AP wrote a bizarre story that claimed FDA's Beth Hoeg was a "friend" of physician Adam Urato which is a "conflict of interest. HHS has no legal definition of "friend" and COI forms don't ask you to list friends.
AP also ignores peer reviewed research
Academic medicine circa 2020-2024:
Dr. Anish Koka and Dr. Anthony DiGiorgio open with the little-known medical story behind the death of the Shah of Iran — how Mohammed Reza Pahlavi came to be operated on in Cairo in 1980 by legendary cardiovascular surgeon Michael DeBakey, and how the "comforting explanation" bias may have contributed to his death from a post-operative abscess rather than his underlying cancer. The case, drawn from a piece by Dr. Li Zhao (NYU Langone), launches a broader conversation about anchoring bias in medicine and the cognitive traps all clinicians face. From there, the hosts turn to the quality metric industrial complex — MIPS, the new low back pain ambulatory model threatening a 12% Medicare penalty for spine surgeons, the hospital readmission program's documented mortality spike, and how 2,266 CMS metrics are costing billions while failing patients. They close with a NEJM perspectives piece from Harvard Business School's Leemore Daphne on health insurance consolidation and her surprisingly free-market prescriptions for reform.
Chapters
00:00 Introduction
02:00 The Shah of Iran — Political Background
03:45 The Shah's Leukemia and Michael DeBakey's 1980 Surgery
06:30 A Spleen the Size of a Football
08:00 The Decision Not to Drain — And Its Consequences
10:00 The Comforting Explanation Bias
12:30 Subspecialization Matters — The Most Famous Surgeon Isn't Always the Right One
14:45 Anchoring Bias in Clinical Medicine
17:00 Modern Imaging and Residents as Checks on Bias
18:30 Surgeons, Complications, and the M&M Conference
21:00 Segue: Judging Doctors by Stats
22:30 The Origins of Quality Metrics — Donabedian 1966
24:00 MIPS and How It Actually Works
26:00 The New Back Pain Ambulatory Specialty Model — A 12% Penalty
28:00 Evidence That Metrics Harm Patients: Hospital Readmission Reduction Program
30:30 Obstetrics and the C-Section Penalty
31:30 Press Ganey and the Cafeteria Problem
33:00 Risk Adjustment Gaming — 40% Margin Increase from Coder Rounding
38:00 2,266 Metrics and 108,000 Person-Hours at Johns Hopkins
40:00 Why Doctors Leave Medicare
42:00 What Good Metrics Could Look Like — Dr. DiGiorgio's JAMA Proposal
44:00 Health Insurance Consolidation — NEJM Perspectives
50:30 FDA, Vinay Prasad, and the WSJ Retraction
55:00 Next Week: Kevin Bass
Subscribe to The Doctor's Lounge: Apple Podcasts | Spotify | YouTube Follow the Show: X: @DrsLoungePod Co-hosts: @anish_koka | @drdigiorgio
An excerpt : When you can't rebut the facts, pharma bros count em dashes.
Sarepta and Duchenne Muscular Dystrophy
To understand what Prasad walked into at CBER, you have to understand what his predecessor Peter Marks had already done there — and what Marks’s predecessor Janet Woodcock had done before him. The Sarepta story is not one bad decision. It is a decade-long institutional pattern of FDA leadership overruling its own scientific staff to approve drugs that didn’t work, under pressure from patient advocates that the companies themselves helped organize and fund.
It starts with Exondys 51 (eteplirsen), approved September 19, 2016. Sarepta applied for accelerated approval based on the claim that the drug increased dystrophin expression in boys with a specific Duchenne variant. The FDA scientific advisory committee reviewed the data and found it inadequate — voting 7-3 against full approval and 7-6 against even accelerated approval. Reviewers cited poor quality biopsy data, no adequate controls, no evidence of clinical benefit, and a dystrophin expression assay that was later independently debunked by the FDA’s own analysts. Committee members also noted on the record the “intense and near-incessant pressure from a large public audience” packed with patient advocates, all of whom testified in favor of approval. Janet Woodcock, then Center director, approved the drug anyway. FDA reviewers responded by filing a formal complaint — a virtually unprecedented act — noting this could be “the first time a Center Director has overruled a review team on a question of whether effectiveness has been demonstrated.” FDA Commissioner Robert Califf issued a 126-page report acknowledging the problems but declined to overrule Woodcock, instead mandating a confirmatory dose-finding study using the North Star Ambulatory Assessment as primary endpoint, which he said would settle the question of whether the drug worked.
