Too Many Medicines Simply Don’t Work

https://www.bloomberg.com/news/articles/2019-05-30/too-many-medicines-simply-don-t-work

by pseudolus • 7 years ago

138 104 7 years ago

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.

jdashg• 7 years ago

Expected value of 95% with 93 trials is 88.3, so right on target.

SamReidHughes• 7 years ago

Passing a 95% significance test doesn't have any connection to the notion that there is a 5% chance the drug is no good.

This is what you would expect from a blind application of a 95% confidence interval only if 50% of tested drugs were good.

rifung3• 7 years ago

Care to clarify?

My understanding was that a 95% confidence interval implies the chance of a false positive of 5%.

From http://www.mit.edu/~6.s085/notes/lecture2.pdf

"In particular, we can ask for an interval around ˆp for any sample so that in 95% of samples, the true mean p will lie inside this interval. Such an interval is called a confidence interval."

refurb2• 7 years ago

It's not so straightforward as the way a positive result is measured is also changing over tim, e.g. biomarker -> overall survival

ncmncm6• 7 years ago

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.

LorenPechtel• 7 years ago

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.

WhiteSage• 7 years ago

You have to fix the hypotheses to test before you begin the experiment, as otherwise you will stumble upon a lot of spurious correlations. That your birthday is the same day than someone's in your class/work group is a rare event, that two people have the same birthday in your class/work group, not at all uncommon. This is the birthday paradox. In the same spirit, with a drug you'll always find groups where it works because of spurious correlations, specially if you don't fix beforehand the group where you want to test it.

rjkennedy98• 7 years ago

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.

ncmncm6• 7 years ago

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.

Checkmate.

pessimizer2• 7 years ago

Yet, for millions of people, the antidepressant they take makes the difference between a productive, engaged life and miserable penury or suicide.

We're begging the question here.

Millions of people who have recovered some stability after a period of profound crisis were begun on a particular treatment at the nadir of that crisis. They very reasonably assign the recovery to that treatment - because they view that treatment as an individual, rather than as a cohort who endured similar crises, responded with various or no treatments, then had various degrees of recovery or mortality.

Additionally, they can't be evaluated based on their reaction after the treatment is withdrawn, because antidepressants are generally physically addictive, and you would expect a subsequent crisis even if withdrawn from a person taking them who had never had a crisis in the first place.

The effectiveness of antidepressant medication can't be assumed through the testimonial of the survivors, then types of depression reified through sorting the survivors by treatment type.

It becomes obviously self-justifying, because people who didn't improve clearly had the wrong depression for the drug. Instead, you have to evaluate the treatment against non-treatment; you can't just assume that survival indicates success, and work to refine tools that filter for the people will be helped by that treatment without material evidence, either of physical mechanisms or by already having strongly predictive tools, that the treatment is more effective than placebo.

I wouldn't deny that defining a disease by its effective treatment could be useful, but the margin for effectiveness would have to be pretty high if there were no other criteria for that definition.

JamesBarney3• 7 years ago

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.

all_blue_chucks• 7 years ago

For anxiety at least, benzos like xanax are extremely effective. If they weren't addictive, chronic anxiety would be pretty much cured.

pessimizer2• 7 years ago

The helpful effects of long-term consumption of Xanax and morphine are far from conclusive. These are both drugs that when given to completely healthy people long-term, then withdrawn, cause the exact symptoms that they are prescribed to treat.

avinium• 7 years ago

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?"

tapland• 7 years ago

He seems to be using small clinical differences over the population as a proxy to insinuate that the effects on the individual are small as well.

They aren't. The average might be small, but the range is wide.

JoeAltmaier2• 7 years ago

tl;dr: sometimes medicines don't achieve their early promise. But what are you gonna do about it?

jfengel• 7 years ago

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.

JoeAltmaier2• 7 years ago

Actually, my sister's full-time job is explaining to folks at the end of their cancer journey that there's actually one more thing they can try. It very likely will not help them survive. Not for themselves, but for people that come after. A drug that might not do anything, or it might do a little, or it might be what we've been praying for.

And those Iowa farmers and shopkeepers and schoolteachers at the end of their lives sign the form. An unreasonable population of them. For no reason but to help.

mjevans2• 7 years ago

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.

rifung3• 7 years ago

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.

I'm pretty sure we do this?

I mean I suppose we don't have laws which mandate this but medical researchers are constantly measuring and publishing how effective existing legal treatments are. I am sure researchers would love to find which treatments do not actually work and since publishing such work would affect treatment guidelines and have a huge impact.

DanBC4• 7 years ago

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.

amelius• 7 years ago

Can you give this "number needed to treat" for some common medications?

DanBC4• 7 years ago

Here's an article that mentions a few of them: http://www.pulsetoday.co.uk/clinical/clinical-specialties/pr...

