This is a three-part story of heroism, intrigue, and ultimately treachery in the world of drug approval.
PART 1
Alex Tabarrok points me this weekend to a righteous rant about the FDA from psychiatrist Scott Alexander at Astral Codex Ten. After blasting them for several COVID-related decisions, he tells us about another example of FDA folly:
I worry that people are going to come away from this with some conclusion like “wow, the FDA seemed really unprepared to handle COVID.” No. It’s not that specific. Every single thing the FDA does is like this. Every single hour of every single day the FDA does things exactly this stupid and destructive, and the only reason you never hear about the others is because they’re about some disease with a name like Schmoe’s Syndrome and a few hundred cases nationwide instead of something big and media-worthy like coronavirus. I am a doctor and sometimes I have to deal with the Schmoe’s Syndromes of the world and every f@$king time there is some story about the FDA doing something exactly this awful and counterproductive. A while back I learned about cholestasis in infant Short Bowel Syndrome, a rare condition with only a few hundred cases nationwide. Babies cannot digest food effectively, but you can save their lives by using an IV line to direct nutrients directly into their veins. But you need to use the right nutrient fluid. The FDA approved one version of the nutrient fluid, but it caused some problems, especially liver damage. Drawing on European research, some scientists suggested that a version with fish oil would cause less liver damage — but the fish oil version wasn’t FDA-approved. A bunch of babies kept getting liver damage, and everyone knew how to stop it, but if anyone did the FDA would take away their licenses and shut them down. 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 for a while if you wanted your baby to get decent treatment for this condition you had to have them spend their infancy in one specific hospital in Massachusetts. Around 2015 the FDA said that if your doctor applied for a special exemption, they would let you import the fish-oil nutritional fluid from Europe, but you were only able to apply after your baby was getting liver damage, and the FDA might just say no. Finally in 2018 the FDA got around to approving the corrected nutritional fluid and now babies with short bowel syndrome do fine, after twenty years of easily preventable state-mandated damage and death. And it’s not just this and coronavirus, I CANNOT STRESS ENOUGH HOW TYPICAL THIS IS OF EVERYTHING THE FDA DOES ALL THE TIME.
PART 2
Something about this didn't seem quite right to me, so I looked around for more details. Luckily, it turns out that Kathleen Gura, who was intimately involved in this case, got an award for her work and delivered an acceptance speech that provided lots of detail about how it all happened.¹ Here are the basics:
2002: Gura had a cancer patient that was having trouble with conventional nutrition delivered via tube. She called around for ideas, and everyone gave her the same advice—the patient just has to suck it up—except for one doctor, who had recently heard about a fish-oil based lipid emulsion from Sweden called Omegaven. Gura got emergency approval from the FDA to try it and then got some shipped over. It worked great.
2002: Gura was also involved with a team looking for ways to treat infant short bowel syndrome, which causes liver failure in some patients. Everyone suspected a toxin of some kind, but Gura convinced one doctor to do some mouse trials with Omegaven. It worked, but no one believed it. "Everyone knows it's not the lipids," she was told.
2004: Gura continued her mouse studies on the side but was unable to get funding for more serious research. Even the Swedish manufacturer had no interest in sponsoring additional research. However, one day a doctor expressed interest in using Omegaven on a child who had no other options. It worked.
2005: A few more babies were treated with Omegaven and had good results. The FDA suggested Gura apply for regular (non-emergency) investigational drug approval. She did and it was approved.
2006: Even so nobody was interested in publishing her results. After a dozen rejections, her paper was eventually published in Pediatrics.
2007: Gura started up a media war to persuade the manufacturer of Omegaven to release it in the US. They didn't want to, but succumbed after getting beaten up over it.
2007-12: Gura faced considerable opposition to her ideas, partly because she had never run a double-blind study. But she continued treating a few patients each year with Omegaven, and by 2012 it was on its way to becoming standard of care used by lots of hospitals around the country on an emergency basis. In 2012 the Swedish manufacturer finally submitted a New Drug Application to the FDA, but they asked for approval of Omegaven only as a treatment for liver disease. However, thanks to FDA guidance the NDA was changed to allow Omegaven to be used as a nutritional fluid that would prevent liver disease.
