11 ms·

A Positive Amyloid Trial, Finally?

37 points by kens 4y ago

resoluteteeth 4y ago
I feel like this should probably be assumed to be a methodological problem or a statistical fluke until proven otherwise at this point.
- bilsbie 4y ago
  It’s sad we’re at this point where we can’t trust anything published. We have to think about funding, politics, peer pressure, publication bias.
  - deleted 4y ago
    [deleted]
- joelthelion 4y ago
  This is not your regular quick scientific paper, though. It's the result of a very large phase three trial, involving hundreds of very qualified people, and a budget of around a billion dollars. It's as serious as it can be. Of course, we should probably wait to see what the outcome of the FDA review will be.
  - jcranmer 4y ago
    It's the press release of the initial analysis of a readout of a clinical trial. Mining the results for good news is a distinct possibility.
    - joelthelion 4y ago
      CDR-SOB is their pre-specified primary endpoint. It's a well accepted measure of dementia. Hard to do any mining there.
  - ekianjo 4y ago
    Oh like none of those has ever been hacked before. Either you have short memory or you are naive.
    - zosima 4y ago
      It definitely looks like a very clean efficacy study. This is an extremely difficult indication and almost all studies on drugs for Alzheimer's has failed previously. A study of this size meetings its primary endpoint in Alzheimer's this cleanly is definitely hard to fake. I could even suspect its easier to make a working drug for it.
- arolihas 4y ago
  Phase 3 trials are highly regulated and basically designed to not be statistical flukes.
  - ekianjo 4y ago
    of course not. you need several phase 3 studies to know if your result is not a fluke. you can always get lucky.
- gizmondo 4y ago
  With p=0.00005 it's very unlikely to be a statistical fluke.
  - ekianjo 4y ago
    Thats not what the p value says at all.
    - zosima 4y ago
      What does it say then?
llamaLord 4y ago
Hasn’t the entire amyloid theory been coming under a huge amount of scrutiny recently for being almost a mafia-like cabal of somewhat questionable science?
- ncmncm 4y ago
  Certainly about every paper nowadays is about stuff going on in a breed of mice engineered to produce lots of amyloid plaques. Hardly nobody knows or cares what happens in actual patients. The best methods we know of to protect real people against dementia are: 1. Get vaccinations. It doesn't seem to matter so much which ones. But Tdap and flu are seen to do the job. 2. Eat plenty of cheese. 3. Get treatment for herpes. I think valacyclovir is the mainstay. 4. Keep your gums healthy. There is no rigorous information to indicate why these seem to make a difference. Precious few people are looking. Certainly the people in charge of grants for Alzheimer's research are not awarding them for any such effort. When the whole house of amyloid cards finally collapses, what will amyloid specialists do with the rest of their careers? Maybe it would be smart to get a jump on that now...
  - bilsbie 4y ago
    How much of that is the healthy user bias though. Those are all things healthy people generally do.
    - macrolime 4y ago
      Healthy people generally eats lots of cheese and valacyclovir?
      - jrussino 4y ago
        You don't serve Emmenthaltrex at your cocktail parties? ;-)
      - ncmncm 4y ago
        "If you think of the vastness of space, and how enormous our galaxy is, and how big our planet is, and how small we are, I am not really eating all that much cheese."
SrslyJosh 4y ago
> As I write, Biogen stock (BIIB) is up about $70/share, a sudden 35% jump that adds billions of dollars to their market captitalization, so there's definitely a lot of optimism out there. Who cares if it's reproducible? =)
- gizmondo 4y ago
  You can short it if you think it definitely won't reproduce. Otherwise it's not clear why adding billions to the market cap is unwarranted.
- ekianjo 4y ago
  Biogen was already caught corrupting the FDA to approve their last fake drugs even though it did not meet any endpoints. Massive systemic failure of institutions.
pessimizer 4y ago
Helpful article. The headlines and editorial coverage of this made it look fantastic, except for any of the concrete information in the story I read, which made it look most likely completely worthless. https://www.theguardian.com/society/2022/sep/28/alzheimers-disease-progression-slowed-by-new-drug-lecanemab https://www.theguardian.com/society/2022/sep/28/alzheimers-d... > Success of experimental Alzheimer’s drug hailed as ‘historic moment’: Study shows cognition in early-stage patients on lecanemab declines by 27% less than those on placebo Wow, something's happening! > The cognition of Alzheimer’s patients given the drug, developed by Eisai and Biogen, declined by 27% less than those on a placebo treatment after 18 months. This is a modest change in clinical outcome but it is the first time any drug has been clearly shown to alter the disease’s trajectory. We've gone from "historic" to "modest" in two paragraphs. > On a 14-point scale used to assess Alzheimer’s progression, patients on the drug scored 0.45 higher than those on the placebo treatment, with an Alzheimer’s patient being expected to decline by about 1 point a year. That is very modest. And it's a questionnaire, not memory testing? > Howard said: “The accepted minimum worthwhile difference ranges from 0.5 to 1.0 points, [meaning] that there are going to be some very difficult conversations and decisions in the next weeks and months.” So it's not even clinically significant? They have a metric that they decided to call the "accepted minimum worthwhile difference," and this is less than that. Doesn't that mean it's not worthwhile? I'm guessing based on the name. Is this just the first of a series of press releases to start building up public sentiment that can be eventually used to avoid the controversy generated when the FDA approved the last Alzheimer's drug that definitely didn't work?
- mmastrac 4y ago
  I don't necessarily disagree with your premise, but something _can_ be both historic and modest. The first, tiny steps can show that there's something we can do about it and that's historic. Whether these benefits actually exist... well I'm on the same page as you with skepticism.
  - pessimizer 4y ago
    > something _can_ be both historic and modest. Totally agreed. But can something be both "historic" and not even "minim[ally] worthwhile"?
keeptrying 4y ago
A bit too many brain bleeds in the sideffects for my liking. :-/

