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 them all subject to oversight, or come up with a 3rd path.
3) Emergency Use Authorization needs to be rethought with the ability for either political leadership or FDA to have broad capability to expand the category of what gets covered
With respect to point #2, the real reason why revamping any regulatory regime "top to bottom" is difficult is because so much organizational, legislative, and administrative cruft has built up over the years in the federal government that means no one individual has the authority to drive reform. See FDA's discussion paper from Jan 2017 on revamping the LDT regulatory regime (https://www.fda.gov/media/102367/download) for more on the inane complexity created by the federal bureaucracy: "For example, a test made by a conventional IVD manufacturer would be regulated by FDA initially. If a laboratory made a significant modification to that test, it would then be regulated by CMS. If the original manufacturer then made another significant modification, the modification would be regulated by FDA."
Also: "In 2015, FDA established an Interagency Task Force on LDT Quality Requirements with CMS, the Center for Disease Control and Prevention, and the National Institutes of Health"
Any manager worth his/her salt can tell you that a task force involving four different agencies is unlikely to ever result in any meaningful change. A cornerstone of effective management is to designate one person who is responsible for execution and hold them accountable. This is exactly how the executive branch, from the president on down, is supposed to function (with oversight from the judicial and legislative branches, of course), but few parts of it are like that after centuries of bolting on overlapping agencies and departments.
I don't think "conflated" is the right word. Romer doesn't imply that these problems have the same cause, or are even correlated (although I suspect they are).
He just lays them out as stark examples of FDA getting in the way of the public interest in this pandemic.
Thing about these problems (and others) is that bottle necks and red tape generally are problems in just about any country.
Political leadership in this situation involves noting the regulatory and bureaucratic hurdles to action and using your authority to supersede them when a pressing situation requires it. Someone has to sit down and say "what needs to happen, what's standing in its way? What orders have to be issue to stop this today?" Someone has to say "this priority is more important than anything else at this point", etc. Just as an example, it shouldn't be hard to notice tests are only being mailed and to stop that this case, etc.
A crisis always requires political leadership because of both the this bureaucracy and the general confusion created by crisis. Many if not all bureaucracy will act ineffectively by default unless someone forces their hand.
Which is to say that the current situation is an abject failure of leadership specifically.
It's not a matter of overriding everything or nothing. Any crisis is going to involve some level of standard operating procedures not working, even with the best planning (though the US through out planning beforehand). Effective action requires a chain of events all happening and some central institution has to look at the process as a whole because 9 out of 10 things happening well can easily not be enough.
In no rational universe should we have to mail data in 2020
I remember a study where the lab reports were printed on there own printer. The FedEx employee showed up with a labeled box, put the huge stack in it, and left. I think that daily stack of labs cost somewhere in the five figure range each day.
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) 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
I find it fascinating that the FDA wants data in SAS 5 transport files [1][2], a file format with very obvious mainframe heritage – 80 byte records and floating point values in IBM hexadecimal floating point instead of IEEE [3].
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.
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.
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.
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.
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.
> 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.
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]
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.
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.
I still don’t understand why the FDA was telling labs not to develop their own tests. After publication of the primers, it’s standard work to create an rtPCR. And being a lab developed test it should be out of the jurisdiction of the FDA.
If I recall correctly, it is due to the declaration of a state of emergency. Usually only a lab would need certification, but the emergency made it necessary for every test to be certified. Don't quote me on this though, I'll try and find a source.
Unfortunately, we need to be skeptical about almost every decision and communication from the CDC, FDA, and a number of other federal agencies. The current administration has done a remarkably effective job of bending these agencies to their will and forcing out anyone who doesn't fall in line.
I think you’re giving the current administration too much credit here.
There’s no reason to claim a grand conspiracy to knee-cap the initial testing response. The CDC and the FDA managed to fail out of pure incompetence and ineptitude all by themselves.
For most conservatives, I guess it's easier to blame the "deep state" or those "evil government bureaucrats" than admitting the leader they elected is incompetent.
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 ago which impeded the response or even actively worsened it, and too many remained in denial once community spread became apparent.
Everything from a stranglehold on testing (FDA) to bungling the test kits (CDC) to flimsy border checks, poor initial contact tracing, to forcing COVID positive patients to nursing homes (Cuomo), to politicizing the quarantine to the point where they lose credibility (open letter from ‘healthcare professionals’ supporting protests).
There’s nothing deep state or evil about it. It’s just the typical failure I expect from my government, blue or red, every time. Sad but true.
To be fair, this was basically America’s first brush with a serious contagion in the modern era. Other countries that did better have had more practice.
