I know it isn't the focus of this specific blog post, but I do want to point out that this is a false premise. These medications don't cost anywhere near $12,000 to manufacturer a year's supply...
Exemplary
how will the economy handle a $12,000/year drug that everyone wants?
I know it isn't the focus of this specific blog post, but I do want to point out that this is a false premise. These medications don't cost anywhere near $12,000 to manufacturer a year's supply of. The success of compound pharmacies is proof enough that these medications could be (and are, in many other countries) sold for much lower prices.
Instead of talking about how much it would cost "the economy" to give everyone who qualifies for these medications (free) access to them, we should instead be talking about:
The cost of not making these medications as accessible as possible, and weighing their benefits against the long-term health costs of an increasingly overweight and obese population.
Why we are not recognizing and addressing obesity for the pandemic that it is, especially by focusing on the obesogenic factors of our environment, our nutrition, and our infrastructure. We cannot and should not rely on pumping everyone full of weight-loss medications as the ultimate solution to the obesity epidemic. These medications should have much wider availability and much easier accessibility, but they are a treatment for a disease, not a preventative measure.
HenryMeds is $297/month, Eden is $296, Mochi is $254 - compared to the $1,300/month you’d pay for the official product. This isn’t covered by insurance, so it’s still not affordable for lots of people. But it’s more affordable than the $1,300/month version. Also, there’s not a shortage of it.
I personally know about a dozen people who have taken semaglutide (Ozempic/Wegovy) or tirzepatide (Mounjaro/Zepbound), but of them, only two were actually able to get a prescription for the name-brand products (the medications in parentheses) and were simultaneously able to get their insurance to cover it at an affordable price. All the others got their medications from compound pharmacies. For all of those people, a month's supply of medication costs between $180 and $200. I find that to be a remarkably consistent price. All of those people live in Texas, which I'm sure helps to explain the price consistency, but Texas is also very large.
Furthermore, all of the pharmacies these people use either package preloaded syringes with exact dosing, or provide a vial of medication and a pack of syringes. All of the pharmacies deliver to anywhere in Texas, with the medication and syringes arriving in an insulated bag or box, kept cool with ice packs.
I don't know what it's like in other states, but at least here in Texas, the compound pharmacies are very consistent with their prices and services offered.
Compounding pharmacies are only allowed to do this because of a law that suspends some drug regulations during a “shortage”, ie when the drug is on the FDA’s drug shortage list.
This is what I worry about the most with these medications. I have no doubt that, despite their record-breaking profits, Novo Nordisk and Eli Lilly will do everything they can to ensure they get their rent. The shareholders have to eat, after all.
It has been clearly demonstrated that the $1,000+ monthly price tag of the name-brand versions of these medications is a pure fabrication. A fabrication over one hundred million Americans have to bear the burden of.
I remain cautiously optimistic that if Democrats win the presidential election, if Democrats secure control of the House and Senate, or at least get close enough, and if the FDA finds itself feeling forced to declare the shortage of these medications over within the next four years...
Then we might actually, finally, have enough of a calamity on our hands to follow the age-old American tradition of trying to solve the major problem of drug prices in America once it has finally become too burdensome and costly, economically or politically, to continue to ignore.
If you're in Texas and interested in using a compound pharmacy (for anything, not even just these medications), you can review a pharmacy's disciplinary history online for free here:
Woe is me to have to trudge through a Scott Alexander blog post, but I just couldn't let this one go. The framing was too slippery.
Finally, I want to briefly mention that semaglutide and tirzepatide represent just yet-another-step in the effectiveness of GLP-1 receptor agonists. There are medications going through trials right now, or entering them in the near future that, if approved, will likely be much more effective than what is currently available. I don't think people who, genuinely or jokingly, refer to semaglutide or tirzepatide as "miracle drugs", really understand what the remainder of the 2020s has the potential to look like for weight loss.
I'm simultaneously cautiously optimistic, but also anxious, about what these medications mean for the future. I know I said earlier "we cannot rely on pumping everyone full of weight-loss medications as the ultimate solution to the obesity epidemic" but if the effectiveness of these medications continues to trend as research and trial results suggest, I would not be surprised if we do end up going down a path of "societal dependence" on these medications to "solve obesity" rather than addressing the underlying causes.
Although it doesn't justify the $12k/year price tag, especially given the customer base, it should be pointed out that a single/double digit costs per dose (as are the manufacturing costs in your...
Although it doesn't justify the $12k/year price tag, especially given the customer base, it should be pointed out that a single/double digit costs per dose (as are the manufacturing costs in your first source) probably wouldn't cover the billions it costs to develop a drug (wiki link), and the investment into future drugs.