37 points by kens 4y ago

I feel like this should probably be assumed to be a methodological problem or a statistical fluke until proven otherwise at this point.

bilsbie 4y ago
It’s sad we’re at this point where we can’t trust anything published. We have to think about funding, politics, peer pressure, publication bias.
- deleted 4y ago
  [deleted]
joelthelion 4y ago
This is not your regular quick scientific paper, though. It's the result of a very large phase three trial, involving hundreds of very qualified people, and a budget of around a billion dollars. It's as serious as it can be. Of course, we should probably wait to see what the outcome of the FDA review will be.
- jcranmer 4y ago
  It's the press release of the initial analysis of a readout of a clinical trial. Mining the results for good news is a distinct possibility.
  - joelthelion 4y ago
    CDR-SOB is their pre-specified primary endpoint. It's a well accepted measure of dementia. Hard to do any mining there.
- ekianjo 4y ago
  Oh like none of those has ever been hacked before. Either you have short memory or you are naive.
  - zosima 4y ago
    It definitely looks like a very clean efficacy study. This is an extremely difficult indication and almost all studies on drugs for Alzheimer's has failed previously. A study of this size meetings its primary endpoint in Alzheimer's this cleanly is definitely hard to fake. I could even suspect its easier to make a working drug for it.
arolihas 4y ago
Phase 3 trials are highly regulated and basically designed to not be statistical flukes.
- ekianjo 4y ago
  of course not. you need several phase 3 studies to know if your result is not a fluke. you can always get lucky.
gizmondo 4y ago
With p=0.00005 it's very unlikely to be a statistical fluke.
- ekianjo 4y ago
  Thats not what the p value says at all.
  - zosima 4y ago
    What does it say then?

llamaLord 4y ago

Hasn’t the entire amyloid theory been coming under a huge amount of scrutiny recently for being almost a mafia-like cabal of somewhat questionable science?

