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I remember Softenon.

> it wasn't only because of low-hanging fruit.

Yeah, right. They had such advanced cancer medication back then.

> Give people with fatal diseases a "right to try" drugs that haven't passed safety testing -- and use that data.

That data is practically worthless.

I'm in favor of having people try out medication, but it will need to be heavily regulated. And we know what happens to regulation: a party comes along that doesn't like regulation, or gets bribed, and the regulation goes out the window. It's a good way to start another opium crisis.

> "B-but Thalidomide!"

This is the reflexive response to every common-sense proposal to roll back the regulatory burden.

I'd raise a couple of points in response:

First, Thalidomide was never approved in the USA -- for safety reasons. The mechanisms that were in place at the time did their job.

Second, the response to Thalidomide was overblown and indeed downright hysterical. "Better to let 100,000 people die of neglect than allow one person to suffer an awful drug reaction" is not rational policy.

> That data is practically worthless.

Enough "practically" worthless data, and you get somewhere. It's a matter of quantity. Obtaining "hiqh quality" data is often unethical in medical practice.

> It's a matter of quantity.

A large data set of highly biased, uncontrolled data is still useless. You can't model yourself out of the factors that have not been recorded. And believe me, the data you'll get on patients that try experimental medication will be very, very incomplete.

It also won't be a large dataset. How many people have squamous cell carcinoma between now and the moment of approval and are willing and wealthy enough to buy this particular medicine? 100 seems too much already.

> The mechanisms that were in place at the time did their job.

Barely, according to wikipedia.

> Second, the response to Thalidomide was overblown and indeed downright hysterical. "Better to let 100,000 people die of neglect than allow one person to suffer an awful drug reaction" is not rational policy.

Thalidomide was never going to save 100,000 people. It did cause 2500 birth defects in West Germany alone, though, plus an unknown number of abortions. Given that it was legal in 46 countries, the number of people with birth defects must be well over 10,000. This drug isn't going to save 100,000 people either, certainly not in the period until admission.

> A large data set of highly biased, uncontrolled data is still useless. You can't model yourself out of the factors that have not been recorded. And believe me, the data you'll get on patients that try experimental medication will be very, very incomplete.

There are many safety issues that placebo-controlled and double-blinded studies didn't catch, but postmarketing surveillance later did. Large data sets are more powerful than you give them credit for --- and, moreover, in the real world drugs are not always used the way they are in clinical trial settings. In the real world, people skip doses, double up on doses, drink grapefruit juice, etc.

If you want a full picture of "factors that have not been recorded," you want as large a dataset as possible, as close to real world conditions as possible. It may not be as clean as you'd like, but it'll give you enough to draw every inference.

> How many people have squamous cell carcinoma between now and the moment of approval and are willing and wealthy enough to buy this particular medicine? 100 seems too much already.

When the alternative is to allow the drug to spend a decade or longer in development hell, I'll take poor data and lives potentially saved over "great data" (not really) and a pile of dead bodies.

Besides, when drugs are potentially curative, and the disease otherwise so invariably fatal, even 50 datapoints should be sufficient. This is trivial to model mathematically.

> Barely, according to wikipedia.

Oh come on. Besides, teratogenicity is now an absolutely basic component of safety tests. You don't need the FDA's failed paradigm of extensive efficacy trials to prevent "Thalidomide part II."

> Thalidomide was never going to save 100,000 people.

The exaggerated response to Thalidomide, exemplified in your first comment, has absolutely condemned more than 100,000 people.

My brother had an excellent metaphor:

> Say you're a runner. In the beginning of your competitive career, you get the most gains by becoming a better runner. And then at some point, you get more gains by shooting (or bribing) the ref.

The world "simple" is doing so much heavy lifting here, it might as well be written as ______ instead.

I’m fine with that as long as insurance does not pay for any drugs without efficacy testing. Also no advertising of any sort.

insurance already gets away with not paying for some highly efficacious drugs, so I don't think this will be a problem

generally, insurance companies do require efficacy. many of them have decided not to cover aducanumab for that very reason. though this also gives insurance an additional excuse to deny stratospherically-expensive gene therapies and other life-saving new treatments, since even the most effective new drugs won't have e.g. 10 year survival rates until they're a decade old.

agreed on advertising though.

I do think that people should have options, especially when there aren't effective treatments, but it's not exactly simple. In most cases, any treatment you pick has the opportunity cost of other treatments, and for life threatening diseases that opportunity cost might be living. Very few, if any, patients are going to be in a position where they can legitimately evaluate the effectiveness of treatments. In most cases, I don't expect health care providers will be in the position to do that either- even most specialists will be treating a wide variety of conditions, and may have relatively little experience with unusual diseases. Even in the best case, this is assuming that drug companies would actually try to make effective drugs rather than looking for other avenues to sell ineffective drugs (or drugs that were only accidentally effective)- I don't that in today's environment that's at all a reasonable assumption. Ultimately, the information asymmetry is vastly weighted in favor of the drug companies, and the cost is lives.

Apparently there is already a Right to Try:

https://www.fda.gov/patients/learn-about-expanded-access-and...

Get rid of prescription requirement too - who needs to see a doc for extra $500 when I can go and pick my own med, and possibly better one.

That's how it works in Mexico. You only need prescription for antibiotics (makes sense as their abuse would create a public problem) and psychologic related drugs (I dont agree with some of them like amitriptyline... ) .

But other than that you can get almost anything even buying it online and get it at home in the next 3 hours.

That's how I buy duloxetine every month.

It's far from a full solution, but it'd be progress.

Ah yes, let’s go back to the days of Thalidomide.

For those that don’t know, the 1962 change is the Kefauver–Harris Amendment, which was a response to one of, if not the, largest overall global crisis of conscience in the medical field. From Wikipedia: “When first released, thalidomide was promoted for anxiety, trouble sleeping, "tension", and morning sickness.” After some time it became increasing obvious that while it worked, it caused birth defects in pregnant or soon to be pregnant women, with its manufacturers actively trying to quash the information about such cases; again, from Wikipedia: “Use of thalidomide in pregnancy can cause fetal abnormalities such as phocomelia (malformation of the limbs). In males who are taking the medication, contraception is essential if a partner could become pregnant.”

Thalidomide disfigurements were disturbing. Children born with these disfigurements were not linked to Thalidomide until much later. Thalidomide was in fact not allowed a safety regulation by the FDA initially. It wasn’t until the company producing it, Grünenthal, pressured the FDA. You see, the FDA reviewer for the medication was leery about it after some reports had floated over her desk about a possible remote risk that this could potentially cause birth defects. Grünenthal’s international licensee to the US refused to explain multiple papers that linked Thalidomide usage in pregnant women to birth defects.

As it turns out, not only had Grünenthal known about the issue they had actively worked to silence the information, a ploy that worked until a major change in leadership in Germany.

It was denied usage in East Germany.

For a longer documentary on the subject and how it changed medical safety testing, Plainly Difficult has a very good video on it: https://youtu.be/Vi03zz6eCik

(Note: I am explicitly ignoring the context that the Thalidomide development program was run by an actual Nazi who was responsible for unethical and frankly awful experience on unwilling human subjects in concentration camps. If anything, it only amplifies his concern to hide adverse effects, which he did quite successfully until the company was given what can only be considered “A slap in the face”.)

Everything you said has absolutely nothing to do with what GP said.

None of that has anything to do with the proposal you're replying to, which is about the efficacy requirement, not safety.