How an Alzheimer’s ‘cabal’ thwarted progress toward a cure • Hacker News Board

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#211

Post by memling » Mon, Dec 30, 2019, 6:24 PM UTC

zosima wrote: post #143

amluto wrote: post #136

Earlier quoted context omitted.

Nothing says p-hacking like a drug company canceling a trial and then, a few months later, re-analyzing the data and magically finding a benefit.

FDA usually puts some quite strict limits on the amount of p-hacking and general shenanigans they allow in clinical trials. But there's no approval yet, and no data to look at, so it's too early to judge. Anyway, usually Alzheimer trials are a jumble of noise. The cognitive measurements are imperfect and patients are improving and deteriorating randomly, taking a very different disease course than you'd expect from t…

Derek Lowe's comments on the reboot were understandably a bit skeptical:

> [W]hile the new larger EMERGE data do look like there’s a dose-responsive effect in the primary measurement (the CDR-SB scale) and three secondary dementia scores, the ENGAGE data actually show worse than placebo for CDR-SB at the higher dose (see slide 19 in Biogen’s presentation). They’re also worse than placebo in the MMSE scoring, but both the ADAS-Cog13 and the ADAS-ADL-MCI scales show apparent dose-responsive improvement. I have no idea why four different dementia rating systems should give such different results, and to a first approximation, no one else seems to have a good idea, either. So we’ve got the EMERGE/ENGAGE difference to explain (you’ve seen Biogen’s explanation, higher dosing later in the trial), and the variable results within the ENGAGE trial itself. And who are these high-dose patients in the ENGAGE study that Biogen says line up with the EMERGE trial? Ed Silverman at Stat quotes an analyst saying that it looks like fewer than 100 patients out of the whole set. That reminds me a bit of Biogen and Eisai’s tease of “We’re seeing positive data!” during the clinical trials, which also turned out to be based on a smaller number of patients than one would want when making a call on Alzheimer’s efficacy.[1]

He's written a fair amount about Alzheimer's,[2] and it's been an informative and useful commentary (at least for me).

[1] https://blogs.sciencemag.org/pipeline/archives/2019/10/23/th...

[2] https://search.sciencemag.org/?searchTerm=Lowe alzheimers&order=tfidf&limit=textFields&pageSize=10&&

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#212

Post by snapetom » Mon, Dec 30, 2019, 6:27 PM UTC

snowwrestler wrote: post #201

leftyted wrote: post #155

Earlier quoted context omitted.

> In this day and age, feeding into the narrative that science is just another competitive team sport where people compete with whatever means necessary is downright dangerous. I think that narrative is correct. We can't fix the problem if we don't discuss it. The whole "I believe in science" thing (which you seem to be pushing) is really quite silly. Funding is a political game and the people who are best at politic…

Scientific funding is a political game only to the extent that the politics are not contradicted by evidence. For example, no matter how good you are at scientific politics, you're not going to get the NSF to give you $1 billion to test whether the Earth is flat, or if gravity is actually caused by little fairies pushing us all down toward the ground. Why? Because, at least for public scientific funding, it is bad po…

> public scientific funding

If you're talking about "politics" in this sense, then yes, I agree with what you're saying. However, I think the person you're responding to is saying "politics" in terms of inter-group and inter-department relationships.

Egos, arrogance, and insecurities run rampant in academia. Science, like any other fields, are not above these issues, which does hurt "good science."

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#213

Post by Gibbon1 » Mon, Dec 30, 2019, 6:35 PM UTC

leftyted wrote: post #155

svara wrote: post #100

A super interesting article, but the title is pure clickbait. In this day and age, feeding into the narrative that science is just another competitive team sport where people compete with whatever means necessary is downright dangerous. Reality is much more nuanced, and the article actually does a good job of detailing that. In some sense this all started from the very beginning, from when Alzheimer's disease (AD) wa…

> In this day and age, feeding into the narrative that science is just another competitive team sport where people compete with whatever means necessary is downright dangerous. I think that narrative is correct. We can't fix the problem if we don't discuss it. The whole "I believe in science" thing (which you seem to be pushing) is really quite silly. Funding is a political game and the people who are best at politic…

> Funding is a political game and the people who are best at politics tend to be the worst at research (and vice-versa).

I'd be interested in a compare and contrast with AIDs research. Same time frame but AIDs researchers threw everything but the kitchen sink at it and made progress.

You got to wonder one field was dominated by status seekers with fat ego's and the other people working on a disease that mostly afflicts people no one cares about.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#214

Post by snowwrestler » Mon, Dec 30, 2019, 6:36 PM UTC

snapetom wrote: post #212

snowwrestler wrote: post #201

Earlier quoted context omitted.

Scientific funding is a political game only to the extent that the politics are not contradicted by evidence. For example, no matter how good you are at scientific politics, you're not going to get the NSF to give you $1 billion to test whether the Earth is flat, or if gravity is actually caused by little fairies pushing us all down toward the ground. Why? Because, at least for public scientific funding, it is bad po…

> public scientific funding If you're talking about "politics" in this sense, then yes, I agree with what you're saying. However, I think the person you're responding to is saying "politics" in terms of inter-group and inter-department relationships. Egos, arrogance, and insecurities run rampant in academia. Science, like any other fields, are not above these issues, which does hurt "good science."

I was also talking about "politics" in terms of inter-group relationships, not electoral political parties.

