Strict? lax? fast? slow? is not the point. FDA does not use cost benefit analysis in it's approval process. Which would not be bad except that nether do doctors or insurance companies including Medicare.
The other thing we need to unbundle, is drug *endorsement*, unbundling "effectiveness" from "safety". Somebody needs to be in the business of looking at the evidence and saying "yes, this drug actually is an effective treatment", because having all the doctors read all the articles in all the medical journals is not a realistic option. And Derek Lowe is too busy and we all want you to occasionally write about things other than pharmacology.
There's no harm in the FDA approving a drug about which the best that can be said is "mostly harmless", if that's all they are doing. That gives us a long list of mostly-harmless, mostly-useless drugs. And if you're going to have a government bureaucracy telling people what they can and can't do, "you can't inject dangerous stuff into other peoples' veins" is probably a good place to draw that line. If someone else is compiling and evaluating the data on efficacy and sorting everything into "wonder drug", "OK treatment", "might help if nothing else does", and "placebo" categories in a readily accessible way, then we get the outcome we want. But if nobody else is doing that, then doctors and patients and insurance companies are all going to look to FDA approval for that.
And that either gets us lots of prescriptions for mostly-harmless, mostly-useless, $50,000 snake oil, or it gets us prohibitions on putting fish oil in IV nutrient for infants.
I have had this exact conversation with my Congressional representative -- that as long as "this drug is safe enough to sometimes try to use" and "this drug is so effective it is a crime for health insurance not to cover it" are conflated, the health care system will both waste tons of money and needlessly delay drugs.
I'm not at all confident anyone will do anything about it. The Democratic majority in the house appears less interested in legislating and more interested in organizing protests. And the Republicans are even less interested in fixing anything with the American health care system.
I think the lawsuit happy legal environment in the US should get a lot of blame for this also. There are many useless and wasteful things that I have to do in medicine mostly because of the fear of getting sued. I believe many guidelines are developed with this as a background threat also and tend to trigger too many follow-up tests and exams.
Do you think there's something to learn from the EU? IIRC Tabarrok has been banging the drum for reciprocity in regulatory approval for years. Not that any of this matters unless and until Congress becomes capable of writing and passing legislation again.
This reads as if it is informed by conversations with CDC personnel and not with conversations with FDA personnel, or just based on a bunch of third-hand reporting. FWIW, the real issue here was Trump/Bannon's dismantling of the Global Health Security and Biodefense unit in the National Security Council, which was responsible for pandemic preparedness. In my opinion, you needed someone at that level to bang heads together as between CDC and FDA, and to get the President to make a decision. The rest of the piece is interesting, occasionally useful, but quite misinformed.
"People are really scared of this solution, because it introduces choice into this system. If you say that insurance companies are allowed to cover a certain drug, but not forced to do so, then different insurances will cover different drugs, and you’ll have the usual capitalism / free market thing."
Unfortunately, you will not. There was a SSC article (or many) covering exactly this. Most health insurance is through employers, and there is often no real choice at all (choose between Plan A or Plan B with minimal differences). Even when there is real choice, it's rarely of the meaningful I'll-take-a-no-aducanumab-plan-for-$100-less-a-month variety - instead, usually it's high-deductible vs low for the same services. And even when there's real choice, it is borderline impossible for anyone to learn enough about the differences to make an informed choice, let alone a rational one comparing risk-adjusted costs and benefits.
Theoretically, sure. But in practice, captitalism/free market choice effects is not how (private, US) health insurance works. SSC has covered this quandary perhaps better than anyone else, so it's odd that this paragraph would be included with a disclaimer or footnote or something.
The police also face incentives to be lax when they should be strict and vice-versa. A crazy guy might fight back - better stay away and not get hurt. And someone making money might have stuff worth seizing through civil asset forfeiture.
If you unbundle allowing doctors to prescribe medicines and mandating insurance coverage, then I see no reason to think a free market will suddenly emerge in the health insurance industry. Changes to FDA procedure would really demand simultaneous changes to health insurance law and tort reform for doctors and probably some other things as well. It sounds like a recipe for a gargantuan bill that will attract special interests for pork and lots of controversy and probably still have negative unintended side effects. In other words, the FDA is totally overdue for reform and I would take 10-to-1 odds it doesn't happen in the next 10 years.
Wait a minute there, Scott. Just because the FDA approves a drug, it doesn't mean private insurance companies legally have to reimburse me for the drug. I'm a Type I diabetic, and every year or so, my insurance company UHC (United Hellish Care) changes up the types of insulins they'll reimburse me for. Since they also have a large retail pharmacy under their wing, [sub]Optum[al]-Rx, I'm sure they're negotiating with the various insulin producers for the best deal. But that means that on short notice I'm given some new insulin which I have to figure out how to recalibrate my regimen around. It's a real pain in the subcutaneous ass tissue.
Or do insurance companies have to cover meds in certain categories, but they're allowed to the select or reject the meds form each category as long as they cover one of them? However, to my mind the effectiveness of meds within those categories seems to be pretty broad. Just sayin...
"The answer is: to a first approximation, insurance companies have to cover anything the FDA approves."
I don't think this true. Novo Nordisk just got approval for a drug called Wegovy (semaglutide) for weight loss. The trials were quite impressive. The drug was first approved as a Type II Diabetes treatment and is sold for that indication as Ozempic.
My daughter lost 100 lbs on Ozempic, so I asked my doctor about it. He is wiling to write a prescription for Wegovy, but Medicare has made it clear that they will not cover it under any circumstance. Their policy is not to cover any weight-loss drugs of any type, ever
I will probably go ahead anyway, even though it is ~$1500/mo.
General article: "How a lizard’s venom inspired the promising weight loss drug Wegovy: Semaglutide is the start of a new chapter in obesity treatments." | By Julia Belluz | July 5, 2021
I want to add another point: IMO, Aducanumab isn't shit, it's just that Alzheimer's is really really hard.
Personal background: We spent a couple of lectures in a molecular neuroscience class I took in the spring to review the clinical trials of aducanumab, including the latest trials (EMERGE and something else, iirc), so I dove quite deeply into them.
Aducanumab is not only excellent at doing its direct job - removing amyloid plaques - but also pretty good at reducing secondary biomarkers like amyloid PET signals and ARIAs (small hemorrhages and edemas that show up in an MRI). The problem is with the final proof of slowing cognitive decline, where most cognitive tests in the different trials failed to show statistically significant difference from placebo.
It is also worth noting that amab has an *excellent* safety profile with a wide therapeutic window and few side effects even given the age of the target population.
So what's going on? You can say that amab IS actually completely useless in slowing cognitive decline, but then you need to explain why the different biomarkers, all with well-established connections to neurodegeneration, fail to predict the (non)effect. The amyloid model is not the only one out there, but it's a central one for very good reasons.
Explaining away this connection is not impossible - you can say that by the time these biomarkers are fixed the neurodegeneration is already well underway and irreversible - but it adds a layer of improbability (and would mean that the drug may work as a prophylactic).
What is more likely in my opinion (specifically intuition from what I learned and going over the clinical data) is that Alzheimer's is pretty wide combination of different and very entangled neurodegenerative processes, with different contributions in different patients. Thus, the drug only works well on a subset of patients (maybe, like I mentioned, only those at the very onset of degeneration), but we don't know enough to predict which, so for the entire population of patients you fail to reach significance. Scott shows repeatedly how we see this in psychiatric drugs, which sometimes only barely squeeze by placebo in global trials but doctors have good experience in finding the one that works for a specific patient (and not knowing why).
This approval will mean (a) Biogen, previously on the cusp of failure, now have a lifeline to investigate which kinds of patients the drug is good for, (b) it is released into the market, which means we will soon be getting efficacy data in big numbers, combined with genetic data.
Other avenues are now also more easy to explore - maybe you need combinations with other treatments, maybe the cognitive tests we use aren't the best (it's not like we had a positive control of a perfect treatment to benchmark them against!).
Overall, the scientific advisory committee was absolutely right in saying the clinical evidence is kinda crappy. But the cost-benefit analysis is still heavily in favor of the drug, as it is very safe, molecularly effective, and with no alternatives, in a very widespread and destructive disease. The only cost being some people paying money for a drug that won't help them, and the benefits are huge both short term (for the people which it will help) and long term (for better understanding and getting closer to more global treatments).
In class we placed bets on what would happen. I said the committee will say no, and the FDA won't approve. I've rarely been so glad to be wrong.
I mostly agree with your conclusion that "if you could only LOOSEN or TIGHTEN" FDA approval, loosen is the better choice and in the case of COVID-19, 95% of the FDA's mistakes were erring on the side of stritness.
But I think the story is a lot murkier for the AIDS drugs story than you think, and there is actually very solid evidence Aduhelm /won't/ work given the 10 other anti-amyloid drugs (semagacestat, bapineuzumab, solanezumab, gantenerumab, crenezumab, verubecestat, lanabecestat, atabecestat, umibecestat, & elenbecesta) that have failed clinical trials in the past.
Since that's is a long argument, I'll write it up and post on my substack and then ping you when I'm done, if that's okay.
We stopped doing the Red Scare even though there were presumably still Communist spies in the government so I'm more optimistic than Scott that the War on Terror could be ended.
Five stars seems like a high bar to clear. While I was reading the article, it occurred to me that a two tier system would probably get most of what was necessary. Approved with warning that risk is high/Approved with high confidence. Do you think that would be good enough?
I agree with this post's overall point that the FDA is not, on average, too lax, and that the Atlantic article's take that the aducanumab approval is a sign of them being too lax is a bad take.
That said, I think the beginning of this article really undersells how uniquely bad the aducanumab approval is. It's not just "pretty unclear whether it actually treats Alzheimers." Nobody in the field thinks there's any serious possibility that it treats Alzheimers.
- The details of the "positive results" are textbook p-hacking of exactly the sort that the whole replication crisis has been about. It's a post-hoc subgroup analysis where the subgroup was selected based on similarity to the patients who had the most positive results; i.e., trivially guaranteed to show "positive" results via group selection. You can read more details in the statistical reviewer's comments in the advisory committee's document (PDF, starting on p. 174): https://www.fda.gov/media/143502/download
- Anecdotally, as someone who used to work in the Alzheimer's research space, nobody in the field seriously thinks the amyloid hypothesis is true. It's been tried, over and over again, every drug that's ever aimed at that mechanism has failed, it's busted.
It's fair to use this Atlantic article as a jumping-off point about how the FDA's approvals system is bad and lots of things get held up there for bad reasons. But I think you're really not engaging with just how bad the aducanumab approval is, and why.
Great piece. I’m mostly thankful the proposed solutions didn’t involve prediction markets or mitigating AI risk :)
I’d be very skeptical of insurance companies doing any kind of innovation. There’s obviously lots of details but even at a high level we can look at health insurance’s less regulated cousins - like P&C or auto - and it’s not like they’re pricing risk or creating products in a way anywhere near to what you’re hoping might happen. Fundamentally the insurance business thrives on aligning incentives more than it does pricing risk. There’s a lot of hype about the latter but we’re probably 5+ years from that shit becoming real and it won’t be lead by the health product lines.
A second-order problem caused by the situation is that, from what I can tell, no one *outside* the FDA has any motivation or bandwidth to think about anything other than “has the FDA approved this.” Pharma companies, doctors, hospitals, etc. aren't making independent judgments about what the evidence says, what risks to take, or how to make tradeoffs. There's no point, because they pretty much have to follow whatever the FDA says, positive or negative.
So instead of a million minds working on any given problem, we only the get the ~10k or so at the FDA.
"The problem was that people might stop trusting the FDA... If you model all FDA/CDC/etc policy as an attempt to avert this outcome, your predictions will be right more often than not."
And on that selected metric, how are they doing?
Do they even track it? Does anyone? Or 'public trust' just a placeholder, a dark matter acknowledgement that the math doesn't add up without some other motive in play... but do things add up with that motive in play?
The gold standard would be a repeated, regular check with stable methodology. There are two obvious recent polls - the Annenberg one in April and July '21, and the RWJ Foundation and Harvard TH Chan School of Health one in March '21. Headlines for them are opposite 'High trust holds steady' vs. 'trust is low'. Neither even attempt to answer how trust compares to 2019, let alone 2009.
It's hard not to wonder whether those hundreds of thousands of lives and 'limitless costs' are buying any public trust, or perhaps even eroding it. After all, the TSA has done wonders to build faith in the War on Terror.
And if the justification for being 'extraordinarily bad' at the job is public trust, and they aren't doing that either... what actually is going on?
We need a wartime FDA and CDC. “First, do no harm (and don’t get sued)” has some issues, but is understandable in “peacetime”. Maintaining that attitude in an actual pandemic is neither understandable nor forgivable.
