Very interesting podcast, much recommended. A few thoughts:
1) The symbolic lynching of Vinay Prasad is a vibrant testimony to the utter mediocrity of legacy media and media-savvy medical commentators. All critical faculties have evaporated since 2020 when the opportunity for self-righteous intellectuals to present themselves as ideological warriors defending "science" presented itself. They just couldn't resist, and thus pounced on a scientist who was a Bernie Sanders supporter and has been fighting against Big Pharma for years with rare integrity - in other words, who was one of them -, all the while presenting this dubious feat as a righteous fight against Trump.
2) The notions of left and right are now in fact completely warped. Instead of wondering why there are so many former liberals in the MAHA administration, starting with RFK Jr who was a Democrat all his life and has the track record for it with his environmental fights, the American intellectual left has decided to go all in on the politicization of science. If people are hired by the Trump administration, then these people's views must be the "wrong science" or "the opposite of science."
It of course never crosses their minds to ask why on earth *they* are supporting Big Pharma with so much gusto, i.e., private interests now openly colonizing the American state to make it essentially fund with taxpayer money their increasingly shady products - increasingly shady because they are openly and covertly influencing regulators, who then close their eyes on minor shortcomings of eyewateringly expensive medicine, such as killing patients. "If it costs 3 million dollars per patient, it must be good" seems to be the new mantra, and never mind if the patient dies, poisoned by the drug: we paid, so it's the proof "we tried to do our best for people because we care."
Prasad should be the left's hero for trying to curb that egregious corruption and distortion of common sense, and instead the left is dogmatic enough to vilify him. Self-righteousness reigns supreme.
3) Which leads me to my third point: be it with Prasad, with the Covid vaccine for infants, or with the glyphosate saga, the pharmaceutical industrial complex is clearly winning. I worry it's already too late to stop its expansion: when an industry owns the media, part of the medical corporation, and a sufficient number of Congresspeople, there already is no one left to curb that power.
The intellectual class could and should have been that last opposition, but they were corrupted with a different currency: hubris. It was enough to dangle in front of them the carrot of "caring for each other" and "being smarter than the idiots" (conveniently all Trump supporters) who "don't understand science", and they were all in. As a historian of Stalinism with a special emphasis on Stalinist intellectuals, I alas know this process all too well.
What I never imagined in a million years is that the history books I was writing would become real life again in my own lifetime. I naively thought the critical mind taught for generations of scholars in the twentieth century would bear fruit and blossom in a wiser, more mature society; instead, we can now bear witness to the fact that critical mind is *still* easily knocked down by ideology.
I'm not sure anything can be done anymore about the financial domination of Big Pharma and its taking over Western and international institutions. I like to periodically remind the genius of John le Carré, who correctly identified Big Pharma as the next big threat after his Cold War novels. And as The Constant Gardener shows, the industry will go to any extent to consolidate its power.
But I do know from history that Stalinist intellectuals do wake up at some point when they realize their lofty beliefs turned into disaster and the bright future they believed in failed to materialize. Years later, they opened their eyes, astonished and ashamed at what they had done. What is more to the point, they set out to repair their own mistakes, which is exactly what we need today.
That road will be long. However, I do have one small hope to accelerate the process, and that hope lies in the uncovering of Covid's origins. Covid has the peculiarity of having been at the crossroads of the pharmaceutical industrial complex (that the left now openly supports) and of the military industrial complex (that the left still opposes.) That Covid was a lab leak or not, the investigation of its origins has at least provided abundant evidence that seriously invested research was led on coronaviruses in the past decade in the lofty, all be it greedy, hope to produce a vaccine and drugs against them (pharma complex), or in the much less lofty, and at least as greedy, hope to produce a biological weapon (military complex.)
That much is a fact. If definitive proof of the lab leak surfaced to cap it all, it might be the last drop that would unleash the watershed that might finally start to awaken people. I'm calling again on people like @DrJBhattacharya to make it happen!
Groupthink or Evidence Based Medicine?
