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Comment by Brakenshire | Hacker News Reader

We do have to make drug discovery vastly more efficient, but we want to make it more efficient at making useful drugs available, not just making drugs available. If you decouple availability from effectiveness then drug companies will just market unproven drugs to people who are desperate or who don't know any better. Or even if the drug companies do nothing people will just start taking drugs on the basis of recommendations from Facebook.

Maybe that means building randomized trials into treatment in a much more regular way (like with the Covid RECOVERY trials, where any doctor could enroll patients with a web form, and source the candidate treatment from the local pharmacy), which vastly reduces cost for treatments already on the market with other indications. And perhaps altering the balance of risk for patients with life-threatening or terminal diseases.

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One reason your proposal isn't happening today might be because we don't want tons of doctors choosing to enroll in these "field" randomized trials, if they might be experimentally treating people with drugs that aren't safe. We want to know about safety first before unleashing on the world, even in a randomized trial context. And since the FDA bundles verification of safety and efficacy together, so we can't do your proposal without unbundling them.

Now, imagine that after safety is verified to a 1 or 2-star level, we don't make the drug approved for general use, but doctors can freely enroll in randomized trials as you proposed? That way we're getting the efficacy data quickly but safely.

Maybe a minor point, but we do have to unbundle safety from efficacy in some sense to get off the ground here. The question is, what exactly is allowed to happen after safety is established but efficacy is not yet established?

I agree, that's well put and I think that could work very well.

I think the key would be having clear centralized standards for how the trials are conducted, or you could have doctors skirting the system and just using it as de-facto prescription, and patients being put at risk for ineffective treatment without producing any valid evidence.

Yeah, if the existing system is built on trust of doctors who run clinical trials, we have to ask whether that trust scales.

If the system were set up so that doctors would have a lot to lose if they didn't follow the system, trust could work here. We already trust doctors as professionals on many other things...

His proposal is to treat a new disease with approved drug you can buy and not experimental drugs. This will give us more data on therapies that might work and we can do more detailed studies on therapies with high percentage of recoveries.

The problem here is letting drug companies market to the uneducated general public - there is a good reason why that practice is banned in most countries.

Is it banned when it isn’t the drug companies doing the marketing to the uneducated general public? It wasn’t the drug companies telling uneducated people to use horse dewormer to combat Covid. That seems just as dangerous (probably more so) as drug companies making claims to the general public.

Banned in every country, except the U.S. and New Zealand.

> If you decouple availability from effectiveness then drug companies will just market unproven drugs to people who are desperate or who don't know any better. Or even if the drug companies do nothing people will just start taking drugs on the basis of recommendations from Facebook.

But this already happens for certain treatments. The FDA already regulates a separate category with loose efficacy requirements for dietary supplements and herbal remedies. These medically irrelevant treatments are immensely popular, they're just forbidden from marketing specific medical claims and being actually toxic. People still end up taking FDA approved treatments like Ivermectin for non-FDA-approved purposes based on Facebook recommendations.

Why do we always have to make people's choices for them? They're grown adults capable of making their own decisions and their own mistakes. If they want to ignore the science and the credibility of the FDA process, they should be free to do so.

One big reason is you're removing the economic incentive to produce good evidence. The herbal remedies industry is a perfect example, there will be valid treatments there but yet the industry is almost entirely medically useless. Some of the treatments might be effective for particular diseases, at particular doses but no one ever knows. These companies have billions in revenue and are vastly profitable but they never look for evidence that treatments work because people buy the remedies anyway, and a company that spent the money to run the trials would be undercut by less scrupulous competition. This is not even a market with asymmetry of knowledge, it's a market where no one knows anything, and the lack of regulation makes sure it continues that way.

There's still an economic incentive for the highest level of FDA approval: Medicare and insurance companies have to cover it and doctors can prescribe it. That ensures a high and consistent level of usage across the whole country, not just among people with more money than sense (usually IMHO; it's possible that they're just smarter & savvier than the notoriously conservative FDA, who knows, this is a big reason why taking away choice is bad on principle).

I don't think the lack of credible evidence of efficacy in the supplement market is for lack of trying. If an alternative medicine is actually effective, it just becomes medicine that the majority of people can trust and use.

> But this already happens for certain treatments. The FDA already regulates a separate category with loose efficacy requirements for dietary supplements and herbal remedies. These medically irrelevant treatments are immensely popular, they're just forbidden from marketing specific medical claims and being actually toxic.

In the US, supplements must be vitamins or minerals, botanical products, amino acids or enzyme products.

Drug companies can't develop a new compound and then try to sell it as a supplement unless it meets those requirements, which it probably won't, because drug companies rarely develop new compounds that are also found in nature or in your body already.

To quote another SA piece, “the categories were made for man, not man for the categories” https://slatestarcodex.com/2014/11/21/the-categories-were-ma...

OP is saying we could change the laws that configure the distinction you draw.

> Why do we always have to make people's choices for them? They're grown adults capable of making their own decisions and their own mistakes. If they want to ignore the science and the credibility of the FDA process, they should be free to do so.

