I have a little insight here from working with ophthalmologists.
When the article mentions "using a cancer drug to treat a leading cause of blindness" it's talking about using Bevacizumab (brand name Avastin) to treat macular degeneration.
Avastin and Lucentis are molecularly the same drug. The difference is that Avastin isn't packaged to be injected into eyeballs, and Lucentis is. Also, Avastin costs about $50/dose, and Lucentis costs around $1,500/dose.
There are compounding pharmacies that will repackage Avastin into a format that can be injected into eyeballs.
However, many ophthalmologists are hesitatnt to use Avastin because that process introduces the potential for contamination. Not that it happens frequently, but every ophthalmologist I know lives in fear of introducing an infection into their patient's eyeballs. And what level of risk is worth saving $1,450 per dose on an injection? 1/100? 1/1000?
I know at least one ophthalmologist who would use Avastin, but would culture a sample from every batch she got from the compounding pharmacy, and had at least one batch that cultured bacteria.
Assumedly, if she hadn't, every patient she injected with that batch would have been at risk of contracting endophthalmitis, and endophthalmitis is no joke. Not infrequently, it can mean losing vision.
I know several of that ophthalmologist's colleagues who had been using compounded Avastin to try and save their patients money, stopped after that incident.
I don't really have a conclusion beyond "drug pricing is insane and the issue is complex for providers."
Compounding pharmacies can get injectibles wrong in a deadly way. Many families are still waiting for justice after the MECC pharmacy caused the deaths of 64 people:
"On July 7, 2021, Barry Cadden's original 9-year sentence was increased to 14.5 years. An appeals court court decision required the trial judge to consider patients, and not only hospitals, as victims of the crime."
The law is always more complex than a layman like me thinks, questions of standing, etc. But I would have simply assumed that the patients hurt and killed would naturally be counted among the victims and not just the organisations left out-of-pocket.
> And what level of risk is worth saving $1,450 per dose on an injection? 1/100? 1/1000?
I've have plenty of friends that would struggle to afford that. I have friends that buy black market drugs because they can't get/afford a prescription. I don't know if I would make the same choice but I can I can understand why some people do.
You can get some branded prescription pharmaceuticals in the U.S. from outside the U.S. via workarounds (1), and find heavily tested peptides via (2), in both cases avoiding the worst of the black or gray markets. If peptides, it's worth passing the hurdles and tests to access resources at https://pep-pedia.org/
(1) Start by filtering for Brand (not generic) and then going though lowest-cost results for reliable branded manufacturing locations (e.g. Germany, New Zealand, Singapore, NOT India) at https://www.pharmacychecker.com/ . Some sources are less picky about accurately checking prescriptions (e.g. https://www.inhousepharmacy.vu/ ). US Gov't allows buying outside U.S. for personal use, but reserves right to block incoming packages, but practically speaking does not.
The reason people get endophthalmitis is rarely due to a contaminated batch, but it certainly happens. But frankly it’s unsustainable to have all patients on branded drug, it would be too costly for patients and payers. Not to mention it is slightly unethical in the US due to drug rebates incentivizing branded drug use.
Endophthalmitis is bad, but we can treat it if caught promptly. Patient education, informed consent, good hygiene practices, and easy access to their ophthalmologist can make a tremendous difference.
> Not to mention it is slightly unethical in the US due to drug rebates incentivizing branded drug use.
This is an area I'm only perephrially aware of, but the way I understand it is:
* Manufacturer sells very expensive injectible eye drug, in the range of $2k/injection.
* It's typically covered by insurance, but patients (in this demogrpahic who are often on medicare) can still have high deductibles and copayments/coinsurance costs.
* To get around this, the manufacturer funds a nonprofit organization that patients can apply to for financial help paying for their deductibles.
* The manufacturer gets a write-off for donating to a nonprofit, and while they might cover, say, $2k or $5k of a patient's deductible over the course of a year, they still get $22k in revenue covered by Medicare for a year's worth of injections for that patient.
* There was some issue recently where maybe someone realized that "a charity funded by a drug manufacturer exclusively for the purpose of reimbursing purchases of that manufacturer's drugs" might not be a wholly above board charity, but I'm not sure if that was resolved.
All this is hearsay from my perspective, but am I in the ballpark of what you were talking about?
> But frankly it’s unsustainable to have all patients on branded drug, it would be too costly for patients and payers.
This is incorrect, the Canadian healthcare system negotiates drug costing at a per province rather than per patient manner and has managed to negotiate down drugs pretty significantly especially in Ontario. A national drug plan doesn't currently exist but it's likely that drug and dental coverage is going to be a goal in the near term.
In the US there is also a complex drug reimbursement program run by most manufacturers to offer rebates to patients in the form of trial cards or direct refunds that does help widen accessibility but those programs are generally limited to patients on private insurance due to the nature of incentives and, well, greed.
I think it's very fair to say "Within this current system brand name drugs are a ridiculous ask for most patients due to the availability of generic alternatives" but the system itself is deeply broken. Generics are sometimes whitelabeled versions of the same product but often what are considered inactive ingredients may be modified significantly from brand name versions leading to issues, especially when it comes to neurological drugs, of drastically different effects to patients. The brand name vs. generic problem is a lot more complex than most people give it credit for and while patients should always prefer generics when they're similarly functional there are very notable scenarios where they are not equivalent for treatment. This comment shouldn't be read in direct opposition to the full comment above as this drug is outside my wheelhouse but rather as a comment on generics in general.
Source: I work in a company that analyzes drug pricing and, more generally, comparative insurance reimbursement for a living.
My quick searching is showing that bevacizumab is the full antibody, but lucentis (ranibizumab) is just the fab. So, very similar, but indeed not the same thing. I would generally expect them to have the same effect, but biology is full of surprises.
The higher manufacturer price of the eyeball-safe formulation is clearly justified, then, i.m.o. Also, is it the doctor's responsibility to assume risk to save the patient money?
Assuming the compounding process is inherently more at risk of contamination. It also gets complicated when the extreme prices are involved: what risk of infection balances out with the risk that the patient will not be treated due to cost or will suffer whatever negative consequences due to bearing the cost? One in two? Probably not. One in a billion? Probably.
Considering that the doctor was able to test the batches and verify contamination, it seems like this is an important step that was skipped by the pharmacy.
Given the litigious nature of medical patients these days, I think most doctors would justifiably avoid the additional responsibility of pharmaceutical QA.
In my opinion this is an unfair risk to the doctor's career in assuming responsibility for the quality of the compounded drug.
In the absence of any other evidence, I assume the 30-fold increase is the cost to the manufacturer of preparing the drug for eye injection "according to Hoyle."
So why isn't the batch checker taking on that responsibility?
Doctors aren't responsible for anything and everything that happens. If they've had a drug tested to check it's safe, after informing the patient, what else is there for them to do? You're creating a hypothetical to enforce the status quo. That's why we end up with this bs to start with.
They are not transforming the drug just the form. For example, elderly patients may have a hard time swallowing pills, for some medicines (not all) a compounding pharmacy can turn the pill into a lollipop. They can also turn things into like a cream or lotion.
/use to write code for a small independent pharmacy that had a couple compounding labs
> How does a lowly pharmacy transform a drug that is not for eye injection into one that is?
New research probably discovered new applications for their product. Investors agree to diversify. Company developed a system to inject it. The system was approved by government agency at charge of this, and they give the green light to put it in the market.
This is totally normal. See Ozempic history.
The price of a treatment reflects also the collateral risks and probability to be sued for the physician and the company. The problem is not that it cost 1000 dollars, the real problem is that US government should be subsiding at least a part of this cost. Tax money is collected exactly for cases like this. The problem is that they are instead burning 14 millions to paint a pool in "American Idiot Green" dye and nobody says, this bill must be wrong. What they used to paint this? titanium?
Just went down a chatgpt rabbit hole because I was also curious - seems it’s literally physical repackaging, no modification of the drug itself- as another commenter pointed out it’s not quite the same molecule but they have the same effect? Someone correct me if I’m wrong
I have been a supporter of Cures Within Reach, a nonprofit that focuses on repurposing drugs, especially for rare diseases. https://www.cureswithinreach.org
They have funded some important repurposed-drug studies for Huntingtons Disease, which runs in my family. For a disease like this, it's never going to make sense for major pharmaceutical companies to invest the effort to develop entirely new drugs, but by repurposing existing drugs, it gives people living with rare diseases a chance to ease symptoms.
> For a disease like [Huntingtons], it's never going to make sense for major pharmaceutical companies to invest the effort to develop entirely new drugs
This is ... not correct.
Roche, Regeneron, and Novartis all have novel HD drugs under development in tandem with smaller labs (Ionis, Alnylam, and PTC respectively), and then smaller labs like uniQure and Wave Life Sciences do too. Novartis have already dropped $1bn on the partnership with a committed $2b more. In addition, there are a bunch of incentive schemes for diseases like HD: both the FDA and EMA have offered orphan-drug designation to therapies for HD, the FDA does expedited programmes and can offer RMAT designation for drugs like AMT-130.
With some luck (which is always in short supply for HD treatments, sadly), people with the disease might be able to get a single-injection treatment in the next 12 months[0].
I’m currently on Spravato, which is fully emblematic of how broken the incentives in the US healthcare system are.
Spravato is esketamine - a modified version of ketamine. Ketamine is made up of mirror image molecules and esketamine is the right-handed molecule. They did this because ketamine is off-patent so they needed to modify it in order to patent it, however there is evidence that esketamine is a less effective treatment than ketamine.
It’s very cheap for me but my insurance company pays about $17k a month for this treatment. Ketamine would be a more effective treatment that would be super cheap for them, but they don’t do it because it’s not FDA-approved. So they’re paying a fortune for a less effective treatment.
It would be in the insurance companies’ interests to band together to fund the research so they can save huge amounts of money in the long term but they do not do this.
> It would be in the insurance companies’ interests to band together to fund the research so they can save huge amounts of money in the long term but they do not do this.
Insurance companies do not want cheaper care.
In the US, insurance companies must spend 80% of premiums on care. So if you pay $1k/mo, they have to pay out at least $800/mo in care. (Not to you specifically, but averaged out across all subscribers.)
This is a cap on their potential profits. They always have to pay out 80% of premiums for care, so how do they make more money?
Well, imagine care is twice as expensive. Instead of paying $800, they have to pay $1600. That sounds worse, but, instead of $200/mo, they now $400/mo for themselves!
So, no, paradoxically, it is not in the interest of people paying for the treatment to save money. Quite the opposite.
It's worse than this. Their cap is 80% of the Insurer's profit. Not the Insurer's Parent company. So often the parent company will own the Insurer as a subsidiary and own the Pharmacy, Hospital, Healthcare etc under the parent company.
This way as costs go up, it's really just bypassing the 80%. Because the hospital can charge the insurance subsidary X amount, and then the hospital profits to the parent company.
There needs to be a law in the US that health insurance organizations cannot be owned by anyone who owns a healthcare provider. Nor can the insurance company own healthcare providers.
I tried to explain to people in The Netherlands this exact problem when they were thinking about switching from single-player to a commercial insurance company model.
Insurance companies always have an incentive to make healthcare services expensive. They have even more incentive to make healthcare expensive and do deals on the backside where their suppliers give them a kickback. Even better if said kickback comes via a side door.
So we went for the commercial insurance companies. It took them 4 years before they change the drug choice from decentralised (Pharmacies deal with drugs companies, received small discounts which funded a good quality of care) to centralised (Insurance deal with drug companies, receives kickbacks) and the Pharmacies funding was drastically cut leading to worse quality of care and more drugs being used. Double-whammy because in the previous system the Pharmacy did medication reviews which almost always result in a reduction in drugs (the thing with drugs is that quite a lot of them are given to reduce side effects of other drugs, the original drug gets cancelled but the side effect reducer gets forgotten and just continues ad infinitum).
Health insurance has been super inflationary since then when controlled for quality of care.
> So, no, paradoxically, it is not in the interest of people paying for the treatment to save money. Quite the opposite.
I'll assume they're on company insurance. Which is often "self-insured" in that the company actually foots the bill as opposed to the insurance company.
Why don't corporations just drop insurance companies that decide to not allow cheaper medicines?
UNH is so big because its customer Apple has its own pool. Apple deducts $24k/y for your healthcare. Healthy 29 year old male doesn't use anything. UNH denies the claims anyway. It gives that money back to Apple, which doesn't give it to you.
The 80% rule has a lot of loopholes. It doesn't apply to employer funded plans. There's a reason UNH is so big!