Power of zero clinical trial data
🤷♂️
If only all these words were based on RCTs
Meanwhile experts stay silent on the massive misuse of this test in the community
The swamp continues their single-product lobbying campaigns.
A fun Fortnight in Medicine today. Interesting articles and some good disagreement. I still can't stop thinking about the hyponatremia, and will have another piece following soon. https://open.substack.com/pub/sensiblemed/p/this-fortnight-in-medicine-xxi?r=n8zko&utm_campaign=post&utm_medium=web&showWelcomeOnShare=true
Decrease in ovarian cancer likely attributable to increased oral contraceptive usage. The rest relate to smoking cessation.
Not sure this is the effect of "war on cancer".
Substantial progress has been made in a few cancers, but in the aggregate still harsh.
Super interesting. This aligns well with FRAIL AF which found > bleeding from switching
But, neither these authors nor the editorialists, cite Nicolau et al [JACC 2025] COMBINE AF substudy, which was an elegant substudy of the 4 DOAC v warfarin trials, which found no net diff in frail Vit K naive pts randomized to DOAC. COMBINE was a substudy but an elegant one in that it preserved randomization
What I worry about w the below obs study is confounding because maybe the switching group was inherently more ill
Will cover on TWIC Friday.
See my Aug 8 2025 coverage of COMBINE AF https://www.medscape.com/viewarticle/1002796
$qure
Serious Q: If you think the FDA should approve any drug (let alone a brain injection that’s $3M a pop) based on a negative RCT with N<40 and a “study” that gave it to 12 people who were then compared to a “historical control” cohort, why not just abolish the FDA?
What I love about this essay is how skillfully TR captures the point of view of the patient with rare disease. And… Why it’s so important for them that new therapies pass an evidentiary bar
Indeed the patients w rare disease should be most sad about Vinay’s departure
FDA's only honest vaccine regulator was ousted by Moderna, a bunch of biotech investors like Martin Shkreli who bet on the wrong multimillion dollar rare disease drug, FDA bureaucrats who don't want to say no to any vaccines, and a pharma trade press full of people with personal resentment toward a skilled communicator with a biting critique of their terrible COVID reporting.
The final press pile-on that did in Vinay Prasad was that he had the temerity to host a press conference. I thought reporters liked those? I guess not if you're writing for pharma rather than the public.
This has been very clarifying for understanding why people in Vinay Prasad's position in the past have been steamrolled by pharma over and over again. If you say no to the wrong drug, you'll face a massive pressure campaign and termination. Seemingly incomprehensible decisions on Elevidys and Aduhelm suddenly make sense. We're witnessing the counter-example of what happens when the FDA doesn't blink.
I could have talked to @AlexBerenson for much longer than one hour about what it all means, and feel that I personally omitted a lot of critical points. But it's a start, with more to come.
but the propensity matched control analysis shows benefit so it must work.
There's no magazine, news outlet or pharma rag that's going to give as thorough, accurate, and objective writing on the FDA than Dr Koka.
Must read.
This is one of the best pieces I’ve read in a long time. Many thanks to @anish_koka for this superb piece and thoughtful recounting. Those who really know @VPrasadMDMPH know he will do even more good and rise even higher.
A brilliantly insightful analysis of an infuriating situation. The same people who drove him out cry about health care costs, and don't connect the dots. And never mind the safety and well-being of patients, which they give lip service to but then turn around and crush with their biased reporting.
"He was, in the parlance, not a team player. Which is another way of saying he was honest about what he saw."
Excellent analysis on the tenure of @VPrasadMDMPH at the FDA and why it was always going to end this way.
Our institutions have been corrupted.
We are tilting at windmills.
https://open.substack.com/pub/anishkokamd/p/how-vinay-prasad-came-to-washington?r=f431i
“A total of 242 pts were randomized…”
I’m not sure I can think of a more effectively marketed medicine than finerenone: NEJM publishes a tiny trial w a surrogate marker
The sky is blue and every F trial is positive. (Except they never use generic MRA as a comparator)
I have a daughter with a rare disease, and I’m a doctor who takes care of patients with rare diseases.