ncmncm 4y ago
Certainly about every paper nowadays is about stuff going on in a breed of mice engineered to produce lots of amyloid plaques. Hardly nobody knows or cares what happens in actual patients. The best methods we know of to protect real people against dementia are: 1. Get vaccinations. It doesn't seem to matter so much which ones. But Tdap and flu are seen to do the job. 2. Eat plenty of cheese. 3. Get treatment for herpes. I think valacyclovir is the mainstay. 4. Keep your gums healthy. There is no rigorous information to indicate why these seem to make a difference. Precious few people are looking. Certainly the people in charge of grants for Alzheimer's research are not awarding them for any such effort. When the whole house of amyloid cards finally collapses, what will amyloid specialists do with the rest of their careers? Maybe it would be smart to get a jump on that now...
- bilsbie 4y ago
  How much of that is the healthy user bias though. Those are all things healthy people generally do.
  - macrolime 4y ago
    Healthy people generally eats lots of cheese and valacyclovir?
    - jrussino 4y ago
      You don't serve Emmenthaltrex at your cocktail parties? ;-)
    - ncmncm 4y ago
      "If you think of the vastness of space, and how enormous our galaxy is, and how big our planet is, and how small we are, I am not really eating all that much cheese."

SrslyJosh 4y ago

> As I write, Biogen stock (BIIB) is up about $70/share, a sudden 35% jump that adds billions of dollars to their market captitalization, so there's definitely a lot of optimism out there. Who cares if it's reproducible? =)

gizmondo 4y ago
You can short it if you think it definitely won't reproduce. Otherwise it's not clear why adding billions to the market cap is unwarranted.
ekianjo 4y ago
Biogen was already caught corrupting the FDA to approve their last fake drugs even though it did not meet any endpoints. Massive systemic failure of institutions.

pessimizer 4y ago

Helpful article. The headlines and editorial coverage of this made it look fantastic, except for any of the concrete information in the story I read, which made it look most likely completely worthless. https://www.theguardian.com/society/2022/sep/28/alzheimers-disease-progression-slowed-by-new-drug-lecanemab https://www.theguardian.com/society/2022/sep/28/alzheimers-d... > Success of experimental Alzheimer’s drug hailed as ‘historic moment’: Study shows cognition in early-stage patients on lecanemab declines by 27% less than those on placebo Wow, something's happening! > The cognition of Alzheimer’s patients given the drug, developed by Eisai and Biogen, declined by 27% less than those on a placebo treatment after 18 months. This is a modest change in clinical outcome but it is the first time any drug has been clearly shown to alter the disease’s trajectory. We've gone from "historic" to "modest" in two paragraphs. > On a 14-point scale used to assess Alzheimer’s progression, patients on the drug scored 0.45 higher than those on the placebo treatment, with an Alzheimer’s patient being expected to decline by about 1 point a year. That is very modest. And it's a questionnaire, not memory testing? > Howard said: “The accepted minimum worthwhile difference ranges from 0.5 to 1.0 points, [meaning] that there are going to be some very difficult conversations and decisions in the next weeks and months.” So it's not even clinically significant? They have a metric that they decided to call the "accepted minimum worthwhile difference," and this is less than that. Doesn't that mean it's not worthwhile? I'm guessing based on the name. Is this just the first of a series of press releases to start building up public sentiment that can be eventually used to avoid the controversy generated when the FDA approved the last Alzheimer's drug that definitely didn't work?

mmastrac 4y ago
I don't necessarily disagree with your premise, but something _can_ be both historic and modest. The first, tiny steps can show that there's something we can do about it and that's historic. Whether these benefits actually exist... well I'm on the same page as you with skepticism.
- pessimizer 4y ago
  > something _can_ be both historic and modest. Totally agreed. But can something be both "historic" and not even "minim[ally] worthwhile"?

keeptrying 4y ago

A bit too many brain bleeds in the sideffects for my liking. :-/