Frankly, I don’t think a full fledged multi-trillion dollar response (50-state hard quarantine) was politically possible on January 20th. Trump was acquitted on Feb 5, and Senators skipping impeachment hearings to get informed on COVID were literally being threatened that they would be dragged into the Senate to sit and listen to Ukraine testimony.
From what I can tell, no one in either party was calling for measures stringent enough and early enough to have stopped the situation we have now. Senator Cotton was one who pushed particular hard to ground planes and is credited for that.
Of course at the time the perplexing WHO guidance was against travel bans. Yes, the US certainly isn’t alone in the world in its missteps.
And even if the lockdown had been harder and more consistent, there was still the flubbed testing, the flubbed medical response (ventilators), and the flubbed patient management.
CDC initial tactical teams wanted to treat COVID patients like Ebola carriers, spending what looked like $100k per person in full isolation wards — I guess they were thinking this was going to be 10 or 20 people coming into the country. Then we end up sending sick people into common areas of nursing homes. Then they told people not to wear masks for weeks... Just totally nonsensical top to bottom.
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.
So much for not playing politics, the only reply I get being one that falsely calls Trump a Nazi sympathizer.
> yes they are but let's not forget one side of politics literally said people carrying swastikas are very fine people as well
I'll assume you're not being sarcastic, and perhaps just inadvertently making my case. What Trump said about Charlottesville was literally the opposite of what the media reported him saying. Watch the actual video of his remarks, or read the full transcript.
If you're willing to examine the actual primary source evidence in that case, perhaps it will help you take a fresh look at how COVID is reported w.r.t Trump as well.
As to your question, no I was not equating that. I am saying just one of many, many flubs was when Democrats called COVID a "manufactured crisis" in the early stages as it was unfolding during impeachment. Instead of pushing the Administration to do me, COVID response was made out to be a red herring or a con used as a distraction. Before we even knew was SARS-CoV-2 was, the response was already being irreparably politicized.
I'll save you a click and paste the transcript. It's actually more relevant than ever considering recent events.
By my count he totally condemns neo-Nazi's, calls them violent, calls them bad, 5 different times before saying there were different people, people who came there to protest a statue being taken down, people who were not neo-Nazis, that were part of the "very fine people on both sides." He then follows that by saying again that he's not talking about neo-Nazi's and they should be condemned totally. He couldn't have made it more clear (over screaming reporters) but they hung him up for it anyway. Read for yourself...
Trump: "I will tell you something. I watched those very closely -- much more closely than you people watched it. And you have -- you had a group on one side that was bad, and you had a group on the other side that was also very violent. And nobody wants to say that, but I’ll say it right now. You had a group -- you had a group on the other side that came charging in, without a permit, and they were very, very violent."
Reporter: "Do you think that what you call the alt-left is the same as neo-Nazis?"
Trump: "Those people -- all of those people – excuse me, I’ve condemned neo-Nazis. I’ve condemned many different groups. But not all of those people were neo-Nazis, believe me. Not all of those people were white supremacists by any stretch. Those people were also there because they wanted to protest the taking down of a statue of Robert E. Lee."
Reporter: "Should that statue be taken down?"
Trump: "Excuse me. If you take a look at some of the groups, and you see -- and you’d know it if you were honest reporters, which in many cases you’re not -- but many of those people were there to protest the taking down of the statue of Robert E. Lee.
"So this week it’s Robert E. Lee. I noticed that Stonewall Jackson is coming down. I wonder, is it George Washington next week? And is it Thomas Jefferson the week after? You know, you really do have to ask yourself, where does it stop?
"But they were there to protest -- excuse me, if you take a look, the night before they were there to protest the taking down of the statue of Robert E. Lee. Infrastructure question. Go ahead."
Reporter: "Should the statues of Robert E. Lee stay up?"
Trump: "I would say that’s up to a local town, community, or the federal government, depending on where it is located."
Reporter: "How concerned are you about race relations in America? And do you think things have gotten worse or better since you took office?"
Trump: "I think they’ve gotten better or the same. Look, they’ve been frayed for a long time. And you can ask President Obama about that, because he’d make speeches about it. But I believe that the fact that I brought in -- it will be soon -- millions of jobs -- you see where companies are moving back into our country -- I think that’s going to have a tremendous, positive impact on race relations.
"We have companies coming back into our country. We have two car companies that just announced. We have Foxconn in Wisconsin just announced. We have many companies, I say, pouring back into the country. I think that’s going to have a huge, positive impact on race relations. You know why? It’s jobs. What people want now, they want jobs. They want great jobs with good pay, and when they have that, you watch how race relations will be.
"And I’ll tell you, we’re spending a lot of money on the inner cities. We’re fixing the inner cities. We’re doing far more than anybody has done with respect to the inner cities. It’s a priority for me, and it’s very important."