Just commenting for balance, since it's really weird you and the source don't factor that in. Although yes, semaglutide is not a new drug per se.
Yeah but a lot of drug development is done with taxpayer dollars, using facilities built using tax breaks and by people who go to public universities with public grants. Like don't get me wrong,...
Yeah but a lot of drug development is done with taxpayer dollars, using facilities built using tax breaks and by people who go to public universities with public grants. Like don't get me wrong, it takes a lot of money to develop new drugs, and it's important work. But to act like the companies are spending all this money to develop drugs without support isn't true. And it's not like drugs are only developed in the US. Plenty of drugs are developed outside the US and sold for far less outside of the US.
As a researcher in biomedical science, let me tell you, this is not really the case. The majority of funding is privately funded. For two reasons. First, most of public research is in basic...
Yeah but a lot of drug development is done with taxpayer dollars, using facilities built using tax breaks and by people who go to public universities with public grants.
As a researcher in biomedical science, let me tell you, this is not really the case. The majority of funding is privately funded. For two reasons. First, most of public research is in basic science, that is, finding out the fundamentals of how e.g. biology works. Maybe a body of work will lead to some new potential drug targets in the future, but at best it just points in the general direction. Clinical work for drug development is rare and not nearly at the scale of private R&D. Second, simply put, private/industry pharma just doesn't trust much of public academic research, it's just not rigorous. This is mainly due to incentives and lack of standards. Academia rewards pushing forward the leading edge with publications and grants (and fame), peer-review also isn't what you think it is (mostly opinion based). Companies that want to sell drugs on the other hand, have merciless regulators to answer to, e.g. FDA. A pharma company can't p-hack their way into approval the way an academic can to get a Nature publication, the former will lead to destroying a company while the latter may get a slap on the wrist.
Again, just to be clear, I'm not shilling for Big Pharma, there's plenty of shady practices in drug pricing and I agree in the US they are overpriced, and that is also a big fault of the insurance companies, but developing medicine is an expensive and largely privately-funded endeavor.
I always appreciate more data, even if it proves me wrong. I also would love to hear more from your expertise since I am not in this field. But just to play devils advocate and poke some holes, I...
I always appreciate more data, even if it proves me wrong. I also would love to hear more from your expertise since I am not in this field.
But just to play devils advocate and poke some holes, I think the article linked has some flaws and might be survivorship bias. Of course companies don't want to just throw money into the void and would rather back a sure bet, but there are many diseases we don't have a solution for right now and conventional drugs don't work. Science is, in my opinion, trying stuff that may not work in a replicatable fashion, and seeing what happens. The article also mentions several times that there may be a connection between government funding and a failure to bring a drug to market but that's exactly what I think public funding should be for. Cause the companies are not going to look into extremely risky bets that won't go to market, but someone has to.
Also, the fact that most money is spent on trials, while necessary, feels a bit weird to me. Those trials feel a bit less like does this drug work for the problem and more can we cover our asses from the FDA, and also are there crazy side effects. Which is very important to bring a drug to market, but feels less like it's actually about the science, and more about the regulation. Which, I guess, is why this whole topic started.
Trials are extremely time consuming. I won't go into details as it isn't my field, but I do happen to know a bit behind the curtain, so let me tell you: the big drug companies are blasting money...
Trials are extremely time consuming. I won't go into details as it isn't my field, but I do happen to know a bit behind the curtain, so let me tell you:
the big drug companies are blasting money and talent at clinical trials, working with sites globally. Working with global sites is hard. China? Have to be there, and that's it's own thing. Japan, yeah. Korea? Mhm. Brazil? Oh yeah, that too. India? No biggie. Germany? Surely that one isn't so bad. Wait, what's this about GDPR? UK? Slow down please. Russia? Uh....... Ukraine? These are really exceptions, right?
These sites operate in their own special ways. They have different cultures, and standards of care, reporting (yeah, can't always trust em) treatments and practices, which have huge impacts on studies and must be controlled, but-
no-one likes to be corrected, sometimes they have reasons for operating differently, the local governments have varying oversight and watchdogs that resist change, and populations respond differently to enrollment at each location.
Oh, and each country has it's own ethics boards (usually). Huh, what does the EU look like? Are there.... multiple ethics boards? Multiple regulators? How often does this stuff change anyway?
Then these trials take years. Sites might drop out. Some might make mistakes, and become invalid data. Regulations change over this time. There might be multiple stages (I'm familiar with three; @patience_limited linked a study of trial costs that also discusses smaller trials with fewer stages).
