the deal:
none of these are complete without posadism
So far I've only read Harry Potter and The Methods of Rationality, but can say it is an excellent place to start.
beware the man of one book
have rules never clearly explained, get banned pretty much immediately. a taste of real reddit experience™ even that i've never got banned sitewide (only on r/conservative) i guess you win if you touch grass or quit
death of millions for profit - solid business practice, congratulations and see you again at next shareholder meeting
I'm with the old man on this one. Antibodies can clear out amyloid and still it has no effect on progression of disease, amyloid secretion can be blocked upstream (like with small molecule protease inhibitors) and it still has no effect. Maybe this one hits something off-target, or maybe that effect is not even real, or maybe it's some sort of statistical artifact. You'd stumble upon some false positive after trying so many times.
Aducanumab is dead in the water, trials shown no effect and it was abandoned by Biogen. This one is about lecanemab. Both have massive problems with brain edema and microhemorrages, which probably means these are not suitable for actual use. But don't worry, they already have received their reward - FDA wanted to have something, anything to show up for Alzheimer and Biogen cashed in when stock price went up
think cold fusion, or EmDrive, or string theory
That's a weird set - cold fusion or EmDrive can be tested and their physical principles are falsifiable - and they were - but string theory is different, because it's not falsifiable.
If it’s marginally but truly effective,
That if makes some mighty heavy lifting here. I think that amyloid hypothesis is closer to cold fusion than to string theory in that it had already a couple of fatal experimental refutations thrown at it, but people still shove effort this way because there's nothing else/copium/sunk cost combination
has he? where?
Derek Lowe has seen it coming years ago https://www.science.org/content/blog-post/lecanemab-and-alzheimer-s-more-data
But let’s stipulate that the result is real, for the sake of argument. That takes us into the very contentious question of real-world utility. As the NEJM paper says, “A definition of clinically meaningful effects in the primary end point of the CDR-SB score has not been established”. Clinicians are already disagreeing over whether the difference between lecanemab and placebo is something that would even be noticeable. That last link features a quote of Madhav Thambisetty, a neurologist at the National Institute on Aging: “From the perspective of a physician caring for Alzheimer’s patients, the difference between lecanemab and placebo is well below what is considered to be a clinically meaningful treatment effect”. This is not an uncommon take.
And that leads to question 3. A constant problem with these anti-amyloid antibody ideas is the complication of brain edema, an inflammation response that can be serious trouble. The term of the art is “amyloid-related imaging abnormalities with edema or effusions”, ARIA-E. This latest trial kept a constant watch for this, as well it should have, and any such trial also has to keep in mind the possibility of “functional unblinding” as any incidents develop. ARIA-E was noted in 0.8% of the treatment group (and in none of the placebo patients, naturally). Overall, adverse events that were enough to lead to patient discontinuation in the trial occurred in 6.9% of the treatment group and 2.9% of the placebo group. Most seriously, two patients in the treatment group have died from what could well be treatment-related vascular issues
There was also earlier anti-amyloid antibody that got approved despite showing no benefit at all https://www.science.org/content/blog-post/they-don-t-know