Employer funded plans are not all the same. Large entities with a lot of money (like universities, big firms) self-insure. Thus the insurance company in those cases is simply managing all the administrative sides of insurance while the plan owner is the actual insurer of risk.
There’s an article about how a Wall St employee’s expensive care came up in C-suite meetings, as a real world consequence of this
> simply managing all the administrative sides of insurance
if you punch into a chatbot questions about the employer pool insurance product, your comment is exactly how the chatbot characterizes it.
of course, "administrative sides of [health] insurance" includes requiring pre-auths and approving/rejecting claims, which is, haha, all the fucking evil parts of what they do! it's not "simply" anything. they need a huge, comprehensive, defensible model of what regulations and customers will accept as valid healthcare. apple does not need to have an opinion on ten thousand treatments and the standard of care across all these things. the insurance company does.
this is a line of investigation that the chatbots are absolutely terrible at informing people about. "administrative" is ALL the work, that is why UNH is big! you are starting from the wrong premise. you must always ask yourself, why are health insurance companies so big?
> if you punch into a chatbot questions about the employer pool insurance product, your comment is exactly how the chatbot characterizes it.
That's because it's the truth? I've taken graduate health policy classes from people like Don Berwick - I assure you that I did not and do not need to ask chatgpt to explain self-insurance to me.
> f course, "administrative sides of [health] insurance" includes...
How does this have anything to do with the fact that the self-insuring entity bears the risk for its insureds? The problem with the GP comment about 'giving money back to Apple' is that the money always belonged to Apple and its co-insurance / copays only exist to steer employee behavior.
it doesn't matter if the "self insuring entity bears the risk for its insured." every word in that quote misses the point. it might as well say "blah blah blah blah blah blah blah." it doesn't tell you why UNH is an interesting and successful business, or why people are pissed off about it.
haha okay, what i am trying to say is that from apple's point of view, it doesn't really matter if UNH is selling them a health insurance product or jacuzzi or eyebrow threading services or whatever.
apple employees say they want it, for some idiosyncratic reason apple is the party that gives it to them, and UNH is providing a uniquely cheap version of it. the gap between what employees think they are getting and what they are actually getting is huge. when you go on hacker news and people are talking about 80% medical loss ratios (that don't apply here, but that's not what you are spending your breath talking about) and "insureds" or whatever, you are enhancing the illusion.
that UNH has people carrying its water in this way: that's another reason, of many, that it is so big.
This comment chain was started to question why limiting profits to 80% of claims has to result in insurance companies denying cheaper options.
I have yet to see an argument as to why a company isn't incentived to drop a health insurer if they're forcing employees _not_ to do a $50/month option and instead pick a $1k/month option.
> I have yet to see an argument as to why a company isn't incentived to drop a health insurer if they're forcing employees _not_ to do a $50/month option and instead pick a $1k/month option.
That definitely does happen, but companies have a lot of levers to pull around how employees select health insurance. When I bought health insurance for a small firm (~60 people), I provided a set number of dollars and workers could use these for any plan they wished (an ICHRA plan).
Large swaths of US insurance are underwritten by employers, with the insurance companies acting as contracted administrators. Employers don't have the incentives you list.
You could get angry about anything I say, I don't really care, you do you.
I guess Medicare and Medicaid also don't have the incentives. Nor does Tri-care or the VA. My employer self insures as far as I know, and we are a few hundred people. Maybe 90% is a bit off?
I'm not angry about what you say, I'm angry at the parasites that have built this system, and the cynical bastards that work their ass off to perpetuate it.
Why is there a continuous stream of healthcare providers threatening to or becoming out of network for various managed care organizations because they cannot come to an agreement on healthcare prices?
I suspect it's because the insurance companies are not in control. The idea would be to drive up costs when they profit on both sides (example: United and OptumRx) and push down reimbursements elsewhere.
The FDA's policy for the last couple of decades is that mixtures of mirror images will not get FDA approval unless there is a strong rationale for it.
Racemic mixture of ketamine was approved decades ago. If you want a new indication for ketamine, you will need to get approval for a single mirror image, as the FDA won't approve the old drug.
They did this because there are numerous examples of racemic mixture drugs having increased side effects from the less active mirror image, so the FDA decided no more racemic approvals.
My guess is your insurer would be happy to pay for the old version, but your doctor is heavily incentivized to use the new version as the markup on the drug is much, much higher.
>but your doctor is heavily incentivized to use the new version as the markup on the drug is much, much higher.
I don't think it is normal/usual for doctors to receive any benefits or profits from which drugs they prescribe. Other than golf outings with the drug company reps? Is there something I'm missing?
> Ketamine is made up of mirror image molecules and esketamine is the right-handed molecule.
Esketamine is their cutesy way of saying the word s-ketamine. The s- comes from the Latin word "sinister" which means this is the left-handed enantiomer, not the right-handed one.
It is stupidly expensive, given how generic ketamine itself is. In our case, sleep apnea treatment proved to be a much better option than that drug, as it was just hiding an underlying condition and the treatments only last for maybe a week or two anyway.
I think there have been some people using ketamine off-label, but I don't know much about that. It does need to be tightly controlled because it can cause breakthrough psychosis in some patients. They try to screen those out, but that's not as effective as one might hope given my experience of seeing that fail. And it that was very nearly a fatal mistake.
What’s so interesting about this that I just learned after googling about Spravato that ketamine is a treatment for serious depression. Why? That’s fascinating! Is it the dissociative effects?
A significant effect is through opioid receptor activation, as demonstrated by Williams et al. <https://doi.org/10.1038/s41380-019-0503-4> by blocking the receptor with naltrexone, which attenuated the antisuicidality effects.
the opiate receptor interaction might be important, but it seems that the antidepressant effect persists even if the opiate pathway is blocked (via naltrexone)
I tried health-tech twice. Opted out both times as there are too many misaligned incentives and useless rent-takers supported by Congress and other entrenched players.
At this point maybe the best solution is door to door doctors using AI.
I feel like the best way to fight this, if I was the government, would be to stop enforcing laws preventing patients and even doctors or hospitals from importing the overpriced pharmaceuticals from overseas generics manufacturers. Like the article points out, each pill costs no more than $0.25 to make. The goal wouldn't necessarily be to get everyone using overseas suppliers but to put downward pressure on the price gougers in the country.
Happy to help. The laws you refer to exist to juice pharma industry profits. Same reason it has been so hard to change the law to allow Medicare to negotiate drug prices. The price gouging is by design for line go up.
Changing the law will take time (election cycles). If you cannot leave the US for a developed country that won't squeeze to extract from you while you're trying to meet your healthcare needs, importing your drugs that can be imported without US approval is your only path in the short term, or potentially traveling to obtain them and bring them back (roughly two-thirds of the entire U.S. population, ~200M people, live within 100 miles of a U.S. land or coastal border).
Such studies are great but there is no regulatory pathway to extend the use of existing drugs for new indications of use without the consent of the manufacturer (or becoming a manufacturer yourself).
This means such studies can give more clarity on which off-label use is beneficial but it can't be an officially allowed usage.
This isn't completely true at least in the UK. It is simply that the manufacturer is no longer responsible legally. The GMC allow prescibing of unlicensed meds. However the change needs to be made to the pathway. So many issues in the NHS has been due to pathway problems.
Also a LDN user, that drug saved my life. I bought it from a shady dude online, the initial effect was so strong that I thought they shipped me meth instead - that wore off after a week but the lifting of the brain fog persisted.
It didn’t have that sort of immediate, intense effect for me (though yours isn’t the only account like this that I’ve seen) but I’m still happy with the outcome; it dropped my average 1-to-10 pain score by about two points at three months.
It is a rare side effect, I helped a bunch of people (~50) get LDN, primarily for LongCovid, and only one other had a similar ‘too much energy’ effect and both of us have multiple TNXB SNPs and a very similar rare personality profile. I think the brain is so starved for dopamine at that point that it becomes hyper sensitive. I do miss the extra high energy but I also know that isn’t maintainable and I try to err on the side of caution.
I’ve had ME/CFS my whole life but the third covid vaccine shot sent me to new lows, to the point LDN just wasn’t cutting it anymore. These days I take a combo of modafinil in the morning and amitryptiline at night. And low dose ozempic has been super helpful as well. I was researching GLP1As prior to the current craze because I was worried about hyper sensitivity so I waited for more data before trying, I started at 1/100th the normal starting dose and still got temporary gastroparesis. These days I take a more regular dose of 1mg/wk but it also seems that my body has largely normalized as the hypersensitivities have worn off. Probably a good sign that I’ve successfully addressed actual deficiencies.
The doctors are assuming liability or let the patient sign waivers, which I guess is fine. But the lack of a pathway prevents a lot of commercial possibilities. For instance it is almost impossible to build a business around supporting off-label use cases (for instance selling necessary accessories).
I have some difficult-to-treat medical issues and about 1/3 of the handful of pills I take every day are off-label. I think when you get into less common medical concerns off-label use becomes much, much more frequent.
E.g. gabapentin is an anti-seizure medication that has been found to reduce neuropathic pain as well. It has shot up to the 5th most prescribed medication in the last decade as it has replaced long-term opioid use for new chronic neuropathic pain patients. This is 100% off-label and is prescribed by everyone from NPs all the way up to neurosurgeons for this purpose.
I’ve never been asked to sign a waiver and I can’t imagine that for-profit hospitals would allow their doctors to prescribe off-label medications willy-nilly if they represented big liability. (I don’t know this for sure, this is just what my experience implies.)
That presumably has to do with the risk profile of the medications you've taken. If there was a high risk of devastating side effects and it was off label presumably the prescriber wouldn't be willing to take on the liability.
I would wager if those waivers actually did anything they'd boilerplate a generic version of it in the legal mumbo jumbo you have to sign even if you come in to have the doctor look at a stubbed toe.
Yup, I've seen this sort of off label prescription at least 3 times.
A lot of drugs require almost no evidence (especially if they are relatively cheap or common) to be given to the insurance company when they are prescribed. And if you are willing to pay for it, you can always pay out of pocket if insurance is being a pain.
To get a drug approved you have to go through regulatory approval for a particular use. If the fuck-fuck game is you can just off-label for whatever but only if first approved by the FDA to solve some other problem, why not just bypass the bullshit and get straight to the point of approving the drug without any approved use? Oh yes, because that assures the barriers to entry are arbitrarily higher, and Pfizer and other ilk can insulate themselves from competition. Thanks FDA!
Like a lot of the systems we have today, it grew from good intentions. We need to figure out a way to refresh our systems without throwing them away. The current system does provide new drugs and benefit. The question is is it limiting, and are the tradeoff of those limits worth while.
In other words it takes hard work, with politically risky outcomes and an upside that becomes invisible as far as political careers go. We need to figure out how to refresh our systems in an environment where that type of thing just stumbles along. Maybe a couple of politicians elected who have lost out because of the status quo, but that want to improve it not throw it away. Maybe working with them to motivate them to take it on as a pet project and move things.
If we're just letting doctors yolo* off-label, i have no problem with that, but that functionally relegates FDA protections to testing risk profile at some particular dose regimen, with a bunch of extra bullshit tacked on that is highly inefficient process for off-label use even if partially applicable.
It's pretty clear if you're allowing off-label use you can just gate dose-risk profile at one gate and then just add additional gates for on-label uses if you want to approve one.
Of course the issue is the FDA regulator gets the hammer and damned if anything goes wrong but nothing good happens to them if they approve something. So they have no real incentive to approve anything except ideological satisfaction to whatever extent it lives within their mind, plus whatever revolving door benefits industry is offering them.
Probably best to reward the FDA employees for approving good drugs so that the prisoners' dilemma doesn't always fall back to erring on the side of denials, and being easier on them for taking some risk that approves bad drugs to the point they're willing to take some risk to let potentially good drugs through. The regulator doesn't get to see all the bad they cause by not approving drugs because that's invisible, and that's the unintended consequence of their activities and something they're not really held to account for.
* --------- re: below due to throttling -------
>Doctors aren't yoloing it.
If you take offense, call it whatever the hell you want, I was using it in the context of using a drug for a non-approved off-label use. You're making no legal distinction, it's not an FDA approved use and telling the FDA you have some evidence elsewhere but you won't be going through the process to approve it doesn't mean dick to the approval process anymore than my disapproved use of the world "yolo" to refer to same does. If the best my counterparties have is disapproving of "yolo" I rest my case.
What's happening is further research on the medicines are being done which show medicinal benefits for off label use. In many cases, it's researchers seeing a drug has a known side effect and saying "Hmm, I wonder if that side effect can counter this symptom".