Reporter: "Mr. President, are you putting what you’re calling the alt-left and white supremacists on the same moral plane?"
Trump: "I’m not putting anybody on a moral plane. What I’m saying is this: You had a group on one side and you had a group on the other, and they came at each other with clubs -- and it was vicious and it was horrible. And it was a horrible thing to watch.
"But there is another side. There was a group on this side. You can call them the left -- you just called them the left -- that came violently attacking the other group. So you can say what you want, but that’s the way it is.
Reporter: (Inaudible) "… both sides, sir. You said there was hatred, there was violence on both sides. Are the --"
Trump: "Yes, I think there’s blame on both sides. If you look at both sides -- I think there’s blame on both sides. And I have no doubt about it, and you don’t have any doubt about it either. And if you reported it accurately, you would say."
Reporter: "The neo-Nazis started this. They showed up in Charlottesville to protest --"
Trump: "Excuse me, excuse me. They didn’t put themselves -- and you had some very bad people in that group, but you also had people that were very fine people, on both sides. You had people in that group. Excuse me, excuse me. I saw the same pictures as you did. You had people in that group that were there to protest the taking down of, to them, a very, very important statue and the renaming of a park from Robert E. Lee to another name."
Reporter: "George Washington and Robert E. Lee are not the same."
Trump: "George Washington was a slave owner. Was George Washington a slave owner? So will George Washington now lose his status? Are we going to take down -- excuse me, are we going to take down statues to George Washington? How about Thomas Jefferson? What do you think of Thomas Jefferson? You like him?"
Reporter: "I do love Thomas Jefferson."
Trump: "Okay, good. Are we going to take down the statue? Because he was a major slave owner. Now, are we going to take down his statue?
"So you know what, it’s fine. You’re changing history. You’re changing culture. And you had people -- and I’m not talking about the neo-Nazis and the white nationalists -- because they should be condemned totally. But you had many people in that group other than neo-Nazis and white nationalists. Okay? And the press has treated them absolutely unfairly.
"Now, in the other group also, you had some fine people. But you also had troublemakers, and you see them come with the black outfits and with the helmets, and with the baseball bats. You had a lot of bad people in the other group."
That isn't a totally unfair equivalence; they were using the impeachment hearing to draw attention to what they considered the biggest problem facing America - Republicans winning the 2016 election. They could have been using the time to agitate for resilience and disaster preparedness. I wish someone would do that, Democrat or otherwise. COVID-19 will not be the last crisis.
> literally said people carrying swastikas are very fine people as well.
Trump, several seconds later [0]: "And you had people -- and I’m not talking about the neo-Nazis and the white nationalists -- because they should be condemned totally. But you had many people in that group other than neo-Nazis and white nationalists. Okay?"
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 administration provide a V-shaped recovery in trust? Or is it just gone forever?
> 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.
I find this interesting as the FDA basically fell over themselves to sign off in treatments. They gave chloroquine the ok based on less than nothing and other drugs have been given breakthrough treatment status without trials.
I can see an arguement to "try anything" in an emergency. But how did the fda end up being BOTH to lose and too tight with their regulation?
Chloroquine and hyrdorchloroquine have been in use for decades (70 years for chloroquine!) with millions taking them daily and a very well known safety profile. It was already FDA approved, could have been used by any doctor for COVID as an off-label treatment already. Everything about CQ/HCQ has been ridiculously politicized to the point that the facts have become very hard to find.
In fact, given the huge number of people taking them for lupus and other diseases (a significant fraction of a percent of the population, having autoimmune disorders and poor health and thus at greater COVID risk), we've basically had a biased but ultra-informative experiemnt already: What percentage of them got covid and what severity, as compared to general population, and compared to other comparable populations (autoimmune that isn't treated by CQ/HCQ)? It's not perfect, but it would have been very informative. CDC has this info. No ethical issues about it.
The main economic function of employees of agencies in DC is the transfer of risk away from the DC housing market, onto the American people. The career employees of the military, as a particularly extreme example, exist to transfer risk away from the DC housing market as far away as possible, which ultimately ends with special forces personnel deployed to hostile territory.
Similarly, the main economic function of employees of big tech companies is transferring risk away from the West Coast housing markets, onto their users.
In my experience, the only way to handle the government side of this is to "not waste the crisis" and execute under conditions where they will see stopping you as more risky than not stopping you.
The only way I know of to manage large corporations is to get the government to create incentives that make it riskier for them to transfer risk onto their customers. That's what financial penalities and anti-trust law are for. The trick is you have to go back to the point about the government: you have to make action less risky for the government actors than non-action.
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 them all subject to oversight, or come up with a 3rd path.
3) Emergency Use Authorization needs to be rethought with the ability for either political leadership or FDA to have broad capability to expand the category of what gets covered