2014: A team in Hong Kong published the results of a double-blind study. It had been shut down early because the Omegaven group was so obviously doing better, but it was enough to convince the FDA that a randomized, controlled trial was not necessary. The FDA would instead accept pair-matched historical controls.
2018: Omegaven gets final approval from the FDA.
PART 3
Gura's narrative is wildly different from Alexander's. She mentions problems with testing; with funding; with publications; with the Swedish company itself; and with the medical community, which didn't accept her results. But the FDA was helpful. They provided emergency IDAs. They suggested she get a regular IDA. They caught a problem with the New Drug Application that would have severely limited Omegaven's usefulness. They accepted the results of the aborted Hong Kong study. And the time it took for FDA approval was not 16 years, but six years, since the manufacturer didn't even submit an application until 2012.
After I had written all this, I went back to Alexander's site and noticed that he had added an update. Several people wanted to know more about the Omegaven affair, so he provided a link to a post he had written about it. It starts like this:
I plucked that from the anti-FDA blogosphere, where it had been floating around for a while in various incarnations. I tried to check it before publishing, but only enough to confirm the basic outline.
Indeed. After getting the questions, he did some more research and it turns out that he relied for this research on exactly the same document I did: Kathleen Gura's speech. After a long summary he says, "There still have not really been any great large-scale studies proving that Omegaven works better than older nutrient fluids, though my impression is that everyone who uses it believes it does." That's not exactly great evidence for his thesis that Omegaven was a miracle drug caught in bureaucratic FDA hell.
Then Alexander admits some specific errors in his initial story but says, "Still, I think the basic structure was right — the new fluid was better than the old fluid, this was pretty clear in terms of miraculous recoveries, and it took 14 years between the first patient saved and full FDA approval."
This is headshakingly dense. As a hit on the FDA, his post wasn't right at all—not its basic structure and not anything else about it. He even admits that although Gura criticizes plenty of other actors, the FDA isn't one of them:
The FDA, in comparison, comes out looking pretty good. They approved the first few original single-patient exemptions to import Omegaven from Europe. They (eventually, after a lot of work) approved the Investigational New Drug application that let Boston Children’s Hospital keep using it (I’m still unclear whether any other hospitals got INDs for this). They even contributed a little funding to get one small study done. It wasn’t enough, but the FDA is not primarily a funding body, actual funding bodies dropped the ball on this one, and so it’s really impressive that the FDA went above and beyond to try to move Omegaven through the pipeline. Dr. Gura seems to have been left with the impression that the FDA was one of her few allies during this fight, which I think is fair.
I mentioned in a section of my recent post, “Sympathy For The Devil”, that I think the FDA as an agency is often quite good. They’re smart, caring people, and they usually carry out their mandate well — so well that the few exceptions, like aducanumab, are highly newsworthy. I have no objection to Dr. Gura’s mostly-positive portrayal of them.
This bears no resemblance—none—to the diatribe in Part 1:
Every single hour of every single day the FDA does things exactly this stupid and destructive....I am a doctor and sometimes I have to deal with the Schmoe’s Syndromes of the world and every f@$king time there is some story about the FDA doing something exactly this awful and counterproductive.
I have no idea how you can write "they usually carry out their mandate well" in one place and then, in your main post, just go ahead and repeat your original belief—backed by an example you know is wrong—that the FDA does stupid and destructive things on practically a daily basis.
This is why I'm automatically skeptical of anything on the web that's excessively critical of the FDA. It's not that I think the FDA is above reproach. It's because of the existence of the "anti-FDA blogosphere" that Alexander mentions. There is indeed an active clique of FDA critics in the blogosphere, mostly of a libertarian bent, who are willing to accept and pass around the most egregious stories imaginable of FDA incompetence. Occasionally they're true, but most often they're very highly exaggerated, like this one. Other times they're little more than urban legends.
The FDA has plenty of problems, and their critics have performed a useful service by pushing them to improve. That said, the FDA doesn't screw up every hour of every day on practically every useful drug ever presented to them. Even taking normal human frustration into account, that's inexcusable.
¹Note that throughout the text I'm using Gura as shorthand for "Gura and other people who were involved in getting Omegaven approved."
From my observations going way back, the FDA heroism in keeping thalidomide from getting approved in America was cancelled out mightily when laetrile came along. Thereafter, and ever since, quacks and flakes and general malcontents have blamed the FDA for its "failures" in facilitating the end of any and every disease.