What's lacking is the final FDA approval for the drugs being used for these off label treatments. That's because these drugs have to go through all the same tests that are required to get FDA approval in the first place.
IMO, for already approved drugs there should be a faster secondary route to getting these drugs approved for current off label usages. Ideally, it'd be something the FDA itself spearheads in partnership with the likes of the NIH.
> For instance it is almost impossible to build a business around supporting off-label use cases (for instance selling necessary accessories).
There is no need for a business. Off label use is hacking around the existing commercial and regulatory system. The innovation to be had is fixing said commercial and regulatory system, not another business. Make cheap drugs or medical supplies, distribute them to those in need with as little margin and risk to the patient as possible. This is a utility system masquerading as a market. More duct tape by way of new businesses is suboptimal.
Yes, but that isn't relevant to what happens after the type of trials described in the article, which tends to happen when the patents are no longer relevant. As the article points out, while the drugs are patented, the manufacturers themselves are generally very interested in repurposing because it broadens their market. The article is discussing trials that mostly happens once the patents have expired.
A research group can file for a new drug application (or abbreviated new drug application) for an existing drug. There is no mandate that an NDA sponsor be a manufacturer or the existing manufacturer.
Only the entity holding an approved NDA can file a supplemental NDA but that’s not the only path.
The real reason no one files for off label use is that there’s high cost and little to no practical benefit to doing so.
On paper you are right. You can file an NDA. But in reality you can't prove that the product on the market (the drug you are adding an NDA to) is sufficiently under your control to enable you to claim that it is safe and effective. Only a manufacturer can control the product. If you want to piggyback on top of an existing product in the market, you have to become a manufacturer or sign a contract with an existing one.
You are absolutely right about the incentives. There are absolutely none except to help humanity which is why only hospitals and universities are doing these off label studies.
I'm in the US, and there are a couple of wrinkles to this: insurance typically won't cover off label use, so patients end up paying the full cost of the medication, and if there is a big enough market, I believe companies can patent the new use even if the patents for the original use have run out.
Doctors here are allowed to prescribe them though.
Insurance will have prior authorization rules for certain drugs that are expensive that require the doctor to submit documentation of the condition, but in most cases the common medication is simply covered if prescribed. The insurance company does not receive documentation of every condition for every prescription to determine if the prescription is on label or off label.
Insurance companies can and do also support some off label treatments that are commonly used under their prior auth requirements.
I don’t know why there are so many comments in this thread making confident assertions that off label prescribing or insurance or so uncommon. This happens all day long at doctors offices and pharmacies.
Agreeing. There is a ton of blatant misinformation being shared in this thread by people who seem utterly confident despite their apparently complete ignorance.
"COM claims can be difficult to gain for repurposed compounds, as the patentee must somehow differentiate their patent claims over what is in the public domain and present data that the drug is a credible candidate for the new indication [41, 42]."
Did you actually read that article that spends many pages explaining how there is no good way for a firm to patent a repurposed drug that is working the same way as it worked in a prior indication, but is being used for a new indication where it has the same function - exactly what you’re asserting and what I said is not possible?
universal health care can be offered even in 3rd world countries but they're really smart about keeping costs low. they drastically cut the costs of medical service by just offering one or two generic drugs bbought in bulk from china and india rather than all those custom expensive drugs that do the same thing. it does the same thing but at a much lower cost
If every drug created with taxpayer dollars at government-funded research institutions was open-sourced, there would be a collapse in monopoly control of drug manufacturing and that would lower prices significantly.
The question is then, if corporations can no longer acquire IP rights to drugs created by taxpayer-funded research programs and transferred to their exclusive control (eg if Bayh-Dole is repealed in the USA), who will invest in clinical trial costs that need to be recouped via a period of inflated pricing?
The answer is government-funded, transparent, and statistically-robust clinical trials of drugs. Once a clinical trial is complete, private manufacturers can compete to produce the drugs at the lowest price by optimizing their manufacturing pipelines against a final product standard regulated by the FDA. If they want to run their own R & D divisions for drug development outside the taxpayer-financed university system to generate exclusive private patents, they certainly can - on their own dime. That’s an investment decision.
If you need to review why this government-linked, tightly regulated system is needed for drugs with clinical effects, just look up ‘patent medicine disasters of the early 20th century’.
This all assumes that the government will do an equal or better job spending money than companies that rely on spending that money well to exist.
What will actually happen is that the government department of repurposing drugs will be efficient once and then get their budget reduced and never be efficient again. Next time they'll make sure to spend every last cent and not worry about the over budget boondoggle that's three years late because their job isn't to get stuff done, it's to make sure politicians can say their doing something on the campaign trail.
Notice I was sure to include ‘revival of corporate R & D divisions’ in the argument? Bell Labs is the archetype - if corporations can do a better job of applied R & D, let them. If corporations are upset about publicly funded research generating open-source discoveries that upset the monopolistic apple cart, that’s not an argument about improving efficiency - that’s an argument about maximizing profits and investor return, not for efficient new drug discovery or old drug repurposing.
The real question is, what is the metric of ‘success’ - improved public health for the entire population at low cost, or bloated returns for pharmaceutical investors?
> The real question is, what is the metric of ‘success’ - improved public health for the entire population at low cost, or bloated returns for pharmaceutical investors?
This is a false dichotomy and this kind of zero sum thinking is exactly the root of so much misunderstanding of economics that's all the rage these days (and probably forever).
Wealth is created by innovation, not transfered. "Rent seeking" is wealth transfer but most companies provide a service that is more valuable than what exists without them.
The goal of capitalism is to allow the capitalist to increase their profits by improving the public good. "Public good" being measured by what people are willing to spend their money on. It isn't to increase the capatalists profits at all costs. The entire idea is built on exploiting the capitalist's impulse to increase profits to also serve the public good.
I hate to break it to you. Private Equity does not care about the common good, only profits. They only bow to increase price and out side of medicine, reduce the qualifying of the product.
Want common good, start creating disdain for the wealths in societies.
> Private Equity does not care about the common good, only profits.
Go back and read what I wrote. The point of capitalism is to align the profit motive of capitalists with the common good. It's not to give free reign to capitalists to do whatever they want at all costs.
Not according to the Friedman doctrine, which more and more companies are latching onto under capitalism [0].
I would also add that rejecting PE as not being apart of capitalism is rejecting reality. It is here and unfortunately to stay. Wealthy prefer to extract as much wealth from a brand, product, or service versus keep it around in good condition. Billionaires are not created by being supporters of the common good.
Replacing product quality indigence with poor quality and substitutions != common good!
Hording money != common good.
Friedman doctrine != common good.
Power to harm the producer and consumer based on product and service provider != common good. Didn't know price fixing is now classified as common good.
Billionaires exist by the exploitation of the common good.
How many billionaires push against living wages vs support them for all their employees for all their businesses?
Providing valuable goods and services for people who voluntarily exchange their money is very good for everyone.
> Exploitation of working class
Paying your employees mutually agreed upon salaries seems good though, right?
> Hording money != common good
Who's hoarding money?
> How many billionaires push against living wages vs support them for all their employees for all their businesses?
Setting government policy isn't the job of billionaires. People speak with their wallets and would rather have the prices for goods go down (something that historically and consistently happens) rather than see their own wages rise. Which is the tradeoff. You can't suddenly raise wages without seeing a commensurate price rise and then your back to square one. Most businesses run on very thin margins due to intense competition.
You're not reading what I'm writing. Capitalism isn't there to serve capitalists so citing what a capitalist wants and saying it's a flaw with capitalism doesn't make sense.
Capitalism is all about providing the right incentives to capitalists so that what's good for them is good for everyone.
> ‘Is curing patients a sustainable business model?’
The goal of capitalism is to make the answer to that question "Yes".
>This all assumes that the government will do an equal or better job spending money than companies that rely on spending that money well to exist.
We know they do because before the government took over the job, the nascent medicine industry would sell you literal poison.
In fact, you can see today what an unregulated pharmaceutical industry looks like. It's the supplements aisle at your local supermarket. The place where you can buy literal homeopathy sugar pills, and various completely unstudied compounds and other scams. You can buy turmeric for hundreds of dollars a pound.
If private industry was better than the government at managing drugs, the American supplements industry would mean we should have dramatically better health outcomes and dramatically cheaper healthcare
> We know they do because before the government took over the job, the nascent medicine industry would sell you literal poison.
I'm not arguing against regulation of private industry, I'm arguing against government competing with private industry. The government has unlimited money, very convoluted incentives and the legal right to use guns.
Private industry which has to make good choices or die is a much better environment for spending money wisely.
While I actually sympathize with your position, I think your argument has a significant flaw: the "unregulated pharmaceutical industry" you reference is actually quite regulated.
My company can put a GRAS compound like turmeric in a pill and sell it over the counter, but the moment I stop calling it a spice and make a treatment claim about it I face enforcement action. And I certainly can't put in an active ingredient that might actually /do something/ - like those gas station "sex enhancer" pills that, surprise, have sildenafil - because then I'm distributing an unapproved/mislabeled drug.
> We know they do because before the government took over the job, the nascent medicine industry would sell you literal poison.
We also know that some reports of poisoned industries in the past were exaggerated (and politically capitalized to lobby monopolistic regulations). This wasn't exclusive to medicine.
> The place where you can buy literal homeopathy sugar pills, and various completely unstudied compounds and other scams.
Presuming that these aren't actual cases of fraud - if they were, they'd already be illegal in a private market, regardless of the FDA - how many are actually buying these? Not many, I presume. For those that are, I think better informing them is much better solution, not only to combat innefective drugs, but also to strengthen trust on actually effective treatments. That said, homeopathy seems more like a yet-to-be cracked down case of fraud, regardless of regulations.
> If private industry was better than the government at managing drugs, the American supplements industry would mean we should have dramatically better health outcomes and dramatically cheaper healthcare.
Why? USA's healthcare system is an overly bureocratic, poorly regulated (not as in lacking in regulations, but that the regulations that exist are bad) goliath. It's closer to a government-funded system, except stupid. It's not an example of a government-free system, but how private actors do their best to exploit existing and lobbied soon-to-be regulations in their favor.
Specialists keep up with the latest research in their domains and talk with other specialists in their field. They usually know about these things before their patients discover them spontaneously.
You can read a lot of published papers on PubMed by searching for a condition or drug. You should be aware that there are a lot of papers published that say disease A can be treated with drug or supplement B that fail to replicate if anyone else tries it. It takes some practice to recognize when a treatment represents a real trend as opposed to a single quack doctor looking for a status boosting publication with some questionable claims.
Big medical systems will post their clinical trails quarterly or so. If you have a big medical system near you you can sign up for emails. I imagine universities would have a mailing list too, if they regularly did clinical trials.
Yes, but it's really tough. I read that 50% of Stanford Medical School budget comes from Big Pharma. It's really hard to get the message out. I believe Pharma (the biggest advertiser on Google) is influencing Google search results, among other things.
fascinating! I'm sure there's quite a bit that can be learned through appropriate research - pathways to solve problems that haven't been thought of before
the thing is while something is better than nothing, new drug development is critical
there is absolutely no cure for certain types of long-covid and me-cfs right now
no repurposing any drug is going to cure it, they've tried everything after six years
it will take a decade to have anything even in the pipeline and won't emerge from the USA because all medical and science research investment by the government has been destroyed by Russell Vought and Heritage Foundation
JAK-STAT inhibitors will be a big treatment, not a cure, but they cost thousands per month in the USA because generics aren't allowed
> the thing is while something is better than nothing, new drug development is critical
> there is absolutely no cure for certain types of long-covid and me-cfs right now
> no repurposing any drug is going to cure it, they've tried everything after six years
Then repurposing should free up resources for new drug development for those conditions that it can't address.
Sounds like a win-win, unless the goal is somehow not to most efficiently allocate resources to maximize health outcomes. But at least in the US, that's clearly not the goal.
The prices of drugs in the USA are especially high. This is interesting
because the USA claims to pursue a maximum capitalistic society - but if
this were the case, you'd have competition in a free market. But you don't
have that. You have a cartel (or rather more than one).
A pure capitalistic society works on assumptions that are not real. People
are often cheaters. This would have to be taken into account. But when you
have an orange Al Capone in charge, it is pillage day. Even before the orange
King you had heavily overcharged prices in the health care system. You need
to realise that you have a mafia in charge that does not want to change this
system. Why kill the cow that you can milk for free?
Look at the development of price and quality of something that is outside the regulated medical system, like eg Lasik, and everything within that system. Its like night and day.