Maybe the worst thing of all, is that a given site will not be enthusiastic about a trial that isn't showing results there. They want to provide the best care for patients. They don't like diverting patients to something that doesn't seem to help, even if it is valuable data.
For as careful and judicious these companies are about avoiding failure, they mess up. They develop drugs that aren't as good, don't work, have side effects. If they're lucky it's no good at what it was supposed to be good at but really good at something else.
Glad it was appreciated! Oh and interestingly (to me), sometimes sites do not have required equipment, which must be provided, but for ethics reasons cannot be used for anything other than this...
Glad it was appreciated! Oh and interestingly (to me), sometimes sites do not have required equipment, which must be provided, but for ethics reasons cannot be used for anything other than this trial.
If that sounds crazy, it is. Sites don't actually want equipment they cant use for anything else, and operators may need to be brought in. Probably just training. I don't totally recall if sometimes offsite equipment at some lab or whatever is contracted out, just that things which seem straightforward aren't, and doubly not when ethics are involved.
Edit: This is really stretching my memory, and I might be wrong, but I seem to recall hearing extensive complaints that China was very... enthusiastic about finding sites that happen to lack equipment. But don't worry, it definitely won't be used for anything else.
Just a note here that clinical trials of a drug for a given indication don't cost billions. Part of the cost is to prove the use of an existing drug for multiple different conditions, and...
Just a note here that clinical trials of a drug for a given indication don't cost billions. Part of the cost is to prove the use of an existing drug for multiple different conditions, and subsidizing all the trials for failed drug candidates.
It might be justifiable for truly game-changing medications that treat previously untreatable or undertreated conditions. However, much of the development is for me-too drugs that affect the same pharmacological targets as existing medications, or to broaden the (patentable) applications like using semaglutide for obesity, heart disease, etc.
That's a really cool study. I just posted a large comment about giant global studies, so it's great to contrast that with clinical trials without phase 3 and massive global enrollment.
That's a really cool study. I just posted a large comment about giant global studies, so it's great to contrast that with clinical trials without phase 3 and massive global enrollment.
Hmm, I think the author was asking how the economy (market) would respond to a drug that everyone wants but expects to pay $12,000 a year for. The answer to which was, "the compounding loophole"....
how will the economy handle a $12,000/year drug that everyone wants?
I know it isn't the focus of this specific blog post, but I do want to point out that this is a false premise. These medications don't cost anywhere near $12,000 to manufacturer a year's supply of.
Hmm, I think the author was asking how the economy (market) would respond to a drug that everyone wants but expects to pay $12,000 a year for. The answer to which was, "the compounding loophole".
Which can exist because it is cheaper to manufacture. And because demand outstrips current supply, thus placing it in a shortage.
I guess I have no idea why you've reacted so strongly to the opening statements, when it seems to be exactly what you've gone in detail to reiterate. Am I missing something?
Compounding pharmacies aren’t supposed to compete with Big Pharma. They’re usually just some storefront where one guy with a PharmD degree pours powders into things. Big Pharma has the patents and heavily-FDA-regulated factories. It would be unfair to let compounding pharmacies ignore the patents and regulations everyone else has to follow. So they’re usually under lots of restrictions.
But the law says that compounding pharmacies are allowed to step in and compete with Big Pharma during a shortage. And guess which drugs are in constant shortage because every obese person in the country has wanted them for the past year?
So enterprising startups have hit upon the business model of connecting would-be patients to friendly doctors and compounding pharmacies. From the customer perspective, this looks like filling in a form on a website and getting cheap GLP-1 agonist drugs in the mail the next day.
...
HenryMeds is $297/month, Eden is $296, Mochi is $254 - compared to the $1,300/month you’d pay for the official product. This isn’t covered by insurance, so it’s still not affordable for lots of people. But it’s more affordable than the $1,300/month version. Also, there’s not a shortage of it.
This seems like a pretty good summary of the situation, but I'm not a fan of how the author deals with efficacy and safety. Those are the most important aspects of a drug, and they are also the...
This seems like a pretty good summary of the situation, but I'm not a fan of how the author deals with efficacy and safety. Those are the most important aspects of a drug, and they are also the most expensive to demonstrate. You can't just say that both official and compounded versions have adverse effects, therefore the safety is about the same. We need better numbers and in-depth analysis to really understand the risk with compounding. We also can't say that different formulations will have the same properties just because it's an injection. Aside from suggesting that the drug is all the same once dissolved, the author doesn't really address efficacy, which is the main purpose of a drug and needs to be well demonstrated.