The FDA has made mistakes, true. But it's methodical efforts (even when maddeningly slow, as science can be) generally save lives.
(And, for sure, had the internet been around from the early 60s on, thalidomide would have been approved, laetrile would have been in widespread use for years, and, hell, copper bracelets might have ended up as the biggest selling prescription device of all times.)
I still remember my aunt showing my mother her copper bracelet and pointing to the green stain on her wrist where it was drawing poisons out of her body. My mother was polite and said nothing but commented later to us kids that green was the color of copper oxide the you got on your skin when you wore a copper bracelet.
I just giggle every time I see ads on TV for some sort of clothing fortified with copper buttons or wires or something like that.
The thinking documented here seems commonplace. All sorts of people like to jump the gun and garner some sort of social status by their proclamations. It takes patience and humility to tease out how things really work.
Thing is, Keven, you could take that quote and plug in ANYTHING and you'd have a good template for "libertarian" commentary on just about any topic.
Observe:
Every single hour of every single day, Kevin Drum does things exactly this stupid and destructive....I have "done the research" and sometimes I have to deal with the silly lib fantasies of the world and every f@$king time there is some story about Kevin Drum writing something exactly this awful and counterproductive.
See?
You could literally just copy and paste that paragraph, change a few bits to be relevant to whatever you wanna rant about, and you'll sound convincingly "conservative."
To borrow a phrase...SAD. 🙁
Can't give up MAGA mode!
A rebel with out a clue?
The nature of the drug approval process in the US is a bit of a mess, but that's all not the FDA's fault. We don't have a centralized way to do clinical trials. For rare diseases, it is very hard to get enough people in trials for them to be statistically meaningful. In the mean time, the FDA is flooded with various applications to keep existing drugs exclusive, i.e. block generics, e.g. new formulations, orphan drug status, etc.
Word
And they are also flooded with (even more, believe it or not) petitions and political arm-twisting by "patient advocacy" groups -- some of which are real and some total astroturf -- demanding approval of / access to medications that haven't been fully clinically tested, beyond the existing "compassionate use" process.
I knew how this story would end as soon as I saw the name Tyler Cowen.
+1
The question is, who didn't? Apart from, apparently, Kevin that is. Any theories as to why he pays any mind at all to what that no-talent, unimaginative and uninspired hack thinks? Especially since TC hasn't been right about anything of significance (Kids, don't do Libertarianism. It's bad for your powers of analysis as well as being extremely hard on your psychic health) since, well, forever, insofar as I know ... or care to inquire into the matter.
>Any theories as to why he pays any mind at all to what that no-talent, unimaginative and uninspired hack thinks?
I honestly don't know. It is crazy how many "smart" libs just gush over TC.
Why I stopped reading Scott Alexander.
Me too. He's occasionally on-target but has so many wild misses and rants about pet peeves that it became too much trouble to filter it out.
However, when Scott discovers he's been proved wrong, he walks back his claims—as he did in this case. Not many people have the integrity to that. Just sayin...
Uh, actually, he didn't. As Kevin points out. See, it's consider de rigour among libertarians to never admit you're wrong in these sorts of discussions. Doing so is considered extremely poor form as well as just generally bad, tactically or rhetorically speaking 😉
"walks back"
He basically lied from the get go.
This kind of a mistake is where you delete your article, delete your blog, admit you know nothing and go back fo private practice and keep your rants to yourself. None of which he did.
Now do the FDA forcing the doctors who by lucky happenstance were tracking the initial spread of Covid in Washington to shut down their study for "privacy". Is there an explanation of this that does not put the FDA on the side of evil?
"tracking the infection" lol.
You seem confused. The Food and Drug Administration doesn't have anything to do with disease tracking (that's the CDC) or privacy and HIPAA (that's HHS).
https://www.statnews.com/2020/05/27/coronavirus-testing-seattle-bill-gates-fda/
Above is the link to one of many stories about this. My apologies for not including a link earlier, I thought it was common knowledge, but the replies show it is not. If you google it, you will find many more stories about it.
It was a bit of an unusual situation, but it was the FDA.
https://www.statnews.com/2020/05/27/coronavirus-testing-seattle-bill-gates-fda/
Name well chosen.
https://www.statnews.com/2020/05/27/coronavirus-testing-seattle-bill-gates-fda/
Google FDA, Covid, and shutdown flu study if you want to see many more stories about this. Glad you like the name, and yeah, sometimes it is appropriate, but this time the facts are on my side.