If we had proper competition and price discovery, things would be much better.
Are you under the impression that dentists are under competitive pressure? The labour supply is artificially limited, similar to other doctor specialisations.
Are you in the US? This is not my experience at all. I've paid in US <2000 for dental invasive surgery including general anesthesia straight cash. That's approaching prices for medical care in Mexico.
Dentists are only slightly more honest as a profession than Chiropractors. More than half of the one's you meet are outright fraudsters/charlatans/scammers. Most who work in that business will reincarnate as cockroaches or durian fruits.
> This is interesting because the USA claims to pursue a maximum capitalistic society
No it doesn't. This is silly.
Drug prices in the US are high for non-generic drugs because patent law gives the patent holder an artificial government-granted monopoly, which is blatantly not "pure" or "maximum capitalistic".
Generic drugs - where the free market does apply - in the US are as cheap or cheaper than in other countries. See [0]:
U.S. prices for brand-name originator drugs were 422 percent of prices in
comparison countries, while U.S. unbranded generics, which we found account for 90
percent of U.S. prescription volume, were on average cheaper at 67 percent of
prices in comparison countries, where on average only 41 percent of prescription
volume is for unbranded generics.
The maximum libertarian alternative to patents isn't free-for-all copying, it's trade secret formulas - e.g. Coca Cola. Drug patents actually exist as a compromise given the clear need for the state to force companies to publish their drug formulas for research. Allowing companies to just keep their drugs secret would be even more capitalistic, and would increase drug prices even more.
They keep their processes secret instead under the current system, achieving a "trade-secret" like result for some drugs. For some drugs it achieves the same thing because finding a practical economic synthesis is the hard part rather than coming upon a small bit of chemical that is proven to be effective. For others it wouldn't matter whether you kept it secret or not, someone would isolate and characterize it and reverse engineer a practical synthesis.
The biggest value protector arguably of the patent-FDA approval process is on the FDA side, who create massive barriers to entry that mitigate close unpatented chemical competitors from outside the pharma oligopoly from competing.
Is the patent not for the synthesis route itself, rather than the drug? Someone can't just plop down a chemical formula on a piece of paper and patent that, can they?
I'm not really happy with the current system either - I tend to think that the state should just mandate that all medical research be fully published, and either have companies compete on research and manufacturing, or pay for it directly if it can't be made to work as a private business. My point was just that this is very much not a capitalist or libertarian position.
This is where prizes come in. If you create a drug and keep it secret, the government can grant you a large prize as an offer to reveal your secret.
This is a much better compromise. The company will end up with more money(and faster!) as a result of this prize than under a patent system - since the patent system induces dead-weight losses, and the government will end up with more lives saved.
That is just an inefficient way to spend taxpayer money than straight up paying researchers from the government’s accounts.
The US has an enormously large higher education system with all the expertise and manpower to facilitate large trials of novel medicines. The only thing missing is political will to spend the money, so instead, Eli Lilly or Novartis or Pfizer etc spend investor’s money to do it.
And then taxpayers pay for it in a super convoluted way.
Prizes pay for working results. Grants pay for possibilities. Grants are therefore riskier, and thus we allocate less resources to them.
Since the people with the money don't understand the science, these possibilities must then be assessed by bureaucrats, and this causes our best to spend half of their time writing proposals instead of working and researching. A complete waste of time. Let the people who know the most about their subject freedom to take risks, and then they are given the spoils of their rewards if they are proven correct.
Prizes are much more efficient than grants. Prizes should be given to academics according to the value they produced. I have no issue if the academics choose to spend some of the windfall profits of their prizes on trials.
> Since the people with the money don't understand the science, these possibilities must then be assessed by bureaucrats, and this causes our best to spend half of their time writing proposals instead of working and researching. A complete waste of time.
What part of this changes when a company is paying for the research, and why can't that same part be used in a government office? It's not like drug company CEOs and CFOs are also world class medical researchers. And if the funding decisions are entirely done by a CTO who is, then why would this model not be possible in a government office?
Ultimately someone needs to pay for all of the trials that don't work, and someone needs to do a cost/benefit/likelihood analysis on any research to decide whether it will be funded or not. With a public funding scheme, the benefit analysis could be based on public health interests. With a private company funding scheme, it has to be based on profitability. In healthcare, there is usually a huge gap between these two, unlike other more traditional markets.
Yes, businesses have the same flaw with a bit of better incentives.
With a prize based approach, what you want is for researchers to make small targetted gambles early in their career, earn their prize profits from those gambles, and work their way up into bigger gambles. There's nothing crazy about this scheme, it's how businesses have formed for hundreds of years. If a company wants to buy equity in the prizes of an independent researcher, I see no issue with this.
> then why would this model not be possible in a government office
I see no issue with governmental workers, or those from a university medial research center, or any other persons who can achieve the results from receiving this prize.
> someone needs to pay for all of the trials that don't work
The researchers. They are the one taking the risk. They are the one who would get the rewards. Skin in the game.
> With a public funding scheme, the benefit analysis could be based on public health interests.
Yes, we should directly pay the organization, or persons, based on the value they generate from their own. The bigger the public health interest, the more they should be paid. Right now we give a tiny piece to these people, and thus harm our incentives. Fully fund the results. It's risk-free.
"Drug prices in the US are high for non-generic drugs because patent law gives the patent holder an artificial government-granted monopoly, which is blatantly not "pure" or "maximum capitalistic"."
This is very much capitalistic. It's not competitive markets (which are good for consumers) but capitalists hate competition once they have made it to the top.
> This is interesting because the USA claims to pursue a maximum capitalistic society
I don’t know why you think this. The US is not a maximally capitalist society. The reason drug prices are so high is due to regulations restriction who can manufacture them due to government-granted temporary monopolies through patent law.
If the US was maximally capitalist it would be a free for all with no patent protection.
> If the US was maximally capitalist it would be a free for all with no patent protection.
The much more likely alternative in a maximally capitalist / free market maximalist society would be keeping all drug formulas as trade secrets, and thereby having all drugs as branded, no generics whatsoever (or few - perhaps some substances could be reverse engineered). In such a society, having the state force companies to publish their formulas would be seen as unacceptable interference in the free market, almost certainly.
I'm not convinced about trade secrets being the capitalistic route here, specially since, as pointed out somewhere else, the current system is basically like trade-secrets already, which suggest inverted causality.
In a pure free market, someone could try to keep the formulas secret, but others can just reverse engineer it into being public, which is basically guaranteed to happen if there's sufficient demand. Given that they aren't wasting money trying to obfuscate the recipe nor the formula, these competitors do have an advantage over the original. As such, I posit that free-to-copy will be default behavior in a pure free market, with trade-scerets being resteicted on niche sectors.
The reason we can't do this today is primarily that reverse engineering is heavily restricted by IP laws.
The recipe for Coca Cola, the most popular soft drink in the world by far, has been a trade secret for over 100 years. And I'd wager a guess that it's slightly simpler to make then most medicines. So I don't see any reason whatsoever to assume that drugs would be easily reverse engineered.
Instead, I'd say that the assertion that today's drug making is hard to reverse engineer is hard even knowing the exact formula, substance, and dosage of every drug is unlikely to be true - is there any example of any drug that generics companies are not producing more cheaply than the original inventor, once the patent has expired?
I don't think Coca Cola is a good counterpoint due to a couple of reasons:
1) there was a recent attempt to find the formula [1], but the primary reason that was infeasible is that, allegedly by the ingredient list, they use coca extract and, IIRC, only one company provides that in the US, due to FDA regulations. Even if they were find the formula behind, it wouldn't help much, so they're are trying to replicate the flavor instead.
2) Coca Cola is, before anything, a brand. It's not comparable to generic medications because people in general don't buy it for the formula specifically, but the expectation of flavor and taste associated with the brand. Even if you were to find the current formula, the Coca Cola Company can just change it.
In regards to the last point, there probably is one (likely in heavily subsidized prices case), but, regardless, I don't see how your point shows patents are the reason anymore than a increase in competition, which we are proposing would happen if patents were abolished.
This is completely backwards read Marx. Superstructure (culture, politics) flows from the economic base (there are some important exceptions, but that’s the dominant arrow).
Popper talks about sociology as though it were physics. Unfortunately, competitive games and the subjective belief of people can influence the course of history if the right material conditions are in place. Sometimes you try different things and get different results in different contexts.
I have a little insight here from working with ophthalmologists.
When the article mentions "using a cancer drug to treat a leading cause of blindness" it's talking about using Bevacizumab (brand name Avastin) to treat macular degeneration.
Avastin and Lucentis are molecularly the same drug. The difference is that Avastin isn't packaged to be injected into eyeballs, and Lucentis is. Also, Avastin costs about $50/dose, and Lucentis costs around $1,500/dose.
There are compounding pharmacies that will repackage Avastin into a format that can be injected into eyeballs.
However, many ophthalmologists are hesitatnt to use Avastin because that process introduces the potential for contamination. Not that it happens frequently, but every ophthalmologist I know lives in fear of introducing an infection into their patient's eyeballs. And what level of risk is worth saving $1,450 per dose on an injection? 1/100? 1/1000?
I know at least one ophthalmologist who would use Avastin, but would culture a sample from every batch she got from the compounding pharmacy, and had at least one batch that cultured bacteria.
Assumedly, if she hadn't, every patient she injected with that batch would have been at risk of contracting endophthalmitis, and endophthalmitis is no joke. Not infrequently, it can mean losing vision.
I know several of that ophthalmologist's colleagues who had been using compounded Avastin to try and save their patients money, stopped after that incident.
I don't really have a conclusion beyond "drug pricing is insane and the issue is complex for providers."
Compounding pharmacies can get injectibles wrong in a deadly way. Many families are still waiting for justice after the MECC pharmacy caused the deaths of 64 people:
https://en.wikipedia.org/wiki/New_England_Compounding_Center...
This note in that WP link is wild:
"On July 7, 2021, Barry Cadden's original 9-year sentence was increased to 14.5 years. An appeals court court decision required the trial judge to consider patients, and not only hospitals, as victims of the crime."
The law is always more complex than a layman like me thinks, questions of standing, etc. But I would have simply assumed that the patients hurt and killed would naturally be counted among the victims and not just the organisations left out-of-pocket.
> And what level of risk is worth saving $1,450 per dose on an injection? 1/100? 1/1000?
I've have plenty of friends that would struggle to afford that. I have friends that buy black market drugs because they can't get/afford a prescription. I don't know if I would make the same choice but I can I can understand why some people do.
You can get some branded prescription pharmaceuticals in the U.S. from outside the U.S. via workarounds (1), and find heavily tested peptides via (2), in both cases avoiding the worst of the black or gray markets. If peptides, it's worth passing the hurdles and tests to access resources at https://pep-pedia.org/
(1) Start by filtering for Brand (not generic) and then going though lowest-cost results for reliable branded manufacturing locations (e.g. Germany, New Zealand, Singapore, NOT India) at https://www.pharmacychecker.com/ . Some sources are less picky about accurately checking prescriptions (e.g. https://www.inhousepharmacy.vu/ ). US Gov't allows buying outside U.S. for personal use, but reserves right to block incoming packages, but practically speaking does not.
(2) Filter for vendors with the best results at https://www.finnrick.com/about/testing-methodology
The reason people get endophthalmitis is rarely due to a contaminated batch, but it certainly happens. But frankly it’s unsustainable to have all patients on branded drug, it would be too costly for patients and payers. Not to mention it is slightly unethical in the US due to drug rebates incentivizing branded drug use.
Endophthalmitis is bad, but we can treat it if caught promptly. Patient education, informed consent, good hygiene practices, and easy access to their ophthalmologist can make a tremendous difference.
Source: I do these injections for a living.
> Not to mention it is slightly unethical in the US due to drug rebates incentivizing branded drug use.
This is an area I'm only perephrially aware of, but the way I understand it is:
* Manufacturer sells very expensive injectible eye drug, in the range of $2k/injection.
* It's typically covered by insurance, but patients (in this demogrpahic who are often on medicare) can still have high deductibles and copayments/coinsurance costs.
* To get around this, the manufacturer funds a nonprofit organization that patients can apply to for financial help paying for their deductibles.
* The manufacturer gets a write-off for donating to a nonprofit, and while they might cover, say, $2k or $5k of a patient's deductible over the course of a year, they still get $22k in revenue covered by Medicare for a year's worth of injections for that patient.
* There was some issue recently where maybe someone realized that "a charity funded by a drug manufacturer exclusively for the purpose of reimbursing purchases of that manufacturer's drugs" might not be a wholly above board charity, but I'm not sure if that was resolved.