The reason why there is a shortage is because of important safety and efficacy regulations, and I'm not a fan of the idea that we can easily sidestep these regulations through compounding pharmacies in a widespread and highly commercialized way. I consider this a loophole that should be closed because we shouldn't allow the sale of drugs that might not be as safe or efficacious as advertised. However, I can't say this without also mentioning that the US healthcare system approach is totally wrong and should be overhauled to be more similar to developed European countries.
Yes, with articles like this one, you do need to take into account the Scott Alexander is a libertarian and criticizes the FDA a lot. But I still think it's a useful overview to get some awareness...
Yes, with articles like this one, you do need to take into account the Scott Alexander is a libertarian and criticizes the FDA a lot. But I still think it's a useful overview to get some awareness of what's going on.
I'm not a fan of taking sides based on vibes on whether a regulation is really necessary. It's sort of like arguing against something because it's illegal. For practical purposes, I recommend against doing illegal things, and there is a presumption that doing illegal things is shady. But that's not relevant when we're talking theoretically about whether it's a good law or not, what effects it has, whether it achieves its purpose. Maybe it does, maybe not? Regulations do get changed sometimes, hopefully for the better?
It would take a deep investigation to understand what the regulations really do in this case to improve safety and what the risks of using a compounding pharmacy really are. I'm not going to do it because I don't need this drug and have no dog in this fight. I don't really expect Scott Alexander to do it, either; I see it as raising basic awareness of a thing going on in the world that might help someone someday?
I agree with your take. As someone who has helped take drugs and medical devices to market, I started to write a top level comment explaining some of the nuance, but gave up when I started...
I agree with your take. As someone who has helped take drugs and medical devices to market, I started to write a top level comment explaining some of the nuance, but gave up when I started thinking through the communication challenge and the level of nuance. I just don't have the time today or even the next few days to try, and I can already imagine the angry replies that think the explanation of nuance is the same as defending the price gouging that does occur side by side with the complexity.
It's complicated and worth fixing. Appreciate the post!
After doing some research and hearing about why the FDA was founded in the early 1900s after people were cutting cows milk, foodstuffs and drugs with whatever they could find, in always going to...
After doing some research and hearing about why the FDA was founded in the early 1900s after people were cutting cows milk, foodstuffs and drugs with whatever they could find, in always going to come down on the side of regulation.
In our current market I have no faith that modern businesses would not resort to the same measures- look at recent scandals about food safety in China. I also think we need more regulation on homeopathic medicine cause while it may help a small portion of our society, a lot of people are being talked off of live saving drugs.
But we as a society do have to start this conversation up again. I speak for the US mostly here, but it's not really been a hot topic for at least 8 years after the Affordable Care Act was fought over. We did get some discussion considering we had an active pandemic, but goodness knows we took some bad lessons from that.
It's just not sustainable for our society to be killing people because insulin manufacturers are charging deadly rates. I have a good friend who's a drug chemist, and they speak about undermanned shifts and failing inspections. We've gotta start having conversations about this again.
Frankly, there's no reason to be so concerned about compounding pharmacies. They have a very long history, and I don't see any reason to distrust pharmacists ability to compound medications....
Frankly, there's no reason to be so concerned about compounding pharmacies. They have a very long history, and I don't see any reason to distrust pharmacists ability to compound medications. That's one of the things they go to school and receive extensive training for.
The other concern you bring up about overwork in the drug industry is 100% real...but also significantly less bad in compounding pharmacies as they're usually smaller local shops that avoid dealing with insurance. They usually pay worse than the big gigs as a trade-off for being much more chill.
A compounder (now in jail) managed to sicken nearly 800 people and kill dozens by contamination of injectable products with a pathogen that caused fungal meningitis.
I got a mis-compounded dose of injectable prednisone at the doctor's office 10 years ago, and passed out at the front desk on my way out the door. No lasting harm done, but I felt ill for a week, and some people suffered much more serious harm from a steroid dosage 10x the labeled amount.
The point remains that compounding pharmacies aren't as reliable as pharmaceutical manufacturers. They're not monitored and regulated the way pharmaceutical manufacturers are, or even hospital pharmacies.
The FDA is already warning of adverse events from mis-compounded or inadequately labeled semaglutide, even if the drug itself is relatively safe.
For anyone interested in the full story, I recommend Jason Dearen’s Kill Shot. A friend who works in a hospital recommended it to me. It is mortifying.
A compounder (now in jail) managed to sicken nearly 800 people and kill dozens by contamination of injectable products with a pathogen that caused fungal meningitis.
For anyone interested in the full story, I recommend Jason Dearen’s Kill Shot.
A friend who works in a hospital recommended it to me. It is mortifying.
I think I didn't make my case very well. I'm less concerned about smaller manufacturers making generics, and more worried about the industry as a whole lowering safety standards, due to the issues...