The FDA comes out of this looking pretty good. Even Gura, the protagonist of this story thinks they did a good job given their remit.
The FDA is in a tough position. It has to deal with the pharmaceutical companies. These are huge, wealthy companies with no moral compass whatever. They place some value on helping humanity, but otherwise they are about making money. If this means killing thousands in the rust belt by pushing opiates or selling a demonstrably worthless cure to the desperate, they will. Anyone who proposes changes to the FDA has to address how our society can control with these entities who can also do a lot of good.
I always compare capitalism to fire. Fire is amazingly useful, but it is extremely dangerous if it is not carefully controlled. You don't set fire to your bed so you can get enough light to find your way to the bathroom.
That’s a great story thanks for researching and publishing it. That title though…may not generate a ton of clicks, is all I’m saying
Confirmation bias is powerful in the pursuit of eyeballs and mouse clicks…
"The rise & fall of Log Qabin Republiqan Nate Silver"...
... a true Son of the South.
I'm more interested in you challenging fuck-shit Tyler Cowen about this.
A minor point: Alex Tabarrok authored the post, not Tyler Cowen. Another point/question: Is there anything--an intellectual or cultural endeavor-- that economists do not know more about than anyone else? Intellectual humility seems not a prevalent attribute among academic economists.
Amen to that. E.g., Florida Gov. De Santis is using a correlational study by know-it-all economist Emily Oster to justify forbidding mask mandates in schools. Besides all the usual limitations of correlational studies, the presence or absence of ask mandates is undoubtedly correlated with the preexisting level of transmission …
Is Emily Oster a Megan Mc Cardle pseudonym?
Dr. Lemonjello Thompson, a leading paediatrics researcher, & his brother, Orangello, dispute the idea that thinly-sourced hitpieces are not trustworthy reporting.
I suspect the title is chosen to get the right kind of clicks.
The biggest problem with the FDA is its funding. And it is 100% Congress that is responsible. FDA is financed by fees paid by the pharma companies. This makes the CEOs of these companies think they are entitled to make the FDA do what they desire, i.e. approve drugs that they think will make lots of money. If something bad happens (like approving a very expensive drugs that most likely does not work or pushing for booster shot approval in an attempt to take control of the Federal Government's COVID policy) this is always part of the problem.
FDA should work for the taxpayer and should be funded by the taxpayer (it should also be given authority to set maximum prices based on a calculated economic value of a drug).
That is a great point. Funding via fees makes it all about the fees - without them things don't get approved. And the bad actors don't pay fees.
KD- what about Tyler Cowen? He gave the story air and even provided an update still agreeing with original story? What a douce bag.
I think that pretty much goes without saying these days. Given his track record, that is, and not just the fact that the generic libertarian has a well-deserved reputation for being a douche bag.
You know, it's hard to pull back after realizing you made a mistake. It's difficult to just say, "Oops, I made a mistake!" We are concerned over the consequences of admitting to an error, whether losing credibility or being looked down on.
Ironically, it only gets worse when we try to stretch logic and truth, using all sorts of devices to defend or minimize the error rather than admit to it. Admit it and move on. Only the troll dwells on other people's errors, at which point you can just block them.
In related news, Sean Spicer stuck his head out of his spiderhole to say it's assured El Jefe Maximo is running for president in 2024...
*Spicerhole
I wanted to know how Spicy remains in the know with the Jefistas.
In defense of Scott Alexander, his blog is, to me, one of the most interesting on the entire internet. He covers a broad range of topics with a fair amount of sensitivity and insight, most of the time. He clearly has a pole up his behind about the FDA and other things relating to medicine and medical research. Given that his "day job" is as a clinician, that's not terribly surprising. His rants against the FDA and the IRB are not much different from what I hear from lots of practicing MDs.
His audience includes a lot of savvy people from all over the political spectrum. So he gets pushback when he publishes stuff that they can see is wrong. And unlike many other bloggers, when he's called out on error, he admits it. He even maintains a page of things he's been wrong about!