All this is hearsay from my perspective, but am I in the ballpark of what you were talking about?
> But frankly it’s unsustainable to have all patients on branded drug, it would be too costly for patients and payers.
This is incorrect, the Canadian healthcare system negotiates drug costing at a per province rather than per patient manner and has managed to negotiate down drugs pretty significantly especially in Ontario. A national drug plan doesn't currently exist but it's likely that drug and dental coverage is going to be a goal in the near term.
In the US there is also a complex drug reimbursement program run by most manufacturers to offer rebates to patients in the form of trial cards or direct refunds that does help widen accessibility but those programs are generally limited to patients on private insurance due to the nature of incentives and, well, greed.
I think it's very fair to say "Within this current system brand name drugs are a ridiculous ask for most patients due to the availability of generic alternatives" but the system itself is deeply broken. Generics are sometimes whitelabeled versions of the same product but often what are considered inactive ingredients may be modified significantly from brand name versions leading to issues, especially when it comes to neurological drugs, of drastically different effects to patients. The brand name vs. generic problem is a lot more complex than most people give it credit for and while patients should always prefer generics when they're similarly functional there are very notable scenarios where they are not equivalent for treatment. This comment shouldn't be read in direct opposition to the full comment above as this drug is outside my wheelhouse but rather as a comment on generics in general.
Source: I work in a company that analyzes drug pricing and, more generally, comparative insurance reimbursement for a living.
They have similar targeting but are not the same molecule.
My quick searching is showing that bevacizumab is the full antibody, but lucentis (ranibizumab) is just the fab. So, very similar, but indeed not the same thing. I would generally expect them to have the same effect, but biology is full of surprises.
The higher manufacturer price of the eyeball-safe formulation is clearly justified, then, i.m.o. Also, is it the doctor's responsibility to assume risk to save the patient money?
Assuming the compounding process is inherently more at risk of contamination. It also gets complicated when the extreme prices are involved: what risk of infection balances out with the risk that the patient will not be treated due to cost or will suffer whatever negative consequences due to bearing the cost? One in two? Probably not. One in a billion? Probably.
Considering that the doctor was able to test the batches and verify contamination, it seems like this is an important step that was skipped by the pharmacy.
Given the litigious nature of medical patients these days, I think most doctors would justifiably avoid the additional responsibility of pharmaceutical QA.
How does that justify a 30 fold increase?
If an individual Dr can get a batch checked while saving the patient money, it obviously isn't justified.
In my opinion this is an unfair risk to the doctor's career in assuming responsibility for the quality of the compounded drug.
In the absence of any other evidence, I assume the 30-fold increase is the cost to the manufacturer of preparing the drug for eye injection "according to Hoyle."
So why isn't the batch checker taking on that responsibility?
Doctors aren't responsible for anything and everything that happens. If they've had a drug tested to check it's safe, after informing the patient, what else is there for them to do? You're creating a hypothetical to enforce the status quo. That's why we end up with this bs to start with.
How does a lowly pharmacy transform a drug that is not for eye injection into one that is?
They are not transforming the drug just the form. For example, elderly patients may have a hard time swallowing pills, for some medicines (not all) a compounding pharmacy can turn the pill into a lollipop. They can also turn things into like a cream or lotion.
/use to write code for a small independent pharmacy that had a couple compounding labs
> How does a lowly pharmacy transform a drug that is not for eye injection into one that is?
New research probably discovered new applications for their product. Investors agree to diversify. Company developed a system to inject it. The system was approved by government agency at charge of this, and they give the green light to put it in the market.
This is totally normal. See Ozempic history.
The price of a treatment reflects also the collateral risks and probability to be sued for the physician and the company. The problem is not that it cost 1000 dollars, the real problem is that US government should be subsiding at least a part of this cost. Tax money is collected exactly for cases like this. The problem is that they are instead burning 14 millions to paint a pool in "American Idiot Green" dye and nobody says, this bill must be wrong. What they used to paint this? titanium?
The US government already was subsidizing the cost: https://www.nei.nih.gov/research-and-training/research-news/...
It subsidizing the cost of developing many drugs. The question is whether their pricing reflects that.
Just went down a chatgpt rabbit hole because I was also curious - seems it’s literally physical repackaging, no modification of the drug itself- as another commenter pointed out it’s not quite the same molecule but they have the same effect? Someone correct me if I’m wrong
E.g., by physically crushing up tablets and dissolving them in a solution.
I have been a supporter of Cures Within Reach, a nonprofit that focuses on repurposing drugs, especially for rare diseases. https://www.cureswithinreach.org
They have funded some important repurposed-drug studies for Huntingtons Disease, which runs in my family. For a disease like this, it's never going to make sense for major pharmaceutical companies to invest the effort to develop entirely new drugs, but by repurposing existing drugs, it gives people living with rare diseases a chance to ease symptoms.
> For a disease like [Huntingtons], it's never going to make sense for major pharmaceutical companies to invest the effort to develop entirely new drugs
This is ... not correct.
Roche, Regeneron, and Novartis all have novel HD drugs under development in tandem with smaller labs (Ionis, Alnylam, and PTC respectively), and then smaller labs like uniQure and Wave Life Sciences do too. Novartis have already dropped $1bn on the partnership with a committed $2b more. In addition, there are a bunch of incentive schemes for diseases like HD: both the FDA and EMA have offered orphan-drug designation to therapies for HD, the FDA does expedited programmes and can offer RMAT designation for drugs like AMT-130.
With some luck (which is always in short supply for HD treatments, sadly), people with the disease might be able to get a single-injection treatment in the next 12 months[0].
0: https://en.hdbuzz.net/the-other-shoe-drops-uniqure-shares-pl...
I'm on my cell phone and I couldn't figure out what diseases can be treated on the site. I'd say it's donor focused and not patient focused
Not exactly what you asked for, but this page lists their impact: https://www.cureswithinreach.org/about-us-repurposing-resear...
Have you looked into UniQure / Clearpoint Neuro ?
Exciting stuff, if it gets FDA approved.
I’m currently on Spravato, which is fully emblematic of how broken the incentives in the US healthcare system are.
Spravato is esketamine - a modified version of ketamine. Ketamine is made up of mirror image molecules and esketamine is the right-handed molecule. They did this because ketamine is off-patent so they needed to modify it in order to patent it, however there is evidence that esketamine is a less effective treatment than ketamine.
It’s very cheap for me but my insurance company pays about $17k a month for this treatment. Ketamine would be a more effective treatment that would be super cheap for them, but they don’t do it because it’s not FDA-approved. So they’re paying a fortune for a less effective treatment.
It would be in the insurance companies’ interests to band together to fund the research so they can save huge amounts of money in the long term but they do not do this.
> It would be in the insurance companies’ interests to band together to fund the research so they can save huge amounts of money in the long term but they do not do this.
Insurance companies do not want cheaper care.
In the US, insurance companies must spend 80% of premiums on care. So if you pay $1k/mo, they have to pay out at least $800/mo in care. (Not to you specifically, but averaged out across all subscribers.)
This is a cap on their potential profits. They always have to pay out 80% of premiums for care, so how do they make more money?
Well, imagine care is twice as expensive. Instead of paying $800, they have to pay $1600. That sounds worse, but, instead of $200/mo, they now $400/mo for themselves!
So, no, paradoxically, it is not in the interest of people paying for the treatment to save money. Quite the opposite.
It's worse than this. Their cap is 80% of the Insurer's profit. Not the Insurer's Parent company. So often the parent company will own the Insurer as a subsidiary and own the Pharmacy, Hospital, Healthcare etc under the parent company.
This way as costs go up, it's really just bypassing the 80%. Because the hospital can charge the insurance subsidary X amount, and then the hospital profits to the parent company.
There needs to be a law in the US that health insurance organizations cannot be owned by anyone who owns a healthcare provider. Nor can the insurance company own healthcare providers.
We've allows the Ma Bell of healthcare to exist.
I tried to explain to people in The Netherlands this exact problem when they were thinking about switching from single-player to a commercial insurance company model.
Insurance companies always have an incentive to make healthcare services expensive. They have even more incentive to make healthcare expensive and do deals on the backside where their suppliers give them a kickback. Even better if said kickback comes via a side door.
So we went for the commercial insurance companies. It took them 4 years before they change the drug choice from decentralised (Pharmacies deal with drugs companies, received small discounts which funded a good quality of care) to centralised (Insurance deal with drug companies, receives kickbacks) and the Pharmacies funding was drastically cut leading to worse quality of care and more drugs being used. Double-whammy because in the previous system the Pharmacy did medication reviews which almost always result in a reduction in drugs (the thing with drugs is that quite a lot of them are given to reduce side effects of other drugs, the original drug gets cancelled but the side effect reducer gets forgotten and just continues ad infinitum).
Health insurance has been super inflationary since then when controlled for quality of care.
> Insurance companies always have an incentive to make healthcare services expensive.
No, it's when their profits are capped by regulation that they have this incentive.
Insurance of other types absolutely seeks to reduce claims payouts.
> So, no, paradoxically, it is not in the interest of people paying for the treatment to save money. Quite the opposite.
I'll assume they're on company insurance. Which is often "self-insured" in that the company actually foots the bill as opposed to the insurance company.
Why don't corporations just drop insurance companies that decide to not allow cheaper medicines?
UNH is so big because its customer Apple has its own pool. Apple deducts $24k/y for your healthcare. Healthy 29 year old male doesn't use anything. UNH denies the claims anyway. It gives that money back to Apple, which doesn't give it to you.
The 80% rule has a lot of loopholes. It doesn't apply to employer funded plans. There's a reason UNH is so big!
Employer funded plans are not all the same. Large entities with a lot of money (like universities, big firms) self-insure. Thus the insurance company in those cases is simply managing all the administrative sides of insurance while the plan owner is the actual insurer of risk.
There’s an article about how a Wall St employee’s expensive care came up in C-suite meetings, as a real world consequence of this
> simply managing all the administrative sides of insurance
if you punch into a chatbot questions about the employer pool insurance product, your comment is exactly how the chatbot characterizes it.
of course, "administrative sides of [health] insurance" includes requiring pre-auths and approving/rejecting claims, which is, haha, all the fucking evil parts of what they do! it's not "simply" anything. they need a huge, comprehensive, defensible model of what regulations and customers will accept as valid healthcare. apple does not need to have an opinion on ten thousand treatments and the standard of care across all these things. the insurance company does.
this is a line of investigation that the chatbots are absolutely terrible at informing people about. "administrative" is ALL the work, that is why UNH is big! you are starting from the wrong premise. you must always ask yourself, why are health insurance companies so big?
> if you punch into a chatbot questions about the employer pool insurance product, your comment is exactly how the chatbot characterizes it.
That's because it's the truth? I've taken graduate health policy classes from people like Don Berwick - I assure you that I did not and do not need to ask chatgpt to explain self-insurance to me.
> f course, "administrative sides of [health] insurance" includes...
How does this have anything to do with the fact that the self-insuring entity bears the risk for its insureds? The problem with the GP comment about 'giving money back to Apple' is that the money always belonged to Apple and its co-insurance / copays only exist to steer employee behavior.
it doesn't matter if the "self insuring entity bears the risk for its insured." every word in that quote misses the point. it might as well say "blah blah blah blah blah blah blah." it doesn't tell you why UNH is an interesting and successful business, or why people are pissed off about it.
Uh ok bud.
haha okay, what i am trying to say is that from apple's point of view, it doesn't really matter if UNH is selling them a health insurance product or jacuzzi or eyebrow threading services or whatever.
apple employees say they want it, for some idiosyncratic reason apple is the party that gives it to them, and UNH is providing a uniquely cheap version of it. the gap between what employees think they are getting and what they are actually getting is huge. when you go on hacker news and people are talking about 80% medical loss ratios (that don't apply here, but that's not what you are spending your breath talking about) and "insureds" or whatever, you are enhancing the illusion.
that UNH has people carrying its water in this way: that's another reason, of many, that it is so big.
Why do we need to ask why UNH is so big?
This comment chain was started to question why limiting profits to 80% of claims has to result in insurance companies denying cheaper options.
I have yet to see an argument as to why a company isn't incentived to drop a health insurer if they're forcing employees _not_ to do a $50/month option and instead pick a $1k/month option.
> I have yet to see an argument as to why a company isn't incentived to drop a health insurer if they're forcing employees _not_ to do a $50/month option and instead pick a $1k/month option.
That definitely does happen, but companies have a lot of levers to pull around how employees select health insurance. When I bought health insurance for a small firm (~60 people), I provided a set number of dollars and workers could use these for any plan they wished (an ICHRA plan).