Pretty good article. My favorite FDA story, which may be apocraphyl alas, is that supposedly you can't test combination therapies unless *all* the ingredients are already approved, which means a lot of potential synergies (which we know sometimes exist) will remain unexplored, because one of the components isn't already approved. As in, X did some good for metastatic breast cancer, and Y did a little good but not enough to exceed the standard of care and so didn't get approved -- and now you can't test X + Y to see if it outperforms everything. Boo.
By the way, I think the only legal mechanism by which insurers end up having to cover stuff the FDA approves is tort lawyers. I don't *think* it's built into any statute, although that might have changed under Obamacare, which set new standards for insurance plans. And I also thought whether Medicare covered stuff was decided by the CMS, which in principle is independent of the FDA. But realistically, in the highly litigious, highly suspicious political air in which we live, *everyone* in all those places is in full CYA mode all the time, and the result is what you observe.
I'm very dubious about your proposed reforms being implemented. They remind me of the endless proposals for voting reform proposed by libertarians and other minority parties, which can't be explained in a Tweet unless you have IQ >115 and which therefore uniformly fail (or when they pass, cf. NYC's recent election, just baffle and annoy most people).
There is a far more radical and yet simpler approach, however: get the government out of paying for healthcare directly, eliminate employer tax deductions for healthcare so it stops being a routine employer benefit (and employer choice), and get the government out of the business of setting standards for insurance plans (except insofar as they might mandate outside review of claims, quadrupole damages with executive horsewhipping for strategic or stupid denials).
The point being, if people have to decide for themselves what the cost (literally, in their own precious $$$) and benefits are, history suggests they will be surprisingly canny about that. You want to buy a smartphone, there are a million private resources that will gather all the critical info you need, and people use those things. Even the dumbest among us don't turn up at Home Depot to buy a new washer without having read the reviews. So we would expect the voters and healthcare consumers to become a lot better customers of high-quality information about the relative value of drugs. Whether that information is provided privately or by a government agency might be largely besides the point, if the key criterion -- which is that the information is consumed by, and used by, and important to, the very person who will spend the money and take the drug -- is in place.
What's the deal with challenge trials and vaccine approvals? Most of the time I see it discussed with the assumption that challenge trials are currently illegal (but they shouldn't be). But challenge trials definitely aren't categorically illegal, at least not everywhere in the world—several of them have been done for various diseases in the last few years. And even if the US doesn't allow them, there are most likely countries I'd expect to be less squeamish (such as China), but I'm unaware they did them either. More generally, no country started mass vaccination until December, even though China started vaccinating a small number of people in the summer (based on weaker evidence rather than challenge trials).
Are we sure it isn't because it took until December for vaccine manufacturers to build mass production capacity, so faster approval wouldn't have mattered anyway?
Also, why did vaccine manufacturers not produce large amounts once it was pretty sure that their vaccines would be approved, ready to use the moment they were approved? The charts of vaccine doses administered definitely suggest this wasn't the case: they started trickling in December and January, and gradually increased over the next months, rather than starting off with a large jump right after approval. This seems to suggest that production was the bottleneck—although I don't know if the lack of challenge trials delayed when the manufacturers became confident enough that they would get approved to invest in manufacturing capacity.
Strongly agree with most of this article. Work at a biopharma and it's so annoying how expensive and slow the process for bringing anything to market it. What's most shocking is always how much the doctors and even internal employees internalize the FDA mentality that you'd let 10,000 people die from approval delays vs one person go to the hospital from an unintended side effect. It's not true that insurance companies cover everything. There's some spaces like obesity where they cover next to nothing (I think semalgutide will be different) and very often they won't cover new medications when there is a cheaper older medication esp if it's generic. Lots of times people also need prior authorization for treatments and insurers can just say this isn't serious enough. I think you could see that happen here. The big issue is though that everyone 65+ qualifies for Medicare, most of those people buy Medicare part D (prescription plan) and Medicare does legally have to cover everything at any price because the pharma lobby owns half of the Democrats and every Republican. This means the government will end up paying biogen billions per year. Also since there aren't really any Alzheimer's drugs it's very hard for an insurer to refuse to cover the only treatment available. The issue here though isn't the FDA. It does do an amazing job at getting rid of amyloid and it's safe. In an ideal world we should be okay saying doctors are allowed to prescribe medications that are safe and possibly effective. It's actually quite dystopian to say we should be arresting people or banning them from their professional for giving people treatments that are definitely safe and may be effective. Maybe then we should just stop giving out research grants because not every project is successful. The problem isn't with the FDA it's with doctors and moreso insurance companies being spineless and covering everything which is really a problem with the legal system. No doctor wants to be hung out to dry for not prescribing a well publicized approved medications just because he had some skepticism and then the family goes after you for malpractice and insurance companies can't afford to be evil boogeymen for refusing to pay $50,000 a year for a drug that may not work and even if it did work have very modest benefit. Also the doctor makes money prescribing the drug and the private insurer makes money covering it because minimum MLR ratios mean the only ways to make money are to spend more on patients or cut down on staff, and spending more is really easy! You cut down wasteful hospital and prescription spending? Great job now give everyone a rebate!
The problem with making it so insurance companies can pick and choose what they cover is that health insurance largely stops functioning as *insurance*, unless the optional category only includes treatments way at the margins, in which case it probably doesn’t make much difference. As someone who isn’t a doctor, I have no ability to evaluate a list of treatments and understand what that means for my expected medical experience, because I have no knowledge of what the probability distribution is for health problems I might have in the future (especially once you get beyond high-profile things like cancer). The whole point of insurance is to trade decreased expected value for decreased variance, but unless coverage is approximately everything, I can’t properly evaluate what the variance benefit I’m getting is (but the insurance companies can and will do so to their advantage).
Personally, I think the most long term stable setup is a single provider system like the NHS in the UK, where the organization that sets the standard of care is the same as the one that pays for treatment, because they’re forced to reckon with cost and benefit in one place. This results in some idiosyncratic standards of care (eg, mammograms every 3 years starting at 50 in the UK instead of every year starting at 45 in the US), and obviously they make plenty of mistakes, but overall seems like it results in a workable system.
Maybe we just need FDA Pre (analogously to TSA Pre) to grant people who are background checked and have given informed consent access to unapproved drugs?
I find it interesting how your proposed 1-3 star rankings look a lot like phase 1-3 in the approval process. So if you compare this to what we have now, the major changes are:
a) Doctors who are expert in a specific field can approve drugs after only a phase 2 trial,
b) Drug companies can't advertise a drug until it's been in the field long enough to get 4*, and
c) Insurance companies are obligated to pay for far less stuff.
This is both wise policy, and the single least popular package of reforms I can imagine which would fit in a single tweet.
Agree with almost all of this, except (somewhat predictably) some of the COVID related stuff.
The small number of apparently honest that look at the NPIs all conclude that none of them correlate with outcomes at all. That includes contact tracing. The only human action that seems to have any effect is vaccines, and even then, only on severe outcomes, not on transmission or mild infection. You assert that Taiwan is a success case for aggressive contact tracing, but in reality they ended up having a recent outbreak anyway and it's really not clear what causes the different time series between countries. Taiwan in particular only seems to test very ill people, as evidenced by their sky-high CFR compared to other countries, and up until recently was basically not testing at all. Everyone likes to read a pet theory into the timeline of a few countries, but these always seem to break down when analyzed against the whole dataset.
The FDA's concern that uncalibrated tests can lead to false positives is at least a genuine one. PCR tests are often claimed to have no false positives, but in reality they can have extremely high FP rates. Medical "science" has fixed this by defining COVID as having received a positive test, which is why they normally claim the tests don't have false positives (gotta love circular logic). E.g. one study found that in 70% of PCR positive samples it was impossible to culture the virus, implying there was no viable virus in the sample and thus that the lucky winner of the positive test wasn't infectious.
FPs have real consequences. Not only the obvious one of confining harmless people to their homes, wrecking travel plans etc, but also by contributing to the rapid degradation of trust in institutions. When scientists claim the tests have no false positives and then make claims on the back of this idea (like calculating re-infection rates based on the assumption that two positives cannot possibly be one true and one false), it worsens people's trust in all science. Lab challenge programmes in pre-COVID times have shown PCR testing to have anywhere between 1% and 15% FP rates, and lab challenges can be done by literally anyone who submits a sample to a PCR lab using a home testing kit. There are or were lots of videos circulating on social media of people who swabbed a puddle, their dogs ass, or nothing at all and then getting back a positive result. Not surprisingly people when people then ask, "well what's the true FP rate?" they discover that governments and scientists are claiming there are none. This leads inevitably to conspiratorial thinking, or at the very least, a sudden willingness to question all medical authority. Exactly what the FDA is trying to avoid.
Does that justify the FDA's stance? No. It would be better if the FDA was privatized and became a charity or something, using kitemarks+trademark law to grant approval of treatments. They've made tons of mistakes. But the underlying problem they were trying to avoid is now biting society on the ass.
"Then they approved a CDC kit which that the CDC could send to places other than their headquarters, but this kit contained a defective component and returned “positive” every time. The defective component was easy to replace, but if you used your own copy like a cowboy then the test wouldn’t be FDA-approved anymore and you could lose your license for administering it."
It's actually worse than that. The CDC developed a three part test. The first two parts looked for two difference parts of the known Covid genome. The third part tried to detect if the virus was mutating. It was this third part that was the really broken one and always said yes. Also some of the tests had a faulty second part. But the first part, which would detect the virus just fine but wouldn't provide information about mutation worked for everybody. In theory hospitals could have just used that first part and gone about their business, that would have been just as good as the tests the South Koreans were using to control the virus. But that wouldn't have been using the kits according to the approved instructions and thus in an unapproved way.
coincidentally, I just had a conversation with coworkers in the hospital today, and when I mentioned that I donated to the most efficient charity according to GiveWell metrics. My coworkers universally denounced the fact that I was trying to do the most good with my money and accused me of paying too much attention to money, also gave me a whole spiel about how it's evil to want more people to live and/or for longer. Like they have no concept of doing good with money. Never before have I felt so alienated from those people. I used to think they were basically decent human beings, now they were just like aliens speaking nonsense. I am so sad.
But like with people like that I can see how this system gets built.
"(T)he long-term solution is to become a different kind of country and different sorts of people"
I know I'm preaching to the choir here, but we will never become that sort of country/people until the people that are start having meaningful interpersonal relationships with the people that aren't.
Brutal twitter owns (assuming that the owner/ownee relationship is not, in fact, inverted) seem to be moving the needle the other direction.
I propose that college professors be allowed to take whatever drugs they want so long as the drugs won't get them high, and the professors agree to waive medical privacy and fully report the effects of the drugs. This proposal might be politically practical because the left would mostly trust professors to make the right decisions, and the right mostly wouldn't care if professors harmed themselves by taking dangerous drugs.
I suspect if drug approval rules were relaxed to a large extent, along with all the good drugs would come a tidal wave of absolutely terrible ones that’d harm a lot of people. And that the severe regulatory regime correctly suppressed a lot of those second ones right now, so the scale of the problem is not visible, and to understand that one should probably think of medical history pre FDa, while it also wrongly suppresses a bunch of good stuff, which is then visible.
Appreciate this summary, Scott; oft thought, ne'er so we'll expressed. Also appreciate the Piers Anthony homage in the title (if I've guessed right) and the fact that you appear to have attracted at least one person formerly shortlisted for FDA head to the comments.
Weird to write a whole article about this without taking a look at how other first-world countries manage this, to see if they're doing better/worse than the US and why.
I think this analysis misses the primary point of FDA caution: Thalidomide.
AFAIK, thalidomide is why the FDA expanded out of food. The horrific birth defects arising from Thalidomide use are extraordinarily costly and the impact was small only because it was prescribed for a small subset of pregnant women.
The fear has always been that some other widely used drug will have comparable negative effects - you know, like those spanking new mRNA vaccines.
If they do prove to cause some sort of nasty long term damage, then administering said mRNA vaccines to literally hundreds of millions to billions of people would net a ginormous problem.
"But when the US declared that the coronavirus was a “public health emergency”, the FDA announced that the emergency was so grave that they were banning all coronavirus testing, so that nobody could take advantage of the emergency to peddle shoddy tests."
To be fair to the FDA when the bargain supermarket chain Lidl starting selling Covid test kits here in Ireland in May, our public health authority was telling people they were useless and not to buy them, and there was a sharp exchange of views on Twitter between duelling experts:
They give quick results. They are cheap. And they are relatively easy to use. But the arrival of rapid antigen tests on supermarket shelves last Friday has not been without controversy.
Lidl stores are selling their Covid-19 test kits at €24.99 for a box of five. NPHET has cautioned consumers not to use them, with Chief Medical Officer Dr Tony Holohan noting that he is very concerned that they will "falsely reassure people".