That study, the MIS51ON trial, was started in 2020 and as of this writing remains active with no results reported — a decade after the drug was approved. But here is the detail that makes the entire exercise even more farcical: MIS51ON has no placebo arm. It compares higher doses of eteplirsen against the already-approved 30mg/kg dose. It cannot, by design, answer whether eteplirsen beats placebo. It cannot confirm clinical benefit. When it eventually concludes, the foundational question Califf said would be settled — does this drug actually work? — will remain exactly as unanswered as the day Woodcock approved it. Exondys and three successor drugs remain on the market, all approved substantially on the basis of dystrophin protein expression levels. Whether any of them meaningfully alter the natural history of Duchenne muscular dystrophy remains, in the precise scientific sense of the word, unknown.
This is the context in which Catherine Collins stood up at a 2024 patient conference and confronted a Sarepta representative directly: five drugs on the market under accelerated approval, confirmatory trials years overdue, a $3.2 million-per-injection gene therapy being promoted on the basis of a failed primary endpoint trial. “You don’t think you can do a little more effort, and give us a little bit more information?” she told them. “You’re just... taking money.” The video is worth watching. As I've documented in detail prior Elevidys was rinse and repeat.
The Phase 3 EMBARK trial — the definitive test of whether the gene therapy actually improved motor function — failed its primary endpoint. North Star Ambulatory Assessment scores showed no significant improvement over placebo. FDA staff again recommended against approval. Peter Marks, who had taken over CBER from Woodcock, overruled them, granting accelerated approval in June 2023 based on micro-dystrophin expression as a surrogate. He then expanded the approval in June 2024 to include all patients four and older, ambulatory or not — including older, non-ambulatory teenagers who had been explicitly excluded from the original trial that formed the basis for that approval.
Then boys started dying.
The toxicity should not have come as a surprise. The AAVrh74 adenoviral vector used to deliver the therapy was known to be highly immunogenic, triggering immune responses that caused severe liver injury requiring heavy steroids and immunosuppressive agents. Two of the teens who died were older, non-ambulatory patients — precisely the group Marks had added to the label on the thinnest of evidence, and precisely the group excluded from the trial. A third death, a 51-year-old man in a separate Sarepta trial using the same vector, was reported to the FDA on July 3, 2025. CEO Doug Ingram had known about it before the company’s June 16 earnings call. He made no mention of it. When later asked why, Ingram explained the death was “neither material nor central to the topics at hand.”
Prasad, now running CBER, responded on July 18 by requesting that Sarepta voluntarily halt Elevidys shipments and pause trials. Sarepta refused — publicly, in a letter stating it saw “no new safety signal in the approved population” and attributing the deaths to “unique patient conditions.” They eventually capitulated on July 21. But behind the scenes, the machine was already in motion.
Laura Loomer — the MAGA influencer who had previously claimed the scalps of several Trump administration officials for insufficient political loyalty — published a hit piece painting Prasad as a “progressive leftist” sabotaging the “Make America Healthy Again” agenda. She cited his past public admiration for progressive politicians and accused him of obstructing Right to Try. The piece arrived with suspiciously precise timing and suspiciously detailed FDA process knowledge for someone with no obvious reason to be tracking CBER’s drug review calendar. The fingerprints of biotech interests protecting a $3.2 million-per-injection franchise were not difficult to find.
The irony was almost too rich: the same MAGA ecosystem that had spent years insisting mRNA COVID vaccines were dangerous gene-modifying experiments was now furious that a regulator was asking hard questions about an actual gene therapy linked to multiple deaths in young boys.
Wang's case shows how politicized medicine has become. We need environments where data comes before ideology, ensuring scientific inquiry doesn't cost you your career.
lol.
Remember, its all about the patients.
I do love it when academics who literally will try to end your career for disagreeing with them give lectures about civility and divisiveness on here.
R to @anish_koka: anishkokamd.substack.com/p/a…
In 2019, cardiologist Norman Wang published a peer reviewed paper on affirmative action in medicine. He argued that the institution of medicine was violating civil rights law by discriminating against Asians/Whites/Males.
Wang was a well liked/respected highly published EP fellowship director at the time. Dr. Katie Berlacher, a good friend of Dr. Gulati, and fellowship director of the same cardiology program took to twitter to call him a racist. In the next few days he was demoted from being fellowship director, banned from future contact with trainees, and his paper retracted.
I wonder if Dr. Gulati finds what happened to Dr. Wang.. divisive ?