For example, for every thousand low-risk patients prescribed statins for primary prevention, only a single stroke is prevented per year. Meanwhile, you would need to treat more than a thousand people with antihypertensive therapy per year to prevent one death. This is a far higher NNT than that of many interventions GPs are advised against prescribing due to lack of efficacy.

https://www.bmj.com/content/348/bmj.g3458/rr/761453

Enas bases his numbers on a 2013 Cochrane review. Enas reports that NNT equals 167 for low risk (less than 1%) and 67 for intermediate risk (1-2%) individuals. Enas reinterprets this as meaning 1000 low-risk people would need to be treated for five years to prevent six major adverse cardiovascular events. Enas notes the increased risk of type II diabetes from statin use and also estimates that 100 of the thousand people treated would have myopathy (that the same might occur with placebo is irrelevant as I will not be taking a placebo). Enas judged that the benefits of treatment in low risk subjects far outweigh any possible hazards and concluded that early and aggressive statin therapy offers the greatest potential for reducing the continuing epidemic of coronary artery disease among Indians.

javadocmd• 7 years ago

And don't forget the related metric: "number needed to harm". Physicians practicing good, Evidence-Based Medicine also weigh how many patients are likely to be impacted by harmful side effects.

In an example from The NNT about PSA Screening for Prostate Cancer: http://www.thennt.com/nnt/psa-test-to-screen-for-prostate-ca...

No benefits were identified to PSA screening, while 1 in 5 will go on to have an unnecessary prostate biopsy (which can itself lead to complications, false-positive diagnosis, and further treatment with associated complications, and so on).

(I feel obliged to mention that I'm not a doctor, btw, just sort of a casual fan of medical science and stats.)

WhompingWindows• 7 years ago

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.

JamesBarney3• 7 years ago

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.

Before they to the test they have to declare a primary outcome to avoid this issue. And most diseases just don't have that many outcomes relevant outcomes you can test for.

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.

They're trying, and they're failing hard. Precision medicine has been pretty useless outside of cancer.

astazangasta• 7 years ago

Even in cancer precision medicine is pretty crap. It works, but only sometimes. Most of the time even a correctly targeted drug results in a resistant tumor.

vkhn• 7 years ago

ctrl+f for phenylephrine.

That was my first thought.

ravenstine• 7 years ago

I thought I was the only one who figured that out! (not literally, but you know what I mean)

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• 7 years ago

The medicines with phenylephrine are usually labeled 'PE,' which stands for Placebo Effect. Nice of them to be honest with the labeling.

frenchy• 7 years ago

I ended up getting phenylephrine once because I was vacationing in the US. Needless to say, I was not impressed. How do you guys treat colds?

mrosett• 7 years ago

Get real Sudafed from behind the counter.

wl2• 7 years ago

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.

shirro• 7 years ago

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.

BadassFractal• 7 years ago

I recently ran into this issue with statins. Doctors are eager to prescribe them, but there seems to be conflicting evidence of them ultimately changing outcomes: https://www.sciencedaily.com/releases/2015/02/150220110850.h...

ncmncm6• 7 years ago

Statins have only ever been shown to help people who have had a heart attack, or were in imminent danger of one -- despite decades of effort by Big Pharma to find other benefits. (Big Pharma wants every drug they sell to be needed continuously from today until you drop dead. Statins would perfect because they are also extremely cheap to make.)

What we do know about statins is that they have terrible long-term side effects that might not put off somebody worried about dropping dead at any moment, but should give everyone else the heebie-jeebies.

They interfere with the liver's production of cholesterol, but we (like every other animal) need cholesterol to live.

hammock• 7 years ago

Please share a link to this stuff that I can share with my parents

naringas• 7 years ago

I wonder how many of these are pushed as mandatory vaccines

dang• 7 years ago

"Eschew flamebait. Don't introduce flamewar topics unless you have something genuinely new to say. Avoid unrelated controversies and generic tangents."

https://news.ycombinator.com/newsguidelines.html

sharadov• 7 years ago

What about the placebo effect? They've done studies where the patients knew that they were taking placebos, but still saw improvements...

boomboomsubban• 7 years ago

I don't think you could publish a clinical trial that does not already consider the placebo effect, so it's unlikely these findings are related to it.

danieltillett• 7 years ago

The placebo effect causes all sorts of problems for drug trials in certain areas where the control arm does much better than expected swamping the statistics of the treatment arm (trials are powered with an assumption of how well the placebo will work).

Interestingly, the unexpectly effective placebo effect seems to be limited to the USA. Why nobody is sure.

refurb2• 7 years ago

This focused mostly on cancer where the placebo effect doesn’t impact things like tumor size or survival.

fabiofzero• 7 years ago

This is the sort of headline that fuels the likes of anti-vaxxers.

avsteele• 7 years ago

Related, Recommended:

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.

vecplane2• 7 years ago

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.

The Accutane subreddit is full of tips and before/after photos - https://www.reddit.com/r/Accutane/

nhooyr• 7 years ago

There are big risks to it from what I've read.

digianarchist• 7 years ago

There was a story on the BBC site about accuntane recently.

