Neurostats Digest #2
Select links and reading on regulatory science, free energy principle, vitamin-D interventions, preterm birth interventions
Contents
1. Links
2. Quick Takes
I’m also starting a private AI study group to learn about new AI papers in many different fields. Starting with a focus on “Evals”. I’m particularly interested in the gap between how tech thinks about evaluations in contrast to different parts of biotech/medicine. Send me an email with the subject “Manjari’s Secret Study Group”
Links
Improving evaluations in AI for chemistry / drug discovery
o1-preview finds a very nuanced problem with non-linear mendelian randomization in a now retracted paper on vitamin-D interventions from Lancet Endocrinology
- take on systemic gaps in innovation on the Good Science Project.
My favorite articulation and critical evaluation of the Free Energy Principle (FEP) and predictive processing theories of the brain is from Dan Williams (@conspicuouscognition) . He gets to the bottom of what has always bugged me about FEP since I first read it as an EECS graduate student stumbling into cognitive neuroscience. He has a few more papers on this worth reading.
Quick Takes
“Let’s have more relevant clinical endpoints and more qualified biomarkers”
In which I strongly disagree with Ben Recht about statistical thinking at the FDA. The gatekeeping of new drugs via statistical hypothesis testing is not the primary or even most important use of statistical thinking at the FDA. It really isn’t about squeezing out the most rigorous p-value at the end, one can be pragmatic about that. It is everything else that comes before that.
Anyone who proposes to replace a clinical endpoint with a biomarker or intermediate endpoint that hasn’t itself been tested in successful clinical trials doesn’t know what they are doing. Consider, the 20-year saga of the failed preterm birth prevention drug, 17-OHPC, that has finally been withdrawn. Yet another reason why we need the proper attitude to biomarkers should be “Let’s have more relevant clinical endpoints and more qualified biomarkers”.
I have been reading the clinical papers, FDA reviews, company submissions from 1999. A deeper dive into 25+ years of scientific drama is forthcoming.
This is how we end up with underpowered clinical trials