He's not perfect. None of us are. His view of the world leans libertarian, so some of his attitudes can make it look like he's never actually met any other living humans. That's true of all libertarians. But on balance, he's still one of my favorite bloggers. My face lights up when I see Astral Codex Ten in my inbox, even if sometimes it makes me angry (as this episode did.)
Disclaimer: While this particular story was a screw-up on his part, let me be clear that I am not a fan of the FDA. We need an agency with their mission, one that is independently funded by government. And we need it staffed with at least some people who know at least a little about public health. Most of their errors in this pandemic were quite serious and were rookie mistakes that you would expect from physicians and pharmacologists and statisticians who don't understand public health. I have occasionally been distantly involved with other public health situations where good products for public health purposes were killed because they were judged by the standards applicable to therapeutic medicine. This is a consistent problem at the FDA--it happens nearly 100% of the time. They are clueless about public health.
Oh dear lord:
I mean, we already knew it from the quality and depth of your discourse, but you do realize that you come across as ignorant, uninformed, and very much an idiot, don't you? Please take some actual classes and inform yourself about whereof you speak before actually, you know, speaking.
"Please take some actual classes and inform yourself about whereof you speak before actually, you know, speaking."
I am a Professor of Family & Social Medicine at Albert Einstein College of Medicine. I am board certified in both General Preventive Medicine/Public Health and Internal Medicine. I served as chair of the American Board of Preventive Medicine from 2007 to 2010. My career in epidemiolog extends back to the mid 1980's and I have over 200 publications in peer reviewed medical journals and a few book chapters.
Which classes did you have in mind? I'm always interested in self-improvement.
Which classes did I have in mind? Sigh. I even quoted that bit which led me to recommend more coursework. Here it is again if you can't be arsed to go back and reread that quote:
Since you thought they made 'rookie mistakes' as you put it (and you're clearly a crank of strong opinions that you think should be treated as fact), you should go back and take those medical, biochemical, and statistics courses and recalibrate. Since I do (and teach) statistics for a living -- among other things -- I'll focus on statistics. No, those statisticians did not make any rookie mistakes, let alone make them because they "don't understand public health". But I'll bite, because for someone who claims that level of expertise, you've been remarkably vague on the specifics: What 'rookie mistakes' did these statisticians make in their analyses, and when or where, geographically speaking? Please be accurate and specific, providing cites and links to support your claims. Finally, why were these mistakes made because those statisticians don't understand public health.
This shouldn't be hard, amirite? I mean if these mistakes were so obvious and all. Be forewarned, I work at Northwestern and know plenty of people who have real expertise and real-world experience; remarkably enough, over the course of what has to be several hundred conversations, none of them has ever said anything about any rookie mistakes that were made, let alone made because of a poorly formed understanding of public health.
Come to think of it, my partner's niece did her graduate work in public health a few (Or was it -- Good God! -- six) years ago and I was extensively called on (I'm the only numbers person they know that they can lean on) to get her through the analysis parts, done in R. So do not attempt to gaslight me, and do not insult me or anyone else the way you did before.
First of all, I was not asserting my opinion as fact. I was stating my opinion. And it was, in a way, tangential to the main point of my comment, which was to opine about Scott Alexander's blog generally. I gave it at the end as context so that people would have some idea where I was coming from with respect to my views of the FDA.
"So do not attempt to gaslight me, and do not insult me or anyone else the way you did before."
Where did I insult you or anybody else here? In fact, as I look up and down this page, I see nobody slinging insults around near as much as you do. In fact, the only reason I responded to you was because you had made an ad hominem response insulting me without raising a single point to counter what I had said.
I'm happy your niece was able to benefit from your knowledge of statistics in her public health work. I've sat on several PhD committees and also provided assistance to one of my cousins with the statistical work on her DrPH degree. So what?
I enjoy teaching statistics, too. So we have something in common.
As for the rookie mistakes, they don't require any deep statistics and all the facts are well and publicly known without my having to dig up cites for them:
1. They resisted approving rapid tests because they were holding them to a criterion of having accuracy equal to that of a PCR test. During a rapidly spreading pandemic this is a terrible error: anyone with a semester of public health training would know that a test that is less accurate but widely accessible and will lead to faster removal of infectious people from the transmission cycle will produce better results. Evidently it depends on the extent of inaccuracy and the specifics of the rate of transmission, duration of infectivity, etc. But the numbers were all there at the time and the FDA wouldn't buy it.
