Balaji Srinivasan discusses the FDA's role during the COVID-19 pandemic

But you brought something up there where the FDA essentially blocked the ability of this health data that currently exists from being applied in a clinical way.

So basically like the Apple Watch was going to have a ton more gizmos in it. And the issue is that when you're an FDA regulated device, if it's under cdrh, there's something called design control which is, I mean imagine filling out forms in triplicate every time you want to do git push, right? That's basically what it is, right? It's like it freezes your design. Now critically, by the way, software engineers do understand that freezing design is sometimes a useful thing to do. So you know, there's something, if you use pip, you know, for Python deployments, PIP freeze, you'll freeze all the versions of different software and you'll have a stable version for deployment. Okay, so there is a value in freezing things, but not too much. You freeze it too much and you can't iterate. And we've definitely erred on the side of freezing it too much. And so one of the reasons I believe that Apple didn't want to do it is it would just freeze their design process. They couldn't iterate on this integrated hardware software device because they have to round trip things through the fda, which is not on your timetable, you know, by the way, one, one thing you know, but you know the FDA will give timetables that are optimized for optics as as much of the federal government is, it's optimized for optics like Potemkin village. You know, healthcare.gov was like this. Also the website looked nice and then when you actually tried to click it, it just fell over like that. Okay, so how is it optimist for optics? Well, they'll give various deadlines, like 90 day deadline or you know, 80, 180 deadline. And that's meant to look good, but that's 90 days. Like a football game is 60 minutes. Every single time the pass goes out of bounds, every single time there's a first down, clock stops, right? And it's actually like a three hour game or something like that, right? So every single time the FDA puts some email back in your inbox asking you to do another study that'll take you six months and $3 million, it stops the clock. And so you spend 17 days, you wait for a response from them, they forced you to take six months, then you reply back, now it's on day 18. Okay, so it's not really 90 day clearance, it's actually much, much longer than that. So that, does that make any sense?

Right.

There's a lot of stuff that's optimized for optics that you only actually understand if you go through the process. And most people don't talk about it. Because if you're a biotech entrepreneur, and then I'll come back to this point about the Apple Watch. If you're a biotech entrepreneur, a good analogy that think about like the tsa, okay, Transportation Security Administration, if you go to the airport, which no one's doing nowadays, okay, but you remember when you did, basically you don't make any jokes when you're in line, okay? You don't talk back to the TSA agent or what have you or make some wisecrack because if you do, you know that they can pull you out of line and harass you and give you basically a retaliatory wait time, which causes you to miss your flight and then you lose effect of the dollar value of that flight plus the dollar value of whatever's on their side, your business deal or your trip or what have you. Okay? And this despite the fact that the regulations that they're imposing on you are transparently ludicrous and non technical. Like, you know, three ounce bottles, you know, which you can take four or three ounce bottles on a plane and you know, there's, you can mix them together or whatever. That's not restricted. So these regulations are clearly nonsensical. You know, the pen knife type stuff or whatever, and everybody's subject to them and the cost, so they're very visible and the cost is relatively low. It's a few thousand dollars to purchase them, but nobody protests them.

Okay?

One of the reasons is you're under the TSA's power for the time you enter to the time you leave. Right? Okay. So now extending that analogy, biotech entrepreneurs and biotech, by the way, I don't, I mean in the broadest sense of biomedicine, so including, you know, diagnostics people, drug people, vaccine people, but also EHR people, you know, medical app people, et cetera, et cetera. Okay? So biomedical entrepreneurs, they don't necessarily always realize it, but when they start a company, it's like they're walking through that metal detector and they're now under the FDA's control. Okay?

Okay.