Link to full story in reply.
Successful hospitals hire teams of medical coders. Why you ask ? @DrDiGiorgio
My own photo finish 27 years ago as I anchored our mile relay. I never heard how close he was, with roar of the crowd. My teammates yelled for me to lean. I won by 2 hundredths of a second. Never quit.
The media bias and mayor's public statement on the Gracie Mansion story is a case study in misleading narrative formation.
1/4
Liar. The only person who ever said control arm was burr holes was the Uniqure CEO, which the journalists printed without seeking confirmation about that from anyone in the FDA.
HHS 2 days later said this was a distortion of the conversation.
Incredibly malignant people.
While my heart aches for Iranians, I have zero sympathy for the regime leaders
Watch the below video and remember what happened on Oct 7
Never forget
And never forget the tens of thousands of Iranians killed in January
More people need to wake up to this.
The arbitrage for biotech is not “does the science work” it’s based on whether or not regulators can withstand the public pressure from investors/ rare disease advocacy groups /
hostile media that aren’t observers, but actual players in the field that are looking to get you fired.
Of course you can’t say that definitively. Generate some evidence that isn’t founded on a not reality historical control and let’s talk.
Otherwise you are asking society to pay $3million/therapy to drill into the brain of desperate ppl based on hopes and prayers not data.
This has significant downsides.
For any HD patients, please read about the sarepta / elevedys story. Yes it is possible to make a bad thing worse.
I have seen some scummy people in my life, but the people on this site pushing UniQure are some of the scummiest I have ever seen. They literally have no shame, although this seems to describe much of biotech. Pushing treatments that don't work, exploiting vulnerable people.
Everyone understands that even extremely low IQ regulators will be unable stop HAART for HIV, Harvoni for Hep C , CAR-T, etc.
The ecosystem wants low IQ / spineless regulators in power to approve slop that doesn’t work.
So the whole debate about threatening true innovation is just a smokescreen.
Yes, the ideological tribe that’s the problem is the one that said:
1. Locking down for infinity (hyperbole) was bad
2. Printing money to allow lockdowns would be bad
3. Masking 2 year olds is ineffective
4. Infinity boosters is the only way for society to suppress and survive COVID
5. Keeping kids remote for > 1 year was best for them
Most recent edition:
Vinay is divisive and chaotic and tribal ! because he
1. tried to pull a gene therapy that didn’t work and was killing young boys
2. Told a company with a gene therapy product with extremely patchy data that it works (oh btw it requires drilling into the brain to deliver it) to come up with better data if they wanted approval.
The real epistemological problem here is Mandrola commenting on a truncated y-axis.
Ok then.
Political tribalism is ignoring the science.
In this case, ideologically motivated to do what?
Which specific decision do you think Vinay ignored the science and made a political decision ? Sarepta? Uniqure? Moderna flu?
I looked under the covers at the actual science behind the decisions, and Vinay was correct based on the evidentiary standards that based on your feed you appear to support.
You either haven’t looked at the Science or are making a political judgement.
Trial after trial shows minimal meaningful decline - except for the company’s external historical control at 1 year.
The entire valuation of this company at this point is based on the company’s unnatural external historical control. (And their ability to control who is head of CBER)
Great job legacy science reporters. Keep speaking truth to power.
Prasad is a moron for saying we shouldn’t approve a non-working drug that requires drilling into your brain to deliver said drug.
I am also a moron for saying Prasad was correct.
Pharmabro in a nutshell.
Agree here with most of what he’s saying, but the story should be the ridiculous decisions with regards to evidentiary standards made under the prior FDA.
Inexplicable/harmful decisions made related to Duchenne’s is a good example - there is little doubt woodcock was wrong to approve exondys, elevidys killed some boys (a Peter marks decision to expand a non working therapy with serious side effects beyond the kids in the trials)
Adu also doesn’t comment on the troubling playbook I write about - to 90% of objective ppl looking at this , this is the FDA closing a loophole opened up inappropriately to give dangerous therapies to desperate patients that don’t work and make biotech loads of money.
Incorrect. I do refer to this in article
This thread demonstrates some major gaps in how to evaluate evidence.
You don’t do a sham control for safety and dose finding.
If you can’t interpret the Uniqure slides below, and identify multiple red flags about efficacy of AMT-130, whether you know it or not, you are a stock pumper not someone who impartially evaluates evidence.