NPHET's Prof Philip Nolan, meanwhile, traded barbs on Twitter with Harvard epidemiologist Prof Michael Mina, saying his "snake oil" comments "further sows confusion".
Prof. Nolan on the Lidl ad for the kits: "Can I get some snake oil with that? It makes for a great salad dressing with a pinch of salt and something acerbic. Stay safe when socialising outdoors over the next few weeks. Small numbers, distance, masks. These antigen tests will not keep you safe."
Prof. Mina to Prof. Nolan: "For an advisor to your government - you don’t appear to know what you are talking about @President_MU wrt rapid tests.
The comment adds nothing of benefit and further sows confusion.
Aducanumab also has nasty side effects, including brain swelling and brain bleeds in 30% of patients. Those should be a factor to consider when weighing the cost-benefit calculations of the drug as well.
"This policy has led to our current situation, where either everyone has to be miserable because of stupid people’s choices (eg everyone has to wear masks forever because a few people won’t get vaccinated) or we get a strong anti-freedom lobby because allowing anyone any freedom means that the rest of us have to suffer for their stupid choices."
I am not so sure I follow your point here. It strikes me that "everyone has to be masked because some people won't get vaccinated" is a by product of really bad risk analysis and systemic knowledge, not so much the FDA's own doing. The FDA is guilty of that same bad analysis, but not because they scared people away from the vaccine, I mean. It seems to me that the real mistake was over promising on the vaccine in general on a few margins.
1: The vaccine was never likely to eliminate COVID. We have eliminated exactly 1 disease in the wild, smallpox; everything else still pops up from time to time. Worse, coronaviruses are notoriously hard to vax against because they mutate all the damned time. Claiming otherwise was a really bad move by the FDA/government/doctors/media/whomever got it into people's heads that we could possibly eliminate the disease like it never existed.
If you think that we could eliminate the disease, how many humans all over the Earth do you think we need to vaccinate before we wipe it out? 5 billion? 6? All 7+ billion? I would put forth that it must be a very high percentage given that COVID spreads easily and hides out in people for a bit, and given then the vaccine behavior below...
2: Overpromising effectiveness of the vaccine. Does the vaccine keep you from getting COVID, or just keep you from getting sick if you get the virus? If you get COVID after being vaccinated, does the vaccine prevent you spreading COVID? I honestly can't tell what the CDC or other public health groups think the answer is here.
If the vax keeps you from contracting the disease at all, that is, you get some virus and it gets destroyed before it infects cells or spreads, you don't need a mask at all. (Unless just breathing in some virus from person B then breathing it back out to infect some person C is possible, but then unless you were holding your breath for a while, C could just get it direct from B.)
If the vaccine keeps you from getting sick but allows you to still be a host/carrier of the virus so you can transmit to others, then the vaccine isn't going to stop anything spreading. It might slow down spreading somewhat, but so long as vaccinated people can host there will always be some vectors for transmission. At that point you are just hoping the spread drops below 1 such that eventually the disease just dwindles. Maybe masks make sense in this context if you have been vaccinated, but there is no logical stopping point to that; you are just going to wear masks forever because anyone might be a stealth host until at some point in the future there are effectively zero cases. (Which will never happen if variants pop up that get around your immunity.) Then again, in this case, if you are vaccinated you have no personal risk, so people who are unvaccinated don't exert any externalities on you. So, why wear a mask? Just let those who chose to be unvaxed pay their price. Those who can't be vaxed will need to take tons of precautions in any case, because you can still spread to them, so there is no difference there.
Or... maybe the vaccine doesn't protect 100%, doesn't stop transmission, and won't wipe out the virus, which will mutate anyway. So we are back to the human norm of having one more minor contagious disease that kills us periodically but can be treated pretty well, and more possibly even largely avoided by getting a shot, possibly yearly. In which case, wearing a mask all the time only makes sense if you are a germaphobe or otherwise around people you expect to be contagiously sick, like doctors.
Anyway, yea, I am not sure I get your argument there. The problem to me seems to stem less from people not trusting the FDA, which they shouldn't, and a lot more from people having a really bad underlying model of reality, one in which people never die unless some monster kills them, and said monsters can be eliminated if only the bad people who allow the monster to keep living could be made to stop doing that. This as opposed to the model where nature is constantly trying to kill us, and we are mostly pretty good at avoiding that, but we are not going to ever get it to stop completely. We just knock the sharp edges off the worst bits and try to sand down the rest while doing the best we can with the time we have.
For some reason, the idea of allowing FDA to grade its approval with stars seems to be dangerous. If the FDA grades a medicine 4 stars, and it causes cancer in a whole city, it can honestly just get away with saying "well we never completely approved it. We just gave it four stars". There's definitely some upside to FDA approvals being binary instead of being graded.
Of course, like Scott said, we have to do a cost benefit analysis, and we might even conclude that in the overall picture, having this graded star system is more beneficial than allowing FDA to drag its feet on things like the coronavirus vaccine. However, it will still be important to hold to FDA accountable for its ratings. Its four star drugs should not be as dangerous as one star drugs (it should have at least an 80% success rate and only a 20% incidence of serious side effects or something like that).
I do think that prediction markets will solve this problem nicely, as noted by another commenter. Worried about taking a four star FDA drug? Well Kalshi says that there's a ~0 chance that this drug is harmful, and this prediction is probably informed by decentralized expert opinion. Hence, it's probably fine.
"Patients will have to choose which insurance to get"
That's not how insurance works in the US as you know...
You also seem to totally discount the existence of bad actors knowingly attempting to get dangerous drugs they know don't work approved. That's where you argument really breaks down.
"I think the current state of the art is something like Isakov, Lo, and Monterhozedjat , which finds that there are a tiny few disease categories where the FDA might be slightly too aggressive, but that overall the FDA is still much too conservative. "
I might have missed something but I think this is a misinterpretation. They say that for severe diseases the FDA is too conservative, but for for more minor ones it's too lax. Since they only ran estimates for the 30 leading causes of premature mortality it shouldn't be surprising that, for most conditions they studied, the FDA is too conservative, because most of those are pretty severe diseases. But I'm not sure you can generalize that to say that there's only a tiny few disease categories where the FDA is too aggressive.
Are you saying that the FDA decisions during Trump years were not at all affected or decided by Trump Admin.? I understand that this cannot be the case with the Altz. drug., but the question remains.
Let's say instead of $50K, the drug is $75K. BUT the $25K is set aside in a 401K type trust fund that invests in the S&P 500 and creates shares in a company. Let's call it the Bad Luck Corp BLC.
Shares of the BLC will be split 1/2 to the patient, 1/2 to the payer (i.e. insurance company or gov't program). At a certain point in time, let's say 20 years, the funds are relesed to BLC if a patient has the disease or has died from it. If the patient does not have the disease or has died previously from something else (motorcycle accident say), then the funds go to the drug company.
BLC stock then will trade over time and go up if it appears the drug works less well and down if it appears it works better than expected. Both patients and payers will get the benefit of a rising stock if they 'overpaid' for the medicine earlier in their lives. They won't get any benefit if the drug works very well, obviously, but then if that is the case it is a win for patients and the rest of society if this drug (or some future drug) ends up being the mRNA vaccine of Alzheimers. Note that the benefit happens even if the patient themselves does not get Alzheimers. If your father takes the drug, gets a lot of BLC shares, but then dies in the motocycle accident, the BLC shares are part of the estate and can still go up should the drug turn out to be a dud.
I'd like to take this one level of abstraction higher and all government and government related agencies are slow and disfunctional at best. Using proof by induction, with the DMV as our base case and the FDA and Congress being random N and N+1. In my semi-formal analysis all government agencies are awful. But the FDA has probably killed the most natural born citizens, while the DMV just annoys and angers them.
That being said, if we can reform the FDA to stop killing people, lets not stop the reforming at just that agency. The only real way I see that change could happen is if incentives changed to where there is competitive pressure to work at these agencies, rather than our golden ticket type standard right now of going through an insane hiring processes but once you're in you're in.
I really liked this post, thanks for writing it. Have you done/would you do a post that focuses specifically on how costs are distributed in the American healthcare system? I get the sense that, aside from being monstrously high, our prices are unpredictable and make absolutely no sense for someone paying out of pocket, but I'm never sure how to describe it. Your experience as a provider would surely shed some light.
Thought 1. There needs to be some way of saying "well, ok, maybe it has bad effects in twenty years time, we don't know, but on balance please freaking take it" when the alternative is worse.
In fact, there seems to be a lack of follow up (in all countries) of "ok we did some studies and approved it, now if MILLIONS of people take it, do we detect any downsides?" I know that's hard to do. But we probably need to sooner or later.
Thought 2. Plenty of countries have an approval process for medicine, and provide healthcare in the form of insurance companies, and are nowhere near as screwed as America. I highly recommend a national health service, but maybe looking at what countries more in the middle do and doing that would be a good guide. It's surprisingly easy to forget that as an option
The problem with endorsing untested drugs is not just their lack of efficacy. It's not just the potentially crippling side effects (see e.g. thalidomide). It's also the fact that people who take treatments that they believe to be effective usually stop taking other treatments, which actually *are* effective.
Right now, there are hundreds if not thousands of people out there dying of treatable cancer, because their pastor told them that Jesus will exorcise their disease from their bodies, hallelujah. In Russia, and even in some places in the US, the same is happening with COVID: people believe that good old vodka and a few cloves of garlic will cure anything, COVID included. But those are just regular folk beliefs and established religions. If you abolish the FDA, you will grant pharmaceutical companies; dietary supplement providers; and your local street-corner kook full power to market their miracle cures with impunity.
Yes, I understand that allowing every potential drug to hit the market as soon as possible would save lives; but you must look at the whole picture in your calculus, and the whole picture also includes lives lost or ruined -- which (as is the case with thalidomide) sometimes don't become apparent for years afterwards. Yes, obviously the FDA can be made more efficient, and it should be, but abolishing it would be like setting your boat on fire because you don't like the gas mileage. While you're on the boat. In the middle of the ocean.
Thinking about Aduhelm and the question of whether it actually treats Alzheimers or just treats beta-amyloid plaques.
Is there a possibility that this applies to some drugs that reduce cholesterol? That they reduce cholesterol is likely true, but that there are no studies showing that the reduction of cholesterol via such drugs actually reduces heart disease? Can anyone point me to some good studies? Thanks.
100% Agree. The system is designed to reward risk aversion, and not just the risk to the public of a dangerous drug getting approved. It's also about their personal risk of making a mistake. No one wants to be the bureaucrat who approves the next thalidomide. So more layers of bureaucracy are added, and along with that comes the inevitable mindset that the procedure is the priority. It's hopelessly broken.
On a separate note, I laughed out loud at the picture of the guy fishing on the ice who burns all the medical bills. That was priceless.
No discussion of FDA intransigence would be complete without a look at the life of John Nestor, https://www.theatlantic.com/health/archive/2012/05/medicines-missing-measure/257901/. I’m surprised he hasn’t been mentioned yet. He spent his spare time causing massive traffic jams on DC-area highways by insisting on driving 55 in the left lane. If an author tried to create an obstinate bureaucrat character based on his life, he would be panned for being too on-the-nose.
I love the idea of unbundling permission-to-prescribe from standard-of-care. But standard-of-care is, in practice, set by the courts, right? If the FDA said, "We approve this for use, but we don't want insurance companies to feel obligated to cover it", would that make any difference?
As is so often the case when confronted with what looks like stupidity, the problem is metaphysics. Humans everywhere construct a dichotomy between the sacred or pure, and the earthly or profane. Humans naturally interpret FDA approval as being like the purification rituals performed by a priesthood. And you can't unbundle holiness. It's the most-basic ontological divide, between the temporal and the transcendent.
What I don't get is why the FDA has any power to tell doctors what they can prescribe--and especially why alleged inefficacy should justify banning a drug's use. The reason for our heavily-regulated system of educating and licensing doctors is to ensure people can trust licensed doctors. We trust them to cut us open and sew us back up, and to keep up with recent research in their field (even though many don't). These things are simple and objective compared to drug approval. The literature on any particular drug's safety is always contradictory, the studies are mostly fatally flawed, the committee doesn't have time to read the literature that took years and hundreds of millions of dollars to produce, and the ultimate decision is often based on the helpful "summary" of some industry flack.
(Also, it's rare even for drugs that fail the safety tests to be as lethal as tobacco, alcohol, or sugar.)
psychiatrists do this cost/benefit every day with patients with less risk/recourse than any politician and still make the same decisions. maybe change should start there first
BRUTAL: "Although the FDA did kill thousands of people by unnecessarily delaying COVID tests, at least it also killed thousands of people by unnecessarily delaying COVID vaccines."