Large swaths of US insurance are underwritten by employers, with the insurance companies acting as contracted administrators. Employers don't have the incentives you list.
Great, just work a well paying megacorp white collar job and you'll get slightly less fucked on healthcare.
What about the other 90% of the country?
You could get angry about anything I say, I don't really care, you do you.
I guess Medicare and Medicaid also don't have the incentives. Nor does Tri-care or the VA. My employer self insures as far as I know, and we are a few hundred people. Maybe 90% is a bit off?
I'm not angry about what you say, I'm angry at the parasites that have built this system, and the cynical bastards that work their ass off to perpetuate it.
They operate with similar supply and demand constraints and competition, even with prices increasing
>Insurance companies do not want cheaper care.
Why is there a continuous stream of healthcare providers threatening to or becoming out of network for various managed care organizations because they cannot come to an agreement on healthcare prices?
I suspect it's because the insurance companies are not in control. The idea would be to drive up costs when they profit on both sides (example: United and OptumRx) and push down reimbursements elsewhere.
We baked the snake charmer problem into the law?
Good lord.
> snake charmer problem
Perhaps you mean the "cobra effect" [0]? I think that's an apocryphal story about killing snakes, rather than using them in a performance.
[0] https://en.wikipedia.org/wiki/Perverse_incentive#Historicity...
So the meaning of what I said was slightly obscured but actually easy to apprehend?
oookay.
If I guessed right, then there are probably readers who haven't heard the term/story before [0], or won't make the same jump to recall it.
If I guessed wrong, then I wanted to hear about the new thing that resisted a casual web-search.
[0] https://xkcd.com/1053/
Blame the FDA on that one.
The FDA's policy for the last couple of decades is that mixtures of mirror images will not get FDA approval unless there is a strong rationale for it.
Racemic mixture of ketamine was approved decades ago. If you want a new indication for ketamine, you will need to get approval for a single mirror image, as the FDA won't approve the old drug.
They did this because there are numerous examples of racemic mixture drugs having increased side effects from the less active mirror image, so the FDA decided no more racemic approvals.
My guess is your insurer would be happy to pay for the old version, but your doctor is heavily incentivized to use the new version as the markup on the drug is much, much higher.
>but your doctor is heavily incentivized to use the new version as the markup on the drug is much, much higher.
I don't think it is normal/usual for doctors to receive any benefits or profits from which drugs they prescribe. Other than golf outings with the drug company reps? Is there something I'm missing?
For drugs administered in office, doctors can markup the cost and insurance pays it. Even Medicare pays 4.3% extra.
For oncologists, it’s most of the revenue for their office since consults pay very little.
The money made on administering $5 worth of ketamine is far less than a $1500 bottle of eskatamine.
Thalidomide being one of the more notable ones (though apparently neither chirality is truly safe)
It's worth noting that thalidomide is still approved, but only for leprosy and certain types of cancer.
> Ketamine is made up of mirror image molecules and esketamine is the right-handed molecule.
Esketamine is their cutesy way of saying the word s-ketamine. The s- comes from the Latin word "sinister" which means this is the left-handed enantiomer, not the right-handed one.
It is stupidly expensive, given how generic ketamine itself is. In our case, sleep apnea treatment proved to be a much better option than that drug, as it was just hiding an underlying condition and the treatments only last for maybe a week or two anyway.
I think there have been some people using ketamine off-label, but I don't know much about that. It does need to be tightly controlled because it can cause breakthrough psychosis in some patients. They try to screen those out, but that's not as effective as one might hope given my experience of seeing that fail. And it that was very nearly a fatal mistake.
What’s so interesting about this that I just learned after googling about Spravato that ketamine is a treatment for serious depression. Why? That’s fascinating! Is it the dissociative effects?
A significant effect is through opioid receptor activation, as demonstrated by Williams et al. <https://doi.org/10.1038/s41380-019-0503-4> by blocking the receptor with naltrexone, which attenuated the antisuicidality effects.
The Huberman Lab episode Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity <https://www.hubermanlab.com/episode/ketamine-benefits-and-ri...> and the referenced journal articles (including the above) have a lot of detail on it.
we don't know.
https://lorienpsych.com/2021/11/02/ketamine/#11_How_does_ket...
the opiate receptor interaction might be important, but it seems that the antidepressant effect persists even if the opiate pathway is blocked (via naltrexone)
https://pmc.ncbi.nlm.nih.gov/articles/PMC6439824/ (though it's an open-label super small study ... n=4)
The NHS in the UK refuses to cover it in part because of the absurd cost.
So in Ketamine approved as a treatment in other countries but not in the US?
Related, one of my all time favorite articles: https://www.propublica.org/article/revlimid-price-cancer-cel...
I tried health-tech twice. Opted out both times as there are too many misaligned incentives and useless rent-takers supported by Congress and other entrenched players.
At this point maybe the best solution is door to door doctors using AI.
The Price of Remission - https://news.ycombinator.com/item?id=43925396 - May 2025 (93 comments)
This was a good read, thanks for sharing.
I feel like the best way to fight this, if I was the government, would be to stop enforcing laws preventing patients and even doctors or hospitals from importing the overpriced pharmaceuticals from overseas generics manufacturers. Like the article points out, each pill costs no more than $0.25 to make. The goal wouldn't necessarily be to get everyone using overseas suppliers but to put downward pressure on the price gougers in the country.
Happy to help. The laws you refer to exist to juice pharma industry profits. Same reason it has been so hard to change the law to allow Medicare to negotiate drug prices. The price gouging is by design for line go up.
Changing the law will take time (election cycles). If you cannot leave the US for a developed country that won't squeeze to extract from you while you're trying to meet your healthcare needs, importing your drugs that can be imported without US approval is your only path in the short term, or potentially traveling to obtain them and bring them back (roughly two-thirds of the entire U.S. population, ~200M people, live within 100 miles of a U.S. land or coastal border).
(not legal advice, i am just an internet rando)
It's too late for this. Many government regulations and policies can be solved with money and this would be one of those squashable problems.
Maybe if Pharma companies didn't get so rich already, this could've been possible.
This was so hurtful and blood boiling to read. How is stuff like this allowed to happen?
The system is broken. Hence Luigi.
lack of disincentives to do this
Thank you, really liked this one.
[dead]
Such studies are great but there is no regulatory pathway to extend the use of existing drugs for new indications of use without the consent of the manufacturer (or becoming a manufacturer yourself).
This means such studies can give more clarity on which off-label use is beneficial but it can't be an officially allowed usage.
This isn't completely true at least in the UK. It is simply that the manufacturer is no longer responsible legally. The GMC allow prescibing of unlicensed meds. However the change needs to be made to the pathway. So many issues in the NHS has been due to pathway problems.
There tens of millions of people being treated off-label.
Can confirm. LDN user here.
I checked this thread for an expansion of that initialism, which I didn't recognize. It likely stands for "low-dose naltrexone." https://ldnresearchtrust.org/what-is-low-dose-naltrexone-ldn
"a prescription medication used primarily to treat alcohol use disorder and opioid use disorder" (in addition to the off-label uses discussed here)
Also a LDN user, that drug saved my life. I bought it from a shady dude online, the initial effect was so strong that I thought they shipped me meth instead - that wore off after a week but the lifting of the brain fog persisted.
It didn’t have that sort of immediate, intense effect for me (though yours isn’t the only account like this that I’ve seen) but I’m still happy with the outcome; it dropped my average 1-to-10 pain score by about two points at three months.
It is a rare side effect, I helped a bunch of people (~50) get LDN, primarily for LongCovid, and only one other had a similar ‘too much energy’ effect and both of us have multiple TNXB SNPs and a very similar rare personality profile. I think the brain is so starved for dopamine at that point that it becomes hyper sensitive. I do miss the extra high energy but I also know that isn’t maintainable and I try to err on the side of caution.
I’ve had ME/CFS my whole life but the third covid vaccine shot sent me to new lows, to the point LDN just wasn’t cutting it anymore. These days I take a combo of modafinil in the morning and amitryptiline at night. And low dose ozempic has been super helpful as well. I was researching GLP1As prior to the current craze because I was worried about hyper sensitivity so I waited for more data before trying, I started at 1/100th the normal starting dose and still got temporary gastroparesis. These days I take a more regular dose of 1mg/wk but it also seems that my body has largely normalized as the hypersensitivities have worn off. Probably a good sign that I’ve successfully addressed actual deficiencies.
The doctors are assuming liability or let the patient sign waivers, which I guess is fine. But the lack of a pathway prevents a lot of commercial possibilities. For instance it is almost impossible to build a business around supporting off-label use cases (for instance selling necessary accessories).
I have some difficult-to-treat medical issues and about 1/3 of the handful of pills I take every day are off-label. I think when you get into less common medical concerns off-label use becomes much, much more frequent.
E.g. gabapentin is an anti-seizure medication that has been found to reduce neuropathic pain as well. It has shot up to the 5th most prescribed medication in the last decade as it has replaced long-term opioid use for new chronic neuropathic pain patients. This is 100% off-label and is prescribed by everyone from NPs all the way up to neurosurgeons for this purpose.
I’ve never been asked to sign a waiver and I can’t imagine that for-profit hospitals would allow their doctors to prescribe off-label medications willy-nilly if they represented big liability. (I don’t know this for sure, this is just what my experience implies.)
> I’ve never been asked to sign a waiver
That presumably has to do with the risk profile of the medications you've taken. If there was a high risk of devastating side effects and it was off label presumably the prescriber wouldn't be willing to take on the liability.
Do you know that for a fact or are you just guessing?
I would wager if those waivers actually did anything they'd boilerplate a generic version of it in the legal mumbo jumbo you have to sign even if you come in to have the doctor look at a stubbed toe.
Yup, I've seen this sort of off label prescription at least 3 times.
A lot of drugs require almost no evidence (especially if they are relatively cheap or common) to be given to the insurance company when they are prescribed. And if you are willing to pay for it, you can always pay out of pocket if insurance is being a pain.
Off label prescribing is extremely common.
This isn’t a new or novel concept. Doctors manage patients with off-label prescriptions all day long.
To get a drug approved you have to go through regulatory approval for a particular use. If the fuck-fuck game is you can just off-label for whatever but only if first approved by the FDA to solve some other problem, why not just bypass the bullshit and get straight to the point of approving the drug without any approved use? Oh yes, because that assures the barriers to entry are arbitrarily higher, and Pfizer and other ilk can insulate themselves from competition. Thanks FDA!
Like a lot of the systems we have today, it grew from good intentions. We need to figure out a way to refresh our systems without throwing them away. The current system does provide new drugs and benefit. The question is is it limiting, and are the tradeoff of those limits worth while.
In other words it takes hard work, with politically risky outcomes and an upside that becomes invisible as far as political careers go. We need to figure out how to refresh our systems in an environment where that type of thing just stumbles along. Maybe a couple of politicians elected who have lost out because of the status quo, but that want to improve it not throw it away. Maybe working with them to motivate them to take it on as a pet project and move things.
If we're just letting doctors yolo* off-label, i have no problem with that, but that functionally relegates FDA protections to testing risk profile at some particular dose regimen, with a bunch of extra bullshit tacked on that is highly inefficient process for off-label use even if partially applicable.
It's pretty clear if you're allowing off-label use you can just gate dose-risk profile at one gate and then just add additional gates for on-label uses if you want to approve one.
Of course the issue is the FDA regulator gets the hammer and damned if anything goes wrong but nothing good happens to them if they approve something. So they have no real incentive to approve anything except ideological satisfaction to whatever extent it lives within their mind, plus whatever revolving door benefits industry is offering them.
Probably best to reward the FDA employees for approving good drugs so that the prisoners' dilemma doesn't always fall back to erring on the side of denials, and being easier on them for taking some risk that approves bad drugs to the point they're willing to take some risk to let potentially good drugs through. The regulator doesn't get to see all the bad they cause by not approving drugs because that's invisible, and that's the unintended consequence of their activities and something they're not really held to account for.
* --------- re: below due to throttling -------
>Doctors aren't yoloing it.
If you take offense, call it whatever the hell you want, I was using it in the context of using a drug for a non-approved off-label use. You're making no legal distinction, it's not an FDA approved use and telling the FDA you have some evidence elsewhere but you won't be going through the process to approve it doesn't mean dick to the approval process anymore than my disapproved use of the world "yolo" to refer to same does. If the best my counterparties have is disapproving of "yolo" I rest my case.
Doctors aren't yoloing it.