Some points for those observing who don’t own stock in the company. (There is no reason other than having a equity position in the company that I can think of for a random dude/dudette sitting at a computer analyzing this)
1. The historical control arm is a suspiciously straight line even though the natural history is actually not like this.
(Don’t believe me? Look at the control arm in the RCT that are doing better than everyone at the end of year 1. )
2. About power - the sample needed to show a difference relates to the size of the effect you are looking for. If the difference is as large as they say, the same 10 person in each arm trial will show a significant gap at the 1 year mark. And for a therapy that literally requires drilling into your brain , if it takes a 100 patients to show benefit, that means a large portion of those 100 are not seeing benefit, but are all still having their brain drilled into.
Even if this is approved, which appears much more likely now that uniqure and its media partners got their way (will
Any other regulator dare to ask Uniqure for additional evidence??), any HD patients should take these serious concerns into account. If I was a HD patient I would 100% not allow them to do this to me based on the data presented because I have no idea if there’s a benefit to having my brain drilled into.
(And before you say it the surrogate data in this space is weak. Need more
Work to validate nfl as a therapeutic target. Clearly mhttt shows you can’t rely on markers of disease progression )
I hold no position in uniqure and never have.
"The law of diminishing returns reminds us: biology isn’t linear.
Pushing LDL from 70 to 30 mg/dL isn’t equivalent to dropping from 130 to 70 — the absolute payoff shrinks as you approach the floor, and the floor doesn’t even get you close to zero risk.
Plaque quantification may create the illusion of precision, but the current state of cardiovascular therapy means that most of the benefit accrues to those selling CAT scans and plaque quantification software, not patients."
I think the FDA shouldn't exist outside of controlling antibiotics, antivirals, & antifungals, but if we are going to have it, it should be a serious regulator that doesn't just rubberstamp industry wants. Vinay was so. His replacement likely won't be.
https://x.com/anish_koka/status/2030313761333031352
From Uniqure’s slide deck.
There's statistically significant separation at one year comparing to historical controls.
That result is directly contradicted by the randomized data at one year.
The sham control arm in the RCT is actually the best performing at 1 year.
I’m not against making all sorts evidentiary leaps for rare disease terminal patients, Uniqure’s data is just crap.
There only source of value is an FDA that will give them approval.
2 options : either this group can’t read graphs, or are unwilling… but please @AppleHelix go on about Mandrola and the y-axis.
These are the statistical geniuses who care so much about rare disease patients.
Then you need a good clinically validated surrogate.
If you don’t have that, you’re just drilling into people’s brains with no real idea about what you’re doing and giving Uniqure $3million each time you do so.
We’ve been down this road before - remember Elevidys killed young men
The 800-pound gorilla
HHS Appointee Study (2023): A study in Health Affairs tracked appointees across the Department of HHS (includes FDA) between 2004-2020. It found that 32% of government appointees exited directly into private industry at the end of tenure
#revolvingdoor
Again.
Complete bull 💩 .
You want to use historically matched controls to allow a drug that REQUIRES BURR HOLES and a deep brain injection.
The drug failed in an RCT. Apparently it’s also a 10hr procedure.
Yes, a working FDA should ask for better data.
“Instead, I would challenge you to embrace uncertainty, even so far as to Believe things you don’t really Know. Until eventually, with time and patience, you realize how much you really do Know – Data be damned!”
Again the hill these knuckleheads chose to defend was Sarepta and Uniqure.
Thats how you know they’re lying about it just being a vinay personality problem.
This was so good.
Consider giving it a read even if you're not interested in cardiology.
There are many homologs of this story in Oncology.
I have been in medicine for 39 years, first in academia, now in private practice. I cannot name another physician with Dr. Prasad's combination of intelligence, integrity, understanding of study methodology, and ability to accurately interpret study results. Sigh. It's hard to have hope.
Not only did the journalist decide to reveal identifying information, someone higher up then ok’d that story not being paywalled to make sure as wide an audience would know.
AI Plaque Quantification: The Billing Code from US @MedicareGov Arrived Before the Evidence Did
https://x.com/i/status/2030273007566889234 via @anish_koka
How @VPrasadMDMPH came to Washington & @US_FDA & why it was always going to end this way
https://substack.com/@anishkokamd/note/p-190196571?r=tduh3 via @anish_koka
Am I getting the journalistic ethics part wrong? Very troubling to this non-journalist.
@neerajadeshp @emilyakopp @AlexBerenson
Wow. My head has been spinning with many of these same thoughts, and Anish pulled them together remarkably quickly. Impressive