July 8, 2021: Joint CDC and FDA Statement on Vaccine Boosters | HHS.gov
Americans who have been fully vaccinated do not need a booster shot at this time. FDA, CDC, and NIH are engaged in a science-based, rigorous process to consider whether or when a booster might be necessary.
August 5 2021:FDA Covid-19 Vaccine Booster Plan Could Be Ready Within Weeks…
The Food and Drug Administration expects to have a strategy on Covid-19 vaccine boosters by early September that would lay out when and which vaccinated individuals should get the follow-up shots, according to people familiar with discussions within the agency.
Seems to be a remarkable turnaround. NBC news had to contact each state to get breakthrough data since the CDC no longer reports on breakthrough deaths and infections:
I’m still stuck on facts of global and American drug development: more new (and effective) drugs get invented in the USA than anywhere else. Every proposal to radically change the way the FDA or any other part of the ecosystem represents implicitly a claim of this nature: “I see the greatest production system for drugs the world has ever seen, and I know how to do better.”
In other contexts we know that imposing strict rules and forcing people to play a somewhat arbitrary game is often a spur to creativity, because it enables direct comparison of things. In medicine, those arbitrary rules look horrifying because they are arbitrarily obstructing people’s access to healthcare. But the gamification seems to be working. Tweak the game, sure, but removing a major plank of it seems reckless.
The lack of early testing really seems like the greatest failure here, but there's also the shamefully poor quality of publicly available information. This is supposed to be the age of big data, but the federal government is such a shit show that we can't even get properly detailed demographics for deaths from covid, let alone infections or hospitalizations. There is no rational excuse for why I don’t have a more detailed risk profile than the “official” (non-standardized) overly broad age ranges and a vague list of comorbidities. This uncertainty makes me skeptical of the whole situation and I have to wonder to what degree mass hysteria is playing a role.
You are wrong about one crucial fact in your argument: neither public payers nor private insurers have to cover any given therapy. Surely you could have just checked with a drug rep friend? One of the huge headaches for pharma, patients, and physicians is that medications with better efficacy, safety or tolerability often require days of paperwork hurdles or are simply not covered.
There is no requirement that payers cover approved drugs. Period.
In fact, this fact probably results in tens of thousands of deaths. When a patient with fulminant acute leukemia cannot get immediate treatment because the paperwork takes three days, he or she often dies in the interim.
My sister has a glioblastoma. She took one anti-seizure medication which left her so tired she couldn't function. Her insurance company refused to authorize a different medication until she and her doctor stumbled on the magic formula: she had lost her appetite. Crazy.
Your argument falls apart if it is based on that faulty premise.
"By March 1, China was testing millions of people a week, South Korea had tested 65,000 people, and the USA had done a grand total of 459 coronavirus tests. The pandemic in these three countries went pretty much how you would expect based on those numbers."
When I look at China's numbers the only thing I'm pretty sure of is that there's no way they represent reality. Do you have some reason for giving them credence here? Either on the testing front, or on the course of the pandemic?
"Around 2010, Boston Children’s Hospital found some loophole that let them add fish oil to their nutrient fluid on site, and infants with short bowel syndrome at that one hospital stopped getting liver damage, and the FDA grudgingly agreed to permit it but banned them from distributing their formulation or letting it cross state lines"
So why couldn't all the other hospitals simply apply the same 'loophole'? How difficult was it to figure out the formaulation?
> So when I talk about unbundling FDA approval, I mean that instead of the FDA approving the following bundle of things…
Or you could push for universal healthcare so that what insurance will cover isn't under FDA's purview at all, so you're just left with the 1 responsibility.
A thought on the star-system - would it make more sense to split it into two sets of ratings?
One representing "confidence that the drug does the (desired) things it says on the label" (A wording chosen to step around off-label/novel uses), and one representing more or less "confidence that all the side effects are on the list of known side effects with risk factors and incidence rates reflecting reality".
I would prefer this split because the single-set system as proposed (at least as I read it) interacts weirdly with, for example, drugs with likely awful side effects that are less bad than what they treat - for example, in a sense at least, a really good five-star chemo drug is less safe than a two-star sugar pill.
That said, it's possible that by "the drug is safe" you mean "we are very confident we know the side effects and risk factors for them"...
Source for "the only reason we can get these at all is through provisional approvals that they wouldn’t have granted without so much political pressure," please?
Scott's dismal assessment of the FDA's incompetence tracks the narrative told by Michael Lewis, in Premonition. The root cause is obviously the dysfunctional incentivize structure inherent in any political bureaucracy. This follows the entire body of microeconomic theory and empirical research, which uniformly stands for the proposition that bureaucrats following their own interests will **always** get the cost-benefit ratios wrong.
Scott's idea of provisional/scaled "approval" levels seems like a great reform. Another reform that might be useful, however, would be to have an entirely independent and alternative path to go around the FDA when it is dragging its feet unnecessarily. Perhaps this consist of some association or jury of specialists in the particular field that could vote to at least allow certain especially qualified members of their specialty to provisionally prescribe the medicine based on an individualized review of the safety/efficacy data as it exists, as compared to a patient's individual risk/benefit circumstances. (For example, a patient who is about to die without the drug, or a patient who is highly unlikely to have potential side effects). This clinical experience could also be monitored and folded into the overall case for and against the drug.
A guess a question for Scott would be how to get a real reform process started in light of the entrenched incentives? But I guess that is always the big question.
As a side note, the bad reporting of the Atlantic seems typical of how the "prestige press" seems generally incompetent to analyze any issue that involves hard technical and economic issues. They usually just aggregate banal quotes, talk around the issues in verbose prose, and then conclude with how "these are complicated issues," people are "trying hard," and "doing their best," but really smart "experts" are on the case and aware of the issues, so they'll keep all this in mind and hopefully do better going forward, blah, blah, blah.
I really like your idea of a more fine-grained rating system for the FDA but I think your single dimension star-rating system in combining two important dimensions: safety and efficacy. The FDA should separately report safety and effectiveness.
Something that may or may not work but is not dangerous may still be worth taking for many people.
Something that definitely works but is also dangerous could still be worthwhile for a different subset of people.
Drug ratings for pregnant women have a similar problem with their one-dimension rating system. Drugs in class C may be safe but with unknown effectiveness, or they may be effective but dangerous. The difference is important to know.
Great article! It feels a bit like the FDA is robbing me of my life. The government is blocking one of the most important things in life, my health. Why are we allowing govt to force what my doctor and I can and cannot use as treatment? If I’m willing buy a drug from a company that’s willing to produce and sell that drug then it’s in my best interest to work with my doctor to decide what’s best for my life. The FDA would be greatly improved if it’s role was simply to protect citizens from false claims (ie: if a doctor or drug company lies to me in order to get me to use their treatment)
Book review request: Upton Sinclair's "The Jungle," would be interesting to see what the pre-FDA world looked like (from the perspective of what I can only imagine is the early 20th century equivalent of a quirky rationalist blogger), and whether there's a reason for the madness.
Scott, if you haven't seen it yet, Matt Yglesias also wrote an essay on the FDA situation (two weeks ago; not subscription-locked), and I think it complements yours quite well: https://www.slowboring.com/p/fda-cost-benefit
CNN interview of Walensky was removed by google. It is now on rumble:
CDC Director Rochelle Walensky stated the vaccine does not prevent COVID-19 infection, nor does it stop the vaccinated person from transmitting the infection or the delta variant. According to Director Walensky, the only benefit from the vaccine now is presumably that it reduces the severity of symptoms.
I just Tweeted a thread with some overlap to this post, including a rec for a good podcast interview with a former FDA person who argues in favor of the Aduhelm approval and the use of the accelerated approval mechanism of the FDA, plus my comments on why that will be good for the aging/longevity space and in particular that the chance of using an aging clock as a surrogate for approval via the accelerated (conditional) approval + phase IV trial mechanism may be fast approaching as it is likely one of these clocks will outperform Abeta in AD prediction soon. See: https://twitter.com/KarlPfleger/status/1423774160321490950
New coronavirus variants could be named after star constellations once letters of the Greek alphabet are exhausted, a senior World Health Organization official has suggested.
In an interview with the Telegraph Maria Van Kerkhove, the WHO’s technical chief for Covid-19, said the UN health agency was already looking at new names for mutations amid fears there will be more concerning variants than the 24 letters of the Greek alphabet.
Medicine is too complex for a uni-dimensional "star" system. FDA should strive for clarity, not simplicity. State what we know, without messaging spin. Others can do the messaging. Be a source of truth, without taking responsibility for all the knock-on effects. Sharpen the blade; don't dull it in the vain hope of improving system-wide outcomes. That's the only way to develop a stable reputation.
The FDA approved an ineffective drug for Alzheimer's, aducanumab. Scott Alexander has a post on it, including a broader discussion on whether the FDA is too lax or too conservative. The right answers is that it is both; Scott doesn't discuss oncology, where arguably it is too lax, enabling multi-million dollar biotech grifts to exist. Scott's framing is puzzling; why "pulling the FDA level" towards being more lax when one can propose both tactically based on cost-benefit analyses. Anyway, the solutions he discusses later are good and go beyond the FDA: the reason we ultimately care about the FDA approving useless drugs is that the US healthcare system will pay for them. That has to change: The FDA could switch to a multi-tiered level of approvals and Medicare should be decoupled from the FDA so that they don't have to cover all drugs coming out of FDA approval. Here's a critique of some of the points that Scott makes.
Liked the article all except for this blurb that makes it seem like there is absolutely no reason not to get a covid vaccine:
"this policy has led to our current situation, where either everyone has to be miserable because of stupid people’s choices (eg everyone has to wear masks forever because a few people won’t get vaccinated) or we get a strong anti-freedom lobby because allowing anyone any freedom means that the rest of us have to suffer for their stupid choices."
There is a 3rd option - which is to let the vaccinated people be protected, and the unvaccinated people live-out the consequences of their choice. In reality a cost-benefit analysis would tell you that there is almost no benefit to anyone for healthy people under 40 to get vaccinated. For older people and people with other risk factors the vaccine is by far the best thing they can do to protect themselves.
Lesné's work is the basis of all the beta-amyloid work (which this drug is based on) -
A quote - "A 6-month investigation by Science provided strong support for Schrag’s suspicions and raised questions about Lesné’s research. A leading independent image analyst ...reviewed most of Schrag’s findings at Science’s request. They concurred with his overall conclusions, which cast doubt on hundreds of images, including more than 70 in Lesné’s papers. Some look like “shockingly blatant” examples of image tampering, says Donna Wilcock, an Alzheimer’s expert at the University of Kentucky."
Strict? lax? fast? slow? is not the point. FDA does not use cost benefit analysis in it's approval process. Which would not be bad except that nether do doctors or insurance companies including Medicare.
The other thing we need to unbundle, is drug *endorsement*, unbundling "effectiveness" from "safety". Somebody needs to be in the business of looking at the evidence and saying "yes, this drug actually is an effective treatment", because having all the doctors read all the articles in all the medical journals is not a realistic option. And Derek Lowe is too busy and we all want you to occasionally write about things other than pharmacology.
There's no harm in the FDA approving a drug about which the best that can be said is "mostly harmless", if that's all they are doing. That gives us a long list of mostly-harmless, mostly-useless drugs. And if you're going to have a government bureaucracy telling people what they can and can't do, "you can't inject dangerous stuff into other peoples' veins" is probably a good place to draw that line. If someone else is compiling and evaluating the data on efficacy and sorting everything into "wonder drug", "OK treatment", "might help if nothing else does", and "placebo" categories in a readily accessible way, then we get the outcome we want. But if nobody else is doing that, then doctors and patients and insurance companies are all going to look to FDA approval for that.
And that either gets us lots of prescriptions for mostly-harmless, mostly-useless, $50,000 snake oil, or it gets us prohibitions on putting fish oil in IV nutrient for infants.
Yes, all these ideas would help. Unfortunately, any healthcare reform efforts immediately get stuck in the fetid mire of U.S. Politics.
(I've written my perspective on aducanumab here: https://denovo.substack.com/p/a-travesty-at-the-fda It's particularly infuriating when compared to the non-approval of COVID vaccines.)
I have had this exact conversation with my Congressional representative -- that as long as "this drug is safe enough to sometimes try to use" and "this drug is so effective it is a crime for health insurance not to cover it" are conflated, the health care system will both waste tons of money and needlessly delay drugs.
I'm not at all confident anyone will do anything about it. The Democratic majority in the house appears less interested in legislating and more interested in organizing protests. And the Republicans are even less interested in fixing anything with the American health care system.
I think the lawsuit happy legal environment in the US should get a lot of blame for this also. There are many useless and wasteful things that I have to do in medicine mostly because of the fear of getting sued. I believe many guidelines are developed with this as a background threat also and tend to trigger too many follow-up tests and exams.