And if you don't make jokes when you're in a TSA line, you definitely don't criticize the FDA when you're under their control because the retaliatory wait time the TSA guy puts on you so you miss your plane The FDA person can do the same thing, except this retaliatory wait time means your company dies. You know, they can come with just some, you know, nonsense to slow it down, and your company's dead. It's out of Runway. Okay. There's a book called Reputation and Power by a guy named Daniel Carpenter. He's a Harvard professor where, you know, he's much more, I'd say, of an apologist than I would be. But I'm not saying that is completely bad, by the way, but it does a lot of bad things. It's just not heard about. What Carpenter does, though, is he quotes a lot of people. And to his great credit, he doesn't, like, butcher their quotes. He gives them the full quote. So you can actually judge for yourself. And the entire book, to me, it reads like, you know, almost like you went to a POW camp and you interviewed a prisoner of war, and they're saying to you, everything's fine, but they're blinking. I'm being tortured like this. Right? And so the interviews that he has in the book of these pharma executives, you know, some of them who are retired are outright and very frank. And they say, you know, the FDA is the guy with a machine gun. It's going to kill you. You better listen to them. And he talks about how they fired executives at pharma companies that were insufficiently compliant with FDA and so on. This is Dingler Carpenter's book, Reputation and Power. Good book on the fda. You just have to read it with a grain of salt. So what's my point? My point is that's what it means to deal with the fda. You're dealing with an agency that will retaliate against you and break your company. If you say something bad about it, it won't care. Moreover, if you complain about the retaliation. Until recently, until really this pandemic, most people thought the FDA was generally good, just like most people thought the CDC was generally good or the who was generally good.

Right.

You just hadn't seen them. Face plant. Right. You're not a biotech entrepreneur or biomedical entrepreneur. You weren't within the bowels of these agencies. You just knew what the press was telling you and what these things are. As I said, they're optimized for optics. The book is called Reputation and Power because what the FDA optimizes for is its reputation because it realizes that's what gives it power. So now, like, a lot of things start to snap into place. You're, like, kind of looking at the Potemkin Village thing. And normally it holds up because there's only a few people who are dying of some rare cancer or of some disease. And they can only make so much noise about the FDA blocking treatments or slowing cures. And frankly, most people just aren't aligned incentivized with that. But now what's happened is, like, 300 million Americans have basically been unionized into a common interest group which wants treatments and cures and diagnostics as fast as possible for this deadly disease. And so it's no longer possible for the FDA to hide things, and it's no longer possible for them to intimidate every single manufacturer, because even those manufacturers have their lives on the line. And so they're coming out and talking about how the FDA was stopping testing. So it's like, does that make any sense? You see the scale it has to get to for the Potomac and Village to kind of topple over?

It reminds me a lot of what we spoke about earlier, where there are physicians in hospitals who are trying to, like, enact tests, and bodies will pile up. So, like, you're waiting in line for the tsa. The TSA stops hassling you once bodies start to pile up.

So that's right.

What's gonna happen here with the fda, you know, if that starts to happen, like, how is that gonna change, you know, short term?

Let me make a remark on the hospital situation as well. So there was a other day, there was an open letter by, like, 50 organizations that was talking about how, like, like, hospitals were retaliating. There's Seattle Times, I think, had someone on the record, but hospitals were retaliating against medical workers who were asking for more PPE and, you know, like. Like just separating out Covid and non COVID patients and just really basic save my life type stuff. And so because of that, of course, if you're retaliated against, you know, if you lose your job, you're not going to speak up, you lose your company, you're not going to speak up unless you might die. And so what that has done is genuine shared fear of death has basically put people into a, you know, dgaf.

Right. Mode.