What's happening is further research on the medicines are being done which show medicinal benefits for off label use. In many cases, it's researchers seeing a drug has a known side effect and saying "Hmm, I wonder if that side effect can counter this symptom".
What's lacking is the final FDA approval for the drugs being used for these off label treatments. That's because these drugs have to go through all the same tests that are required to get FDA approval in the first place.
IMO, for already approved drugs there should be a faster secondary route to getting these drugs approved for current off label usages. Ideally, it'd be something the FDA itself spearheads in partnership with the likes of the NIH.
Problem with FDA is that they try the "one size fits all" what often leads to blocking something that works onlu for a group of patients.
Problem with doctors preascribing against FDA is that it can lead to problems or abuse.
Om an unrelated note, FDA could have been bribed to ban something same way a doctor cpuld have been bribed to prescribe it.
> For instance it is almost impossible to build a business around supporting off-label use cases (for instance selling necessary accessories).
There is no need for a business. Off label use is hacking around the existing commercial and regulatory system. The innovation to be had is fixing said commercial and regulatory system, not another business. Make cheap drugs or medical supplies, distribute them to those in need with as little margin and risk to the patient as possible. This is a utility system masquerading as a market. More duct tape by way of new businesses is suboptimal.
That's not my experience at all, my doctor's have prescribed plenty of things off label. No special waivers.
The business is already built given the drug in question is already being manufactured and available on the market.
The article points out that it is typically after patent expiry that the universities and hospitals start looking at repurposing.
The patents aren't hindering off-label use. The hinder commercial exploitation by others.
Yes, but that isn't relevant to what happens after the type of trials described in the article, which tends to happen when the patents are no longer relevant. As the article points out, while the drugs are patented, the manufacturers themselves are generally very interested in repurposing because it broadens their market. The article is discussing trials that mostly happens once the patents have expired.
This is all untrue so far as I understand.
A research group can file for a new drug application (or abbreviated new drug application) for an existing drug. There is no mandate that an NDA sponsor be a manufacturer or the existing manufacturer.
Only the entity holding an approved NDA can file a supplemental NDA but that’s not the only path.
The real reason no one files for off label use is that there’s high cost and little to no practical benefit to doing so.
On paper you are right. You can file an NDA. But in reality you can't prove that the product on the market (the drug you are adding an NDA to) is sufficiently under your control to enable you to claim that it is safe and effective. Only a manufacturer can control the product. If you want to piggyback on top of an existing product in the market, you have to become a manufacturer or sign a contract with an existing one.
You are absolutely right about the incentives. There are absolutely none except to help humanity which is why only hospitals and universities are doing these off label studies.
That seems wild. Do you have a citation to back that up? And in what country/countries?
I'm in the US, and there are a couple of wrinkles to this: insurance typically won't cover off label use, so patients end up paying the full cost of the medication, and if there is a big enough market, I believe companies can patent the new use even if the patents for the original use have run out.
Doctors here are allowed to prescribe them though.
> insurance typically won't cover off label use
I’m in the US. This is not true.
Insurance will have prior authorization rules for certain drugs that are expensive that require the doctor to submit documentation of the condition, but in most cases the common medication is simply covered if prescribed. The insurance company does not receive documentation of every condition for every prescription to determine if the prescription is on label or off label.
Insurance companies can and do also support some off label treatments that are commonly used under their prior auth requirements.
I don’t know why there are so many comments in this thread making confident assertions that off label prescribing or insurance or so uncommon. This happens all day long at doctors offices and pharmacies.
Yeah I definitely misspoke on that one. I believe they aren't required to cover off label use, so it's up to them whether they do or not.
So much weirdly confident misinformation here. When LLMs do this we can it hallucination.
Can't tell if this comment is agreeing with Aurornis or calling them out.
Agreeing. There is a ton of blatant misinformation being shared in this thread by people who seem utterly confident despite their apparently complete ignorance.
Insurance absolutely covers off label use. And depending on the area of medicine, off label use can be incredibly common (see cardiac pediatrics).
> I believe companies can patent the new use even if the patents for the original use have run out.
This is not true
> insurance typically won't cover off label use
Generally not true but it can be the case, especially for expensive medications
Yes new uses of existing drugs can be patented:
https://www.drugpatentwatch.com/blog/patenting-new-uses-for-...
This is clearly made by an LLM and thus not a credible resource.
From:
https://pmc.ncbi.nlm.nih.gov/articles/PMC9336118/
"COM claims can be difficult to gain for repurposed compounds, as the patentee must somehow differentiate their patent claims over what is in the public domain and present data that the drug is a credible candidate for the new indication [41, 42]."
citing
41 https://pubmed.ncbi.nlm.nih.gov/32241561/
42 https://pubmed.ncbi.nlm.nih.gov/30310233/
Do you like this source better?
https://synapse.patsnap.com/blog/what-are-the-types-of-pharm...?
It’s somebody’s random blog instead of three published, peer reviewed articles. I’m not sure what you expect to hear
It's a matter of law, not science. Ask a patent attorney.
If you like, here is a paper from the Vanderbilt law review: https://scholarship.law.vanderbilt.edu/cgi/viewcontent.cgi?a...
Did you actually read that article that spends many pages explaining how there is no good way for a firm to patent a repurposed drug that is working the same way as it worked in a prior indication, but is being used for a new indication where it has the same function - exactly what you’re asserting and what I said is not possible?
Thanks for the article, it is a good one.
> insurance typically won't cover off label use
That's a lie, I get off-label drugs prescribed monthly covered.
If you haven't watched this talk by Matt Might on Precision Medicine with MiniKanren, you will surely find it inspiring https://www.youtube.com/watch?v=Rt3XyeFHvt4
universal health care can be offered even in 3rd world countries but they're really smart about keeping costs low. they drastically cut the costs of medical service by just offering one or two generic drugs bbought in bulk from china and india rather than all those custom expensive drugs that do the same thing. it does the same thing but at a much lower cost
If every drug created with taxpayer dollars at government-funded research institutions was open-sourced, there would be a collapse in monopoly control of drug manufacturing and that would lower prices significantly.
The question is then, if corporations can no longer acquire IP rights to drugs created by taxpayer-funded research programs and transferred to their exclusive control (eg if Bayh-Dole is repealed in the USA), who will invest in clinical trial costs that need to be recouped via a period of inflated pricing?
The answer is government-funded, transparent, and statistically-robust clinical trials of drugs. Once a clinical trial is complete, private manufacturers can compete to produce the drugs at the lowest price by optimizing their manufacturing pipelines against a final product standard regulated by the FDA. If they want to run their own R & D divisions for drug development outside the taxpayer-financed university system to generate exclusive private patents, they certainly can - on their own dime. That’s an investment decision.
If you need to review why this government-linked, tightly regulated system is needed for drugs with clinical effects, just look up ‘patent medicine disasters of the early 20th century’.
This all assumes that the government will do an equal or better job spending money than companies that rely on spending that money well to exist.
What will actually happen is that the government department of repurposing drugs will be efficient once and then get their budget reduced and never be efficient again. Next time they'll make sure to spend every last cent and not worry about the over budget boondoggle that's three years late because their job isn't to get stuff done, it's to make sure politicians can say their doing something on the campaign trail.
Notice I was sure to include ‘revival of corporate R & D divisions’ in the argument? Bell Labs is the archetype - if corporations can do a better job of applied R & D, let them. If corporations are upset about publicly funded research generating open-source discoveries that upset the monopolistic apple cart, that’s not an argument about improving efficiency - that’s an argument about maximizing profits and investor return, not for efficient new drug discovery or old drug repurposing.
The real question is, what is the metric of ‘success’ - improved public health for the entire population at low cost, or bloated returns for pharmaceutical investors?
> The real question is, what is the metric of ‘success’ - improved public health for the entire population at low cost, or bloated returns for pharmaceutical investors?
This is a false dichotomy and this kind of zero sum thinking is exactly the root of so much misunderstanding of economics that's all the rage these days (and probably forever).
Wealth is created by innovation, not transfered. "Rent seeking" is wealth transfer but most companies provide a service that is more valuable than what exists without them.
The goal of capitalism is to allow the capitalist to increase their profits by improving the public good. "Public good" being measured by what people are willing to spend their money on. It isn't to increase the capatalists profits at all costs. The entire idea is built on exploiting the capitalist's impulse to increase profits to also serve the public good.
I hate to break it to you. Private Equity does not care about the common good, only profits. They only bow to increase price and out side of medicine, reduce the qualifying of the product.
Want common good, start creating disdain for the wealths in societies.
> Private Equity does not care about the common good, only profits.
Go back and read what I wrote. The point of capitalism is to align the profit motive of capitalists with the common good. It's not to give free reign to capitalists to do whatever they want at all costs.
Not according to the Friedman doctrine, which more and more companies are latching onto under capitalism [0].
I would also add that rejecting PE as not being apart of capitalism is rejecting reality. It is here and unfortunately to stay. Wealthy prefer to extract as much wealth from a brand, product, or service versus keep it around in good condition. Billionaires are not created by being supporters of the common good.
[0] https://en.wikipedia.org/wiki/Friedman_doctrine
> Billionaires are not created by being supporters of the common good.
Yes they are. Name a billionaire who didn't make their money providing a service people voluntarily paid for.
Common good != making money!
Exploitation of working class != common good!
Replacing product quality indigence with poor quality and substitutions != common good!
Hording money != common good.
Friedman doctrine != common good.
Power to harm the producer and consumer based on product and service provider != common good. Didn't know price fixing is now classified as common good.
Billionaires exist by the exploitation of the common good.
How many billionaires push against living wages vs support them for all their employees for all their businesses?
> Common good != making money!
Providing valuable goods and services for people who voluntarily exchange their money is very good for everyone.
> Exploitation of working class
Paying your employees mutually agreed upon salaries seems good though, right?
> Hording money != common good
Who's hoarding money?
> How many billionaires push against living wages vs support them for all their employees for all their businesses?
Setting government policy isn't the job of billionaires. People speak with their wallets and would rather have the prices for goods go down (something that historically and consistently happens) rather than see their own wages rise. Which is the tradeoff. You can't suddenly raise wages without seeing a commensurate price rise and then your back to square one. Most businesses run on very thin margins due to intense competition.
[dead]
You're not reading what I'm writing. Capitalism isn't there to serve capitalists so citing what a capitalist wants and saying it's a flaw with capitalism doesn't make sense.
Capitalism is all about providing the right incentives to capitalists so that what's good for them is good for everyone.
> ‘Is curing patients a sustainable business model?’
The goal of capitalism is to make the answer to that question "Yes".
All the same problems exist in corporations. That disconnected idiocy is a function of size, not government vs private.
Is this an argument for small government?
It's an argument for moving more autonomy towards the people actually doing the work, whether in government or corporations.
>This all assumes that the government will do an equal or better job spending money than companies that rely on spending that money well to exist.
We know they do because before the government took over the job, the nascent medicine industry would sell you literal poison.
In fact, you can see today what an unregulated pharmaceutical industry looks like. It's the supplements aisle at your local supermarket. The place where you can buy literal homeopathy sugar pills, and various completely unstudied compounds and other scams. You can buy turmeric for hundreds of dollars a pound.
If private industry was better than the government at managing drugs, the American supplements industry would mean we should have dramatically better health outcomes and dramatically cheaper healthcare
Neither are true.
> We know they do because before the government took over the job, the nascent medicine industry would sell you literal poison.
I'm not arguing against regulation of private industry, I'm arguing against government competing with private industry. The government has unlimited money, very convoluted incentives and the legal right to use guns.
Private industry which has to make good choices or die is a much better environment for spending money wisely.
While I actually sympathize with your position, I think your argument has a significant flaw: the "unregulated pharmaceutical industry" you reference is actually quite regulated.
My company can put a GRAS compound like turmeric in a pill and sell it over the counter, but the moment I stop calling it a spice and make a treatment claim about it I face enforcement action. And I certainly can't put in an active ingredient that might actually /do something/ - like those gas station "sex enhancer" pills that, surprise, have sildenafil - because then I'm distributing an unapproved/mislabeled drug.
> We know they do because before the government took over the job, the nascent medicine industry would sell you literal poison.
We also know that some reports of poisoned industries in the past were exaggerated (and politically capitalized to lobby monopolistic regulations). This wasn't exclusive to medicine.
> The place where you can buy literal homeopathy sugar pills, and various completely unstudied compounds and other scams.