Do you think there's something to learn from the EU? IIRC Tabarrok has been banging the drum for reciprocity in regulatory approval for years. Not that any of this matters unless and until Congress becomes capable of writing and passing legislation again.
This reads as if it is informed by conversations with CDC personnel and not with conversations with FDA personnel, or just based on a bunch of third-hand reporting. FWIW, the real issue here was Trump/Bannon's dismantling of the Global Health Security and Biodefense unit in the National Security Council, which was responsible for pandemic preparedness. In my opinion, you needed someone at that level to bang heads together as between CDC and FDA, and to get the President to make a decision. The rest of the piece is interesting, occasionally useful, but quite misinformed.
"People are really scared of this solution, because it introduces choice into this system. If you say that insurance companies are allowed to cover a certain drug, but not forced to do so, then different insurances will cover different drugs, and you’ll have the usual capitalism / free market thing."
Unfortunately, you will not. There was a SSC article (or many) covering exactly this. Most health insurance is through employers, and there is often no real choice at all (choose between Plan A or Plan B with minimal differences). Even when there is real choice, it's rarely of the meaningful I'll-take-a-no-aducanumab-plan-for-$100-less-a-month variety - instead, usually it's high-deductible vs low for the same services. And even when there's real choice, it is borderline impossible for anyone to learn enough about the differences to make an informed choice, let alone a rational one comparing risk-adjusted costs and benefits.
Theoretically, sure. But in practice, captitalism/free market choice effects is not how (private, US) health insurance works. SSC has covered this quandary perhaps better than anyone else, so it's odd that this paragraph would be included with a disclaimer or footnote or something.
"Consider the police..."
The police also face incentives to be lax when they should be strict and vice-versa. A crazy guy might fight back - better stay away and not get hurt. And someone making money might have stuff worth seizing through civil asset forfeiture.
You cannot overstate the degree to which the culture of the FDA was shaped by the Frances Kelsey/thalidomide experience.
If you unbundle allowing doctors to prescribe medicines and mandating insurance coverage, then I see no reason to think a free market will suddenly emerge in the health insurance industry. Changes to FDA procedure would really demand simultaneous changes to health insurance law and tort reform for doctors and probably some other things as well. It sounds like a recipe for a gargantuan bill that will attract special interests for pork and lots of controversy and probably still have negative unintended side effects. In other words, the FDA is totally overdue for reform and I would take 10-to-1 odds it doesn't happen in the next 10 years.
Wait a minute there, Scott. Just because the FDA approves a drug, it doesn't mean private insurance companies legally have to reimburse me for the drug. I'm a Type I diabetic, and every year or so, my insurance company UHC (United Hellish Care) changes up the types of insulins they'll reimburse me for. Since they also have a large retail pharmacy under their wing, [sub]Optum[al]-Rx, I'm sure they're negotiating with the various insulin producers for the best deal. But that means that on short notice I'm given some new insulin which I have to figure out how to recalibrate my regimen around. It's a real pain in the subcutaneous ass tissue.
Or do insurance companies have to cover meds in certain categories, but they're allowed to the select or reject the meds form each category as long as they cover one of them? However, to my mind the effectiveness of meds within those categories seems to be pretty broad. Just sayin...
"The answer is: to a first approximation, insurance companies have to cover anything the FDA approves."
I don't think this true. Novo Nordisk just got approval for a drug called Wegovy (semaglutide) for weight loss. The trials were quite impressive. The drug was first approved as a Type II Diabetes treatment and is sold for that indication as Ozempic.
My daughter lost 100 lbs on Ozempic, so I asked my doctor about it. He is wiling to write a prescription for Wegovy, but Medicare has made it clear that they will not cover it under any circumstance. Their policy is not to cover any weight-loss drugs of any type, ever
I will probably go ahead anyway, even though it is ~$1500/mo.
Wegovy website: https://www.wegovy.com/
FDA news Release: https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014
NEJM report on Trial: DOI: 10.1056/NEJMoa2032183
General article: "How a lizard’s venom inspired the promising weight loss drug Wegovy: Semaglutide is the start of a new chapter in obesity treatments." | By Julia Belluz | July 5, 2021
https://www.vox.com/22553793/gila-monster-lizard-venom-inspired-obesity-drug-semaglutide
I want to add another point: IMO, Aducanumab isn't shit, it's just that Alzheimer's is really really hard.
Personal background: We spent a couple of lectures in a molecular neuroscience class I took in the spring to review the clinical trials of aducanumab, including the latest trials (EMERGE and something else, iirc), so I dove quite deeply into them.
Aducanumab is not only excellent at doing its direct job - removing amyloid plaques - but also pretty good at reducing secondary biomarkers like amyloid PET signals and ARIAs (small hemorrhages and edemas that show up in an MRI). The problem is with the final proof of slowing cognitive decline, where most cognitive tests in the different trials failed to show statistically significant difference from placebo.
It is also worth noting that amab has an *excellent* safety profile with a wide therapeutic window and few side effects even given the age of the target population.
So what's going on? You can say that amab IS actually completely useless in slowing cognitive decline, but then you need to explain why the different biomarkers, all with well-established connections to neurodegeneration, fail to predict the (non)effect. The amyloid model is not the only one out there, but it's a central one for very good reasons.
Explaining away this connection is not impossible - you can say that by the time these biomarkers are fixed the neurodegeneration is already well underway and irreversible - but it adds a layer of improbability (and would mean that the drug may work as a prophylactic).
What is more likely in my opinion (specifically intuition from what I learned and going over the clinical data) is that Alzheimer's is pretty wide combination of different and very entangled neurodegenerative processes, with different contributions in different patients. Thus, the drug only works well on a subset of patients (maybe, like I mentioned, only those at the very onset of degeneration), but we don't know enough to predict which, so for the entire population of patients you fail to reach significance. Scott shows repeatedly how we see this in psychiatric drugs, which sometimes only barely squeeze by placebo in global trials but doctors have good experience in finding the one that works for a specific patient (and not knowing why).
This approval will mean (a) Biogen, previously on the cusp of failure, now have a lifeline to investigate which kinds of patients the drug is good for, (b) it is released into the market, which means we will soon be getting efficacy data in big numbers, combined with genetic data.
Other avenues are now also more easy to explore - maybe you need combinations with other treatments, maybe the cognitive tests we use aren't the best (it's not like we had a positive control of a perfect treatment to benchmark them against!).
Overall, the scientific advisory committee was absolutely right in saying the clinical evidence is kinda crappy. But the cost-benefit analysis is still heavily in favor of the drug, as it is very safe, molecularly effective, and with no alternatives, in a very widespread and destructive disease. The only cost being some people paying money for a drug that won't help them, and the benefits are huge both short term (for the people which it will help) and long term (for better understanding and getting closer to more global treatments).
In class we placed bets on what would happen. I said the committee will say no, and the FDA won't approve. I've rarely been so glad to be wrong.
I mostly agree with your conclusion that "if you could only LOOSEN or TIGHTEN" FDA approval, loosen is the better choice and in the case of COVID-19, 95% of the FDA's mistakes were erring on the side of stritness.
But I think the story is a lot murkier for the AIDS drugs story than you think, and there is actually very solid evidence Aduhelm /won't/ work given the 10 other anti-amyloid drugs (semagacestat, bapineuzumab, solanezumab, gantenerumab, crenezumab, verubecestat, lanabecestat, atabecestat, umibecestat, & elenbecesta) that have failed clinical trials in the past.
Since that's is a long argument, I'll write it up and post on my substack and then ping you when I'm done, if that's okay.
We stopped doing the Red Scare even though there were presumably still Communist spies in the government so I'm more optimistic than Scott that the War on Terror could be ended.
Five stars seems like a high bar to clear. While I was reading the article, it occurred to me that a two tier system would probably get most of what was necessary. Approved with warning that risk is high/Approved with high confidence. Do you think that would be good enough?
I agree with this post's overall point that the FDA is not, on average, too lax, and that the Atlantic article's take that the aducanumab approval is a sign of them being too lax is a bad take.
That said, I think the beginning of this article really undersells how uniquely bad the aducanumab approval is. It's not just "pretty unclear whether it actually treats Alzheimers." Nobody in the field thinks there's any serious possibility that it treats Alzheimers.
- Here's Derek Lowe talking about it: https://blogs.sciencemag.org/pipeline/archives/2021/06/08/the-aducanumab-approval
- The FDA's advisory committee doesn't think it treats Alzheimers: https://alzheimersnewstoday.com/2020/11/11/fda-committee-votes-aducanumab-trial-data-fail-support-alzhimers-treatment-benefit/
- The trial was halted for futility: https://www.reuters.com/article/us-biogen-alzheimers/biogen-eisai-scrap-alzheimer-drug-trials-idUSKCN1R213G
- The details of the "positive results" are textbook p-hacking of exactly the sort that the whole replication crisis has been about. It's a post-hoc subgroup analysis where the subgroup was selected based on similarity to the patients who had the most positive results; i.e., trivially guaranteed to show "positive" results via group selection. You can read more details in the statistical reviewer's comments in the advisory committee's document (PDF, starting on p. 174): https://www.fda.gov/media/143502/download
- Anecdotally, as someone who used to work in the Alzheimer's research space, nobody in the field seriously thinks the amyloid hypothesis is true. It's been tried, over and over again, every drug that's ever aimed at that mechanism has failed, it's busted.
It's fair to use this Atlantic article as a jumping-off point about how the FDA's approvals system is bad and lots of things get held up there for bad reasons. But I think you're really not engaging with just how bad the aducanumab approval is, and why.
Great piece. I’m mostly thankful the proposed solutions didn’t involve prediction markets or mitigating AI risk :)
I’d be very skeptical of insurance companies doing any kind of innovation. There’s obviously lots of details but even at a high level we can look at health insurance’s less regulated cousins - like P&C or auto - and it’s not like they’re pricing risk or creating products in a way anywhere near to what you’re hoping might happen. Fundamentally the insurance business thrives on aligning incentives more than it does pricing risk. There’s a lot of hype about the latter but we’re probably 5+ years from that shit becoming real and it won’t be lead by the health product lines.
Strong agree.
A second-order problem caused by the situation is that, from what I can tell, no one *outside* the FDA has any motivation or bandwidth to think about anything other than “has the FDA approved this.” Pharma companies, doctors, hospitals, etc. aren't making independent judgments about what the evidence says, what risks to take, or how to make tradeoffs. There's no point, because they pretty much have to follow whatever the FDA says, positive or negative.
So instead of a million minds working on any given problem, we only the get the ~10k or so at the FDA.
"The problem was that people might stop trusting the FDA... If you model all FDA/CDC/etc policy as an attempt to avert this outcome, your predictions will be right more often than not."
And on that selected metric, how are they doing?
Do they even track it? Does anyone? Or 'public trust' just a placeholder, a dark matter acknowledgement that the math doesn't add up without some other motive in play... but do things add up with that motive in play?
The gold standard would be a repeated, regular check with stable methodology. There are two obvious recent polls - the Annenberg one in April and July '21, and the RWJ Foundation and Harvard TH Chan School of Health one in March '21. Headlines for them are opposite 'High trust holds steady' vs. 'trust is low'. Neither even attempt to answer how trust compares to 2019, let alone 2009.
It's hard not to wonder whether those hundreds of thousands of lives and 'limitless costs' are buying any public trust, or perhaps even eroding it. After all, the TSA has done wonders to build faith in the War on Terror.
And if the justification for being 'extraordinarily bad' at the job is public trust, and they aren't doing that either... what actually is going on?
We need a wartime FDA and CDC. “First, do no harm (and don’t get sued)” has some issues, but is understandable in “peacetime”. Maintaining that attitude in an actual pandemic is neither understandable nor forgivable.
Man, reading this so close to bed was a bad idea.
Pretty good article. My favorite FDA story, which may be apocraphyl alas, is that supposedly you can't test combination therapies unless *all* the ingredients are already approved, which means a lot of potential synergies (which we know sometimes exist) will remain unexplored, because one of the components isn't already approved. As in, X did some good for metastatic breast cancer, and Y did a little good but not enough to exceed the standard of care and so didn't get approved -- and now you can't test X + Y to see if it outperforms everything. Boo.
By the way, I think the only legal mechanism by which insurers end up having to cover stuff the FDA approves is tort lawyers. I don't *think* it's built into any statute, although that might have changed under Obamacare, which set new standards for insurance plans. And I also thought whether Medicare covered stuff was decided by the CMS, which in principle is independent of the FDA. But realistically, in the highly litigious, highly suspicious political air in which we live, *everyone* in all those places is in full CYA mode all the time, and the result is what you observe.