What I meant by "public" is that the funding decisions are publicly reviewable in some way; i.e. other scientists can see and judge the funding decisions after the fact. As opposed to going to a company or rich person for private funding, which is less common but does happen.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#215

Post by lopmotr » Mon, Dec 30, 2019, 6:41 PM UTC

igorkraw wrote: post #190

asdfman123 wrote: post #152

Earlier quoted context omitted.

I mean, the system is working but it could work better. Politics is actually working right now too -- we have roads and jobs and we aren't starving -- but it could definitely work better. It sounds like what science needs then is a cultural shift to supporting and funding more controversial ideas, and being more content with dissent. Maybe we need to make a more intentional effort to fund the contrarians with the und…

What controversial ideas are missing funding, which dissent is missing please? What's the bar. I'm genuinely asking constructively, because I would like to find a scalable improvement on the rather slow moving funding structure (unless driven by hype). But there are hundreds of free energy, "race realist", AGW deniers etc. being blocked by the current system, as well as genuine con men. Also, I dislike the idea that…

You have to be careful with "race realist". It can mean people who believe there is only a small number of sharply divided races, such as mongoloid, negroid, and caucasoid. But it can also be used to describe hereditarians who identify meaningful classifications of people with boundaries roughly corresponding to traditional races. Those latter ideas are quite respectable scientifically even though they're demonized in popular culture.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#216

Post by shakil » Mon, Dec 30, 2019, 6:49 PM UTC

dccoolgai wrote: post #165

dekhn wrote: post #159

Earlier quoted context omitted.

"""feeding into the narrative that science is just another competitive team sport where people compete with whatever means necessary is downright dangerous.""" This is precisely what modern science is (well, a major subset). The competition for grant funding and attention space is extremely intense. I agree there was no "alzheimer's cabal" but it's not uncommon in science for the prevailing mainstream position to (in…

Interesting... Are there any current issues you can think of in academia where disagreeing with the prevailing opinion can make one a pariah... Even, perhaps, assigned an epithet like "denier"? I think whenever this happens in academia/science, it is incredibly dangerous. Proper science invites and celebrates denial - seeks to deconstruct it and understand it to be more certain of the truth. The mere presence of any…

Dr Atkins invited the wrath of the medical community because he pushed for a low carb, high fat diet at a time when the medical consensus was that fats are the root of all evil. They eventually took his license for some unrelated issue but the driving force was the fact he went against the medical establishment and ridiculed low-fat but high-carb diets

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#217

Post by Gibbon1 » Mon, Dec 30, 2019, 6:56 PM UTC

superpermutat0r wrote: post #73

Gibbon1 wrote: post #46

Earlier quoted context omitted.

Fred Kummerow died at 102. And unlike Keys got to eat eggs and butter every morning. https://en.wikipedia.org/wiki/Fred_Kummerow

People living over 100 years old obviously have huge genetic factors that allow them to have unhealthy habits (or at least unhealthy for the normal person). I mean, there are people over 100 that smoke every day.

parent tried bolstering his claim by mentioning the Keys lived to 100. I point out that Kummerow who did good research outlived him.

Seriously Keys work is garbage. Where the publicly unknown Kummerow's research was spot on. If you don't know who Kummerow is he's the guy that finally forced the FDA to ban transfats decades after they were known to be poison.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#218

Post by lopmotr » Mon, Dec 30, 2019, 7:08 PM UTC

g42gregory wrote: post #47

An honest question: How does this compare to the group-think in the climate change/global warming research? Are we similarly rejecting funding to any research that does not fit into the common consensus? The fact that we call some people "climate change deniers" tells me that we have an unhealthy dynamics going on there. Will it take 30 years to get to the same point?

I saw a hint of this in a paper describing how something in climate change was found to be positive or not as bad as previously thought. It ended with a call to action for people to reduce greenhouse gas emissions, despite the paper itself not being about that. Why? Maybe either the scientists were activists uncomfortable with their own findings or they were afraid of being rejected for denialism.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#219

Post by JimBrimble35 » Mon, Dec 30, 2019, 7:10 PM UTC

"“Once a field commits to a particular hypothesis, the research resources — funding, experimental models, and training — all get in line,” she wrote in a 2018 analysis. That brings backers of the dominant idea accolades, awards, lucrative consulting deals, and well-paid academic appointments. Admitting doubt, let alone error, would be not only be a blow to the ego but also a threat to livelihood."

Is this not extremely controversial? It was always my belief that "not creating a cure for X disease keeps the money flowing" was the calling card of tinfoil hat wearing conspiracy nuts. This statement, and the following paragraphs seem to suggest this is somewhat commonplace

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#220

Post by blaser-waffle » Mon, Dec 30, 2019, 7:10 PM UTC

pharke wrote: post #150

dmix wrote: post #111

Earlier quoted context omitted.

If you watched the NBA the top 5% of players/top 5 teams get 90% of the media attention. The rest who are still doing good and interesting things fight for the last 10% of the crumbs and are forever complaining they are being excluded despite performance and other factors. It happens in a lot of places. And to be honest it’s what most of the people want and while places like r/nba are more neutral and give respect wh…

Exactly, it's human nature. No matter what arena it plays out in we only have so many patterns of behaviour at our disposal and you'll see the same types of power plays, favouritism, backbiting, and underhanded dealing. We're good at disguising this behaviour, dressing it up as professional ambition or rationalizing it but it's still the same dogged fight for a spot in the social hierarchy. We're not good at thinking…

> We're good at disguising this behaviour, dressing it up as professional ambition or rationalizing it but it's still the same dogged fight for a spot in the social hierarchy.

If you're in a modern, first-world country you get to decide which part of the Pareto 80/20 divide you sit on.

The world doesn't need more mediocre people.