The catastrophic failure of FenPhen also cooled the industry's interest in obesity medication.
Part of the problem is that it is so slow and expensive to bring a drug to market, which encourages risk aversion. It'd be interesting if we found better regulatory and financial engineering strategies here. There is a gigantic hidden graveyard of people who have died due not having access to medications that could have been produced and approved (which may have even been massively profitable) but were it just didn't make sense to try with today's incentives.
Maybe FDA works in classes where class 0 is entirely experimental and only available to terminal patients, class 1 is shown to be safe in animals and approved only for extreme cases, class 2 evidence of safety in humans and some evidence of efficacy, and class 3 is what we have today.
I personally like the idea of a "accredited ingestor". You get a certification indicating you understand enough about drug development and associated risks and then you are allowed to decide for yourself what you are willing to take.
In general I am a big fan of FDA approval just becoming a stamp on a product like the Nintendo Seal of Approval and letting consumers and insurers decide what they make of it, but that would never fly
I do admin work for a pharma-related company. I would never want to be in charge of verifying with my own body what treatment is safe and/or effective.
Drug development and clinical trials are expensive for a reason. Not doing them in an orderly manner is more expensive.
One far less scary version is to allow drugs approved by other reputable agencies (EU, Japan, UK, maybe) to be used in some limited capacity in the US.
From what I've heard from some friends working with regulatory agencies worldwide, this is currently the case or is about to happen. FDA-EMEA-(whatever the japanese regulatory agency's called) have agreements for treatments approved in one of the other two agencies to be easily approved.
There is a history of these agencies later withdrawing approvals and FDA conservatism protecting US healthcare consumers. The same pattern applies with these other agencies not basing decisions on FDA approval. Overall, the combination of approval authorities and global surveillance delivers the best results by ensuring the broadest coverage and continued research.
The rarely understood tradeoff in this arena is that no matter what you do, your decisions kill people!
Everyone understands the case when (A) you approve something that later turns out to kill people.
The other case (B), when you don't approve something that would have saved lives is much less understood, but those people are just as dead as those from case A.
One famous case B is when the FDA only approved beta blockers 17 years after other major countries. This cost ~10k US lives per year, or ~170k lives total.
Because A errors produces headlines and scandals, while B errors are just the normal deaths we are used to, the FDA is heavily incentivized to minimize A errors, regardless of the B error rate.
An important thing to remember when thinking about this thing: the downside of approving a drug that was dangerous is bounded: it kills people or causes some unexpected side effect and then it gets pulled. Meanwhile, the downside of failing to approve something that could have saved/improved lives is at least potentially unbounded: if it never gets approved that's the entire futures worth of humanity who is unable to take advantage of it (although admittedly I'd like to imagine that _eventually_ tech will improve to the point that we either figure out we should approve the drug and/or invent something else that obviates the need).
The point is that case B is both harder to notice and at least potentially _much_ worse than case A. And it's the case that the FDA currently errs towards.
And I hope we've all seen Dallas Buyers Club which showed the real, historical problem of drug approval being slow-rolled because it was killing a controversial minority
You might be a big fan of the work the FDA does to keep us safe in light of past industry abuses, but keeping good drugs off the market - whether by outright fiat or by making them too expensive to develop, test, and deploy -- also has a terrible human cost. It's not clear that the FDA has found the right balance between risk reduction and upside potential.
What criteria would you suggest to measure in an effort to make it clear that the FDA has >found the right balance between risk reduction and upside potential?
Not OP, but it's certainly not by leaving drugs unapproved in the US that have been in wide use in Canada, England, Japan, etc for years (and in some cases decades). The incentives are so misaligned for the FDA that the bias for inaction is enormous.
I also find it a bit patronizing that a federal agency determines whether or not a drug they've deemed safe has enough upside potential for me. That's a value judgement I'd like to make for myself.
Sorry if this sounds harsh, but the FDA's inability to approve drugs inside of a decade has personally impacted me quite a bit.
I don't think there's a good answer to that question, unfortunately. What we're doing now seems to be working for most people most of the time, but it'd be absurd to think there's no further room for optimization. And it seems unlikely that the best approach is more restrictive regulation, given that extremely-useful drugs are going undeveloped for decades.
So... that leaves more flexible regulation as a worthwhile approach going forward. I like the idea of making limited human trials easier to carry out and less costly in general.
Drug development is a conservative industry. Even with researchers/companies/FDA all doing their best to develop good treatments, there are still many drug failures due to efficacy or safety.
Being more lassiez faire is going to lead to direct harm of some patients. Is it a worthwhile tradeoff vs potentially addressing some unmet need is a tough calculus.
that already exists, it’s called doing research chemicals. You can do survodutide or whatever other next-gen drug right now and “do your own research” on the supply chain and efficacy and safety. They’re everywhere and functionally the FDA can’t stop you.
should that be officially legitimized in any way by the FDA? fuck no.
As soon as you break down the barrier in any way, companies will spring up exploiting it and promising miracle cures etc. even if you want to do RCs the FDA keeping a minimal wall there benefits you.
Agreed. RCs were great when you had to know what you were doing to get them. It only became a problem when cathinones and synthetic cannabinoids started being sold at headshops.
The only way to ensure no profit would be to provide them for free. Which, granted, may be good still for the pharmaceutical companies to lessen the costs for approvals, but Hollywood accounting makes it impossible to have any price depend on profits, because profits are more an accounting fantasy than a fact.
It is a philosophical question: Would you rather people die due to taking a harmful compound or die due to lack of access to something that may have helped them.
Access to experimental treatments also opens up more perverse incentives where desperate people are likely to try anything.