I'm very dubious about your proposed reforms being implemented. They remind me of the endless proposals for voting reform proposed by libertarians and other minority parties, which can't be explained in a Tweet unless you have IQ >115 and which therefore uniformly fail (or when they pass, cf. NYC's recent election, just baffle and annoy most people).
There is a far more radical and yet simpler approach, however: get the government out of paying for healthcare directly, eliminate employer tax deductions for healthcare so it stops being a routine employer benefit (and employer choice), and get the government out of the business of setting standards for insurance plans (except insofar as they might mandate outside review of claims, quadrupole damages with executive horsewhipping for strategic or stupid denials).
The point being, if people have to decide for themselves what the cost (literally, in their own precious $$$) and benefits are, history suggests they will be surprisingly canny about that. You want to buy a smartphone, there are a million private resources that will gather all the critical info you need, and people use those things. Even the dumbest among us don't turn up at Home Depot to buy a new washer without having read the reviews. So we would expect the voters and healthcare consumers to become a lot better customers of high-quality information about the relative value of drugs. Whether that information is provided privately or by a government agency might be largely besides the point, if the key criterion -- which is that the information is consumed by, and used by, and important to, the very person who will spend the money and take the drug -- is in place.
What's the deal with challenge trials and vaccine approvals? Most of the time I see it discussed with the assumption that challenge trials are currently illegal (but they shouldn't be). But challenge trials definitely aren't categorically illegal, at least not everywhere in the world—several of them have been done for various diseases in the last few years. And even if the US doesn't allow them, there are most likely countries I'd expect to be less squeamish (such as China), but I'm unaware they did them either. More generally, no country started mass vaccination until December, even though China started vaccinating a small number of people in the summer (based on weaker evidence rather than challenge trials).
Are we sure it isn't because it took until December for vaccine manufacturers to build mass production capacity, so faster approval wouldn't have mattered anyway?
Also, why did vaccine manufacturers not produce large amounts once it was pretty sure that their vaccines would be approved, ready to use the moment they were approved? The charts of vaccine doses administered definitely suggest this wasn't the case: they started trickling in December and January, and gradually increased over the next months, rather than starting off with a large jump right after approval. This seems to suggest that production was the bottleneck—although I don't know if the lack of challenge trials delayed when the manufacturers became confident enough that they would get approved to invest in manufacturing capacity.
https://ourworldindata.org/explorers/coronavirus-data-explorer?time=2020-03-01..latest&Metric=Vaccine+doses&Interval=7-day+rolling+average&Relative+to+Population=true&country=USA~OWID_WRL~CHN
Strongly agree with most of this article. Work at a biopharma and it's so annoying how expensive and slow the process for bringing anything to market it. What's most shocking is always how much the doctors and even internal employees internalize the FDA mentality that you'd let 10,000 people die from approval delays vs one person go to the hospital from an unintended side effect. It's not true that insurance companies cover everything. There's some spaces like obesity where they cover next to nothing (I think semalgutide will be different) and very often they won't cover new medications when there is a cheaper older medication esp if it's generic. Lots of times people also need prior authorization for treatments and insurers can just say this isn't serious enough. I think you could see that happen here. The big issue is though that everyone 65+ qualifies for Medicare, most of those people buy Medicare part D (prescription plan) and Medicare does legally have to cover everything at any price because the pharma lobby owns half of the Democrats and every Republican. This means the government will end up paying biogen billions per year. Also since there aren't really any Alzheimer's drugs it's very hard for an insurer to refuse to cover the only treatment available. The issue here though isn't the FDA. It does do an amazing job at getting rid of amyloid and it's safe. In an ideal world we should be okay saying doctors are allowed to prescribe medications that are safe and possibly effective. It's actually quite dystopian to say we should be arresting people or banning them from their professional for giving people treatments that are definitely safe and may be effective. Maybe then we should just stop giving out research grants because not every project is successful. The problem isn't with the FDA it's with doctors and moreso insurance companies being spineless and covering everything which is really a problem with the legal system. No doctor wants to be hung out to dry for not prescribing a well publicized approved medications just because he had some skepticism and then the family goes after you for malpractice and insurance companies can't afford to be evil boogeymen for refusing to pay $50,000 a year for a drug that may not work and even if it did work have very modest benefit. Also the doctor makes money prescribing the drug and the private insurer makes money covering it because minimum MLR ratios mean the only ways to make money are to spend more on patients or cut down on staff, and spending more is really easy! You cut down wasteful hospital and prescription spending? Great job now give everyone a rebate!
"anti-freedom lobby" is rich with meaning, and accurately describes at least a couple of my positions. I like it a lot.
The problem with making it so insurance companies can pick and choose what they cover is that health insurance largely stops functioning as *insurance*, unless the optional category only includes treatments way at the margins, in which case it probably doesn’t make much difference. As someone who isn’t a doctor, I have no ability to evaluate a list of treatments and understand what that means for my expected medical experience, because I have no knowledge of what the probability distribution is for health problems I might have in the future (especially once you get beyond high-profile things like cancer). The whole point of insurance is to trade decreased expected value for decreased variance, but unless coverage is approximately everything, I can’t properly evaluate what the variance benefit I’m getting is (but the insurance companies can and will do so to their advantage).
Personally, I think the most long term stable setup is a single provider system like the NHS in the UK, where the organization that sets the standard of care is the same as the one that pays for treatment, because they’re forced to reckon with cost and benefit in one place. This results in some idiosyncratic standards of care (eg, mammograms every 3 years starting at 50 in the UK instead of every year starting at 45 in the US), and obviously they make plenty of mistakes, but overall seems like it results in a workable system.
Maybe we just need FDA Pre (analogously to TSA Pre) to grant people who are background checked and have given informed consent access to unapproved drugs?
Science-Based Medicine _tore_ into aducanumab.
https://sciencebasedmedicine.org/fdas-decision-to-approve-aduhelm-aducanumab-for-alzheimers/
I find it interesting how your proposed 1-3 star rankings look a lot like phase 1-3 in the approval process. So if you compare this to what we have now, the major changes are:
a) Doctors who are expert in a specific field can approve drugs after only a phase 2 trial,
b) Drug companies can't advertise a drug until it's been in the field long enough to get 4*, and
c) Insurance companies are obligated to pay for far less stuff.
This is both wise policy, and the single least popular package of reforms I can imagine which would fit in a single tweet.
Agree with almost all of this, except (somewhat predictably) some of the COVID related stuff.
The small number of apparently honest that look at the NPIs all conclude that none of them correlate with outcomes at all. That includes contact tracing. The only human action that seems to have any effect is vaccines, and even then, only on severe outcomes, not on transmission or mild infection. You assert that Taiwan is a success case for aggressive contact tracing, but in reality they ended up having a recent outbreak anyway and it's really not clear what causes the different time series between countries. Taiwan in particular only seems to test very ill people, as evidenced by their sky-high CFR compared to other countries, and up until recently was basically not testing at all. Everyone likes to read a pet theory into the timeline of a few countries, but these always seem to break down when analyzed against the whole dataset.
The FDA's concern that uncalibrated tests can lead to false positives is at least a genuine one. PCR tests are often claimed to have no false positives, but in reality they can have extremely high FP rates. Medical "science" has fixed this by defining COVID as having received a positive test, which is why they normally claim the tests don't have false positives (gotta love circular logic). E.g. one study found that in 70% of PCR positive samples it was impossible to culture the virus, implying there was no viable virus in the sample and thus that the lucky winner of the positive test wasn't infectious.
FPs have real consequences. Not only the obvious one of confining harmless people to their homes, wrecking travel plans etc, but also by contributing to the rapid degradation of trust in institutions. When scientists claim the tests have no false positives and then make claims on the back of this idea (like calculating re-infection rates based on the assumption that two positives cannot possibly be one true and one false), it worsens people's trust in all science. Lab challenge programmes in pre-COVID times have shown PCR testing to have anywhere between 1% and 15% FP rates, and lab challenges can be done by literally anyone who submits a sample to a PCR lab using a home testing kit. There are or were lots of videos circulating on social media of people who swabbed a puddle, their dogs ass, or nothing at all and then getting back a positive result. Not surprisingly people when people then ask, "well what's the true FP rate?" they discover that governments and scientists are claiming there are none. This leads inevitably to conspiratorial thinking, or at the very least, a sudden willingness to question all medical authority. Exactly what the FDA is trying to avoid.
Does that justify the FDA's stance? No. It would be better if the FDA was privatized and became a charity or something, using kitemarks+trademark law to grant approval of treatments. They've made tons of mistakes. But the underlying problem they were trying to avoid is now biting society on the ass.
"Then they approved a CDC kit which that the CDC could send to places other than their headquarters, but this kit contained a defective component and returned “positive” every time. The defective component was easy to replace, but if you used your own copy like a cowboy then the test wouldn’t be FDA-approved anymore and you could lose your license for administering it."
It's actually worse than that. The CDC developed a three part test. The first two parts looked for two difference parts of the known Covid genome. The third part tried to detect if the virus was mutating. It was this third part that was the really broken one and always said yes. Also some of the tests had a faulty second part. But the first part, which would detect the virus just fine but wouldn't provide information about mutation worked for everybody. In theory hospitals could have just used that first part and gone about their business, that would have been just as good as the tests the South Koreans were using to control the virus. But that wouldn't have been using the kits according to the approved instructions and thus in an unapproved way.
coincidentally, I just had a conversation with coworkers in the hospital today, and when I mentioned that I donated to the most efficient charity according to GiveWell metrics. My coworkers universally denounced the fact that I was trying to do the most good with my money and accused me of paying too much attention to money, also gave me a whole spiel about how it's evil to want more people to live and/or for longer. Like they have no concept of doing good with money. Never before have I felt so alienated from those people. I used to think they were basically decent human beings, now they were just like aliens speaking nonsense. I am so sad.
But like with people like that I can see how this system gets built.
Shame...normally I really like the Atlantic. I hope all their other reporting isn't like this and I just didn't notice it.
"(T)he long-term solution is to become a different kind of country and different sorts of people"
I know I'm preaching to the choir here, but we will never become that sort of country/people until the people that are start having meaningful interpersonal relationships with the people that aren't.
Brutal twitter owns (assuming that the owner/ownee relationship is not, in fact, inverted) seem to be moving the needle the other direction.
I propose that college professors be allowed to take whatever drugs they want so long as the drugs won't get them high, and the professors agree to waive medical privacy and fully report the effects of the drugs. This proposal might be politically practical because the left would mostly trust professors to make the right decisions, and the right mostly wouldn't care if professors harmed themselves by taking dangerous drugs.
I suspect if drug approval rules were relaxed to a large extent, along with all the good drugs would come a tidal wave of absolutely terrible ones that’d harm a lot of people. And that the severe regulatory regime correctly suppressed a lot of those second ones right now, so the scale of the problem is not visible, and to understand that one should probably think of medical history pre FDa, while it also wrongly suppresses a bunch of good stuff, which is then visible.
Appreciate this summary, Scott; oft thought, ne'er so we'll expressed. Also appreciate the Piers Anthony homage in the title (if I've guessed right) and the fact that you appear to have attracted at least one person formerly shortlisted for FDA head to the comments.
This is by far my favorite ACX article until now
I wish you would do an article regarding the deaths associated with the vaccine itself.
The UK reports 466 deaths from the Pfizer vaccine alone ( see total on last page ):
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1007272/Pfizer_DAP.pdf
Close to 12,000 deaths from the vaccines in the United States
https://www.medalerts.org/vaersdb/findfield.php
CDC reports 6,340 deaths from the vaccine
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html
A US patent was just awarded to a Finish for a nasal spray drug that includes Hydroxychloroquine & Ivermectin. Any thoughts?
https://welovetrump.com/2021/08/03/finnish-firm-scores-us-patent-for-nasal-spray-drug-that-includes-hydroxychloroquine-ivermectin/
Weird to write a whole article about this without taking a look at how other first-world countries manage this, to see if they're doing better/worse than the US and why.
I think this analysis misses the primary point of FDA caution: Thalidomide.
AFAIK, thalidomide is why the FDA expanded out of food. The horrific birth defects arising from Thalidomide use are extraordinarily costly and the impact was small only because it was prescribed for a small subset of pregnant women.
The fear has always been that some other widely used drug will have comparable negative effects - you know, like those spanking new mRNA vaccines.
If they do prove to cause some sort of nasty long term damage, then administering said mRNA vaccines to literally hundreds of millions to billions of people would net a ginormous problem.
"But when the US declared that the coronavirus was a “public health emergency”, the FDA announced that the emergency was so grave that they were banning all coronavirus testing, so that nobody could take advantage of the emergency to peddle shoddy tests."
