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The sorry state of the FDA and drug development and deployment as a whole is in my opinion due to a preponderance of two types of people: Type A will happily bankrupt their customers while giving them heart failure in order to reduce allergy symptoms by 10%, and Type B would rather let ten thousand people die in unmedicated screaming agony than have a drug show up in a news story saying it killed three of them, regardless of how many hundreds of lives it saved.

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The FDA is largely composed of Type B people. They are very risk averse and will often delay a new technology simply because there might be unknown risks. There are technologies widely used in European ventilators such as automatic alarm control or adaptive alarm limits which the FDA views as unsafe based on their fear that the alarm system might fail somehow.

It doesn’t surprise me that they tried to slow the approval process down. Anyone that believes the FDAs mandate is to foster progress is severely misinformed. Their actual mandate as I understand it is specifically to protect the public from injury by making progress really slow and making sure there are enough barriers to prevent someone selling a product which makes patients worse off than competitors.

In this case they probably caused a lot more damage than they prevented.

I work with the FDA as a part of my job and I disagree they are overly risk adverse. When we previewed our development plan with the FDA, they actually asked us "can't you move faster?". When a safety signal showed up, they were more than willing to work with us to develop a protocol to reduce the risk while still providing patients with drugs.

I don't disagree that the FDA is very concerned about safety, but in situations where there is a very strong need, the FDA is willing to move quickly and accept a level of risk.

It's nice that they offered to slightly tweak the protocol for you. How very generous and magnanimous of them.

On the other hand: coronavirus.

I honestly don't think it's fair to crap all over the FDA for Covid. One day we read that people become immune, the next day they lose it. One day hydroxychloroquine works, then next day it doesn't.

It's hard enough managing drug approvals when you have all the data and plenty of time.

> They are very risk averse and will often delay a new technology simply because there might be unknown risks.

I think this is smart simply because of how difficult it is to undo something that's been approved. You have people coming forward with side effects and the company simply shrugging their shoulders and saying there's no way you can prove that it's from this vs something else.

the company simply shrugging their shoulders and saying there's no way you can prove that it's from this vs something else

That's not how it works. It doesn't matter if the company "shrugs their shoulders", if the FDA wants to pull the drug, it gets pulled.

The FDA has a requirement that all adverse events reported to a company must be reported to the FDA (massive fines if you don't). The FDA will then take that data and do their own analysis. Yes, they will work with the company to discuss the data and it's implications, but have zero qualms with yanking a drug if the company thinks it's still safe.

When we were negotiating our label with the FDA, we asked for a wording change because we thought the current wording was confusing. FDA came back with "we don't agree". So we added more explanation and they came back with "we're not changing it". We just accepted it as it was just delaying launch and it was clear we werne't going to get our way.

The big question is whether any other country has processes and a market that is leading to faster drug discovery, development and launch ? If yes, that may help and in the current circumstances there is only 1 country big and powerful enough that i can think of, China.

There were some great drugs that were blocked because it raised blood pressure slightly :/

Higher blood pressure is linked to increased mortality. It's not like they are blocking the drug for fun.

It depends what ur treating . For some disease an increase in blood pressure is nothing ,taking BP meds fixes this issue

You really need to look at all cause mortality. You can’t just say A is associated with B, therefore we should keep A low. We make that mistake all the time as far as I can tell.

My understanding is that connection has already been made through several robust trials.

There may be drugs that raise blood pressure, but not mortality, but so far we haven’t actual data on one of them.

Especially in a country where 2/3rds of the adult population are overweight or obese and likely already have elevated blood pressure.

How would you classify Frances Kesley who prevented thalidomide from being sold in the USA. And how would you rank the German authorities who allowed it to be sold over the counter?

Type C reduces people to the caricatures demonstrated in Type A and Type B?

Not that it's impossible that either type exists, but we know that plenty of drugs make it through the system and are regularly prescribed that nevertheless have non-trivial risks, so the idea that the FDA is only evaluating the downsides seems pretty limited in its explaining power.

And as posters frequenting HN should know, systems are hard. Good systems over a domain of any complexity aren't trivial even when incentives are aligned. Economic and political incentives in medical domains aren't always well-aligned.

