Does the cost to get a drug approved depend on how novel or irreplaceable it might be? Did it cost the same amount to approve Silenor for insomnia as it would cost to approve a really novel drug much better at combating insomnia than any existing one?
If the FDA imposes equal costs on any new drug, then it's not "imposing [costs] on a company trying to [...] parasitize the healthcare system". It's neutrally imposing costs on all companies developing drugs. And this probably does a lot more harm on net (fewer drugs marketed) then it does good (punishes some drugs that harm society).
Silenor may be a bad example for the anti-FDA narrative, but I don't think this is strong evidence against the narrative, given all the other (hopefully good) examples that we have.
To be clear, it's very important and beneficial to call out bad examples in a narrative, thank you for doing that. We should update on this information. But I don't agree with your conclusions.
Pharma companies can probably estimate the cost of bringing a new drug to market, and make a rational cost-benefit decision (citation needed). Somaxon presumably made a bad decision with Silenor, and was 'punished' by losing money.
That's what happens to any companies in a market. Even if it was cheap to bring a drug to market, companies would still make money on some drugs but lose money on others. Why do we need an agency like the FDA imposing extra costs?
One of the complaints about the FDA is that only big and well-established companies can afford to bring a drug to market. It's a moat against new competitors, and a net harm to society because fewer good drugs are developed and approved.
Suppose the FDA found a way to make drug approval cost 50% less, while still approving the same drugs in the same amount of time. That is, pharma companies would pay half what they do now to go through the process. Most people would say this is a good thing, i.e. less dead loss. Would you call it a bad thing because it would reduce the 'punishment' of companies? If so, do you think the cost should be increased, or does it happen to be just right?
Did it cost the same amount to approve Silenor for insomnia as it would cost to approve a really novel drug much better at combating insomnia than any existing one?
The FDA wants proof that drugs have a statistical significant effect. The stronger the effect of your drug happens to be the less people you need in your phase III trials.
When a company pays $170M to get a drug approved, where does that money go? To the FDA? To compensate trial participants? To a third-party that actually runs the trial or verifies its validity?
On GoodRx, you can buy 30 doses of Sinequan for about $10, but Silenor costs at least $100. But these are two names for exactly the same chemical.
Just because something contains the same active ingredient doesn't mean that the same clinical effect happens. There's more then just the active ingredient that goes into a drug as the Ranbaxy saga demonstrates very well. There's no good quality control mechanism for generic drugs.
I do not think that is true, at least in Europe where hundreds of millions of people use generic drugs every day. In Germany, in the UK and in Austria a doctor will amost always prescribe a generic when available and people will often buy a generic over the counter. While sometimes too conservative, the very reason why we need the FDA, the EMA, et al. is exactly to make sure that generics* work well -- and they almost always do, one cannot use rare counter examples to disprove that. Do we have any hard data to suggest that generics are somehow unsafe?
* i.e. not some Indian blackmarket knock-off that isn't FDA/EMA approved
Do we have any hard data to suggest that generics are somehow unsafe?
As I said, the Ranbaxy saga. It shows that even when there's a whistleblower from the manufacturer that tells the FDA that a manufacturer is fraudulent it takes the FDA years to do something about it.
* i.e. not some Indian blackmarket knock-off that isn't FDA/EMA approved
The approval consists of believing the company that the studies they provide are true. The FDA doesn't have subpoena power over Indian factories producing generics and it doesn't do independent quality checking beyond believing the companies.
Do you have a THEORY of what you WANT out of "a good medical system"?
The thing I want is MEDICINE that generates PATIENT HEALTH. Period.
It's not at all clear that the story of Silenor is best interpreted as an indictment of the FDA. Instead, the FDA comes out looking to me like it successfully imposed a devastating cost on a company trying to use marketing and regulatory manipulations to parasitize the healthcare system.
