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"Gholam says that the process of FDA approval for Silibinin is slow, primarily because it only works for amatoxin poisoning, from the Amanita mushroom species. Those poisonings are rare – so gathering enough data to satisfy the safety and efficacy requirements of the FDA takes time. And there is little financial incentive by the company that owns the drug to invest in its research and development."

Incidentally, these protections exist because of several breakdowns in drug safety in the past, notably Elixir sulfanilamide and Thalidomide.

I'm not suggesting that there should be no improvements, I think there should be a conditional use waiver program that allows these drugs to be in the field. But suggesting that it should be criminal that it's not is over the top moralizing and provocation of outrage for little return.

Also, there are good reasons why this drug is restricted access too - https://en.wikipedia.org/wiki/Silibinin



My question is: why does the FDA need to (get domestic pharma companies to) conduct its own studies here? If the drug has been used in Europe for 30 years, presumably there are 30 years of evidence in European clinical practice that can be used as evidence. Maybe even existing meta-analyses of said evidence in European medical journals. Why isn't that sufficient?


I'd trust European data more than , say chinese or pakistani data. However, that kind of exclusivity is politically untenable.


I would imagine you could create a shared medicine treaty group and structure it with explicit membership qualifications and then a voting on membership and long enough delay to make the membership politically tenable.


It would be a very tough job to align the health and testing requirements for even the US and European countries


How would that be politically untenable? There are tons of similar situations.

Similar rules are applied to passports and driving licenses too, some countries are trusted more than others.


Fortunately, realpolitik can still prevail over wokeism in international affairs in which there are obvious life and death consequences.


What does this have to do with wokeism?


Treating different countries differently, even for completely objective and common sensical reasons violates the woke desire for equality of outcome.


The FDA does not accept any studies conducted overseas as clinical evidence. They request studies to contain at least 50% US citizens and be analyzed by US certified physicians.

Now whether that leads to better outcomes or is just a protectionist measure for the local industry is anyone’s guess. A bit of both, I would imagine.


This is completely untrue. Foreign data may be used as the sole basis for marketing approval [1].

[1]: https://www.govinfo.gov/content/pkg/CFR-2006-title21-vol5/pd...


Why not? They could, and at least have strict criteria for how good the studies must be.


The cynic in me says that the FDA wants the company that makes the drug to put up the money for the studies, they won't do it for free and without any possibilities of kickbacks.


Well the FDA doesn’t conduct clinical trials. So they also can’t get kickbacks for doing them.


I think Thalidomide is exactly the wrong reason to not approve drugs like Silibinin and what is wrong with the drug system. Yes, it was a huge scandal. But we are not talking about a drung for general usage, especially not for taking as a healthy person. There should be entirely different approval paths for drugs which are to be taken in a live-and-death situation. Which can be clearly diagnosed. Especially, if it also has been approved and used for a long time in the EU.


There's a difference between measuring safety against morning sickness in pregnant women and a drug that literally saves your life

Drug safety is important but I think we can agree you can't beat the alternative in the case of poison antidote


Exactly. Even if lead and mercury with a cyanide microdose was the only antidote you would still choose it over certain death.


> There's a difference between measuring safety against morning sickness in pregnant women and a drug that literally saves your life

That's why the FDA approves chemotherapies for cancer. Safety is always relative to the condition being treated.

> Drug safety is important but I think we can agree you can't beat the alternative in the case of poison antidote

Only 40% die or require a liver transplant. You need a treatment that would not make things even worse.


>And there is little financial incentive by the company that owns the drug to invest in its research and development.

This is the real reason it hasn't been approved. If only we had some kind of system in place where profit wasn't the main, and often only, motivator for getting life-saving medications approved by the FDA.


> Those poisonings are rare – so gathering enough data to satisfy the safety and efficacy requirements of the FDA takes time.

Since we're talking about something that cause death or liver transplant to such an enormous proportion of the patients (for efficiency, you just need a sample of 6 cases to get a result with p<0.05).


>I think there should be a conditional use waiver program that allows these drugs to be in the field.

There absolutely is. It is called an investigational drug application (AKA clinical trial).

There was a clinical trial running for Silibinin until the manufacturer stopped it in 2020

https://clinicaltrials.gov/ct2/show/NCT00915681

Perhaps this is an opportunity for doctors to conduct an investigator initiated trial?


Seems like the barrier ought to be lower if the alternative is death though…


> Incidentally, these protections exist because of several breakdowns in drug safety in the past, notably Elixir sulfanilamide and Thalidomide.

Those protections are immaterial when the patient is going to die anyway.


> Those protections are immaterial when the patient is going to die anyway.

Only 40% are going to die or require a liver transplant. There is no a-priori reason to assume it won't make things even worse.

We have the recent experience of the early months of Covid. In retrospect, it is quite evident that over treatment, especially aggressive intubation and experimental drugs, caused more harm than good.

The question is always whether the proposed treatment is safe and effective. Safety, of course, should be relative to the condition being treated.


> The question is always whether the proposed treatment is safe and effective. Safety, of course, should be relative to the condition being treated.

Right, which is why the doctors actually treating the patient should be free to make judgment calls without a bureaucrat looking over their shoulder.


Which is why the FDA allows it for patients who will have consumed the mushrooms.

The paperwork is to show the patient is going to die anyways, and doesnt just have a trivial problem.


I think you're dramatically underselling how complicated and slow this "paperwork" really is. People on their death bed don't have the luxury of bureaucratic approval processes.


I understand full well how complicated it is. Speed is the challenge, not the lack of a process for this type of situation. Unfortunately, it is a hard one.


Thalidomide is a very useful drug that is still prescribed today.


>Thalidomide is a very useful drug that is still prescribed today.

With a metric shit ton of caveats, that were outright denied until the public raised an unholy fuss with regulators to get it clamped down on in light of the severity of birth defects/reproductive complications it produces.




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