The FDA's perpetual process machine • Hacker News Board

Re: The FDA's perpetual process machine

#31

Post by refurb » Sun, Jun 28, 2020, 4:35 AM UTC

hanniabu wrote: post #5

jschwartzi wrote: post #4

Earlier quoted context omitted.

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 approv…

> 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.

Re: The FDA's perpetual process machine

#32

Post by refurb » Sun, Jun 28, 2020, 4:41 AM UTC

Symmetry wrote: post #15

BurningFrog wrote: post #13

Earlier quoted context omitted.

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-....

Re: The FDA's perpetual process machine

#33

Post by refurb » Sun, Jun 28, 2020, 4:43 AM UTC

causality0 wrote: post #24

bsder wrote: post #17

Earlier quoted context omitted.

> 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 ge…

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.

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

Re: The FDA's perpetual process machine

#34

Post by entee » Sun, Jun 28, 2020, 6:41 AM UTC

seehafer wrote: post #3

There are number of conflated regulatory problems in this piece: 1) FDA needs to move its data ingestion into the 21st century (note: large industry can be as resistant to changing current process as bureaucracy). In no rational universe should we have to mail data in 2020 2) In vitro diagnostic regulation is a mess and needs to be revamped top to bottom. Either exempt all Lab Developed Tests, rewrite the law to make…

Agreed on the conflation, and clearly there are many parts of the FDA that need attention. However this article is misleading because it focuses heavily on one teams (basically then Seattle Flu Study) of extremely competent people hamstrung by onerous requirements. It ignores the many more incompetent people stopped by more scrutiny and the errors that low scrutiny produce.

As an example for the latter I point to antibody tests, many of which were given approval despite being poorly validated (1). These cause at least as much harm as good.

The FDA needs to improve and we need to remove some counterproductive regulatory steps (when the emergency was declared, in some ways it got harder to approve a test under EUA, that should be adjusted). But lets remember that hasty decisions in medicine can cost lives (see thalidomide, which the FDA mostly dodged unlike Europe, or Viox). We shouldn’t make broad decisions on examples cherry picked from the best case scenarios.

1.) https://khn.org/news/antibody-tests-were-hailed-as-way-to-en...

Re: The FDA's perpetual process machine

#35

Post by newyankee » Sun, Jun 28, 2020, 7:04 AM UTC

jschwartzi wrote: post #4

causality0 wrote: post #2

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, regar…

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 approv…

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.

Re: The FDA's perpetual process machine

#36

Post by teddyh » Sun, Jun 28, 2020, 7:12 AM UTC

bsder wrote: post #14

wonnage wrote: post #8

Earlier quoted context omitted.

I think this is one of the great side tragedies of the coronavirus. The US generally had a lot of trust in these federal agencies. They've always been susceptible to political interference, as demonstrated now. But it's never (?) gotten to the point it has now, where you simply can't trust the CDC to provide accurate information, or information that every other country has accepted months ago. Will the next administr…

> Will the next administration provide a V-shaped recovery in trust? Or is it just gone forever? The big problem is that in order to fix trust, you will need to purge a lot of the senior bureaucrats who decided that keeping their job was more important than serving the public. If you don't do this, then you have sent the signal that being a political operator is more important than doing your actual job .

Pournelle's Iron Law of Bureaucracy states that in any bureaucratic organization there will be two kinds of people:

First, there will be those who are devoted to the goals of the organization. Examples are dedicated classroom teachers in an educational bureaucracy, many of the engineers and launch technicians and scientists at NASA, even some agricultural scientists and advisors in the former Soviet Union collective farming administration.

Secondly, there will be those dedicated to the organization itself. Examples are many of the administrators in the education system, many professors of education, many teachers union officials, much of the NASA headquarters staff, etc.

The Iron Law states that in every case the second group will gain and keep control of the organization. It will write the rules, and control promotions within the organization.

— https://www.jerrypournelle.com/reports/jerryp/iron.html

Re: The FDA's perpetual process machine

#37

Post by throw-away_42 » Sun, Jun 28, 2020, 8:21 AM UTC

tridentlead wrote: post #16

wonnage wrote: post #8

Earlier quoted context omitted.

I think this is one of the great side tragedies of the coronavirus. The US generally had a lot of trust in these federal agencies. They've always been susceptible to political interference, as demonstrated now. But it's never (?) gotten to the point it has now, where you simply can't trust the CDC to provide accurate information, or information that every other country has accepted months ago. Will the next administr…

It's not the administration. It's just the general ineptitude of many government processes. The current crisis has just laid inadequacies bare.

It is this Republican administration. They were left a playbook for this scenario. They threw it out, and then lied about it.

https://www.mercurynews.com/2020/05/12/fact-check-obama-left...

Re: The FDA's perpetual process machine

#38

Post by cyphar » Sun, Jun 28, 2020, 9:06 AM UTC

refurb wrote: post #10

jokowueu wrote: post #7

Earlier quoted context omitted.

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.

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

Re: The FDA's perpetual process machine

#39

Post by cycomanic » Sun, Jun 28, 2020, 10:34 AM UTC

zaroth wrote: post #30

hitekker wrote: post #27

Earlier quoted context omitted.

I'm no fan of the CDC and FDA, but you'd have to be blind to ignore the failure of leadership at the top of the totem poll. https://www.politico.com/news/2020/03/25/trump-coronavirus-n... https://www.cnn.com/2020/04/18/politics/kfile-trump-official... The links go on and on. For most conservatives, I guess it's easier to blame the "deep state" or those "evil government bureaucrats" than admitting the leader they elec…

There’s no reason to play partisan politics here. If we want we can say Democrats were too busy trying to impeach Trump and calling Wuhan a “manufactured crisis” back when Trump ordered the borders closed Jan 30. The simple fact is non-partisan non-evil, simply incompetent bureaucrats at the State and Federal levels all failed to adequately prepare (PPE stockpiles) and had actively harmful policies set in place years…

So you are equating democratic legislators taking part in the impeachment hearings to the trump administration dismantling the CDC pandemic response team? Let's not even get into the "corona will just disappear... or it's just like the flu..."

These arguments about "let's not make this a partisan issue" completely ignores the reality. The same about how news and politics are so divisive at the moment, yes they are but let's not forget one side of politics literally said people carrying swastikas are very fine people as well.

Calling for "not politicising issues and all sides are bad" completely ignores the reality that who is in power at the moment and how exceptionally incompetent and corrupt the current administration is.

Re: The FDA's perpetual process machine

#40

Post by Symmetry » Sun, Jun 28, 2020, 10:43 AM UTC

refurb wrote: post #32

Symmetry wrote: post #15

Earlier quoted context omitted.

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.