I don't want to punish parasites (corporate or otherwise). I just want them to stop sucking my blood so that I can use my blood for my own life and my own ends.
Also, why would you split out the company as particularly distinct from the company's regulators? At this point I've seen so many examples of regulatory capture that my priors START there, and I am joyfully surprised when I stumble on a situation that works a different way.
I'm highly sympathetic to the idea that there should be a better way to promote FDA approved drugs known to be effective for some off-label use... Whatever it is, it's going to have to balance the needs of patients, physicians, regulators, pharma companies, and, perhaps insurers.
I. ONLY VENDORS WHO SELL ACTUAL HEALTH IMPROVEMENTS DESERVE RESPECT
So, I do not give a single flying fuck about any of those people except the patients.
As humans: sure physicians are humans and everybody gotta eat. But, as physicians, if they are somehow NOT improving the health of their patients by figuring out what their medical problems are and using medicine to heal them then maybe they should get a job at a gas station instead?
Or maybe go to prison if they are committing fraud by promising good health and producing the opposite?
So long as physicians don't promise good health, if something other than good health happens that would count as NOT fraud, and so... you know... just don't give unjustified warranties? Say "caveat emptor" which is the default with everything else already?
This cuts both ways. I'm happy to throw physicians under the bus if they don't produce health, but if nurses or engineers or homeopathic crystal wavers OR ANYONE generates more health, for more patients, for less money, them PROBLEM SOLVED. Whatever produces the most health is good. Whatever does not is bad.
Knowing what my goal is, I can judge everything else in how it helps or hurts this outcome.
II. ONLY HEALTH REGULATORS WHO CAUSE HEALTH DESERVE RESPECT
Regulators are public servants. They have no valid independent needs to cater to. If they are not engaged in a positive public service to the voting public, then the voting public should fire them. The voting public shouldn't be pleading with them, or soliciting their concerns, or worrying about their feelings.
The voting public should not be trying to "work with them to make them comfortable". That's how peasants interact with nobles, or cringing employees interact with bad bosses, not how a free people interacts with their own elected leaders whose job is to make the community of the free people run better for those free people.
The regulators are simply the factotums of congress and the president, whose authority to make laws derives from the voters and whose will the regulators should implement... or else the regulators should be eliminated by the elected officials.
If the elected officials can't get rid of bad regulators, then we should vote in elected officials in who WILL get rid of bad regulators.
Congress passed (and Kennedy signed) the Kefauver Harris Amendment in 1962... so therefore they can and should repeal these laws.
If the law is repealed then the FDA would not have a mandate (and thus power (and thus the ability to demand moral-maze-like-comfort)) to perform prior review on every possible medical innovation to ensure, in advance, that every medical innovation is "Safe(TM)" and "Effective(TM)"...
If the law is repealed then the FDA can... go back to inspecting meat? Or just get pink slips? If they're looking for something to do: I'm a big fan of market surveillance to find impurities and contaminants.
The amount of testing that happens seems to be... weirdly rare... so that testing things can lead to surprises? The hard and expensive part of keeping quality high and cost low seems to be generating valuable knowledge based on new facts. Running the random surprise assays as close to the point of use as possible? Collating the results of assays performed in different locations? That kind of stuff. Actual work, not just vetoing other people's work.
It would be great to have someone randomly sampling things from the consumer product purchasing stream inside of pharmacies and so on, and verifying the accuracy of their dosing and purity claims. It would be great if vitamins were randomly grabbed off of grocery shelves here and there and tested for lead. Heck, it would be great if someone was checking rice for its arsenic levels. (This is mostly, however, NOT what the FDA does.)
III. PHARMA COMPANIES HAVE ONLY INSTRUMENTAL VALUE
Patients first.
Then physicians if the physicians cause better health outcomes for patients...
Then the pharma companies are even LESS intrinsically worth paying attention to the needs of. They are not moral patients. They don't feel pain. They are mere virtual agents that the legal system grants a legal existence to for their instrumental utility in coordinating groups of people on worthwhile projects.