To be fair to the FDA when the bargain supermarket chain Lidl starting selling Covid test kits here in Ireland in May, our public health authority was telling people they were useless and not to buy them, and there was a sharp exchange of views on Twitter between duelling experts:
https://www.rte.ie/news/primetime/2021/0511/1221060-antigen-testing-controversy-general-public/
They give quick results. They are cheap. And they are relatively easy to use. But the arrival of rapid antigen tests on supermarket shelves last Friday has not been without controversy.
Lidl stores are selling their Covid-19 test kits at €24.99 for a box of five. NPHET has cautioned consumers not to use them, with Chief Medical Officer Dr Tony Holohan noting that he is very concerned that they will "falsely reassure people".
NPHET's Prof Philip Nolan, meanwhile, traded barbs on Twitter with Harvard epidemiologist Prof Michael Mina, saying his "snake oil" comments "further sows confusion".
Prof. Nolan on the Lidl ad for the kits: "Can I get some snake oil with that? It makes for a great salad dressing with a pinch of salt and something acerbic. Stay safe when socialising outdoors over the next few weeks. Small numbers, distance, masks. These antigen tests will not keep you safe."
Prof. Mina to Prof. Nolan: "For an advisor to your government - you don’t appear to know what you are talking about @President_MU wrt rapid tests.
The comment adds nothing of benefit and further sows confusion.
You should be ashamed of your demeanor here."
Aducanumab also has nasty side effects, including brain swelling and brain bleeds in 30% of patients. Those should be a factor to consider when weighing the cost-benefit calculations of the drug as well.
"This policy has led to our current situation, where either everyone has to be miserable because of stupid people’s choices (eg everyone has to wear masks forever because a few people won’t get vaccinated) or we get a strong anti-freedom lobby because allowing anyone any freedom means that the rest of us have to suffer for their stupid choices."
I am not so sure I follow your point here. It strikes me that "everyone has to be masked because some people won't get vaccinated" is a by product of really bad risk analysis and systemic knowledge, not so much the FDA's own doing. The FDA is guilty of that same bad analysis, but not because they scared people away from the vaccine, I mean. It seems to me that the real mistake was over promising on the vaccine in general on a few margins.
1: The vaccine was never likely to eliminate COVID. We have eliminated exactly 1 disease in the wild, smallpox; everything else still pops up from time to time. Worse, coronaviruses are notoriously hard to vax against because they mutate all the damned time. Claiming otherwise was a really bad move by the FDA/government/doctors/media/whomever got it into people's heads that we could possibly eliminate the disease like it never existed.
If you think that we could eliminate the disease, how many humans all over the Earth do you think we need to vaccinate before we wipe it out? 5 billion? 6? All 7+ billion? I would put forth that it must be a very high percentage given that COVID spreads easily and hides out in people for a bit, and given then the vaccine behavior below...
2: Overpromising effectiveness of the vaccine. Does the vaccine keep you from getting COVID, or just keep you from getting sick if you get the virus? If you get COVID after being vaccinated, does the vaccine prevent you spreading COVID? I honestly can't tell what the CDC or other public health groups think the answer is here.
If the vax keeps you from contracting the disease at all, that is, you get some virus and it gets destroyed before it infects cells or spreads, you don't need a mask at all. (Unless just breathing in some virus from person B then breathing it back out to infect some person C is possible, but then unless you were holding your breath for a while, C could just get it direct from B.)
If the vaccine keeps you from getting sick but allows you to still be a host/carrier of the virus so you can transmit to others, then the vaccine isn't going to stop anything spreading. It might slow down spreading somewhat, but so long as vaccinated people can host there will always be some vectors for transmission. At that point you are just hoping the spread drops below 1 such that eventually the disease just dwindles. Maybe masks make sense in this context if you have been vaccinated, but there is no logical stopping point to that; you are just going to wear masks forever because anyone might be a stealth host until at some point in the future there are effectively zero cases. (Which will never happen if variants pop up that get around your immunity.) Then again, in this case, if you are vaccinated you have no personal risk, so people who are unvaccinated don't exert any externalities on you. So, why wear a mask? Just let those who chose to be unvaxed pay their price. Those who can't be vaxed will need to take tons of precautions in any case, because you can still spread to them, so there is no difference there.
Or... maybe the vaccine doesn't protect 100%, doesn't stop transmission, and won't wipe out the virus, which will mutate anyway. So we are back to the human norm of having one more minor contagious disease that kills us periodically but can be treated pretty well, and more possibly even largely avoided by getting a shot, possibly yearly. In which case, wearing a mask all the time only makes sense if you are a germaphobe or otherwise around people you expect to be contagiously sick, like doctors.
Anyway, yea, I am not sure I get your argument there. The problem to me seems to stem less from people not trusting the FDA, which they shouldn't, and a lot more from people having a really bad underlying model of reality, one in which people never die unless some monster kills them, and said monsters can be eliminated if only the bad people who allow the monster to keep living could be made to stop doing that. This as opposed to the model where nature is constantly trying to kill us, and we are mostly pretty good at avoiding that, but we are not going to ever get it to stop completely. We just knock the sharp edges off the worst bits and try to sand down the rest while doing the best we can with the time we have.
For some reason, the idea of allowing FDA to grade its approval with stars seems to be dangerous. If the FDA grades a medicine 4 stars, and it causes cancer in a whole city, it can honestly just get away with saying "well we never completely approved it. We just gave it four stars". There's definitely some upside to FDA approvals being binary instead of being graded.
Of course, like Scott said, we have to do a cost benefit analysis, and we might even conclude that in the overall picture, having this graded star system is more beneficial than allowing FDA to drag its feet on things like the coronavirus vaccine. However, it will still be important to hold to FDA accountable for its ratings. Its four star drugs should not be as dangerous as one star drugs (it should have at least an 80% success rate and only a 20% incidence of serious side effects or something like that).
I do think that prediction markets will solve this problem nicely, as noted by another commenter. Worried about taking a four star FDA drug? Well Kalshi says that there's a ~0 chance that this drug is harmful, and this prediction is probably informed by decentralized expert opinion. Hence, it's probably fine.
"Patients will have to choose which insurance to get"
That's not how insurance works in the US as you know...
You also seem to totally discount the existence of bad actors knowingly attempting to get dangerous drugs they know don't work approved. That's where you argument really breaks down.
"I think the current state of the art is something like Isakov, Lo, and Monterhozedjat , which finds that there are a tiny few disease categories where the FDA might be slightly too aggressive, but that overall the FDA is still much too conservative. "
I might have missed something but I think this is a misinterpretation. They say that for severe diseases the FDA is too conservative, but for for more minor ones it's too lax. Since they only ran estimates for the 30 leading causes of premature mortality it shouldn't be surprising that, for most conditions they studied, the FDA is too conservative, because most of those are pretty severe diseases. But I'm not sure you can generalize that to say that there's only a tiny few disease categories where the FDA is too aggressive.
Could something similar to the UL model work for drug approvals?
Are you saying that the FDA decisions during Trump years were not at all affected or decided by Trump Admin.? I understand that this cannot be the case with the Altz. drug., but the question remains.
So modest proposal.
Let's say instead of $50K, the drug is $75K. BUT the $25K is set aside in a 401K type trust fund that invests in the S&P 500 and creates shares in a company. Let's call it the Bad Luck Corp BLC.
Shares of the BLC will be split 1/2 to the patient, 1/2 to the payer (i.e. insurance company or gov't program). At a certain point in time, let's say 20 years, the funds are relesed to BLC if a patient has the disease or has died from it. If the patient does not have the disease or has died previously from something else (motorcycle accident say), then the funds go to the drug company.
BLC stock then will trade over time and go up if it appears the drug works less well and down if it appears it works better than expected. Both patients and payers will get the benefit of a rising stock if they 'overpaid' for the medicine earlier in their lives. They won't get any benefit if the drug works very well, obviously, but then if that is the case it is a win for patients and the rest of society if this drug (or some future drug) ends up being the mRNA vaccine of Alzheimers. Note that the benefit happens even if the patient themselves does not get Alzheimers. If your father takes the drug, gets a lot of BLC shares, but then dies in the motocycle accident, the BLC shares are part of the estate and can still go up should the drug turn out to be a dud.
Thoughts?
I'd like to take this one level of abstraction higher and all government and government related agencies are slow and disfunctional at best. Using proof by induction, with the DMV as our base case and the FDA and Congress being random N and N+1. In my semi-formal analysis all government agencies are awful. But the FDA has probably killed the most natural born citizens, while the DMV just annoys and angers them.
That being said, if we can reform the FDA to stop killing people, lets not stop the reforming at just that agency. The only real way I see that change could happen is if incentives changed to where there is competitive pressure to work at these agencies, rather than our golden ticket type standard right now of going through an insane hiring processes but once you're in you're in.
I'm not holding my breath.
This Cochrane review says that fish oil doesn't make a difference in IV infant formula: https://www.cochrane.org/CD013163/NEONATAL_systematic-review-lipid-emulsions-intravenous-nutrition-preterm-infants
Federal Dementor Association?
I really liked this post, thanks for writing it. Have you done/would you do a post that focuses specifically on how costs are distributed in the American healthcare system? I get the sense that, aside from being monstrously high, our prices are unpredictable and make absolutely no sense for someone paying out of pocket, but I'm never sure how to describe it. Your experience as a provider would surely shed some light.
If Yagmuk and his family can herd moose, they have superhuman powers. So they won't have to worry about the bills.
Thought 1. There needs to be some way of saying "well, ok, maybe it has bad effects in twenty years time, we don't know, but on balance please freaking take it" when the alternative is worse.
In fact, there seems to be a lack of follow up (in all countries) of "ok we did some studies and approved it, now if MILLIONS of people take it, do we detect any downsides?" I know that's hard to do. But we probably need to sooner or later.
Thought 2. Plenty of countries have an approval process for medicine, and provide healthcare in the form of insurance companies, and are nowhere near as screwed as America. I highly recommend a national health service, but maybe looking at what countries more in the middle do and doing that would be a good guide. It's surprisingly easy to forget that as an option
The problem with endorsing untested drugs is not just their lack of efficacy. It's not just the potentially crippling side effects (see e.g. thalidomide). It's also the fact that people who take treatments that they believe to be effective usually stop taking other treatments, which actually *are* effective.
Right now, there are hundreds if not thousands of people out there dying of treatable cancer, because their pastor told them that Jesus will exorcise their disease from their bodies, hallelujah. In Russia, and even in some places in the US, the same is happening with COVID: people believe that good old vodka and a few cloves of garlic will cure anything, COVID included. But those are just regular folk beliefs and established religions. If you abolish the FDA, you will grant pharmaceutical companies; dietary supplement providers; and your local street-corner kook full power to market their miracle cures with impunity.
Yes, I understand that allowing every potential drug to hit the market as soon as possible would save lives; but you must look at the whole picture in your calculus, and the whole picture also includes lives lost or ruined -- which (as is the case with thalidomide) sometimes don't become apparent for years afterwards. Yes, obviously the FDA can be made more efficient, and it should be, but abolishing it would be like setting your boat on fire because you don't like the gas mileage. While you're on the boat. In the middle of the ocean.
Thinking about Aduhelm and the question of whether it actually treats Alzheimers or just treats beta-amyloid plaques.
Is there a possibility that this applies to some drugs that reduce cholesterol? That they reduce cholesterol is likely true, but that there are no studies showing that the reduction of cholesterol via such drugs actually reduces heart disease? Can anyone point me to some good studies? Thanks.
100% Agree. The system is designed to reward risk aversion, and not just the risk to the public of a dangerous drug getting approved. It's also about their personal risk of making a mistake. No one wants to be the bureaucrat who approves the next thalidomide. So more layers of bureaucracy are added, and along with that comes the inevitable mindset that the procedure is the priority. It's hopelessly broken.
On a separate note, I laughed out loud at the picture of the guy fishing on the ice who burns all the medical bills. That was priceless.
No discussion of FDA intransigence would be complete without a look at the life of John Nestor, https://www.theatlantic.com/health/archive/2012/05/medicines-missing-measure/257901/. I’m surprised he hasn’t been mentioned yet. He spent his spare time causing massive traffic jams on DC-area highways by insisting on driving 55 in the left lane. If an author tried to create an obstinate bureaucrat character based on his life, he would be panned for being too on-the-nose.
I love the idea of unbundling permission-to-prescribe from standard-of-care. But standard-of-care is, in practice, set by the courts, right? If the FDA said, "We approve this for use, but we don't want insurance companies to feel obligated to cover it", would that make any difference?
As is so often the case when confronted with what looks like stupidity, the problem is metaphysics. Humans everywhere construct a dichotomy between the sacred or pure, and the earthly or profane. Humans naturally interpret FDA approval as being like the purification rituals performed by a priesthood. And you can't unbundle holiness. It's the most-basic ontological divide, between the temporal and the transcendent.