Most people -- including myself -- are unequipped to evaluate the science behind most drugs. That supposed to be why the FDA exists. I do not want to make my own mistakes here, since they can very easily be fatal, or at least have long-term consequences. I want a trusted body of experts to give me a recommendation that's as well-informed and unbiased as possible. The FDA may or may not be as good as they should be at being that body, but it is absolutely needed.

This thread is about decoupling efficacy from safety, not releasing potentially fatal treatments. The whole point of Scott's article is that we can keep basic safety requirements but the efficacy requirements for FDA approval are much stricter and should be decoupled. The FDA can give a lower level of approval to treatments like this Alzheimer one that has controversial/borderline efficacy evidence instead of making a black & white choice between "not allowed at all" and "fully endorsed and must be covered by Medicare & insurance".

No one is arguing to get rid of safety requirements or the FDA. The FDA will still be empowered to give a recommendation based on efficacy, but the lack of an efficacy recommendation should not prevent people from getting a treatment. The FDA is necessarily conservative, slow, and sometimes makes mistakes. That has a real cost if it acts as the sole gatekeeper for efficacy, a prime example being early COVID-19 test kits.

why would we want to sell drugs that are "safe" but ineffective?

imagine someone is in need of an effective treatment, but they don't like it or heard some rumors on tv or youtube, then instead they take an ineffective drug and think they aren't contagious, yet now they are potential spreaders of a disease... that doesn't sound safe at all to me.

> why would we want to sell drugs that are "safe" but ineffective?

Because "ineffective" in your question actually means "not proven by the FDA to be effective" and the FDA, like all organizations, isn't perfect or perfectly responsive. For example, early COVID testing kits by third party labs that were safe and realistically effective but not yet approved. For example, this Alzheimer treatment that has controversial efficacy but the FDA could only choose between banning it completely or forcing insurance & Medicare to cover it.

We can make exceptions in scenarios where ineffective treatments have unusually high external risks such as the COVID-19 pandemic before effective vaccines were available. Now, someone who pays attention to the FDA can use an FDA approved vaccine to immunize themselves to the disease spread by people who make decisions based on YouTube rumors. Sounds safe enough to me. We each make our own choices.

  > We each make our own choices.

yes we do, but the caveat is, we dont live in isolation from one another, so in cases such as covid, people being able to take "proven safe but unknown effectiveness" medications is a recipe for unintentional spread to others... this is the opposite of safe imo

Because I am not a scientist and need an authoritative body that I can have some semblance of trust in to decide what medicine I can put in my body and a Dr can prescribe to me. And we have tried the unregulated route before and we had people taking cough syrup with heroine in it and other snake oils.

I mean, even with the FDA, we have people using animal dosage de-wormer to treat Covid with no evidence that it works and a lot of evidence that it will fuck up your guts...so as much as you want to play the "we're adults capable of making decisions" card, that statement really doesn't mean much in reality.

Is anyone even reading my comment or any of the comments above me? I'm not arguing against the FDA's safety requirements. The argument is for decoupling safety from efficacy requirements to make a treatment available to acquire. Right now availability is coupled with mandatory coverage by Medicare & insurance, which means treatments with borderline/controversial efficacy results like this Alzheimer one is either totally banned or mandatory for prescription & coverage. You wouldn't be able to sell heroin.

decoupling safety from efficacy requirements to make a treatment available to acquire

That'll only serve to increase distrust in the FDA. Yeah, it's safe, but also, it's no good for anything. You wonder if that's the purpose of such initiatives, destroying trust in the public authorities to better be able to sell snake oil.

I'm sure that people who can read an FDA safety-only mark clearly labelled as safety-only will be just fine.

The benefits of separating them are relevant to this exact Alzheimer treatment; It has controversial efficacy, but now the FDA had to decide between "all doctors, insurance, and Medicare must cover/prescribe it" or "no one is allowed to do anything with it".

It will also serve to speed up the notoriously slow and expensive process to make something available and make grey-area treatments available. This completely fucked the FDA's early response to the initial need for COVID-19 testing kits. The FDA made a mistake as all organizations do, but its approval system is so inflexible it prevented many safe and realistically effective testing kits from being made available.

  > They're grown adults capable of making their own decisions and their own mistakes.

in a society, "ones own mistakes" can have effects on those around you (e.g mask wearing, vaccine (not)taking, spreading misinformation etc) which can result in unintentional hospitalization or death of others

we dont live in isolated bubbles, so there is a limit to how far we can go with putting everything on the shelf and let everyone do what they want with it

Because desperate sick people and their loved ones make excellent marks. Without standards, some doctor or medical company will milk every last penny from someone with the false promise of some sort of hope.

Not to mention second order effects. The more common it is for medicine to be seen not working, the more people will distrust the medical system.

A treatment that is safe but not proven by the FDA to be effective would not be part of the medical system (ie. doctors, insurance, Medicare), just an available and minimally safe product.

People are already "milked" on supplements and herbal remedies (which is at least still regulated to be safe, not necessarily true for a lot of informal quackery out there): people buy a lot of them without FDA approval or a medical prescription in the hopes that it somehow helps them. It's just fine. Rigorous FDA approval has & will always be available for people to use. They're grown adults, let them make that decision.

If people distrust the medical system because products outside the medical system have failed them, well, people are allowed to be stupid.

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