I want effective therapies to come to market with a reasonable safety profile.
The current ecosystem prevents that.
But sure @bioxxtrader is the one with the ethical takes
It shocks me that those who holler about disparities of US healthcare and its outlandish costs are happy that pharma $$ ousted a person interested in preserving value. Just shocking. @VPrasadMDMPH we are happy to have you back at @Sensible__Med
Vinay Prasad was incorruptible and he was rewarded for that with smears in the press (including a widely broadcast fake sexual harassment accusation) and now a legal threat from a sitting congressman. As corrupt as I knew the FDA was, it’s so much worse than I realized.
Gosh. “Propensity matched” AND “historical control”. That’s bad x bad.
If that’s the bar for approving million dollar therapies, regulation is utterly broken
this is good
if we don't care about evidence and let regulation be led by what pharma wants, just gut the entire FDA, let the market decide, and let CMS negotiate prices
i would prefer an fda that approved based on efficacy and safety
absent that, gutting the fda is preferred over this lousy compromise of fake regulation
does the gene therapy for HD work?
what is the evidence other than the company being upset?
was it better than the placebo?
not surprised, but disappointed not part of the story
summed up in the closing:
"The agency’s maximal flexibility in Duchenne stands in stark contrast to the way Huntington’s patients are being treated..."
that DMD therapy had horrible evidence and killed young boys without benefit
Tristan (@SharkStats ) is on target.
Approving a $3million/pop gene therapy drug that requires drilling into the skull and a brain injection should be based on... checks notes... a propensity score matched historical control arm. (If you can't appreciate the insanity of this sentence, you should comment zero times about science and evidence)
That is exactly what the biotech/investor community who cares so much about Huntington's disease patients would base approval on.
And then comes the surrogate data. It takes a few minutes of reading to understand how incredibly flimsy that is in the case of Huntington's disease.
The Roche/Genentech product tominersen you haven't heard of that failed was also very promising because it decreased a key surrogate biomarker: mutant huntingtin (mHTT) levels in CSF. But when the Phase III GENERATION HD1 trial ran, lowering mHTT didn't translate to clinical benefit.
The failure was particularly alarming precisely because tominersen did lower mutant huntingtin levels — the surrogate worked — but patients didn't benefit clinically. In fact, patients receiving the drug more frequently actually did worse than placebo.
From the GENERATION HD1 data:
The every-8-week group (higher exposure) showed:
cUHDRS scores significantly worse than placebo (–0.54 points, p=0.001) — this is a composite of cognition, motor function, and functional capacity, trends toward worse Total Functional Capacity (TFC) scores, and elevated CSF NfL at week 21 — suggesting active neuroaxonal damage was occurring.
So now since we can't use mHTT as a surrogate -- we have another unvalidated surrogate --
NfL (neurofilament light chain) is a marker of neuroaxonal damage/neurodegeneration. It's validated as a marker of injury, meaning it rises when neurons are damaged, correlates with disease severity and progression rate across multiple neurodegenerative diseases (HD, MS, ALS, Alzheimer's), and tracks with known disease milestones
But same issue with mHTT : it's validated against disease activity, not against treatment response leading to clinical outcomes. So we know high NfL = more neurodegeneration, we know NfL falls with some treatments, but we have zero robust proof that drug-induced NfL reduction → clinical benefit.
So of course we should get excited about nFL changes and scream bloody murder when someone asks to actually do an RCT to make sure we aren't hurting people, and are paying for something that actually has benefit.
If I was VP, I would get the hell out of this toxic dump, where the only people that care about rare diseases weirdly enough are biotech investors.
He has done a great service to expose the various players within the existing corrupt ecosystem of "news" reporters, pharmaceutical companies and the biotech investor communities.
The FDA has evolved into a giant wealth extraction tool that siphons US citizen dollars in the form of taxes and premiums to various bank accounts domestically and around the world for products that don't work or work marginally better than what already exists on the market.