The pharma companies are not clamoring for a huge surge in compassionate use (emergency use of unapproved drugs) either.
Who is going to pay? Early stage drugs are still figuring out their manufacturing process, and quantities can be extremely limited. Say you give drug X to a sick patient and they die, what then? Was it because of the novel drug? Not a favorable position to have more deaths associated with your treatment. Can you draw any data from these patients to inform further trials? Also complicated because end stage patients have already exhausted other options and the interaction with other compounds can make disentangling this harder.
It feels like the odds a drug is perfect and a few years too late for you unless you skip the tests is exceedingly low compared to the odds that a drug will not pan out or might even be unsafe.
The perverse incentives is also a very real issue.
How is this the trolley problem for someone with a terminal disease? I assume the sick population are the people in the trolley and the experimental patient is the person on the track? In this scenario, by not pulling the lever you just extend the life of the people on the trolley to the end of the ride for a dangerous drug. Where as, pulling the level could save the life of the person on the track and the people in the trolley if the drug is successful.
What am I missing? For non-terminal diseases, it's a bit murkier, but still I don't follow the analogy.
Some people do go into remission from a terminal cancer diagnosis, either because the diagnosis was wrong or because they live long enough for an approved treatment to come on the market. Also, that you have terminal cancer doesn’t say anything about how long you’re going to live. You can live for many years with terminal cancer.
I do think we’re overly cautious with drug approvals and I think we should be more open to leaving the decision to patients and their medical teams, but it’s not as simple as saying someone’s terminally ill, so just do whatever. Reducing it down to the trolley problem makes it seem much more black and white and immediate than it really is.
Or even a graduated approval scale with categories of limited liability, etc.: For example, when Vioxx and other cox-2 inhibitors were withdrawn from the market, some employees really stocked up on the reps' samples. And in the present it is said that some vets prefer the off-label-for-humans options per [0]
I found some phentermine tablets next to my neighbors trash bin, still in the blister pack. So I thought maybe if I snorted one I'd get high. I didn't. Just got really jittery and nauseous then puked on a tree while a woman who looked like she worked for the government walked by (this was in the capitol city of another country). Would not recommend. And then I accidentally brought it back with me through customs.
Fen-phen was an obesity medication that caused valvular heart disease and pulmonary hypertension. If you've never heard of fen-phen, check out this article from Sept. 23, 1997 in the New York Times: https://archive.is/ottWQ
Norway is big on oil and gas. One of the incentives we give out is a cost sharing model for the initial exploration phase.
Not sure how that would translate, but an important factor would be that the health care providers (private or state) have some say in what kinds of illnesses need better drugs.
That's a nice incentive but Norway's tax policy is a major disincentive to any new venture. I'm currently helping a founder relocate his Series A company as a result.
I believe that that is more of a temporary thing. A lot of rich people have been avoiding taxes by moving to Switzerland. They run a company in Norway for several years, then move to Switzerland when things are profitable and they want to avoid paying their taxes to society.
We pay tax on dividends in Norway, but if your company doesn’t pay out any dividends for 10 years then you don’t pay any taxes on them until the day you take the money out of the company. So you can run a company in Norway while paying quite little in taxes, then move to Switzerland and pay yourself all the dividends that have accumulated over the years. After 5 years you can move back and not have to pay a cent in taxes.
The new tax laws are just a temporary blocker that incentivises any current owners to move out of Norway move before the new laws come into effect.
That's incorrect based on my experience. The law exposes startup founders to large tax liabilities immediately after a financing. We've hired some of the top lawyers in Norway and the consensus is the only alternative is to relocate. There's plenty of articles about it in the Norwegian startup press.
Even better, you have to pay Norway on your unrealized capital gains but they won't credit you on future losses from the startup. Essentially they have socialized the profits and privatized the losses.
You are mixing two different taxes. The article is about the new exit tax. The other relevant tax is our wealth tax.
You don’t sound like a person who likes taxes much. In Norway they are very important since we have good infrastructure in most areas such as telecom, roads, trains, airports, electricity and water. We also have great healthcare. And lots of benefits for parents with children.
Not knowing what FenPhen was I checked the wiki page and wow, it looks remarkably similar to those sketchy amphetamine analogs people sell on the internet like 3-FA, of course selling that as an anti-obesity drug was going to go sideways.
That Thalidomide was not approved by the FDA, while it hurt thousands of babies around the the world is probably a big reason that FDA has been very restrictive in the 60 years since, and often bans drugs that are available in the rest of the world.
Thalidomide was used and approved around the world, not just in the US. It’s an interesting example of something but not millions of deaths.
But I get a sense that the original poster isn’t sincerely interested in talking about the complex question, how should the FDA regulate drugs?
One thing’s for sure: High drama personalities have always had a tenuous understanding of the facts behind their “shock” and outrages. Or maybe one of the commenters has learned a valuable lesson about copy and pasting from chatbots.
Speaking of factual drama, Thalidomide was not approved in the US during all the drama in the 60s.
It has since been approved for cancer where its benefits outweigh the side effects, but it doesn't negate that the FDA prevented harm to babies by blocking it in the 60s.
Part of the problem is that it is so slow and expensive to bring a drug to market, which encourages risk aversion. It'd be interesting if we found better regulatory and financial engineering strategies here. There is a gigantic hidden graveyard of people who have died due not having access to medications that could have been produced and approved (which may have even been massively profitable) but were it just didn't make sense to try with today's incentives.
Maybe FDA works in classes where class 0 is entirely experimental and only available to terminal patients, class 1 is shown to be safe in animals and approved only for extreme cases, class 2 evidence of safety in humans and some evidence of efficacy, and class 3 is what we have today.