Okay. And. And that is the only thing that's enough of a wrecking ball to like, knock through some of this red tape. Now you asked, basically. And so that's at the hospital level. That's also an insurance. There's like, 10 other different areas where they're finally getting stressed. Right? Oh, someone put a comment here. Oh, okay. I don't know everybody on the call. Well, I'm sure, there's people who work hard in these agencies, but I think that the feedback process isn't there. The reason for that is, you know, most people don't know this, but you know, like there's two different kinds of, you know, federal workers. There's political appointees and public roles. Those are appointed by, for example, Trump or previously Obama said be like very senior positions like FDA commissioner or things like that. But most positions within these bureaucracies are career appointees or rather they have career tenure. And you can get career tenure in different ways. But one way is you have three years, I believe, of non contiguous, not necessarily contiguous service. And if you have career tenure, it's actually very difficult to terminate somebody. I might be getting the exact numbers wrong. It might be like 3.5 or something like that. I don't remember the exact number. I'll have to look it up. But the thing about if you're a tenure, there's something called the Douglas factors, which are sort of like the Miranda rights for federal employees. And with the Douglas factors, essentially they mitigate any penalty that's applied to a federal employee if they do something wrong. So that is to say something that would normally get you fired, gets knocked down to a suspension or a suspension is just a slap on the wrist and so on and over. The person who's pushing for that firing has to go through this long process with the person they're trying to fire or discipline, you know, sitting a few desks down and complaining to all the co workers, oh my God, this person is trying to fire me. They're going to come after you next. And so it's like a long drawn out kind of process. So these agencies do not work like people think companies work. People are not at low employees. They have tenure and so they're basically not accountable to the electorate. There's no elections and they're not accountable to the market. So whether you subscribe to a democratic or a capitalist theory of accountability or both, the people who have a lot of power, who are anonymous, who aren't elected, who can't be fired, and that's actually a lot of federal bureaucracy. Moreover, there's something called harmonization where just in the same way that like a small website will often outsource its login to, you know, Facebook because it can't like code its login, they will, a lot of, you know, these smaller countries will outsource their regulation to the USA because they are what's McCall? They're essentially relying on the FDA to do regulation for them. That's called harmonization, where the FDA or the FCC or the FAA essentially harmonizes everybody's regulations globally under the FDA's, you know, or whatever regulatory agency's banner. And so now you've got incredible leverage. You've got a person who, you don't know their name, they weren't elected, they can't be fired. They have career tenure and they're not covered in the press, typically, because the press usually believes that the FDA is good and usually doesn't have a technical enough background to press one more step. And then they have harmonization, which gives essentially just one anonymous person in Silver Spring, like a chokehold on a regulatory approval for the entire world. So that's like the situation. And no matter how well intentioned these people are, you know, power, power corrupts, absolute power corrupts absolutely. And in the absence of competition or alternatives, you have like disasters like what we just had, where essentially over the month of February, emergency use authorizations were not given out for the tests that America needed. And it turned a containable situation into, into a pandemic. And so the thing about this is, this is a culture that you just can't, I mean, you can press it to do things and it's being pressed right now politically to, you know, put out drug approvals and approve convalescent serum and those kinds of things, you know, mask guidelines being pushed like it's never been pushed before in modern times. The closest thing to this is what happened act up in the late 80s and early 90s where also people dying from the deadly virus. At that time AIDS organized and they went and protested on the front steps of the FDA saying, you know, hey, if I die, like put my body on the steps of the fda, right? And that was actually what pushed. That's the closest thing to this that's happened in like kind of relatively recent memory, like living memory in the late 80s, early 90s. But this is on a scale that's beyond that. With that said, I don't actually believe the agency can be reformed culturally because it assigns basically zero weight to the cost and time penalties that it imposes upon the, the scientists, engineers, entrepreneurs are going through its process. It just assigns that no weight. And because it assigns that no weight, it also assigns that, you know, basically no weight to the patients. And there's exceptions like, you know, orphan drugs and compassionate use. But as a general rule, urgency is not a big thing as, as evidenced by the slowness of granting EUAs for these, these COVID 19 tests and you know, them Stopping at home testing and so on, which I can come back to. So what's the alternative? Okay, if you can't reform it, you can. I mean like you should do both and like it's fine to actually go and press bills. I'm sure there's going to be a bunch of different FDA reform bills after this and during this. But I think what you really want is alternatives. Okay. So you know, I had a tweet on this. But essentially there are basically there's pathways that are outside the FDA that are known to people in industry who are actually doing these things. For example, right. To try. You can get some kinds of things approved at the state level where FDA is just notified, they don't have veto anymore. Clia labs and the LDT process. Typically Clia labs are under cms which has a fairly