Any process that can make molecules of medicine physically exist and then end up in the medicine cabinet of a patient (who can take it over time, and thereby become more healthy) would, I think, be a valid output from a working medical industry from the perspective of patients. The cheaper the better.
If this can be done without giant pharma companies that extract huge profits, that would be GOOD. Costs are bad. Health is good. Up is up. Down is down. Yes?
If we could buy chemical printers and chemical feedstock at Walmart, and then tell the machine to print any molecule in any reasonable medical quantity and quality, and then just 3D print drugs, like mRNA vaccines, or aspirin, or whatever... that would be fantastic!
We could perhaps go to doctors for advice on which chemicals to 3D print (because the human body is complicated and expertise is helpful).
That might be hard (and I do think it is hard... chemical manufacturing has economies of scale and can be done poorly or well and a drug printing machine is currently just an imaginary wonderfulness right now) and so maybe we can't just print drugs in the home yet, and so maybe we still mechanically need huge pharma companies manufacturing helpful chemicals in huge batches.
That manufacturing challenge in the world, where it is hard to do complex things in an efficient way gives these organizations a human-serving reason to exist.
But we don't have big companies FOR THE SAKE of having big companies. Big pharma companies are not intrinsically valuable. If they have value, their value arises from them being a way to make health-producing medicines at higher quality and lower cost than other methods, which can be sold to patients. Hypothetically, it is an economy. They make a product. If the purchaser isn't improved by the product then something is deeply broken?
IV. INSURANCE COMPANIES SHOULD DEFEND THE FDA, BECAUSE ONCE THE FDA IS GONE, BAD INSURANCE IS PROBABLY NEXT ON THE CHOPPING BLOCK
Insurance is the LEAST worthy of having needs that are respected in a conversation about improved medical regulatory systems.
Insurance companies are almost literally the devil.
There is a "charity shaped hole" in people's hearts and minds where "the bigger social entity that takes care of people in their tribe" is supposed to go, and insurers despite all sane evidence and theory to the contrary, have somehow slid into that mental slot in the minds of many people by pretending that they are some kind of "method of caring for people"? Or something?
(I don't object to the concept of insurance. Betting that you will fail at something, with a bookie, can help finite agents manage risk of failure. There's some moral hazard, but... anyway, it is something that responsible and moral people could hypothetically do as part of sane contingency planning. Bookies who we think of as bookies are great at being bookies.)
But insurance is a terrible way of causing charitable contributions to go to people in need. Insurance is for risk management, not charitable transfers. Trying to use insurance to accomplish charity is just dumb.
It is like using a pump-free system of canals... to get water to the top of a mountain. That is not how gravity works! That is not how insurance works!
If we need to make sure poor people can get medicine then maybe we should give them cash so they can buy medicine, and perhaps hire doctors to give them advice about which medicine to buy. If they don't use the cash to buy what we think they should buy, maybe we don't really understand what their actual needs are?
Also, in practice, I think America is insanely rich, and the medicine that actually works isn't that hard.
Maybe this is false? My prior is that once we unravel the corrupt bullshit (insurance and government monopolies and "scientistic" top-down management and so on), then things will snap into place of their own accord in a pretty good way.
I guess there's a deeper model here, which is that the reason it all seems to cost so much is that a lot of the dollars are being spent paying the salaries of privately employed bean counters who are engaged in trench warfare with each other, who watch bills bounce around from computer to computer. A bunch of people at a bunch of different corporations are pressing buttons on their computer all day to try to trick someone else (sitting at a computer in different building, working for a different organization) to pay each bill, which is very dissociated from whatever physically happened in the actual clinic.
You give your money to your employer. Your employer gives the money to insurance. The insurance gives it to the hospital bean counters. The hospital admins give it to the doctors. This is why doctors cater to profiteering hospital CEOs rather than patients. Whoever controls the money flow calls the shots.
