
[+] [-] avsteele|6 years ago|reply
https://www.amazon.com/Medical-Nihilism-Jacob-Stegenga/dp/01...
You can listen to a recent EconTalk podcast for a one hour summary of the book.
[+] [-] icegreentea2|6 years ago|reply
[+] [-] awalton|6 years ago|reply
[+] [-] ddenisen|6 years ago|reply
[+] [-] village-idiot|6 years ago|reply
[+] [-] sharadov|6 years ago|reply
[+] [-] vkhn|6 years ago|reply
That was my first thought.
[+] [-] ravenstine|6 years ago|reply
When I took it, after pseudoephedrine was placed behind the counter, I never thought phenylephrine did anything. Turns out that it really doesn't:
https://www.jwatch.org/na39054/2015/09/17/phenylephrine-no-m... https://www.washingtonpost.com/news/wonk/wp/2015/11/04/the-t...
[+] [-] mullingitover|6 years ago|reply
[+] [-] shirro|6 years ago|reply
But then the war on opiates happened and they removed all OTC codeine. I understand the evidence on codeine's efficacy as an antitussive in the amounts used was mixed but the tablets seemed to work for me. Alternatives like dextromethorphan probably work as well or better but the pseudoephedrine containing cold and flu meds seem to have disappeared instead of being reformulated. I am guessing the market was getting too small and higher volume OTC placebos make more money.
[+] [-] wl|6 years ago|reply
[+] [-] frenchy|6 years ago|reply
[+] [-] vecplane|6 years ago|reply
I came across it on reddit a while back and it's basically solved my acne problem. You get a super dry face and chapped lips, but there are lots of products to help mitigate that.
The Accutane subreddit is full of tips and before/after photos - https://www.reddit.com/r/Accutane/
[+] [-] bbulkow|6 years ago|reply
[+] [-] stevesimmons|6 years ago|reply
Accutane worked amazingly, and very fast. Acne gone in a week, and never returned. I stayed on Accutane til I hit the target dose (maybe 3 months, I forget exactly). Twenty years later, I'm still acne free.
Though without a doubt, Accutane is the strongest drug I've ever taken. I needed a liver function test before starting, and monthly during the treatment. My nasal lining and lips were unbelievably dry. I carried lip moisturiser and creams with me everywhere, used them several times an hour. I remember my dermatologist telling me to avoid the sun, and treatment was over the winter months.
To anyone on long-term courses of tetracycline, I suggest trying Accutane. Be prepared for the side effects. And only do it under medical supervision.
[+] [-] airstrike|6 years ago|reply
It's also been linked to increased suicide rates https://www.nejm.org/doi/full/10.1056/NEJM200102083440616
[+] [-] digianarchist|6 years ago|reply
https://www.bbc.com/news/health-47952076?intlink_from_url=ht...
I approached my GP after suffering with acne who put me on tetracycline which has some horrible side-effects such as staining your teeth and it didn't work for me at all.
I bypassed my GP and bought accutane online. The side-effects are some of the worst I've had from a medicine, dry skin and eyes, regular nose bleeds, sensitivity to the sun etc. Nothing mental though. That said. It works.
Before I used accutane I had several acne spots turn into keloid scars which I have been treating over the last decade with corticosteroid injections.
[+] [-] SubiculumCode|6 years ago|reply
Update: Spironolactone (Aldactone) is an androgen blocker drug that, at a lower dose, can help with hormonal acne.
[+] [-] pps43|6 years ago|reply
[+] [-] nhooyr|6 years ago|reply
[+] [-] dorchadas|6 years ago|reply
[+] [-] debug-desperado|6 years ago|reply
[+] [-] bbulkow|6 years ago|reply
We need to end off label use. Saying a drug is approved for one diagnosis and then allowing it for any other diagnosis is, in the modern age, simply crazy. One might as well not have fda approval.
The problem of tainted and ineffective generics confounds the analysis. A recent investigation shows the fda's proceedure of unannounced inspections only in the us means that 75 percent of indian and Chinese generics makers failed inspections during the few years when unannounced inspections were done. Now they have moved back to announcing. It is not sure that each failure meant there are bad drugs out there, but a majority of failures were 100 percent faked test data regarding the chemicals inside the drugs.
[+] [-] klipklop|6 years ago|reply
There are many cases where off-label drug use gives a minority of people tremendous benefit. Take a look at the people with various brain disorders using Ambien off-label. It can literally bring people out of coma-like states temporarily.
Other examples off-label use: * Propranolol for anxiety. * Guanfacine for blood pressure issues, now used on label for ADHD.
[+] [-] apsec112|6 years ago|reply
[+] [-] klodolph|6 years ago|reply
How would you propose doing that? Under the current system, we would simply be redirecting people to on-label prescriptions, which are higher priced but not better.
> Saying a drug is approved for one diagnosis and then allowing it for any other diagnosis is, in the modern age, simply crazy.
That's not what off-label is. Off-label just means that it's not an approved indication for the drug. The approved indications are what the drug companies are allowed to market / recommend.
> One might as well not have fda approval.
This is a fairly absurd comment to make, so I'm not even sure how to respond to it. Surely you are already aware that the FDA approval process requires studying the safety, contraindications, etc for a medication, and that these do not need to be redone from scratch for new applications?
