Sarah Ackley

Such a cool paper. #EpiSky @amjepi.bsky.social #DataScience #Reproducibility Led by @sfackley.bsky.social at
@brown-epi.bsky.social
Research on reproducible research funded by NIH/NIA - thank you!

There is a lot of literature with highly visible peaks just below 0.05. And the easiest way to get that is to p-hack under the null bc that's the scenario with the most density in the neighborhood of 0.04.

Before writing this I had somehow assumed if you had lowish power you'd be more likely to get 0.04+delta than 0.01 + delta. But the p-curves, increase as you move towards zero. So a lot of p-hacking practices will show up in ways that aren't particularly visible--e.g. 0.01.

This work illustrates how large-scale text analysis, combined with extensions of p-curve methods to variable-power settings, can determine how efforts to improve research rigor are influencing the quality and credibility of large bodies of the scientific literature.

The fraction of borderline significant P values has modestly declined. But this appears to reflect increased study power, not reductions in P hacking or publication bias.

Check out our recently published paper at AJE!

academic.oup.com/aje/advance-...

We analyzed 21,332 abstracts (2000-2024) from four major epidemiology journals, extracting 25,288 P values using ChatGPT’s 4o model with few-shot in-context prompting.

#episky #reproducibility #metasci #metascience

#TIME-AD is heading to #AAIC25!

📊 We’ll be sharing results from our latest preprint examining whether reductions in brain amyloid—a key Alzheimer’s biomarker—can meaningfully predict changes in cognition and functioning.

🔗 Read the preprint: tinyurl.com/5n8psura

Evaluation of Amyloid Removal as a Surrogate for Cognitive Decline: Pilot Analysis in Individual-Level Data from the A4 Study of Solanezumab Background Amyloid removal has been used as a surrogate outcome in Alzheimer’s disease trials, allowing accelerated approval of aducanumab and lecanemab. The A4 (Alzheimer’s Clinical Trial Consortium ...

Looking forward to presenting this renanalysis of the A4 study, as well as a simulation study evaluating SILA's ability to detect ceilings in amyloid accumulation at #AAIC25. #ENDALZ

www.medrxiv.org/content/10.1...

🧠 TIME-AD is now on Bluesky!

#TIME-AD brings together results from different study designs and populations to find what really works to prevent and delay dementia.

Follow along as we share what we’re learning and check out our website to learn more: www.time-ad.org

#EndALZ #EpiSky #NeuroSky

Evaluation of Amyloid Removal as a Surrogate for Cognitive Decline: Pilot Analysis in Individual-Level Data from the A4 Study of Solanezumab Background: Amyloid removal has been used as a surrogate outcome in Alzheimer's disease trials, allowing accelerated approval of aducanumab and lecanemab. The A4 (Alzheimer's Clinical Trial Consortium...

This link might be better!

These methods should be replicated in trials with greater clinical decline in placebo groups and larger treatment effects (e.g., lecanemab, donanemab) to assess whether amyloid truly works as a surrogate.

... and does not find evidence that amyloid is a good surrogate marker.

But: A4 had minimal progression and modest amyloid removal.

FDA accelerated approvals for Alzheimer’s drugs have relied on amyloid reduction as a surrogate marker, but does it actually lead to cognitive benefit?

This preprint uses individual-level A4 trial data to ask that question rigorously ...

New preprint up!

Evaluation of Amyloid Removal as a Surrogate for Cognitive Decline: Pilot Analysis in Individual-Level Data from the A4 Study of Solanezumab

www.medrxiv.org/content/10.1...

Excellent talk at #MELODEM2025 by @sfackley.bsky.social evaluating amyloid as a surrogate marker with individual level A4 trial data

One big take away — 5 years was not enough time to see cognitive decline in the placebo group == a major challenge

Now at #MELODEM2025 Is reducing/removing amyloid from the brain a reasonable surrogate for slowing/stopping cognitive decline in dementia? @sfackley.bsky.social uses data from the A4 RCT (of solanezumab) to answer this q, ...

@melodem.bsky.social

Thanks!

I was invited to comment for AlzForum on GLP-1s and dementia.

GLP-1s show promise, but RCTs like GRADE have not demonstrated clear cognitive benefits. Observational studies may be confounded by socioeconomic factors and prescribing patterns.

Read the full comment: www.alzforum.org/papers/gluco...

In addition to today's NIH-grant-related anxiety, a cat vomited a fur ball in my shoe.

Harvard Will Not Comply With a List of Trump Administration Demands (Gift Article) Federal officials said Harvard must enact “merit-based reform” in hiring and admissions and report international students who broke rules, among other steps. Harvard called the demands unlawful.

www.nytimes.com/2025/04/14/u...

headings only: significance, innovation, approach, future directions

I wrote 1/3 of a page of my grant!

This would seem to contradict that, at least for the most recent death. Looking into the other 2.

bsky.app/profile/kaka...

So many more people than I realized!

& Not sure what to make of the hospitalizations here--seems much lower than the oft cited 1 in 3 cases.

People aren't going or can't go to the hospitial when they need to?
Or people aren't that sick?

bsky.app/profile/mega...

Note on my previous calculation--arguably 1/1000 is too high.

Fair point. 1/1000 could be wrong for this setting.

It seems like (from some sloppy googling) that since 2003, there has only been one other US measles death:
www.usatoday.com/story/news/2...

7/ Without knowing more about the deaths(like if they had other health conditions) and with small Ns, I would be cautious drawing any strong conclusions.

But--as I think most in PH would agree--concern about loss of elimination is increasingly warranted.

6/ This could indicate--among other possibilities--that there are cases that are not being reported.

Mild cases w/o rash among the vaccinated?
Avoidance of healthcare/interaction with public health workers?

5/ Other post-elimination US outbreaks have reached 100s of cases (tho typically in more isolated religious communities), but the number of deaths in this one is starting to seem high.

4/ Today, with 3 deaths and 544 cases, the probability is even lower:
1-dbinom(0,544,1/1000) - dbinom(1,544,1/1000) - dbinom(2,544,1/1000)
[1] 0.01788214

That’s just a 1.8% probability of seeing 3+ deaths.