2. They initially refused to allow labs that were ready to do PCR testing to do so and instead granted a monopoly on that to the CDC. Now, I can't fault them for not foreseeing that the CDC's test would itself be severely flawed. But it was perfectly foreseeable that the CDC lab could not by itself produce PCR testing on the scale needed to deal with this pandemic. By the time the first cases in the US were recognized, it was already known from the experience in Hubei province that this virus was highly transmissible and also highly lethal. There were no known pharmacological treatments nor vaccines available at the time. Only non-pharmacological measures could be brought to bear. Test and trace with quarantine of contacts and isolation of the infected needed to be ramped up as rapidly as possible if there was to be any chance of avoiding either a decimating epidemic or economic catastrophe. Taiwan, for example, did this quite well. Given the rate of spread observed in China, there is no way that a single lab in Atlanta could fulfill the need. In fact, even just the delays involved in transporting specimens to Atlanta were a serious problem since you need to get the infectious people out of circulation as fast as possible. None of that is rocket science.
No doubt there were plenty of people at the FDA who knew better. But their voices did not prevail and the institution as a whole failed in this regard.
I mentioned my areas of competence as fair warning to you to not get the slightest bit shifty; I _will_ sniff it out. That's the 'what' to your 'so what'. Now, on to what you said:
Oh really? For someone who was just 'stating his opinion' rather than making an observation about facts on the ground, you came across as awfully sure that you were right. That's insulting, BTW, not clearly labelling your opinion as just that, an opinion, and then presenting it with an air of certitude as if it were a fact. Don't do that. Ever.
I'll close for now and address your points 1 - 3 later. But I'll close for now this this:
See, this is what I mean by being insulting: no one is claiming that the FDA did not make mistakes. They did. But you seem to be employing a rhetorical tactic -- there's that insult thing again -- wherein the refusal to admit that the FDA made rookie mistakes -- purely on your say-so at this point I might add -- is exactly the same as a refusal to admit they made mistakes. IOW, if I refuse to admit the FDA made mistakes the implication is that my objections totally discountable, but if I do, then that must mean I've conceded that the FDA did, in fact, make rookie mistakes. That's neither kosher nor civil, bro. At all. I suspect that what's going on here is that you've just realized that actually showing -- rather than telling -- that rather damningly elementary errors were made is going to be a lot tougher than you first thought when someone with the requisite competence challenged what you on what you were trying to sneak in the back door and that in the end the actual details will be a lot more complex and a lot less damning then you're trying to darkly hint at.
So hindsight turns out to be such a very witty little mofo? Again? Who coulda seen that one coming, I asks ya? Quite a few people, as it turns out.
Institutional review boards (IRB's) can range from useless to a nightmare, and will delay things. But they are a needed, and if done well, can be useful.
As for the FDA, it's just paperwork--until it isn't--so the FDA does have to be anal retentive.
No one likes people looking over their shoulders or second guessing them. But in drug development, that is needed. And when people go off on their horror stories, remember Kevin's post.
If he's a self proclaimed libertarian best not to take anything he writes too seriously.
This is just very, very good Journalism by Mr Drum. He brings forth an obscure issue and adds light, context and understanding.
This is not to say that Kevin is always right, but a prerequisite to anything is being smart and questioning...and Kevin deserves a lot of credit for this.
Best Wishes, Traveller
Glibertarians want foreigners telling Americans how we should live our lives. They want the FDA gone so they can force Americans to buy their rotted products.
"In this Rio de Janeiro hilltop redoubt..."
So in other words, a public agency requires verifiable information to address a problem that scientists, geneticists and medical staff are invested in finding solutions to. And one of the solutions is to keep knocking on their door and saying 'look at this.'
That, too, seems like an essential role that citizens play a part in. Could the agency be faster and devise criteria to gain faster emergency approvals? Maybe. Maybe an agency independent of political pressure could work better.
We like the government programs that are effective, like the USPS had been for over a century. Until a politician bent on stealing the election appointed a supporter to slow it down. So even a non-Libertarian like me has incentive to keep the politicians out of the hair of the FDA, the USPS, etc.
The FDA is fine. It can do better, no doubt. In a time when it's under pandemic pressure, several mistakes were made. They should publish a record of what was said when and whether they conduct ongoing internal reviews and define the correctives they're employing to prevent recurrence.