What I don't get is why the FDA has any power to tell doctors what they can prescribe--and especially why alleged inefficacy should justify banning a drug's use. The reason for our heavily-regulated system of educating and licensing doctors is to ensure people can trust licensed doctors. We trust them to cut us open and sew us back up, and to keep up with recent research in their field (even though many don't). These things are simple and objective compared to drug approval. The literature on any particular drug's safety is always contradictory, the studies are mostly fatally flawed, the committee doesn't have time to read the literature that took years and hundreds of millions of dollars to produce, and the ultimate decision is often based on the helpful "summary" of some industry flack.
(Also, it's rare even for drugs that fail the safety tests to be as lethal as tobacco, alcohol, or sugar.)
psychiatrists do this cost/benefit every day with patients with less risk/recourse than any politician and still make the same decisions. maybe change should start there first
BRUTAL: "Although the FDA did kill thousands of people by unnecessarily delaying COVID tests, at least it also killed thousands of people by unnecessarily delaying COVID vaccines."
July 8, 2021: Joint CDC and FDA Statement on Vaccine Boosters | HHS.gov
Americans who have been fully vaccinated do not need a booster shot at this time. FDA, CDC, and NIH are engaged in a science-based, rigorous process to consider whether or when a booster might be necessary.
https://www.hhs.gov/about/news/2021/07/08/joint-cdc-and-fda-statement-vaccine-boosters.html
August 5 2021:FDA Covid-19 Vaccine Booster Plan Could Be Ready Within Weeks…
The Food and Drug Administration expects to have a strategy on Covid-19 vaccine boosters by early September that would lay out when and which vaccinated individuals should get the follow-up shots, according to people familiar with discussions within the agency.
https://archive.is/Lxmdq
Seems to be a remarkable turnaround. NBC news had to contact each state to get breakthrough data since the CDC no longer reports on breakthrough deaths and infections:
https://www.nbcnews.com/health/health-news/breakthrough-covid-cases-least-125-000-fully-vaccinated-americans-have-n1275500
CDC Scaled Back Breakthrough Case Hunt Just as Delta Grew
https://archive.is/Zgnme#selection-1459.0-1459.57
I’m still stuck on facts of global and American drug development: more new (and effective) drugs get invented in the USA than anywhere else. Every proposal to radically change the way the FDA or any other part of the ecosystem represents implicitly a claim of this nature: “I see the greatest production system for drugs the world has ever seen, and I know how to do better.”
In other contexts we know that imposing strict rules and forcing people to play a somewhat arbitrary game is often a spur to creativity, because it enables direct comparison of things. In medicine, those arbitrary rules look horrifying because they are arbitrarily obstructing people’s access to healthcare. But the gamification seems to be working. Tweak the game, sure, but removing a major plank of it seems reckless.
> So the long-term solution is to become a different kind of country and different sorts of people
The simplest way to do this is to break up the United States into several smaller countries. The amount of problems this would solve is truly huge.
The lack of early testing really seems like the greatest failure here, but there's also the shamefully poor quality of publicly available information. This is supposed to be the age of big data, but the federal government is such a shit show that we can't even get properly detailed demographics for deaths from covid, let alone infections or hospitalizations. There is no rational excuse for why I don’t have a more detailed risk profile than the “official” (non-standardized) overly broad age ranges and a vague list of comorbidities. This uncertainty makes me skeptical of the whole situation and I have to wonder to what degree mass hysteria is playing a role.
You are wrong about one crucial fact in your argument: neither public payers nor private insurers have to cover any given therapy. Surely you could have just checked with a drug rep friend? One of the huge headaches for pharma, patients, and physicians is that medications with better efficacy, safety or tolerability often require days of paperwork hurdles or are simply not covered.
There is no requirement that payers cover approved drugs. Period.
In fact, this fact probably results in tens of thousands of deaths. When a patient with fulminant acute leukemia cannot get immediate treatment because the paperwork takes three days, he or she often dies in the interim.
My sister has a glioblastoma. She took one anti-seizure medication which left her so tired she couldn't function. Her insurance company refused to authorize a different medication until she and her doctor stumbled on the magic formula: she had lost her appetite. Crazy.
Your argument falls apart if it is based on that faulty premise.
"By March 1, China was testing millions of people a week, South Korea had tested 65,000 people, and the USA had done a grand total of 459 coronavirus tests. The pandemic in these three countries went pretty much how you would expect based on those numbers."
When I look at China's numbers the only thing I'm pretty sure of is that there's no way they represent reality. Do you have some reason for giving them credence here? Either on the testing front, or on the course of the pandemic?
"Around 2010, Boston Children’s Hospital found some loophole that let them add fish oil to their nutrient fluid on site, and infants with short bowel syndrome at that one hospital stopped getting liver damage, and the FDA grudgingly agreed to permit it but banned them from distributing their formulation or letting it cross state lines"
So why couldn't all the other hospitals simply apply the same 'loophole'? How difficult was it to figure out the formaulation?
Great now I'm depressed
> So when I talk about unbundling FDA approval, I mean that instead of the FDA approving the following bundle of things…
Or you could push for universal healthcare so that what insurance will cover isn't under FDA's purview at all, so you're just left with the 1 responsibility.
Fascinating.
A thought on the star-system - would it make more sense to split it into two sets of ratings?
One representing "confidence that the drug does the (desired) things it says on the label" (A wording chosen to step around off-label/novel uses), and one representing more or less "confidence that all the side effects are on the list of known side effects with risk factors and incidence rates reflecting reality".
I would prefer this split because the single-set system as proposed (at least as I read it) interacts weirdly with, for example, drugs with likely awful side effects that are less bad than what they treat - for example, in a sense at least, a really good five-star chemo drug is less safe than a two-star sugar pill.
That said, it's possible that by "the drug is safe" you mean "we are very confident we know the side effects and risk factors for them"...
Source for "the only reason we can get these at all is through provisional approvals that they wouldn’t have granted without so much political pressure," please?
Scott's dismal assessment of the FDA's incompetence tracks the narrative told by Michael Lewis, in Premonition. The root cause is obviously the dysfunctional incentivize structure inherent in any political bureaucracy. This follows the entire body of microeconomic theory and empirical research, which uniformly stands for the proposition that bureaucrats following their own interests will **always** get the cost-benefit ratios wrong.
Scott's idea of provisional/scaled "approval" levels seems like a great reform. Another reform that might be useful, however, would be to have an entirely independent and alternative path to go around the FDA when it is dragging its feet unnecessarily. Perhaps this consist of some association or jury of specialists in the particular field that could vote to at least allow certain especially qualified members of their specialty to provisionally prescribe the medicine based on an individualized review of the safety/efficacy data as it exists, as compared to a patient's individual risk/benefit circumstances. (For example, a patient who is about to die without the drug, or a patient who is highly unlikely to have potential side effects). This clinical experience could also be monitored and folded into the overall case for and against the drug.
A guess a question for Scott would be how to get a real reform process started in light of the entrenched incentives? But I guess that is always the big question.
As a side note, the bad reporting of the Atlantic seems typical of how the "prestige press" seems generally incompetent to analyze any issue that involves hard technical and economic issues. They usually just aggregate banal quotes, talk around the issues in verbose prose, and then conclude with how "these are complicated issues," people are "trying hard," and "doing their best," but really smart "experts" are on the case and aware of the issues, so they'll keep all this in mind and hopefully do better going forward, blah, blah, blah.
I really like your idea of a more fine-grained rating system for the FDA but I think your single dimension star-rating system in combining two important dimensions: safety and efficacy. The FDA should separately report safety and effectiveness.
Something that may or may not work but is not dangerous may still be worth taking for many people.
Something that definitely works but is also dangerous could still be worthwhile for a different subset of people.
Drug ratings for pregnant women have a similar problem with their one-dimension rating system. Drugs in class C may be safe but with unknown effectiveness, or they may be effective but dangerous. The difference is important to know.
Great article! It feels a bit like the FDA is robbing me of my life. The government is blocking one of the most important things in life, my health. Why are we allowing govt to force what my doctor and I can and cannot use as treatment? If I’m willing buy a drug from a company that’s willing to produce and sell that drug then it’s in my best interest to work with my doctor to decide what’s best for my life. The FDA would be greatly improved if it’s role was simply to protect citizens from false claims (ie: if a doctor or drug company lies to me in order to get me to use their treatment)
Book review request: Upton Sinclair's "The Jungle," would be interesting to see what the pre-FDA world looked like (from the perspective of what I can only imagine is the early 20th century equivalent of a quirky rationalist blogger), and whether there's a reason for the madness.
Scott, if you haven't seen it yet, Matt Yglesias also wrote an essay on the FDA situation (two weeks ago; not subscription-locked), and I think it complements yours quite well: https://www.slowboring.com/p/fda-cost-benefit
CNN interview of Walensky was removed by google. It is now on rumble:
CDC Director Rochelle Walensky stated the vaccine does not prevent COVID-19 infection, nor does it stop the vaccinated person from transmitting the infection or the delta variant. According to Director Walensky, the only benefit from the vaccine now is presumably that it reduces the severity of symptoms.
https://rumble.com/vkscco-cdcs-dr.-rochelle-walensky-admits.html
I just Tweeted a thread with some overlap to this post, including a rec for a good podcast interview with a former FDA person who argues in favor of the Aduhelm approval and the use of the accelerated approval mechanism of the FDA, plus my comments on why that will be good for the aging/longevity space and in particular that the chance of using an aging clock as a surrogate for approval via the accelerated (conditional) approval + phase IV trial mechanism may be fast approaching as it is likely one of these clocks will outperform Abeta in AD prediction soon. See: https://twitter.com/KarlPfleger/status/1423774160321490950
The biggest concern right now?
New coronavirus variants could be named after star constellations once letters of the Greek alphabet are exhausted, a senior World Health Organization official has suggested.
In an interview with the Telegraph Maria Van Kerkhove, the WHO’s technical chief for Covid-19, said the UN health agency was already looking at new names for mutations amid fears there will be more concerning variants than the 24 letters of the Greek alphabet.
https://www.telegraph.co.uk/global-health/science-and-disease/variants-could-named-star-constellations-greek-alphabet-runs/
Medicine is too complex for a uni-dimensional "star" system. FDA should strive for clarity, not simplicity. State what we know, without messaging spin. Others can do the messaging. Be a source of truth, without taking responsibility for all the knock-on effects. Sharpen the blade; don't dull it in the vain hope of improving system-wide outcomes. That's the only way to develop a stable reputation.
From nintil-
The FDA approved an ineffective drug for Alzheimer's, aducanumab. Scott Alexander has a post on it, including a broader discussion on whether the FDA is too lax or too conservative. The right answers is that it is both; Scott doesn't discuss oncology, where arguably it is too lax, enabling multi-million dollar biotech grifts to exist. Scott's framing is puzzling; why "pulling the FDA level" towards being more lax when one can propose both tactically based on cost-benefit analyses. Anyway, the solutions he discusses later are good and go beyond the FDA: the reason we ultimately care about the FDA approving useless drugs is that the US healthcare system will pay for them. That has to change: The FDA could switch to a multi-tiered level of approvals and Medicare should be decoupled from the FDA so that they don't have to cover all drugs coming out of FDA approval. Here's a critique of some of the points that Scott makes.
https://willyreads.substack.com/p/slightly-contra-ssc-on-aduhelm
Liked the article all except for this blurb that makes it seem like there is absolutely no reason not to get a covid vaccine:
"this policy has led to our current situation, where either everyone has to be miserable because of stupid people’s choices (eg everyone has to wear masks forever because a few people won’t get vaccinated) or we get a strong anti-freedom lobby because allowing anyone any freedom means that the rest of us have to suffer for their stupid choices."
There is a 3rd option - which is to let the vaccinated people be protected, and the unvaccinated people live-out the consequences of their choice. In reality a cost-benefit analysis would tell you that there is almost no benefit to anyone for healthy people under 40 to get vaccinated. For older people and people with other risk factors the vaccine is by far the best thing they can do to protect themselves.
What is the justification for the FDA to exist at all? Surely we'd be better off without it.
I know it's like a year later, but here's a Science article - https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease
Lesné's work is the basis of all the beta-amyloid work (which this drug is based on) -
A quote - "A 6-month investigation by Science provided strong support for Schrag’s suspicions and raised questions about Lesné’s research. A leading independent image analyst ...reviewed most of Schrag’s findings at Science’s request. They concurred with his overall conclusions, which cast doubt on hundreds of images, including more than 70 in Lesné’s papers. Some look like “shockingly blatant” examples of image tampering, says Donna Wilcock, an Alzheimer’s expert at the University of Kentucky."
So, there you go.