decentralized process. They contract with state agencies and they basically certify the laboratory director and the laboratory and they can roll out a new test. FDA has been in a long war with LDTs to try to bring them under FDA's, you know, kind of thumb. And this was basically just another battle in that long war where essentially, you know, they gained a power over lbts they don't normally have, which is ability to block them. The pathway that was usually outside going through clia where a lab director could just roll out a test that was suddenly cut off, where you had to get an EUA from the fda, they bottlenecked it. Another example, you know, of a path outside the FDA compounding pharmacies. Again, something that FDA has not liked. There's off little prescription by mds where a drug that's proof of purpose A can be prescribed by the MD for purpose B. FD has not liked this at all. And they've gone after people for so called off label marketing where it's a really paradoxical situation. You can have something that is a true fact that is known to be medically true. In the literature that drug B works for this. Okay, but if a pharma rep would go so much as to say that to a doctor, they could be prosecuted. They could be prosecuted for off label marketing. This was recently basically judged to be a free speech issue. If you look at US vs Coronia, essentially that was knocked down. FDA was actually chin checked on this where it was something where off label marketing was not. The ability to prevent people from making true statements. Okay, was seen as a restriction on freedom of speech. But okay, so that's another pathway. But I'm pointing out outside the fda, which is also a prescription. Then the fifth is countries which aren't harmonized with fda. For example, people go to Germany for stem cells. Just to recap, these are pathways outside the FDA right to try. You could have state regulator approve something. FDA just gets notified clia. You have basically a state agency that works at CMS to approve a labor. FDA can't block it. Compounding pharmacies, another pathway, pharmacists outside the FDA off label prescription MDs have a pathway outside the FDA. Countries that aren't harmonized, they have different regulations, the pathway outside. And for each of these, by the way, FDA has an argument as to why this is bad. For example, why is it bad to go to other countries rather than use a drug that the FDA has proved? Well, thalidomide. Thalidomide was in Europe first. And you know, it's because Francis Kelsey heroically stopped that from coming to the US that the US didn't have birth defects in Europe did. So therefore you shouldn't use, you know, drugs from other countries, only the FDA's best. Now, you know, there's an argument that says that Frances Kelsey was actually looking at neurological issues rather than teratological issues. That is to say, I think her hypothesis was like that there's brain related stuff as opposed to birth defects. And so this was just delayed for bureaucrack reasons. But she was made a hero out of it. I have to look into that. But I've read that somewhere, I might be able to pull the reference later. So the point though is that they've always got an argument as to, oh, it has to be under FDA's thumb and you must eliminate all other paths outside of it because otherwise people will die, etc. But if you're thinking about regulatory science, you need controls. You know, insofar as you're making a policy choice that has massive impact on people in the absence of control, you can't actually see if that policy choice was good. And so, you know, you can't just like flip a switch and say it's good. You know, that's not evidence based medicine, so to speak. It's not evidence based regulation. So the alternative to the fda, I think it's a practical alternative, is to expand, right? To try. And by that what I mean is basically designate COVID 19 enough of a life threatening disease that anything that falls under the broad COP19 umbrella, which is a large chunk of medicine, governors could approve it at the. Or rather governors could give state regulators the ability to approve it. And in practice that would be in collaboration with local prestigious brands, like, you know, brands or universities, right? Like Stanford, UCSF, Mayo Clinic, Cedars Sinai, you know, Mass General, etc. Harvard, blah, blah, blah. The point being that actually the expert reviewers or, you know, the panels and so on, that FDA convenes are typically staffed by people from those institutions anyway, right? So, for example, you're in Minnesota or like upper Midwest, you have like, you know, the state regulators work with the Mayo Clinic, and that's a pathway that's outside the fda. They can just sign off on everything, whether it's drugs, whether it's devices, whether it's this, whether it's that. And the critical thing is you've got a reputational bridge, right? It is a state. It's like a legitimate, you know, American state, and it's a very legitimate American institution that has a brand name. And now you might have maybe not 50. You might have 10 possible ways to get your drug or device or what have you through. And these are then going to differentiate because some of them will say, oh, we're the highest standard and they're going to be the biggest pain to deal with. Maybe arguably, I would say have the highest quality and others will be more entrepreneurial, you know, or what have you. Right. And this is kind of what's happened, for example, with incorporation law. Delaware has come out in front as a place that companies go and incorporate because it has most sophisticated chance records and so on. So in this fashion, by the way, you could actually decentralize the fda. You could have multiple regulatory agencies. And by the way, the states that I'm talking about, like California or New York, those are at the same scale as sovereign countries, you know, like they are. I mean, you know, New York is bigger than a lot of European states in population and gdp. And those countries, at least nominally have sovereign bodies that do drug and device and so on regulation. So it's not crazy to think these states within the U.S. or groups of states like the upper Midwest would have the economic scale to approve drugs and devices.