The flow of money is currently in the hands of the bureaucrats. This is why bureaucrats are prospering and humans are dying. The FDA is currently the de facto gatekeeper for access to this rich and beautiful flow of money that can be extracted from oblivious and weak consumers. If the gatekeeper disappears, then swiftly afterward the money flow will have to be re-engineered as well.
I think that this would almost certainly be good. Because America is insanely rich, and medicine isn't rocket science. All we have to do is not tie ourselves in knots or shoot ourselves in the foot, you know?
At this point, "cash for service and begging on the internet for help with your medical bills" might well be an improvement over the status quo.
I'm not saying this to say that "cash for service and begging on the internet for help with your medical bills" is good. I'm saying that our current system is even worse than this. The current system ALSO HAS begging on the internet for help with your medical bills, but in the current system these bills can come from out of the blue because no one in a private clinic can actually say how much anything will cost.
The system right now SEEMS DESIGNED to make everyone price insensitive?
It is crazy to me, unless I model it as Out To Get You.
( V. A BRIEF RANT ABOUT THE NON-EXISTENCE OF "ACTUAL PUBLIC HEALTH" IN THE US
In the meantime (speaking of crazy): communicable diseases are a public goods problem. This public goods problem should be solved by positive efforts by our benevolent elected central authority to MANUFACTURE the public good of "HERD HEALTH".
They should be testing for communicable diseases, and doing vaccines and antibiotics to snuff out chains of disease transmission. This is medicine, but it is naturally public medicine. It should be financially free for every human body in the physical US. If we can't control our border with Mexico then we should give them free public health too so that shit doesn't leak in from dirty places? But doing any such border thingy is pointless while we, ourselves, are also dirty and dysfunctional. FIRST: get our house in order. SECOND: insist on guests being tidy.
If the communicable disease fighters find a Typhoid Mary here and there, who knowingly carry and transmit a disease over and over to innocent third parties, and somehow can't be cured, they should regretfully and sadly arrest such people for the crime of knowingly transmitting a disease to other people. If someone was running over pedestrians with their car over and over, that would be a crime, even if it wasn't their intentional fault. Same principle. I don't care if this means people with Herpes can be sued or jailed for knowingly transmitting their herpes to people they date. (That's exactly what SHOULD happen in any sane society.)
The government doctors who can arrest you for knowingly transmitting a disease to other people should not be the same doctors as the private doctors who perform heart surgery, and do healthy baby checkups, and set broken bones, and help you program your artificial pancreas.
Broken heart valves are not communicable. I'm not afraid to be in the same room as someone with a broken heart valve because I might catch their "disease". It is not selfishly rational for me to want someone with a broken heart valve to get their shit fixed so that I don't catch it. It would be insane to lock up people with broken heart valves so they don't spread their problem to other members of the herd.
This is the economic difference between private health problems (like heart conditions) and public health problems (like covid).
To call the FDA a "public health system" is an insult to the word "system" and to "health" and to "public".
)
The FDA generates no positive benefits. All it does is forbid things and slow things down.
VI. A POSSIBLE CRUX: MAYBE AT THIS POINT ALL MEDICAL INNOVATION IS BAD, AND THE FDA PROTECTS US FROM THIS BADNESS?
If you think that doctors and pill sellers and medical innovation is bad by default, and if you think that only a few carefully vetted changes to how the medical industry works could possibly be good (out of a torrent of otherwise bad innovations (that neither doctors not patients wouldn't be BETTER able to reject at the clinical level))... then maybe censoring medical innovation, by default, is wise?
The alternative is basically to ALLOW by default, and then notice bad patterns when they sometimes arise, and then canceling the bad innovations based on negative experience.
You know something interesting? This pattern of "try it, more and more, and then pull back when tragedies are detected" approach is actually how medical innovation already works under the hood (when it does manage to happen). The errors(?) still occur.