I think I didn't make my case very well. I'm less concerned about smaller manufacturers making generics, and more worried about the industry as a whole lowering safety standards, due to the issues in the past. Though the other reply to you does point out that there can be issues with generic manufacturing.
Just to be clear, generic drug manufacturers are subject to the same regulatory standards as brand-name drug manufacturers, even if enforcement is lax on imports. They have to prove safety and...
Just to be clear, generic drug manufacturers are subject to the same regulatory standards as brand-name drug manufacturers, even if enforcement is lax on imports. They have to prove safety and efficacy for every product.
Compounding pharmacies are not subject to the same standards and laws for their formulated products, even if they use USP drug ingredients (which they're not required to do).
Here's a comment from a compounding pharmacist going into more detail on the differences between semaglutide injections versus oral delivery. Apparently he likes sublingual, but it's difficult to...
Here's a comment from a compounding pharmacist going into more detail on the differences between semaglutide injections versus oral delivery. Apparently he likes sublingual, but it's difficult to get people to do it.
Huh that's interesting. I've never had to inject myself with anything so the lack of familiarity with that would put me off from injections. I have tested my blood sugar a few times with those...
Apparently he likes sublingual, but it's difficult to get people to do it.
Huh that's interesting. I've never had to inject myself with anything so the lack of familiarity with that would put me off from injections. I have tested my blood sugar a few times with those finger prick setups and got my blood drawn etc. so I'm not deathly afraid of needles exactly (though I generally don't look when someone is sticking a needle in me). If the oral delivery is not very good as he said, I do find that surprising that people wouldn't do sublingual. I've not really taken medication that way myself either, but I don't feel like it would be that bad. It would have to be super unpleasant to put me off of that since he said it only takes 2-5 minutes, as it doesn't seem that inconvenient, especially considering the downsides of the alternatives.
I really didn't understand his instructions on how to acquire the compound, but I suspect it requires a prescription so that puts it out of my reach in any case.
I know it isn't the focus of this specific blog post, but I do want to point out that this is a false premise. These medications don't cost anywhere near $12,000 to manufacturer a year's supply of. The success of compound pharmacies is proof enough that these medications could be (and are, in many other countries) sold for much lower prices.
Instead of talking about how much it would cost "the economy" to give everyone who qualifies for these medications (free) access to them, we should instead be talking about:
The cost of not making these medications as accessible as possible, and weighing their benefits against the long-term health costs of an increasingly overweight and obese population.
Why the federal government continues to allow pharmaceutical corporations to charge astronomical prices for medications in the United States when in other countries these medications are sold for so little that it would cost less for an American to fly across the Atlantic, purchase the medication in the United Kingdom, and fly back home.
Why we are not recognizing and addressing obesity for the pandemic that it is, especially by focusing on the obesogenic factors of our environment, our nutrition, and our infrastructure. We cannot and should not rely on pumping everyone full of weight-loss medications as the ultimate solution to the obesity epidemic. These medications should have much wider availability and much easier accessibility, but they are a treatment for a disease, not a preventative measure.
I personally know about a dozen people who have taken semaglutide (Ozempic/Wegovy) or tirzepatide (Mounjaro/Zepbound), but of them, only two were actually able to get a prescription for the name-brand products (the medications in parentheses) and were simultaneously able to get their insurance to cover it at an affordable price. All the others got their medications from compound pharmacies. For all of those people, a month's supply of medication costs between $180 and $200. I find that to be a remarkably consistent price. All of those people live in Texas, which I'm sure helps to explain the price consistency, but Texas is also very large.
Furthermore, all of the pharmacies these people use either package preloaded syringes with exact dosing, or provide a vial of medication and a pack of syringes. All of the pharmacies deliver to anywhere in Texas, with the medication and syringes arriving in an insulated bag or box, kept cool with ice packs.
I don't know what it's like in other states, but at least here in Texas, the compound pharmacies are very consistent with their prices and services offered.
This is what I worry about the most with these medications. I have no doubt that, despite their record-breaking profits, Novo Nordisk and Eli Lilly will do everything they can to ensure they get their rent. The shareholders have to eat, after all.
It has been clearly demonstrated that the $1,000+ monthly price tag of the name-brand versions of these medications is a pure fabrication. A fabrication over one hundred million Americans have to bear the burden of.
I remain cautiously optimistic that if Democrats win the presidential election, if Democrats secure control of the House and Senate, or at least get close enough, and if the FDA finds itself feeling forced to declare the shortage of these medications over within the next four years...