Go ahead. Yeah. So we're getting to just about an hour now, and I want to thank you for walking through all that because it's definitely a complex situation. And you actually transitioned into one last question that I have. It's okay with you. You've spoken a little bit about red and green zones through your Twitter account. And I'm curious how you see the next maybe 12 to 18 months playing out with what you just said in the back of your mind where each state might be able to decentralize the healthcare response to this disease.

Yeah, well, if you heard the saying health as well, that is the most literal possible thing when you talk about red and green zones. So the concept is a society which has a competent state and a cooperative citizenry that'll do social distancing or, you know, that'll basically do what's necessary. That society can keep the virus out because it can keep the virus out. It doesn't have to go into lockdown because it doesn't have to go into lockdown. It has economic growth and has the money to pay to keep the virus out. So it's a positive feedback loop. The negative feedback loop is you let the virus in, you go into lockdown. All your economy crashes. Now you don't have money to buy PPE and drugs and vaccines, and you're stuck in a red loop. Right. And that's bad. And so red zone, green zone, I think from red state and blue state is our future, the future of the world, at least for a while. And everybody who's in a red zone will want to get to green because health literally is wealthy, because people in a red zone will want to flee and people who are. And they'll want to flee to green zones. So there's like a economic and a human migration. Green zones will want and are having very strong borders on that migration. For example, the quarantine periods and so on that Rhode island and Alaska, Hawaii, Florida, I believe, have all set up.

Right.

So basically I tweeted this, but it used to be in real estate. The most important thing was location, location, location. Now for a while, it might be infection, Infection, infection. Like, what's your infection rate? Are you a red zone or a green zone? And to just give a stab at what a technical definition of a green zone would be, it'd basically be a place that has had no new cases, let's say, for the last four weeks, despite comprehensive testing. You say you've given me zero tests, you have no new cases. Well, that's not very convincing. Right. But if you've done, like, you know, serious surveys and, you know, tests have been available and you're still not finding anything, well, congratulations to you. That's a real green zone. You can send the concept down to, like, an individual level where individuals would have proof of health, which is ultimately a vaccination certificate, which is already required, by the way, to get into many countries, including the US for other kinds of diseases, ultimately a vaccination certificate. But serology would do maybe like a very recent PCR test. Or, you know, more imperfectly, a CT scan or a forehead scan from that morning and so on. And so for two, you have essentially a proof of health. And I think that you could extend the red zone, green zone concept to an individual's red or green status, which they would want to know for themselves at a particular time. What everybody wants is to get to green.

Go ahead. Absolutely.

It sounds like it.

I think that's all the questions that I have. If anybody else has any in the audience, feel free to share them. But aside from that, thank you so much for taking the time to speak with us and answer those questions. I think it's a fascinating topic and I've personally learned a lot from you over the past couple of months, so very much appreciate it.

Great. And also, by the way, Nasarina is still on thing. I'm a PhD non MD, so, you know, I'm a doctor, but you know, Dr. Chinross and PhD. And I think there's plenty of smart people in regulatory agencies. I think the incentives are set up wrong and that people might be able to shine under different circumstances if we decentralize it. So thank you guys all and hopefully this was interesting.