They are visible as a litany of recalls AFTER the "so-called science" was done to the FDA's satisfaction and people started to relax into the oblivious comfortable posture of business as usual with someone else standing nearby looking "official and willing to take the blame for fuckups".
Lorcaserin (Belviq(R)) had a New Drug Application in 2009. It was approved in 2012. In 2016 an extended release version was approved. In 2020 an increased risk of cancer was noticed and the drug was recalled.
(Either there was an error in 2012 and 2016, or else there was an error in 2020. Maybe the cancer risk is "worth it" for some patients sometimes? One extremely cynical model is that some people, in the 8 years from 2012 to 2020, performed an experiment on the public without being honest about the risks? An even more cynical model: maybe the drug is fine for some use cases and patients, but the company didn't bribe the right people at the FDA enough to stay on the gravy train? I have no idea. There are many hypotheses that could explain the behavior in terms of selfish people acting selfishly. I don't see any hypotheses that explain the behavior in terms of competence and honesty.)
In 2012, ingenol mebutate (Picato(R)) was approved by the FDA (it is basically turpentine from milkweed pods that kills cells) for... killing skin cells that you want dead for some reason (old person skin with "scales", basically). In January of 2020 the European Union decided to pull it because they THINK it probably causes skin cancer? This does not surprise me. But the company that markets imiquimod seems to have generated some research showing that imiquimod plausibly causes LESS skin cancer than Picato? The FDA still allows Picato however.
(The whole thing seems crazy to me, but then again I've never had scaly skin and also been "close to death no matter what I do", so maybe that changes the balance of risks and rewards? Personally I'm in favor of a patient's right to choose things all the way out to physician assisted euthanasia... freedom baby! But it seems weird to pretend that just because something is legal that it has zero risks and zero side effects. Its all a local specific tradeoff-based balancing act.)
Ranitidine (Zantac(R) and Tagamet(R)) had a New Drug Application with the FDA in 1989. It seems to decrease stomach acid based on blockage of hisitidine receptors while having various side effects. By 2018 there were 18 million prescriptions. Then in 2019 someone (the Canadians?) noticed that it had NDMA in it (as manufactured by... it looks like maybe ALL of the manufacturers?) and so in 2020 it was recalled.
(I have no idea if this was smart or not. Maybe those 18 million prescriptions were a net harm even despite the NDMA? Maybe it was good for some people and bad for others? Details matter. Doctoring is a real skill. I'm not a doctor. So assuming the NDMA was really a dramatic and real problem, where the fuck was the FDA in 2018 or 2017 or 2016 or 2015 or... etc? Its almost like the way they try to make people safe isn't making people safe??)
VII. MAKING SENSE OF DECADES OF APPARENT FAILURES IN GUARANTEEING MEDICAL SAFETY
And so on. Every single drug recall is its own little crazy story and there have been ~2.6 recalls per year for 60 years.
The lesson I draw is that the market and the clinical practice of doctors is itself doing "science" or learning or whatever you want to call "knowing things better over time based on careful observation".
And the real "story about the tradeoffs inherent to any given therapy" is that better stories tend to arise only after the market has seen LOTS of patients try the therapy with LOTS of doctors over MANY years. In my model is is INEVITABLY risky at the beginning and calculated risks are perfectly OK.
The system might still be absurd and dysfunctional. But the precise nature of that absurdity and dysfunction might be quite different from what best suits the transmissibility of a healthcare story. And understanding those mechanistic details is important for understanding what actually needs to be done to make the situation any better. Furthermore, if those stories comprise most of the "data" that forms the judgments of activists interested in changing the healthcare system, there's a huge risk of bias.
Part of the data is more than a hundred examples over decades of operation where the ongoing inevitable contradictions of:
- asking a federal agency
- to do a conceptually impossible task
- whose side effects determine the winners and losers in the game
- of "feeding at the money trough that is the totally broken health insurance system".