Then we might actually, finally, have enough of a calamity on our hands to follow the age-old American tradition of trying to solve the major problem of drug prices in America once it has finally become too burdensome and costly, economically or politically, to continue to ignore.
If you're in Texas and interested in using a compound pharmacy (for anything, not even just these medications), you can review a pharmacy's disciplinary history online for free here:
Texas Pharmacy Search
Here is an example of a pharmacy that has been subject to disciplinary action in the past:
Stonegate Pharmacy
Woe is me to have to trudge through a Scott Alexander blog post, but I just couldn't let this one go. The framing was too slippery.
Finally, I want to briefly mention that semaglutide and tirzepatide represent just yet-another-step in the effectiveness of GLP-1 receptor agonists. There are medications going through trials right now, or entering them in the near future that, if approved, will likely be much more effective than what is currently available. I don't think people who, genuinely or jokingly, refer to semaglutide or tirzepatide as "miracle drugs", really understand what the remainder of the 2020s has the potential to look like for weight loss.
I'm simultaneously cautiously optimistic, but also anxious, about what these medications mean for the future. I know I said earlier "we cannot rely on pumping everyone full of weight-loss medications as the ultimate solution to the obesity epidemic" but if the effectiveness of these medications continues to trend as research and trial results suggest, I would not be surprised if we do end up going down a path of "societal dependence" on these medications to "solve obesity" rather than addressing the underlying causes.
Although it doesn't justify the $12k/year price tag, especially given the customer base, it should be pointed out that a single/double digit costs per dose (as are the manufacturing costs in your first source) probably wouldn't cover the billions it costs to develop a drug (wiki link), and the investment into future drugs.
Just commenting for balance, since it's really weird you and the source don't factor that in. Although yes, semaglutide is not a new drug per se.
Yeah but a lot of drug development is done with taxpayer dollars, using facilities built using tax breaks and by people who go to public universities with public grants. Like don't get me wrong, it takes a lot of money to develop new drugs, and it's important work. But to act like the companies are spending all this money to develop drugs without support isn't true. And it's not like drugs are only developed in the US. Plenty of drugs are developed outside the US and sold for far less outside of the US.
As a researcher in biomedical science, let me tell you, this is not really the case. The majority of funding is privately funded. For two reasons. First, most of public research is in basic science, that is, finding out the fundamentals of how e.g. biology works. Maybe a body of work will lead to some new potential drug targets in the future, but at best it just points in the general direction. Clinical work for drug development is rare and not nearly at the scale of private R&D. Second, simply put, private/industry pharma just doesn't trust much of public academic research, it's just not rigorous. This is mainly due to incentives and lack of standards. Academia rewards pushing forward the leading edge with publications and grants (and fame), peer-review also isn't what you think it is (mostly opinion based). Companies that want to sell drugs on the other hand, have merciless regulators to answer to, e.g. FDA. A pharma company can't p-hack their way into approval the way an academic can to get a Nature publication, the former will lead to destroying a company while the latter may get a slap on the wrist.
Here's a start comparing numbers, but there's more information out there.
https://pubmed.ncbi.nlm.nih.gov/30231735/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440766/
Again, just to be clear, I'm not shilling for Big Pharma, there's plenty of shady practices in drug pricing and I agree in the US they are overpriced, and that is also a big fault of the insurance companies, but developing medicine is an expensive and largely privately-funded endeavor.
I always appreciate more data, even if it proves me wrong. I also would love to hear more from your expertise since I am not in this field.
But just to play devils advocate and poke some holes, I think the article linked has some flaws and might be survivorship bias. Of course companies don't want to just throw money into the void and would rather back a sure bet, but there are many diseases we don't have a solution for right now and conventional drugs don't work. Science is, in my opinion, trying stuff that may not work in a replicatable fashion, and seeing what happens. The article also mentions several times that there may be a connection between government funding and a failure to bring a drug to market but that's exactly what I think public funding should be for. Cause the companies are not going to look into extremely risky bets that won't go to market, but someone has to.
Also, the fact that most money is spent on trials, while necessary, feels a bit weird to me. Those trials feel a bit less like does this drug work for the problem and more can we cover our asses from the FDA, and also are there crazy side effects. Which is very important to bring a drug to market, but feels less like it's actually about the science, and more about the regulation. Which, I guess, is why this whole topic started.
Trials are extremely time consuming. I won't go into details as it isn't my field, but I do happen to know a bit behind the curtain, so let me tell you:
the big drug companies are blasting money and talent at clinical trials, working with sites globally. Working with global sites is hard. China? Have to be there, and that's it's own thing. Japan, yeah. Korea? Mhm. Brazil? Oh yeah, that too. India? No biggie. Germany? Surely that one isn't so bad. Wait, what's this about GDPR? UK? Slow down please. Russia? Uh....... Ukraine? These are really exceptions, right?