I'm sure the FDA and industrial incentives could both be improved, but I think it's going to take sharper and more detailed insights than imagining a personality binary.

I said there is a preponderance of those two types, not that everyone involved falls into one of them.

> Type B would rather let ten thousand people die in unmedicated screaming agony than have a drug show up in a news story saying it killed three of them, regardless of how many hundreds of lives it saved.

Who gets to set those numbers and by what process? And, probably more importantly, who gets the indemnification liability for the ones who die?

If you don't have good, solid answers for those questions, you don't get to bitch about the FDA.

This isn't theoretical. It's playing itself out in the Type-1 Diabetes arena right now. Nobody wants to be holding the liability bag, so progress is glacially slow.

Informed consent. If you have the probability numbers let people decide if they want to risk it. Make them as well as their next of kin sign ironclad contracts releasing the hospital and manufacturer from any and all liability.

1) Good luck with getting informed consent from every patient on all the myriad drugs and treatments that the FDA approves in a year. The bureaucracy that ensures that will make the FDA look like a fleet-footed fox.

2) Informed consent only holds until someone's child dies. Then you're in court no matter how good your contract is.

3) Who defines the informed consent boundaries? It's turtles all the way down. All you did was push the complexity around--you didn't get rid of it.

The FDA is where ethics and economics intersect. The problems don't have easy, magical answers.

That would never work. People sign disclaimers all the time and still sue.

Those types of people exist in all countries. Yet the FDA is uniquely American.

A different agency working under different incentives could produce much different, and hopefully better outcomes.

I think the Europeans Medicine Agency is a model for making sensible tradeoffs here, at least compared to the FDA. I sort of with the US could just outsource drug approval to them.

The EMA is? The EMA typically takes longer on average to approve a drug than the FDA.[1]

And if you want to look up an EU scandal, check out the Servier and Mediator. Hundreds of deaths reports and it took France almost 20 years to pull it off the market.[2]

[1]https://news.yale.edu/2017/04/05/fda-approves-drugs-more-qui...

[2]https://www.fiercepharma.com/pharma/servier-faces-courtroom-....

Sure but I'm thinking of different metrics here.Europe has a variety of competing EpiPen equivalents so no price gouging. They had beta-blockers approved a decade before they were available in the US, with a small risk of liver failure for that first drug true, but many, many more lives were saved than lost. They had sunscreen that stopped UV A a decade before the US because the FDA's test only looked at skin burning so it took a long time to get the framework in place to examine sunscreens that block both.

And yes you do have failures like Mediator or Thalidomide but on net I'd rather have their system.

Valid point for EpiPen, but a part of the reason for the US price gouging was physician prescribing - there were/are non-equivalent EpiPens available in the US (different, but still effective). Doctor choose or don’t know to prescribe it.

The beta-blockers is also valid, but back then (mid-20th century) the EMA (or constituent countries) were consistently approving faster than the FDA. It wasn’t until the 80’a when the FDA was revamped to be more like the EMA.

Regardless, even though some may prefer failures like Mediator or Thalidomide, I just don’t think there is the political appetite to tell folks “yeah, the drug turned out to hurt people, but that’s the price we pay for having faster approvals”.

Logically it makes sense, but when it’s your child who is hurt by a drug, people get very risk adverse very quickly.

There are two types of risks in this field:

1. Approve something too soon. This kills/hurts patients using it.

2. Wait too long approving something. This kills/hurts sick people who are deprived of good treatment.

The classic big FDA flaw is to heavily lean towards type 2 errors, because type 1 deaths lead to bad PR, while no one notices type 2 errors.

So that EMA apparently made a type 1 error here is possibly a good sign!

It's worth noting that in medical culture, knowingly implementing a process that does not aim to eliminate all type #1 errors as much as possible would violate the spirit of the Hippocratic oath, whereas #2 would not.

EMA and FDA make different tradeoffs. They’re not necessarily easier. But I agree with you in part, I wish we had more harmonization or at least regulatory overlap — approved in EU you can sell in US, and vice versa, for instance.

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