Love that @Sensible__Med publishes these 👇🏻
From 0 to 1: My take on the NEJM single-trial FDA paper
I went in somewhat skeptical but came away much less so. My overall impression is that this is a clever way of pushing toward better single-trial applications, which in many cases has already been the practical status quo. Framing the approach as one trial plus confirmatory evidence judged on robustness across several factors (with rights reserved) makes sense, and I can see how it could lead not only to stronger trials, particularly with good comparators and ideally clinical endpoints, but also to stronger reviews.
A few things that stood out to me:
• The emphasis on internal credibility across multiple dimensions was compelling. I read it as prioritizing internal validity over automatic external replication, while still keeping replication as a tool the FDA can require when needed.
• It also seemed loud and clear that using the best comparators will be key.
• The mention of surrogate outcomes seemed to subtly advantage clinical outcome endpoints, maybe intentionally.
• I also thought it was good to note this is being rolled out synchronously with an initiative to collect robust data postmarket. That feels like a key element people will be watching closely as this plays out.
Overall, I found the argument thoughtful and more nuanced than I expected going in. And the more I sat with it, the less this read as a shift from two trials to one, and more like a push from zero robust trials toward one truly robust trial.
Excellent story by @emilyakopp that highlights how much of a rubber stamp for big pharma the FDA had become.
This is the biomedical industrial complex again in plain sight.
Funding is the metric, funding becomes the goal.
A department chair celebrates the amount of federal money extracted. A ranking metric and his compensation are tied to grant volume. Notice what’s missing: no mention of scientific breakthroughs, no discussion of patient outcomes — just money.
It’s really quite striking.
Fluarix is approved for > 50 year olds, despite the fact that:
1. Clinical efficacy RCT showed benefit that was entirely in 18-50 year olds.
2. 50-64 year old efficacy was 13.6% , CI lower bound -135.
3. No clinical data in > 65 year olds, only antibody thresholds hit which may not clinically correlate in >65 year olds
CDC ACIP specifically recommends three other flu vaccines for >65
What does Moderna do when choosing comparator to its mRNA flu vaccine targeted to >50 year olds —> Fluarix!
😂
I read the NEJM piece carefully and read Vinay's previous paper on the same topic (screenshots in thread)
Moves from strict adherence to 1-2 RCTs toward a more context-sensitive position (because once in the shoes of the regulator different perspectives to now consider?)
What I like:
Still maintains a high evidentiary standard for trials, which we often did not see before (ie surrogacy, bad controls)
Retains flexibility to ensure a 2nd trial if first one sucks or is unclear
What I (really) don't like:
Creates a framework that works best under a regulator with higher evidentiary bar since a lot of this is in the eye of the beholder. So yes if Vinay, but slippery slope if Peter Marks (or any other past predecessor). That worries me since gives more wiggle room to lower the bar
Who decides whether vaccines are safe? Is it the FDA, or all of the editorial boards that Blackstone Life Sciences can buy?
If you thought after COVID the press would make more of an effort to assess evidence soberly instead of dutifully reciting pharma talking points and swaying along to online tribal loyalties, you'd be DEAD WRONG.
The Moderna mRNA flu vaccine has ambiguous benefits and extraordinary side effects and could be a net negative for public health.
https://www.racket.news/p/fdas-straight-shooter-dont-bring
🚨 WHOA: Dr. Marty Makary says the FDA caught Moderna using a “substandard of care” in the elderly control group for their new mRNA flu vaccine clinical trial, which “needlessly exposed” those unvaxxed patients to a higher risk of influenza complications
Why would Moderna do this? 🤔
The media learned nothing from COVID. Reporters covered what happened with Moderna's mRNA flu vaccine in a deliberately confusing way, as if they work for the drug company.
Here are some things you wouldn't know from reading the legacy press but will read in RACKET:
- Moderna compared its mRNA flu vaccine against a flu vaccine that CDC doesn't recommended for seniors and only has ~14% efficacy in people >50. It could be as low as 0%. This is a trick drug companies use to inflate apparent efficacy, but it's unethical. You're not supposed to deny people in the control group the best standard of care. And Moderna didn't answer my questions about that.
- Both the Biden and Trump administrations told Moderna that it should pick a vaccine that the CDC actually recommends in seniors to compare with its mRNA one.
- Moderna had evidence four years ago its mRNA flu vaccine was actually worse than the standard of care for seniors, but plowed hundreds of millions into the vaccine anyway, daring the FDA to say no (and it actually did!).
- Rates of fever and chills were higher after the mRNA flu vaccine than after flu cases in Moderna's clinical trial. Rates of serious side effects that keep you in bed were much higher for the mRNA flu vaccine.
- It took the refusal to file to force Moderna into finally committing to study the efficacy of its mRNA vaccine against one of the flu vaccines that CDC actually recommends for seniors. This has been painted by the media either as a dangerously unhinged move (last week) or a capitulation to Moderna (this week) depending on which makes Vinay Prasad look worse any given day. The end result: FDA is finally getting the data it wanted.
I’m not sure there are any therapies w more negative trials than cooling after cardiac arrest