These sites operate in their own special ways. They have different cultures, and standards of care, reporting (yeah, can't always trust em) treatments and practices, which have huge impacts on studies and must be controlled, but-
no-one likes to be corrected, sometimes they have reasons for operating differently, the local governments have varying oversight and watchdogs that resist change, and populations respond differently to enrollment at each location.
Oh, and each country has it's own ethics boards (usually). Huh, what does the EU look like? Are there.... multiple ethics boards? Multiple regulators? How often does this stuff change anyway?
Then these trials take years. Sites might drop out. Some might make mistakes, and become invalid data. Regulations change over this time. There might be multiple stages (I'm familiar with three; @patience_limited linked a study of trial costs that also discusses smaller trials with fewer stages).
Maybe the worst thing of all, is that a given site will not be enthusiastic about a trial that isn't showing results there. They want to provide the best care for patients. They don't like diverting patients to something that doesn't seem to help, even if it is valuable data.
For as careful and judicious these companies are about avoiding failure, they mess up. They develop drugs that aren't as good, don't work, have side effects. If they're lucky it's no good at what it was supposed to be good at but really good at something else.
I appreciate the look behind the curtain. Don't really have much else to add right now, but thanks for taking the time to reply.
Glad it was appreciated! Oh and interestingly (to me), sometimes sites do not have required equipment, which must be provided, but for ethics reasons cannot be used for anything other than this trial.
If that sounds crazy, it is. Sites don't actually want equipment they cant use for anything else, and operators may need to be brought in. Probably just training. I don't totally recall if sometimes offsite equipment at some lab or whatever is contracted out, just that things which seem straightforward aren't, and doubly not when ethics are involved.
Edit: This is really stretching my memory, and I might be wrong, but I seem to recall hearing extensive complaints that China was very... enthusiastic about finding sites that happen to lack equipment. But don't worry, it definitely won't be used for anything else.
So what happens to that equipment when the study is done? Is it sent back or just donated to the site?
Not sure! Just DM me and I'll try to reply next time I have a chance to ask.
Just a note here that clinical trials of a drug for a given indication don't cost billions. Part of the cost is to prove the use of an existing drug for multiple different conditions, and subsidizing all the trials for failed drug candidates.
It might be justifiable for truly game-changing medications that treat previously untreatable or undertreated conditions. However, much of the development is for me-too drugs that affect the same pharmacological targets as existing medications, or to broaden the (patentable) applications like using semaglutide for obesity, heart disease, etc.
That's a really cool study. I just posted a large comment about giant global studies, so it's great to contrast that with clinical trials without phase 3 and massive global enrollment.
Hmm, I think the author was asking how the economy (market) would respond to a drug that everyone wants but expects to pay $12,000 a year for. The answer to which was, "the compounding loophole".
Which can exist because it is cheaper to manufacture. And because demand outstrips current supply, thus placing it in a shortage.
I guess I have no idea why you've reacted so strongly to the opening statements, when it seems to be exactly what you've gone in detail to reiterate. Am I missing something?
From the blog post:
...
This seems like a pretty good summary of the situation, but I'm not a fan of how the author deals with efficacy and safety. Those are the most important aspects of a drug, and they are also the most expensive to demonstrate. You can't just say that both official and compounded versions have adverse effects, therefore the safety is about the same. We need better numbers and in-depth analysis to really understand the risk with compounding. We also can't say that different formulations will have the same properties just because it's an injection. Aside from suggesting that the drug is all the same once dissolved, the author doesn't really address efficacy, which is the main purpose of a drug and needs to be well demonstrated.
The reason why there is a shortage is because of important safety and efficacy regulations, and I'm not a fan of the idea that we can easily sidestep these regulations through compounding pharmacies in a widespread and highly commercialized way. I consider this a loophole that should be closed because we shouldn't allow the sale of drugs that might not be as safe or efficacious as advertised. However, I can't say this without also mentioning that the US healthcare system approach is totally wrong and should be overhauled to be more similar to developed European countries.
Yes, with articles like this one, you do need to take into account the Scott Alexander is a libertarian and criticizes the FDA a lot. But I still think it's a useful overview to get some awareness of what's going on.
I'm not a fan of taking sides based on vibes on whether a regulation is really necessary. It's sort of like arguing against something because it's illegal. For practical purposes, I recommend against doing illegal things, and there is a presumption that doing illegal things is shady. But that's not relevant when we're talking theoretically about whether it's a good law or not, what effects it has, whether it achieves its purpose. Maybe it does, maybe not? Regulations do get changed sometimes, hopefully for the better?