Off-label use is just cutting through a small bit of regulatory box-ticking, box-ticking that doesn't add much value. Off-label use is common and standard of care often involves off-label use.
There are simply not enough resources to research the combination of every drug with every indication, not enough to provide the level of care that we can provide with off-label use.
[+] [-] maxxxxx|6 years ago|reply
[+] [-] DanBC|6 years ago|reply
Everyday in England 30,000 people with learning disability take a psychotropic medication when they don't have the condition that the medication is licensed for.
NHS England has a programme to stop this misuse of medication. It's called STOMP - STop Over Medicating People with LD. https://www.england.nhs.uk/learning-disabilities/improving-h...
This medication is often off-label use of anti-psychotic medication, used for a "sedative" effect.
People with learning disability are at increased risk of constipation (sensory issues around food; reduced range of food being eaten; not much say about what they eat; reduced access to exercise; etc etc), and these meds often have constipation as a side effect.
This combination causes harm. It sometimes kills people.
There's variable awareness of constipation as a side effect of clozapine. Most doctors know about agranularcytosis, and they're aware constipation can be a problem. But there are some doctors who don't know that the constipation side effect kills more people than agranularcytosis.
I agree. It's really important to stop misuse of medication.
[+] [-] wl|6 years ago|reply
The approval process itself is what's crazy. Drugs are approved for treating disease X, but drugs don't work that way. They are chemicals that modify processes in the body to produce collections of effects that help treat some medical issue. What does prednisone treat? It's an immunosuppressant, an anti-inflamatory, and it reduces blood calcium levels. That's useful in treating a range of conditions like heart failure, cancer, autoimmune diseases, and many, many others.
One example of the insanity of this regime is the HPV vaccine. What does the drug do? It helps the immune system fight off certain strands of HPV. What was it approved for? Preventing cervical cancer. Since men don't have cervixes, it wasn't FDA-approved for men and any administration of that vaccine was strictly off-label. It took an additional approval and many years to get it approved for men, even though there was no reason to believe the vaccine would work in women but not in men.
[+] [-] eitally|6 years ago|reply
[+] [-] dillondoyle|6 years ago|reply
But even from a more mainstream viewpoint, there are lots of examples of for-profit medicine where a drug company pays for an on-label use via a study where off-label use is cheaper and similarly effective. For example Ketamine and Esketamine. One is very cheap and widely available one is very expensive and not widely available.
I hope we can address the fundamental problems with for profit medicine, I think this is just one negative externality of our crazy system.
[+] [-] awalton|6 years ago|reply
This is patently ridiculous. The FDA just proved the drug was safe in therapeutic doses and that it treated what it said it treated. They didn't say that the drug wasn't safe to treat other things, and they didn't say the drug was generally unsafe. If doctors are prescribing non-therapeutic doses, yeah, that might be a problem, but there are entire clades of diseases that would otherwise be untreatable without off-label use. (And the frank alternative - labeling all of the drugs as being usable for all of the various conditions - can't keep up with reality. The FDA is slow and meticulous, and if we forced that on off-label used drugs, there'd be a lot more suffering for literally no good reason. And it probably wouldn't do anything for actually stopping off-label usage - doctors would just start lying and overclassifying their patients as having diseases to give them the meds. E.g. there'd be a whole lot of autoimmune patients with various "overlap syndromes" that suddenly have lupus and/or rheumatoid arthritis, despite not meeting the current diagnostic criteria, just so they could keep taking adalimumab, methotrexate and/or hydroxychloroquine. It's just red tape they don't need nor care about.)
We've done actual wonders in the world by simply scanning through approved drug combinations to find treatments for ailments. An example of this is in cancer treatment: it's fairly common one cancer drug will treat multiple classes of cancer, especially in combinations with other drugs (even ones not designed to fight cancer specifically). It's so commonly the case that this is now its own entire enterprise: high throughput scanning of drug combinations to fight tumors. https://www.biorxiv.org/content/10.1101/051698v1.full It's also been done to treat viruses and autoimmune diseases.
I'm not a super libertarian or anything, but I believe if a doctor has a reasonable belief that a drug will treat a condition, and therapeutic trial evidence bears it out, there's not a good reason not to prescribe it, whether or not it says on the bottle that that's okay. I've benefited from this in the past and I will continue to in the future.
[+] [-] fabiofzero|6 years ago|reply
[+] [-] JoeAltmaier|6 years ago|reply
[+] [-] jfengel|6 years ago|reply
We have a hard enough time keeping desperate people from trying things that we know for a fact are scams. Perhaps doctors could put the studies in clearer context when prescribing, but they are always clear that these drugs aren't perfectly effective and that it's kind of a crapshoot.
When you've got patients who will die anyway, it's no surprise that we end up treating them as a final stage of clinical trials. You need to be honest about that and get consent, but many will give it willingly.
[+] [-] mjevans|6 years ago|reply
That would allow outcome based decisions about keeping that approval or comparing new treatments to the actual efficiency of existing treatments.
[+] [-] fitnesshealth|6 years ago|reply
[deleted]
[+] [-] SketchySeaBeast|6 years ago|reply
>In a Day one or two tablets is used as dose for adults
Was there a thought to follow this?
[+] [-] naringas|6 years ago|reply
[+] [-] dang|6 years ago|reply
https://news.ycombinator.com/newsguidelines.html