Also, a blogger erred. He, too, should issue a statement to retract them.
The less power and influence these people have, the more likely they are to double down on their original idiocy. It kinda goes with the territory if you're a libertarian.
Thank you. Awesome correction!
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I would love to know which journals declined to publish.
There's a lot of "how do I write my article so I dont offend reviewers when I explain how they've been doing it wrong all this time." She probably didn't get that balance right.
In the medical field, it can be tricky to get the proper reviewers. To many people going after the same pot of money.
Alternatively, extra-ordinary claims require extraordinary evidence. A small trail, no matter how impressive, does not carry a lot of weight.
The topic is somewhat esoteric: the audience for that article is mostly people who manage parenteral nutrition in children. It isn't clear that the results hold important general lessons for other branches of medicine. So I think the number of journals that would be interested in the topic is pretty small. Some nutrition journals, or maybe a hepatology journal might go for it. It's not going to get picked up by a broad-based journal like JAMA or NEJM. Actually landing a paper anywhere can be hard in those circumstances.
I actually think publication in Pediatrics was a surprisingly good "hit" for that paper--it's not like this information is something that pediatricians in general are involved with. So I think they ended well.
So... it all hinged on the company submitting an application, not that we had an unintentional single-blind study going on with kids dying in the US to something they weren't in the EU?
Ancient history
The FDA has historically been slower than other countries. Thalidomide was approved in the UK but was still pending in the US when the link to birth defects was established. The US avoided this disaster by FDA slow process. More recently, the process was made faster.
In 1998, signed legislation reduced the approval time
Clearly these patients should skip the drugs and instead drink the miracle spring water provided by Peter Popoff.
https://www.truthinadvertising.org/peter-popoffs-miracle-spring-water/
I work in an FDA regulated site They all seem pretty smart to me, but anyone who works for the government is an idiot if you are a libertarian.
Lots of interesting information here from the initial details Kevin discusses actually being from a well known crank to Kevin’s investigation of the matter and exposing more misinformation from this fellow. I’m a researcher/educator in biological sciences and the simple fact is that the scientific review process relies on asking very busy people to do more things, which they readily do as that is part of the job. Yet, it is only part of the job which means very little can happen quickly especially in medical sciences in which humans are involved that, logically, require much scrutinizing before appropriate paperwork is approved just to initiate the studies themselves, never mind publishing the results. Mistakes, bad science and fraud happens which is why science is peer reviewed and, when mistakes are discovered and verified retractions are usually made. One can only get funding, internal or external, if one plays by the rules and has earned the respect and trust of colleagues.
I think this is somewhat unfair by Kevin.
If you read Scott's entire article, the point he REALLY cares about is something Kevin completely ignores:
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I mentioned in a section of my recent post, “Sympathy For The Devil”, that I think the FDA as an agency is often quite good. They’re smart, caring people, and they usually carry out their mandate well - so well that the few exceptions, like aducanumab, are highly newsworthy. I have no objection to Dr. Gura’s mostly-positive portrayal of them.
My problem is: doing anything in medicine is illegal until you clear a giant hurdle. To clear the hurdle, you have to pay millions (sometimes billions) of dollars, fill in thousands of pages of forms, conduct a bunch of studies that can be sabotaged for reasons like “this drug is too good so it would be unethical to have a control group”, and wait approximately ten years. You have to clear this hurdle to do anything, even the most obviously correct actions. Everything starts out illegal, and then a tiny set of possible actions is exempted from the general illegality. The easiest name for this hurdle is “the FDA”, since they’re the agency charged with enforcing it.
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This is part of a larger social issue that US society has become paralyzed at the very idea of having to make tradeoffs. It's considered unacceptable to even consider that one person might be hurt along the way to helping a future ten million people. We all know that that blindly allowing anything goes is problematic, but we've pivoted so aggressively to nothing goes that we are (by the standards of any sort of ethical calculus) hurting future humans.
This is Scott's real complain, a preference for virtue signaling by demanding "no-one should ever suffer ever [as a result of medical experimentation]" while ignoring the flip side of that, how many people will suffer as result of not doing those medical experiments. His point is: doctors are not demanding to construct human centipedes; even the most ridiculously non-problematic interventions are thwarted by "the system". And this is not being done on rational grounds, it's being done on virtue signaling grounds, by people who have no idea of the carnage they are causing because they have no interest in medicine beyond how it can be one more club in their political arguments.