It would take a deep investigation to understand what the regulations really do in this case to improve safety and what the risks of using a compounding pharmacy really are. I'm not going to do it because I don't need this drug and have no dog in this fight. I don't really expect Scott Alexander to do it, either; I see it as raising basic awareness of a thing going on in the world that might help someone someday?
I agree with your take. As someone who has helped take drugs and medical devices to market, I started to write a top level comment explaining some of the nuance, but gave up when I started thinking through the communication challenge and the level of nuance. I just don't have the time today or even the next few days to try, and I can already imagine the angry replies that think the explanation of nuance is the same as defending the price gouging that does occur side by side with the complexity.
It's complicated and worth fixing. Appreciate the post!
After doing some research and hearing about why the FDA was founded in the early 1900s after people were cutting cows milk, foodstuffs and drugs with whatever they could find, in always going to come down on the side of regulation.
In our current market I have no faith that modern businesses would not resort to the same measures- look at recent scandals about food safety in China. I also think we need more regulation on homeopathic medicine cause while it may help a small portion of our society, a lot of people are being talked off of live saving drugs.
But we as a society do have to start this conversation up again. I speak for the US mostly here, but it's not really been a hot topic for at least 8 years after the Affordable Care Act was fought over. We did get some discussion considering we had an active pandemic, but goodness knows we took some bad lessons from that.
It's just not sustainable for our society to be killing people because insulin manufacturers are charging deadly rates. I have a good friend who's a drug chemist, and they speak about undermanned shifts and failing inspections. We've gotta start having conversations about this again.
Frankly, there's no reason to be so concerned about compounding pharmacies. They have a very long history, and I don't see any reason to distrust pharmacists ability to compound medications. That's one of the things they go to school and receive extensive training for.
The other concern you bring up about overwork in the drug industry is 100% real...but also significantly less bad in compounding pharmacies as they're usually smaller local shops that avoid dealing with insurance. They usually pay worse than the big gigs as a trade-off for being much more chill.
It's absolutely reasonable to be concerned about U.S. compounding pharmacies. Here's an incident list for 2011-2019: https://www.pewtrusts.org/-/media/assets/2021/11/us-illnesses-and-deaths-associated-with-compounded-or-repackaged-medications.pdf
A compounder (now in jail) managed to sicken nearly 800 people and kill dozens by contamination of injectable products with a pathogen that caused fungal meningitis.
I got a mis-compounded dose of injectable prednisone at the doctor's office 10 years ago, and passed out at the front desk on my way out the door. No lasting harm done, but I felt ill for a week, and some people suffered much more serious harm from a steroid dosage 10x the labeled amount.
The point remains that compounding pharmacies aren't as reliable as pharmaceutical manufacturers. They're not monitored and regulated the way pharmaceutical manufacturers are, or even hospital pharmacies.
The FDA is already warning of adverse events from mis-compounded or inadequately labeled semaglutide, even if the drug itself is relatively safe.
For anyone interested in the full story, I recommend Jason Dearen’s Kill Shot.
A friend who works in a hospital recommended it to me. It is mortifying.
Thank you for the recommendation!
I think I didn't make my case very well. I'm less concerned about smaller manufacturers making generics, and more worried about the industry as a whole lowering safety standards, due to the issues in the past. Though the other reply to you does point out that there can be issues with generic manufacturing.
Just to be clear, generic drug manufacturers are subject to the same regulatory standards as brand-name drug manufacturers, even if enforcement is lax on imports. They have to prove safety and efficacy for every product.
Compounding pharmacies are not subject to the same standards and laws for their formulated products, even if they use USP drug ingredients (which they're not required to do).
Here's a comment from a compounding pharmacist going into more detail on the differences between semaglutide injections versus oral delivery. Apparently he likes sublingual, but it's difficult to get people to do it.
Huh that's interesting. I've never had to inject myself with anything so the lack of familiarity with that would put me off from injections. I have tested my blood sugar a few times with those finger prick setups and got my blood drawn etc. so I'm not deathly afraid of needles exactly (though I generally don't look when someone is sticking a needle in me). If the oral delivery is not very good as he said, I do find that surprising that people wouldn't do sublingual. I've not really taken medication that way myself either, but I don't feel like it would be that bad. It would have to be super unpleasant to put me off of that since he said it only takes 2-5 minutes, as it doesn't seem that inconvenient, especially considering the downsides of the alternatives.
I really didn't understand his instructions on how to acquire the compound, but I suspect it requires a prescription so that puts it out of my reach in any case.