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.

vecplane2• 7 years ago

Yeah I didn't have the dry eyes, but I did have some nosebleeds 2-3 times a week for a while. The dry skin was the worst part for me, and I kept having to moisturize my face here at work.

I also wasn't used to chap stick before, but now I carry it all the time.

irq11• 7 years ago

PSA to anyone reading this thread: Do not take Accutane without a prescription. There are very good reasons that doctors don’t want to prescribe it, and if you can’t find someone willing to do it, it means that the risks very likely don’t outweigh the benefits in your case. Doctors are going to want you to try more conservative treatments first, and you shouldn’t second-guess that.

Accutane makes the “horrible side-effects” of Tetracycline look like a mild headache. Aside from being a powerful teratogen (i.e. it causes nasty birth defects), Accutane is linked to suicidal tendencies, liver damage, heart damage, and more. It’s not a drug anyone should be taking without supervision.

phkahler• 7 years ago

For your keloids try Lugols iodine solution.

debug-desperado• 7 years ago

Aren’t retinol creams just as effective and much safer? They worked well for me from in my late teenage years.

eq_sd_2• 7 years ago

No? Accutane is often the last resort option when everything else fails.

NikolaeVarius• 7 years ago

Not in the same solar system in terms of effectiveness.

airstrike3• 7 years ago

I've used it for multiple cycles and still have acne. I'm going to be 34 in a couple weeks.

It's also been linked to increased suicide rates https://www.nejm.org/doi/full/10.1056/NEJM200102083440616

acneedum3• 7 years ago

I was acne free as a teen, but was put on Acutane anyway. (Ah, the wonders of middle America being the testing bed and profit source of Pharma)

Remained acne free until suddenly getting cystic acne in my early 30s.

Here's what helped me:

- Do laundry more often ( Increase the rate you clean your: sheets and pillow cases!, face cloths, clothes. If this is impractical you can simply buy more pillowcases and swap out clean ones more regularly; especially if you're a prone to sleep drooling or have greasy hair. )

- Stop washing your face with soap ( Just use water and a wash cloth on your face; use firm pressure to get into pores but light enough to avoid giving yourself 'rug' burns or tears. This is great for exfoliating dead skin and removing surface oil. Do this twice a day; morning and evening. Buy multiple face cloths and use newly cleaned ones regularly; every 2-3 days. )

- Apply moisturizers twice a day; morning and evening ( My skin had an amazing response to Sea Buckthorn: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438513/ . Its coloring is very intense so for my twice daily moisturizer I cut it with Rosehip Oil usually only putting 5-10 drops per 2 oz of Rosehip; experiment for your skin color. To increase my skin's recover time and the effectiveness of the Sea Buckthorn I will take a regular long bath where I apply it directly, almost like a mask, and wipe it off after the bath. It has proved great at reducing redness and blemishes as well as healing open wounds such as exfoliated dead skin and bleeding pores. )

- Spot care for cystic acne with pure Salicylic Acid ( Only rub this on cystic pores. Avoid trying to pop any pores without a clear white 'head'. )

- Cold showers ( Or at the very least end the shower by holding your face under cold water to close your pores. )

- Exercise ( General health will aide skin health. Also great for hormone balance which can be a cause factor for acne. )

- Wrangle your hormones ( Through masturbating less, and eating a hormone nutrition informed diet. For example, if male, eat more cruciferous foods for Testosterone maintenance. )

Hope these suggestions can make the difference they made for me for you too.

pps43• 7 years ago

Be careful, Accutane can have some pretty bad side effects. I decided not to use it, and many years later still think it was the right choice.

SubiculumCode• 7 years ago

My wife conquered her acne with low doses of a blood pressure drug, which apparently alters the expression of hormones.

Update: Spironolactone (Aldactone) is an androgen blocker drug that, at a lower dose, can help with hormonal acne.

dorchadas• 7 years ago

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.

bbulkow2• 7 years ago

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.

gnulinux2• 7 years ago

Huh, I used accutane for years for acne (no acne now) and my doctor never mentioned this to me. The only thing they mentioned is I shouldn't take vitamin A supplements with it.

stevesimmons• 7 years ago

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.

eq_sd_2• 7 years ago

It's possible to take a lower dose for a longer time period to lessen the side effects.

bbulkow2• 7 years ago

Other points not covered.

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.

eitally• 7 years ago

Can you point me to reference material supporting those numbers? I'd like to read more detail (and share with my partner, who works in pharma).

klipklop• 7 years ago

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.

DanBC4• 7 years ago

Propranolol for anxiety.

Is that off-label?

https://bnf.nice.org.uk/drug/propranolol-hydrochloride.html

maxxxxx• 7 years ago

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.

klodolph• 7 years ago

We need to end off label use.

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.

dillondoyle• 7 years ago

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.

apsec112• 7 years ago

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?

wl2• 7 years ago

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.

DanBC4• 7 years ago

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.

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.

awalton3• 7 years ago

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.

village-idiot• 7 years ago

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.

awalton3• 7 years ago

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!)

ddenisen• 7 years ago

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.

Too Many Medicines Simply Don’t Work

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