Presuming that these aren't actual cases of fraud - if they were, they'd already be illegal in a private market, regardless of the FDA - how many are actually buying these? Not many, I presume. For those that are, I think better informing them is much better solution, not only to combat innefective drugs, but also to strengthen trust on actually effective treatments. That said, homeopathy seems more like a yet-to-be cracked down case of fraud, regardless of regulations.
> If private industry was better than the government at managing drugs, the American supplements industry would mean we should have dramatically better health outcomes and dramatically cheaper healthcare.
Why? USA's healthcare system is an overly bureocratic, poorly regulated (not as in lacking in regulations, but that the regulations that exist are bad) goliath. It's closer to a government-funded system, except stupid. It's not an example of a government-free system, but how private actors do their best to exploit existing and lobbied soon-to-be regulations in their favor.
How do people needing (and willing to risk) treatment hear about repurposing studies?
Specialists keep up with the latest research in their domains and talk with other specialists in their field. They usually know about these things before their patients discover them spontaneously.
You can read a lot of published papers on PubMed by searching for a condition or drug. You should be aware that there are a lot of papers published that say disease A can be treated with drug or supplement B that fail to replicate if anyone else tries it. It takes some practice to recognize when a treatment represents a real trend as opposed to a single quack doctor looking for a status boosting publication with some questionable claims.
Big medical systems will post their clinical trails quarterly or so. If you have a big medical system near you you can sign up for emails. I imagine universities would have a mailing list too, if they regularly did clinical trials.
You can also search here: https://clinicaltrials.gov/
I was a clinical trial participant once and it was a positive experience for me.
I think in the same way they participate in other clinical trials.
Communities (on-line or off-line) of people who share your disorder, and maybe health care professionals who see many patients with your disorder.
Yes, but it's really tough. I read that 50% of Stanford Medical School budget comes from Big Pharma. It's really hard to get the message out. I believe Pharma (the biggest advertiser on Google) is influencing Google search results, among other things.
Here is a site that focuses on COVID and Cancer: https://imahealth.org/
fascinating! I'm sure there's quite a bit that can be learned through appropriate research - pathways to solve problems that haven't been thought of before
the thing is while something is better than nothing, new drug development is critical
there is absolutely no cure for certain types of long-covid and me-cfs right now
no repurposing any drug is going to cure it, they've tried everything after six years
it will take a decade to have anything even in the pipeline and won't emerge from the USA because all medical and science research investment by the government has been destroyed by Russell Vought and Heritage Foundation
JAK-STAT inhibitors will be a big treatment, not a cure, but they cost thousands per month in the USA because generics aren't allowed
> the thing is while something is better than nothing, new drug development is critical
> there is absolutely no cure for certain types of long-covid and me-cfs right now
> no repurposing any drug is going to cure it, they've tried everything after six years
Then repurposing should free up resources for new drug development for those conditions that it can't address.
Sounds like a win-win, unless the goal is somehow not to most efficiently allocate resources to maximize health outcomes. But at least in the US, that's clearly not the goal.
What is repurposing drugs?
The prices of drugs in the USA are especially high. This is interesting because the USA claims to pursue a maximum capitalistic society - but if this were the case, you'd have competition in a free market. But you don't have that. You have a cartel (or rather more than one).
A pure capitalistic society works on assumptions that are not real. People are often cheaters. This would have to be taken into account. But when you have an orange Al Capone in charge, it is pillage day. Even before the orange King you had heavily overcharged prices in the health care system. You need to realise that you have a mafia in charge that does not want to change this system. Why kill the cow that you can milk for free?
Look at the development of price and quality of something that is outside the regulated medical system, like eg Lasik, and everything within that system. Its like night and day.
If we had proper competition and price discovery, things would be much better.
On the other hand, dental work, especially anything above basic filings, are prohibitively expensive. I'd say Lasik is the exception, not the rule.
Are you under the impression that dentists are under competitive pressure? The labour supply is artificially limited, similar to other doctor specialisations.
Are you in the US? This is not my experience at all. I've paid in US <2000 for dental invasive surgery including general anesthesia straight cash. That's approaching prices for medical care in Mexico.
Dentists are only slightly more honest as a profession than Chiropractors. More than half of the one's you meet are outright fraudsters/charlatans/scammers. Most who work in that business will reincarnate as cockroaches or durian fruits.
> This is interesting because the USA claims to pursue a maximum capitalistic society
No it doesn't. This is silly.
Drug prices in the US are high for non-generic drugs because patent law gives the patent holder an artificial government-granted monopoly, which is blatantly not "pure" or "maximum capitalistic".
Generic drugs - where the free market does apply - in the US are as cheap or cheaper than in other countries. See [0]:
[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC11147645/I believe you two are arguing the same thing. Maybe the poster could have better worded it "general thought among most people is that the USA ..."
Because you are both absolutely right.
The maximum libertarian alternative to patents isn't free-for-all copying, it's trade secret formulas - e.g. Coca Cola. Drug patents actually exist as a compromise given the clear need for the state to force companies to publish their drug formulas for research. Allowing companies to just keep their drugs secret would be even more capitalistic, and would increase drug prices even more.
They keep their processes secret instead under the current system, achieving a "trade-secret" like result for some drugs. For some drugs it achieves the same thing because finding a practical economic synthesis is the hard part rather than coming upon a small bit of chemical that is proven to be effective. For others it wouldn't matter whether you kept it secret or not, someone would isolate and characterize it and reverse engineer a practical synthesis.
The biggest value protector arguably of the patent-FDA approval process is on the FDA side, who create massive barriers to entry that mitigate close unpatented chemical competitors from outside the pharma oligopoly from competing.
Is the patent not for the synthesis route itself, rather than the drug? Someone can't just plop down a chemical formula on a piece of paper and patent that, can they?
I'm not really happy with the current system either - I tend to think that the state should just mandate that all medical research be fully published, and either have companies compete on research and manufacturing, or pay for it directly if it can't be made to work as a private business. My point was just that this is very much not a capitalist or libertarian position.
This is where prizes come in. If you create a drug and keep it secret, the government can grant you a large prize as an offer to reveal your secret.
This is a much better compromise. The company will end up with more money(and faster!) as a result of this prize than under a patent system - since the patent system induces dead-weight losses, and the government will end up with more lives saved.
That is just an inefficient way to spend taxpayer money than straight up paying researchers from the government’s accounts.
The US has an enormously large higher education system with all the expertise and manpower to facilitate large trials of novel medicines. The only thing missing is political will to spend the money, so instead, Eli Lilly or Novartis or Pfizer etc spend investor’s money to do it.
And then taxpayers pay for it in a super convoluted way.
Prizes pay for working results. Grants pay for possibilities. Grants are therefore riskier, and thus we allocate less resources to them.
Since the people with the money don't understand the science, these possibilities must then be assessed by bureaucrats, and this causes our best to spend half of their time writing proposals instead of working and researching. A complete waste of time. Let the people who know the most about their subject freedom to take risks, and then they are given the spoils of their rewards if they are proven correct.
Prizes are much more efficient than grants. Prizes should be given to academics according to the value they produced. I have no issue if the academics choose to spend some of the windfall profits of their prizes on trials.
> https://en.wikipedia.org/wiki/Innovation_prize_model
> Since the people with the money don't understand the science, these possibilities must then be assessed by bureaucrats, and this causes our best to spend half of their time writing proposals instead of working and researching. A complete waste of time.
What part of this changes when a company is paying for the research, and why can't that same part be used in a government office? It's not like drug company CEOs and CFOs are also world class medical researchers. And if the funding decisions are entirely done by a CTO who is, then why would this model not be possible in a government office?
Ultimately someone needs to pay for all of the trials that don't work, and someone needs to do a cost/benefit/likelihood analysis on any research to decide whether it will be funded or not. With a public funding scheme, the benefit analysis could be based on public health interests. With a private company funding scheme, it has to be based on profitability. In healthcare, there is usually a huge gap between these two, unlike other more traditional markets.
Yes, businesses have the same flaw with a bit of better incentives.
With a prize based approach, what you want is for researchers to make small targetted gambles early in their career, earn their prize profits from those gambles, and work their way up into bigger gambles. There's nothing crazy about this scheme, it's how businesses have formed for hundreds of years. If a company wants to buy equity in the prizes of an independent researcher, I see no issue with this.
> then why would this model not be possible in a government office
I see no issue with governmental workers, or those from a university medial research center, or any other persons who can achieve the results from receiving this prize.
> someone needs to pay for all of the trials that don't work
The researchers. They are the one taking the risk. They are the one who would get the rewards. Skin in the game.
> With a public funding scheme, the benefit analysis could be based on public health interests.
Yes, we should directly pay the organization, or persons, based on the value they generate from their own. The bigger the public health interest, the more they should be paid. Right now we give a tiny piece to these people, and thus harm our incentives. Fully fund the results. It's risk-free.
"Drug prices in the US are high for non-generic drugs because patent law gives the patent holder an artificial government-granted monopoly, which is blatantly not "pure" or "maximum capitalistic"."
This is very much capitalistic. It's not competitive markets (which are good for consumers) but capitalists hate competition once they have made it to the top.
Capitalism doesn't serve capitalists. It's built to create an environment where the capitalist, doing what they do best, also serves the community.
Monopolies are anti-capitalism, despite it being something that capital strives for.
This is like being upset that bug spray doesn't actually spray bugs, in fact, it actually deters them.
And yet, the defense of the status quo often relies on the supposition that the US is a capitalist nation, perhaps even a “maximally capitalist” one.
I’ll have to keep this in mind the next time it comes up…
> This is interesting because the USA claims to pursue a maximum capitalistic society
I don’t know why you think this. The US is not a maximally capitalist society. The reason drug prices are so high is due to regulations restriction who can manufacture them due to government-granted temporary monopolies through patent law.
If the US was maximally capitalist it would be a free for all with no patent protection.
> If the US was maximally capitalist it would be a free for all with no patent protection.
The much more likely alternative in a maximally capitalist / free market maximalist society would be keeping all drug formulas as trade secrets, and thereby having all drugs as branded, no generics whatsoever (or few - perhaps some substances could be reverse engineered). In such a society, having the state force companies to publish their formulas would be seen as unacceptable interference in the free market, almost certainly.
I'm not convinced about trade secrets being the capitalistic route here, specially since, as pointed out somewhere else, the current system is basically like trade-secrets already, which suggest inverted causality.
In a pure free market, someone could try to keep the formulas secret, but others can just reverse engineer it into being public, which is basically guaranteed to happen if there's sufficient demand. Given that they aren't wasting money trying to obfuscate the recipe nor the formula, these competitors do have an advantage over the original. As such, I posit that free-to-copy will be default behavior in a pure free market, with trade-scerets being resteicted on niche sectors.
The reason we can't do this today is primarily that reverse engineering is heavily restricted by IP laws.
The recipe for Coca Cola, the most popular soft drink in the world by far, has been a trade secret for over 100 years. And I'd wager a guess that it's slightly simpler to make then most medicines. So I don't see any reason whatsoever to assume that drugs would be easily reverse engineered.
Instead, I'd say that the assertion that today's drug making is hard to reverse engineer is hard even knowing the exact formula, substance, and dosage of every drug is unlikely to be true - is there any example of any drug that generics companies are not producing more cheaply than the original inventor, once the patent has expired?
I don't think Coca Cola is a good counterpoint due to a couple of reasons:
1) there was a recent attempt to find the formula [1], but the primary reason that was infeasible is that, allegedly by the ingredient list, they use coca extract and, IIRC, only one company provides that in the US, due to FDA regulations. Even if they were find the formula behind, it wouldn't help much, so they're are trying to replicate the flavor instead.
2) Coca Cola is, before anything, a brand. It's not comparable to generic medications because people in general don't buy it for the formula specifically, but the expectation of flavor and taste associated with the brand. Even if you were to find the current formula, the Coca Cola Company can just change it.
In regards to the last point, there probably is one (likely in heavily subsidized prices case), but, regardless, I don't see how your point shows patents are the reason anymore than a increase in competition, which we are proposing would happen if patents were abolished.
[1] https://www.youtube.com/watch?v=TDkH3EbWTYc
You are confusing capitalism with competitive markets. These are very different things.
The US is not a capitalist society, it is a liberal society. Capitalism is a consequence of that but it isn't the reason.
This is completely backwards read Marx. Superstructure (culture, politics) flows from the economic base (there are some important exceptions, but that’s the dominant arrow).
Marx can say what he wants but history itself disagrees.
> read Marx
read Popper
Popper talks about sociology as though it were physics. Unfortunately, competitive games and the subjective belief of people can influence the course of history if the right material conditions are in place. Sometimes you try different things and get different results in different contexts.