Basically all of these drugs could be used to kill someone at the wrong dose. They aren't "safe" in a magical immutable essential way.
They are only safe if skillfully used in the context of a balanced and adequate risk-aware cost/benefit analysis that is local to the specific patient with specific needs.
The FDA already said all of these things that were recalled were "safe".
In 1961 they ALREADY HAD a "safety mandate" from congress and then they got a bunch of new powers to vet every drug for "efficacy" before it came out. This new power makes no sense to me.
The new power seems to have put an end to basically all of the small short fast "try it and see" efforts by doctors?
My proposal is that we should take the powers to pre-judge clinical efficacy using high church science at gunpoint away from the bureaucrats, because the powers are obviously stupid and bad if you Simply Look At Them And Think.
The REAL WAY of figuring out if the medical economy can find a reasonably safe reasonably cheap plausibly effective use for various potions: just TRY THEM and SEE.
Doctors with skill and knowledge and malpractice insurance and a relationship with a patient can probably do this. IF THEY CAN'T then maybe they should NOT HAVE A MEDICAL LICENSE?
Granting doctor competence, why have a second layer of reasoning that restrains the layer of reasoning that is actually closest to the problem and thus the most likely to be able to make good decisions?
Also, if doctors fuck up sometimes... Are there no courts? Do doctors not already have a layer of regulation in the form of malpractice lawsuits? (Incidentally: I'm not opposed to medical tort reform, but I currently have no coherent theory on how to do it right. I think if it was done right one indicator would be that medical science would resume doing autopsies?)
If we let experiments happen by default, I think there would still also be a pile of accidents.
My claim is that it would be basically OK to have a small pile of accidents when the plan is to let people do dangerous things sometimes of their own choosing.
Each negative result is a lesson. There are negative results inside of FDA trials as well. People can get honest and credible warnings up front from their doctor when risks exist, and they could take the risk or not, based on their right as a patient to make private choices about things that privately affect them.
What's not OK is a pile of errors and accidents in a system whose entire design justification is predicated on preventing the accidents by being very very diligent and safe about EVERYTHING, in advance, in order specifically to prevent accidents. In a system like that, where things are very very slow, and full of the costs of slowness, and the putative benefit is "no tragedies"... tragic accidents in that case are a that the institutional wasn't even constructed in any sane or coherent way.
VIII. THE FDA IS BASICALLY INCORRIGIBLE
In fact, there are more layers of that can give helpful advice and guidance than "the patients themselves" or "smart doctors" or "malpractice lawsuits to catch bad doctoring".
There's also meta-analyses of science, and condensations of meta-analyses, and so on. Here's collated advice on Actinic Keratosis which includes positive words about Picato... which is now banned in Europe.
Maybe the European FDA made the wrong call? Or maybe they're just making up bullshit out of protectionist impulses? Or maybe UpToDate is slow to update? I dunno. The world is big and complicated. People make mistakes all the time. So long as the people making mistakes aren't imposing THEIR mistakes on YOU at gunpoint, what's the big deal?
I've tried talking to doctor(s) I know who work at various big HMO(s) to find out if they think the FDA should exist. Maybe I'm wrong? Shouldn't I ask them? Shouldn't I learn?
Doctors often initially sometimes talk about it being helpful to have a central authority to figure out what is "the right thing" to prescribe or not, when crazy new conditions show up in their clinical practice... but then with just a little questioning they do note that honestly the HMOs already suck a lot of expertise out of their work, coming up with system wide best practices for most stuff (based on data science and literature reviews and so on) that they are expected to follow. That amount of local, voluntary, employment-contract-mediated "restriction" on their clinical judgement chafes sometimes, but... it is also sort of duplicating what the FDA hypothetically does?
It turns out: doctors don't seem to be economists or institution designers for the most part? They just want money basically, and to feel good about helping patients maybe, and will accept any CYA stuff that the ambient normalcy field of our culture says is a morally valid way for them use to cover their asses.