Deep structural changes are needed, and it can't happen from inside this ecosystem.
We literally have academics now defending drinks with 100 g+ of sugar!
There are many choices short of bans of sugar:
* education
* bully pulpit
* warning labels
* surcharges/taxes
* age requirements
We did all of that for tobacco and it has been massively helpful!
Why is a governor defending drinks with 180g of sugar?!?
That is like 5 slices of chocolate cake or 12+ glazed donuts in one drink
Seems like a recipe for obesity, diabetes, fatty liver disease, and more
@dunkindonuts should do better
false equivalency
If we truly don't know one way or another then the philosophy question is relevant
but when you overrule on hype with scathing evidence to the contrary, that is not a philosophical decision
Peter Marks is responsible for those boys with DMD who died. I don't say that lightly
Not hindsight bias either. Was known at the time. Read piece in thread
RE: UniQure's experimental treatment for Huntington's
I don't think there is enough publicly available info to properly adjudicate
It seems like the reasons this is "bad" is coming from the company who stands to profit mightily and because of who the FDA regulator is
FWIW, this journalist has a clear public record of bias against said regulator, so take his reporting with a grain of salt. You know the take before its even written
And this journalist, like many health journalists, function more like Jim Cramer of biotech than someone steeped in regulatory science. You actually need to appreciate trial design and appraisal to have thoughtful reporting
Because the 12-month results were the random blinded results. At best, after a failed trial, open-label results can only be seen as hypothesis-generating.
In fact one can argue this therapy has already failed and even testing it again is unethical, though I wouldn't go that far.
The real problem here is that scientific reporters who used to be properly skeptical of novel, high-risk biotechnologies went all in on mRNA and are now stuck defending it and every hype job the industry offers. They're being used, but they hate @realDonaldTrump too much to care.
If the company ACTUALLY believes the drug works, it should be happy to run this new trial. In fact, it should have started it years ago.
I don’t appreciate Janet Woodcock being quoted in a new The New York Times piece as saying:
“The Huntington’s refusal I thought was truly evil. I just feel so bad for those people.”
These are difficult regulatory decisions involving uncertainty, evidence, and patient risk. Regulators are often weighing two difficult possibilities: delaying access to something that might help, or approving something that ultimately does not help or could even cause harm.
Reducing those trade-offs to moral language like “evil” does not help the public understand the real scientific and regulatory questions at stake.
When you see people criticizing @US_FDA decisions, FOLLOW THE MONEY.
💰 Former FDA commissioner on Pharma's payroll.
💰 Former Senator (who received the most Pharma $$ of any incumbent in his last race) turned paid Pharma consultant.
💰 Massachusetts politician funded by more than a dozen Pharma donors.
The Trump administration is fighting the swamp & ending FDA corruption.
@DrMakaryFDA is enacting historic reforms to deliver more cures in record time.
The FDA does not belong to Pharma.
It belongs to the American people. 🇺🇸
This is a lie -
At least per http://clinicaltrials.gov site : sham surgery defined as “simulated surgical procedure with skin incisions only, “ .. specifically says : “ no intrastriatal injections and no burrholes through the skull”
Link to which fda official is demanding burrholes as sham?
https://clinicaltrials.gov/study/NCT04120493?tab=study
😂
Albert Bourla has your best interest at heart.
I swear.
I’m not sure it’s a bad thing that an industry CEO has a problem w a regulator. https://www.fiercepharma.com/pharma/pfizer-ceo-bourla-cber-chief-prasad-we-have-problem-leadership-cber
This is because it fundamentally cannot complete the single most important exam in all of medicine: does the patient look sick?
no, can't use survival
it bakes in lead time and length time biases and will always make screening look better, even if it doesn't change mortality at all
wrong metric
need to look at age-adjusted mortality
Something a little different today on @Sensible__Med
Diagnosing the Dead https://open.substack.com/pub/sensiblemed/p/diagnosing-the-dead?utm_campaign=post-expanded-share&utm_medium=web