Department meetings at @UCSF_Epibiostat have become surprisingly fabulous. Every meeting a thoughtful covid update from George Rutherford. +Today new faculty member @Jean_J_Fengjeanfeng.com re fair machine learning algorithms in medical care.
She thinks of ML apps along 2 dimensions: severity of healthcare situation (low=apple watch for Afib) (high=viz.ai contact to id stroke in process) and along significance of the information provided (low=apple watch) (high=idx-DR diabetic retinopathy).
Nothing approved yet with high severity and high significance of information. Suggests we are really uncomfortable deferring decisions to ML algorithm instead of our Doctor. Why?
Doctor has multiple priorities to balance: Hippocratic oath, health of individuals, public health.
ML algorithm: 1 goal: predictive accuracy across entire population.
Can we do better? 3 goals:
Encode self-awareness /know what it doesn't know in the algorithm.
Interpretability: clarify how important is each variable for making predictions?
Regulation: figure out how to regulate continuously evolving machine learning algorithms?
#1: self-awareness: the case of misleading predictions. Linear regressions allow us to extrapolate off-support. Very high dimensional data hard to tell if you're far away from your training data. So: train a model to tell us if we should even be doing predictions for new obsv'n.
2 types of uncertainty that would lead us to abstain from making a prediction. Aleatoric uncertainty: response is inherently noisy at x.
Epistemic uncertainty: the input query is for a rare set of predictors- eg you haven't seen patients like this in your training data
Need a model that considers both types of uncertainty. Approach: penalized selective prediction models. (I may not have this right) include fake input data in your testing data, and penalize the model for making predictions for these people.
Next project: re interpretability/variable importance. Example you're trying to predict patient survival based on different medical tests. Current measures of variable importance problematic for highly correlated variables.
So they turned to Shapley-Values, a game-theory formulation. Game: predict the outcome. Players: variables. Payout: prediction accuracy. How do we assign payouts to players based on their contribution to the total payout?
The importance of variable Xi is the average increase in prediction accuracy when adding Xi to all possible variable subsets. So if evaluating say the GCS test, add it onto all possible subsets of other variables and see how much it improves accuracy in each.
This is challenging to calculate b/c too many possible subsets. Their solution: randomly sample feature subsets! So cool. How many such subsets do you need to sample? It must be at least the same as the # of observations.
This approach of sampling from the set of all possible variable subsets is computationally feasible. You get CIs! agreement across different ML algorithms.
3rd project: online machine learning in healthcare systems w/ feedback. Risks associated with modifying ML algorithms are a more severe version of the risks associated with modifying drugs. Length of iteration for ML algorithm might be days or weeks, but for drugs months to years
So need to decide what is an acceptable modification? Might want to specify a non-inferiority margin. What is an acceptable sequence of modifications? Even if each modification is acceptable, in combination, they may not be. Bio-creep!
They've proposed an online hypothesis testing framework: approval contingent on showing acceptability w/r/t all previously approved modifications. You also need to correct for multiple comparisons over the entire time period. Awesome talk.
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Plenary at #SER2022 with @zeynep re aspects of human behavior that were not adequately incorporated into pandemic response. This is a very dense talk w/o slides so livetweet is a bit bumpy... but talk was super interesting so I did my best.
For example, because of stigma, it doesn't make sense/isn't possible to have effective rules that only sick people wear masks.
Idea that masking or testing would make people 'reckless' just didn't make any sense and inconsistent w/ prior research.
Plenary from @michaelmina_lab at #SER2022.
Testing is not just a medical tool! Most of the discussion of testing is focused on medical diagnostics but testing is a public health tool. We need to start thinking/evaluating testing as a population health tool.
Applications of tests for public health? test to isolate; test to exit isolation; test to enter/stay; test to go; contact tracing. Medical testing is for patient; testing for public health is for others.
Conflating what are medical vs public health tools is a major problem. Priority for medical tests (FDA's priority): high sensitivity. Secondary considerations: cost and speed. For public health, we need to prioritize fast, frequent, accessibility, affordability over sensitivity.
Outline: 1. why we've failed to find cures for AD. 2. Establishing a pipeline for id'ing drug targets w/ systems biology (APOE-signature, PREVENT AD based on candidate drugs in mouse models, and the DREAM study, real world analyses of pharmacotherapies)
Reminder is that it's been more than 100 years since Alzheimer described the key pathologic features. Year on year publications on AD have grown - now>1000 pubs/month! Yet shockingly little to offer patients.
Capstone of @UCSF_Epibiostat Sampling Knowledge Hub series with @EpidByDesign talking about generalizability and transportability in research.
Two issues in interpreting an intent-to-treat estimate as a public health. 1. Internal vs external validity (difference between the study sample and people in general) and 2. Exposures vs population interventions (not everyone in real world will take up intervention).
Thread about @manlyepic & my @jamaneuro commentary re one especially shameful aspect of the FDA approval of #aduhelm. Before working w/ @manlyepic on this, I knew it was bad, but I didn’t know how bad. doi:10.1001/jamaneurol.2021.3404 1/27
In @Biogen’s FDA filing, only 0.6% (ie 19 people) of 3285 trial participants identified as Black, 3% as Hispanic, 0.03% (1 person) American Indian or Alaska Native, and 0.03% as Native Hawaiian or Pacific Islander. Of 9% identified as Asian, 94% were recruited in Asia. 2/n
But it gets even worse: of those 19 Black participants, most were randomly assigned to control or low-dose treatment arms. FDA approved a medication with known increases in risk for brain bleeding after only 6 Black people had received the approve dose. How is that okay? 3/n
This guy's incredible. Silicon valley background- made software to help people safely document human rights violations. Started in 1991, when a grad student at @UMich soc and demography. Struggled after seeing what was happening in Guatemala and El Salvador- many crimes.
Adopted as personal motivation defense of human rights. In El Salvador, began non-violent accompaniment: accompany someone who is under threat of violence, eg a religious leader. You are 'noisy' & use privilege to try to protect, w/ camera, passport, & home country network