Confounding Masquerading as Improvement: A Systematic Evaluation of Offline Reinforcement Learning for Stroke Antithrombotic Treatment in a 129,000-Patient Registry

Recent offline reinforcement learning (RL) studies report policies that outperform physician decisions on clinical outcomes. We conduct a systematic, partially crossed evaluation of five offline RL algorithm families and 14 reward designs in 44,894 post-2018 acute ischemic stroke patients from a nationwide registry (N = 129,033). Standard Fitted Q-Evaluation (FQE) yields an apparent policy-improvement estimate of +0.0069; adding an Early Neurological Deterioration penalty increases it to +0.0101. We identify reward-embedded confounding, in which a proxy terminal reward encodes baseline severity and prognosis as well as treatment efficacy. A 2 x 2 factorial analysis finds that terminal reward confounding accounts for 218.6% of the observed signal change, so its removal overshoots the null. After DML-inspired GBM reward residualization, the FQE estimate attenuates to +0.0033 (p = 0.132), and full deconfounding yields +0.0025 (p = 0.291). FQE-based diagnostics, T-learner analyses, and direct recurrence analyses converge away from a clinically meaningful aggregate improvement. A 1-year mRS factorial analysis replicates the attenuation. We provide an empirically motivated six-step evaluation checklist. NIHSS-stratified heterogeneity is hypothesis-generating for prospective trial design; hospital-level disagreement does not persist after full reward deconfounding.

Separating Voice from Age in COPD Screening

Voice has been proposed as a low-cost screening signal for chronic obstructive pulmonary disease (COPD). COPD is strongly age-associated and voice changes with age, thus such results admit a trivial alternative explanation. We re-evaluate a public sustained-phonation corpus ($1246$ recordings, $68$ participants) under a strictly participant-level protocol. We therefore evaluate on repeatedly drawn age-matched cohorts and report the discrimination achieved by the confounders themselves on those same cohorts. Where raw (unmodelled) age ($0.510$ $[0.469, 0.551]$) and raw gender ($0.479$) are both measured at chance, acoustic models excluding age retain ROC-AUC $0.717$ $[0.552, 0.859]$ and average precision $0.747$ $[0.581, 0.892]$ against a one-to-one baseline of $0.5$, whereas models containing age fall to $0.531$--$0.679$. The separation is reproduced by two further learners with fixed hyperparameters. Two findings have broader methodological implications: models trained with age transfer less effectively to an age-balanced target cohort than otherwise identical models trained without age, and fourteen classical voice-quality and perturbation measures achieve comparable discrimination to a $55$-dimensional combined representation. We conclude that a non-age acoustic signal is present, that confounding by recording conditions cannot be excluded from the released features, and that the evaluation protocol in standard use cannot distinguish these possibilities.

Negative controls reveal volume-driven confounding in radiomics and imaging foundation model features

Radiomics and imaging foundation models promise non-invasive biomarkers of tumour biology, yet predictive signatures may reflect tumour volume or acquisition artifacts rather than meaningful image structure. We introduce READII-2-ROQC, an open-source framework that uses volume-preserving negative controls to assess whether radiomic and deep imaging features capture independent spatial signals. READII-2-ROQC generates voxel-perturbed images across tumour, background and whole-image regions using configurable randomization strategies, then compares feature behaviour and model performance between original and control images. Applied to three public cancer imaging cohorts, the framework processed 3,552 tumour volumes and extracted PyRadiomics and foundation-model features from original images and nine matched controls. Reproducing published survival and HPV-status signatures, we show that multiple models retain performance after spatial structure is destroyed, revealing volume-driven or contextual confounding, whereas others show perturbation-sensitive signal. READII-2-ROQC provides a scalable quality-control strategy for developing interpretable, biologically grounded imaging biomarkers and reproducible radiomics workflows.