Basically, the FDA is the only layer I know of that practices prior review at gunpoint on everything, pro-actively helps with basically nothing, and can destroy and/or slow promising innovations by accident while having no skin in the game. AND IT HAS A POSITIVE HALO SOMEHOW?
I don't think that the FDA is the only thing wrong with existing American institutions, but I was going crazy for a while, because it seemed clear to me that MANY MANY American institutions are pathologically broken and stupid, and I kept feeling like I was taking crazy pills when no one else seemed to be able to see it too.
It caused me to question myself. It caused me to wonder how I might be out of calibration... or whether maybe it really was just that the system is broken in the ways it obviously seemed to be.
Then covid happened, and many of the things that seemed like they were obviously bad... were even more obviously bad. I became disgusted with myself for my past unwillingness to say that stupid evil things were stupid and evil. So it felt like it was time to generate a test case, basically? A clean example.
IX. CLARITY OF ANY SORT WOULD BE NICE
The FDA functions for me as this test case in many ways. For me. For others. For the system.
Either eventually someone will offer a coherent positive theory of the FDA's true valid purpose and show how the FDA's design and powers and operations match what you would expect to find as "design criteria" or "competence milestones" in service to the FDA's true valid purpose.
I want a coherent positive step-by-step defense of a system of jailing and fining people for innovating in medicine unless they jump through a large number of specific expensive bureaucratic hoops that don't obviously-to-me generate the outcomes that one would hope from such a costly and risk-avoiding process...
...or else maybe many people will start to agree that we should remove something bad, that is a blight on our country, and a cause of enormous numbers of potentially preventable medical tragedies?
Either way I would feel happy!
I would LOVE to be able to think that the most obviously visibly "evil and dumb" part of my government isn't actually evil and dumb. It would be so comforting to LEARN SOMETHING and have it result in a feeling like "the system is actually benevolent and powerful and wise and well-designed".
Can you imagine if we have actually been safe and cared this whole time, despite so much evidence to the contrary? Wouldn't that be... just like... gosh darned nice?
But for now, since no one can defend the FDA even half cogently, and it seems obviously dumb and evil, FDA Delenda Est is my motto, and repealing this 60 year old dumpster fire is a minimal but maybe adequate proposed solution.
Doxepin is an old drug that functions as a sedative and, at high doses, as an antidepressant. It goes by many names, including Silenor and Sinequan. On GoodRx, you can buy 30 doses of Sinequan for about $10, but Silenor costs at least $100. But these are two names for exactly the same chemical. Physicians have been able to write off-label prescriptions for doxepin since the drug was first approved in 1969. It's a second-rate and unpopular drug relative to other antidepressants and sedatives, but the very expensive Silenor is still generating revenue for its parent company.
Scott Alexander interprets Silenor as an example of the FDA's role in perpetuating the high costs of our healthcare system. The company that brought it to market, Somaxon, spent $170 million on 3-4 phase III trials and other costs of winning FDA approval for its brand name of doxepin as an insomnia drug. Why don't physicians just prescribe the much cheaper Sinequan?
...there are various regulations that make off label prescriptions less convenient than the usual type, so most people stick with Silenor...
So the idea is that FDA approval creates trivial inconveniences for physicians writing off-label prescriptions. This creates an opportunity for drug companies to needlessly spend the money to get FDA approval for their brand so that physicians can prescribe it on-label. This alleviates a trivial inconvenience created by the FDA, but at tremendous cost to the public.
We should interrogate this hypothesis. Is it really inconvenient enough to write off-label prescriptions that it creates a market for companies to profit?
I spoke with a psychiatrist who's been practicing for decades, who had this to say about writing off-label prescriptions:
Once a drug has been approved by the FDA for any indication, a physician can prescribe it for anything without hassle or limitation. On occasion – but certainly not in a case like Silenor – there may be insurance hassles, refusal to cover medication for which the indication is suspect.