With all due sympathy to Scott Alexander about the difficulties he faced with his IRB, he simply has no understanding of the flip side of the equation. Like many libertarians, Scott has a rose-colored view of human nature and thinks that if people are just freed of all constraints, wonderful things happen. Would that it were so; but the rest of us have to live in the real world, which is full of predatory people.
I served on the IRBs of two different institutions for a total of 21 years. And while I never saw an application proposing to construct human centipedes, I can tell you that at every monthly meeting there would be at least one application for a study that was truly scary. One example that stands out in my mind was to get people drunk on alcohol and then test the effects on some part of their brain by having them drive a car (on a road, not a simulator) while wearing electrodes attached to their heads. Seriously! Every month there would be at least one study where the consent form contained language that was seriously misleading, usually in the direction of concealing risks or hyping (possibly non-existent) benefits. It's unfortunate that the extreme cases push us to create hard-to-deal-with bureaucracies when most researchers are smart, competent, and well-intentioned. But much of life is like that. The few spoil things for the many.
In my 21 years on those two IRBs I can recall only one occasion where the IRB, in the end, disapproved a study that I thought was reasonable to do. In truth, with a little patience and good writing skills, nobody faces a real obstacle to sound research from their IRB. Delays, yes, but obstacle no. Getting funding is far more of an obstacle. Lots of good ideas never even make it to the IRB because the resources to do them just aren't there.
Also, experienced researchers soon learn how to write clearer protocols and consent forms, and how to design their studies in ways that minimize unnecessary risk. The experiences Scott had with his IRB were, if I recall correctly, on his first IRB application. Well, yes, there is a learning curve for this. If he had pursued a research career, I have no doubt he would have mastered the task.
So you think that, to take an especially pertinent example the unwillingness to allow human challenge trials for covid was justified? That these either
- represented a monstrous manipulation of individuals or
- would not result in data we could not otherwise learn or
- would not have enough payoff to be ethically justifiable?
Before you answer, remember that the rest of the world outside the rich countries also gets covid...
I don't know enough to make an assertion either way but I would say
- the people I mostly respect are mostly in favor of such trials
- we have at least 250 years of history in this space with, overall, massive payoffs
"thinks that if people are just freed of all constraints, wonderful things happen"
How can any rational person believe this. It's the triumph of wish over reality.
This is not about the FDA. It is about whether humans, as a species, possess language.
What Alexander writes is not language. It has affect, and the affect is a signal. But it has no semantic content, even though it is quasi-verbal. It could be translated, without difficulty, into interpretive dance; it could be replaced, with some loss of topicality, by a primal scream. To engage with it, or with anything like it, as if it were language is a category error.
You got it entirely correct, both the analysis and the prescription. Good show, sir! To which I would add that you should treat people like this as if they are very directly insulting you to your face. Which they are.
Some are, some aren't. (Not an excuse.) There is more than one kind of performance; and for each performance, there is the audience, the anti-audience, and the non-audience. Even within this example, the audiences for Alexander's original post, and those for his re-rebuttal, seem not to be the same.
Someone has pointed out that the beautiful birdsong that greets each sunrise actually consists of an equal mixture of indecent propositions and death threats. At least they know their audience(s).
Yeah, well, maybe they don't think they're being insulting when, say, they refer to someone's minority ethnic or racial background by using an old and demeaning epithet for that group -- "Hey, that's what everyone called them when I was growing up!" -- but that doesn't mean that gives them an automatic pass on their objectionable conduct. No, the correct response when that happens is to call the offender on their conduct and tell them that they aren't going get to unilaterally decide what's insulting and what's not. Not now, not in the future, not ever.
Nasty, brutish, irritable short bowel controversy.
It does seem to me that there's something wrong with the idea of a binary yes/no decision on a drug / treatment. For example, people were criticizing the decision to approve the Alzheimer's drug. It seems to me that the FDA should not have to render a binary yes/no judgement on that drug, but a mild presumption for, or a mild presumption against, with exceptions allowed in either case. And the company should perhaps be compensated for their fixed costs with some kind of lump sum payment, and then have to charge close to the marginal cost to patients who choose to try the drug.