So the idea that off-label prescription writing is inconvenient enough to make physicians prefer expensive Silenor over cheap generic doxepin is controversial. But none of these claims are precise. We could be dealing with any number of physician concerns. It might take more time to prescribe off-label, patients may request a particular brand name, there might be concerns about the evidence basis of off-label prescriptions, it takes time to learn about the relative costs of Silenor vs. generic doxepin, and evaluating evidence takes time relative to just prescribing whatever is FDA approved for a given indication.
In any case, what you might miss if you assume that predatory practices = profit is that Silenor has been a disaster for its manufacturer. It cost Somaxon $170 million to get Silenor FDA approved for insomnia. They're making a couple million dollars per quarter in revenue (not profit).
If you're a critic of the FDA, you might look at that $170 million price tag and think, "it's crazy that the FDA imposes such high costs to bring a drug to market, and that it creates the opportunity for companies to profit off of needless regulations." But you could also look at that $170 million as a punishment for corporate parasitism. Pernix Therapeutics acquired Somaxon, and through it, its FDA-approved Silenor, for $25 million in 2012 - $145 million less than Somaxon paid to get it approved just a couple years before! Pernix itself went bankrupt in 2019.
It's not at all clear that the story of Silenor is best interpreted as an indictment of the FDA. Instead, the FDA comes out looking to me like it successfully imposed a devastating cost on a company trying to use marketing and regulatory manipulations to parasitize the healthcare system. That doesn't mean the FDA doesn't have major problems. I'd be hesitant to assume that other stories about the nature of FDA regulation making drugs unnecessarily expensive or unavailable are false, just because this one is more complex than it first appears.
What I would take away from this is the complexities of the healthcare system are going to make the process of evaluating the systemic causes of "weird healthcare outcomes" equally complex. Such an investigation requires considering the history of both the active ingredient of the drug and the particular brand in question; the working conditions and pressures that doctors face; the business practices of companies and regulatory practices of the FDA; and the financial outcomes both for the healthcare system and the company marketing the drug.
My guess is that a lot of even doctors' attitudes about the healthcare system are shaped by strong gut reactions to vivid stories and personal experiences of absurd and frustrating problems with the healthcare system. They share those stories, which get simplified and enhanced for transmissibility like any other meme. The details are lost. It's a gigantic game of telephone.
The system might still be absurd and dysfunctional. But the precise nature of that absurdity and dysfunction might be quite different from what best suits the transmissibility of a healthcare story. And understanding those mechanistic details is important for understanding what actually needs to be done to make the situation any better. Furthermore, if those stories comprise most of the "data" that forms the judgments of activists interested in changing the healthcare system, there's a huge risk of bias.
One way of cutting through to clearer insight might be to focus on proposing particular changes to the system, then making predictions about what effects this might have. Being generally critical of the FDA is a fine stance to have, but it's not very enlightening about what in particular needs to be done to improve things. In the case of Silenor, it seems like the outcome is actually pretty good: a predatory company blew its own foot off trying to profit off a pointless drug because the FDA required it to pay for trials demonstrating the efficacy of a drug already widely known to be effective, just to achieve "on-label" status.
I'm highly sympathetic to the idea that there should be a better way to promote FDA approved drugs known to be effective for some off-label use to a similar status as those that have passed a phase III trial. Whatever it is, it's going to have to balance the needs of patients, physicians, regulators, pharma companies, and, perhaps insurers. It will also have to balance a range of policy goals including how we incentivize and evaluate innovation, protect and police physicians, and manage healthcare costs and access. And then there's the little problem of getting that dream solution implemented.
For most people, myself very much included, it seems best to focus on gathering data about why the system currently produces the outcomes it does, and pursuing a deeper understanding of those Healthcare System Disaster Stories circulating around.