Differential Subgroup Discovery: Characterizing Where Two Populations Differ, and Why

In biomedical Subgroup Discovery, practitioners are interested in discovering interpretable and homogeneous subgroups within a group of patients. In this paper, assuming that healthy subjects (i.e., controls) share common but irrelevant factors of variation with the patients, we motivate and develop a Contrastive Subgroup Discovery method, entitled Deep UCSL. By contrasting patients with controls, Deep UCSL identifies subgroups driven solely by pathological factors, ignoring common variability shared with healthy subjects. Our framework employs a deep feature extractor to learn a discriminative representation space. Mathematically, we derive a novel loss based on the conditional joint likelihood of latent clusters and patient/control labels, optimized via an Expectation-Maximization strategy alternating between subgroup inference and feature encoder updates. A regularization term further encourages representations to capture disease-specific variability while ignoring variability shared with controls. Compared to previous related works, our approach quantitatively improves the quality of the estimated subgroups, as demonstrated on a MNIST example and four distinct real medical imaging datasets. Code and datasets are available at: https://github.com/rlouiset/deep_ucsl.

Conventional subgroup analyses can yield unstable and difficult-to-interpret conclusions, especially in observational biomedical data where each individual is observed under only one exposure state, true individual treatment effects are unavailable, and causal structure is uncertain. We investigate whether subgroups constructed from pretreatment characteristics, without using exposure, outcome, or estimated treatment-effect information, can serve as interpretable units for budget-constrained policy prioritization. We propose a framework combining causal-discovery-informed covariate selection, discovery-evaluation sample splitting, inductive unsupervised clustering, uncertainty-aware subgroup selection, and held-out doubly robust policy evaluation. We compare K-means, hard, membership-weighted, and stochastic Fuzzy C-means, Bayesian Gaussian mixture models, and a supervised causal-forest-derived CATE-tree comparator. Policies are evaluated under a 70% budget for hypothetical obesity-to-non-obesity and elevated-to-lower-glucose state shifts in the PIMA Indians Diabetes dataset and for a lifetime-smoking-history contrast in NHANES. The highest estimated ungated utilities were 0.799 for the BMI policy using Bayesian GMM, 0.735 for the glucose policy using hard or membership-weighted FCM, and 0.775 for the smoking-history policy using K-means. All paired 95% confidence intervals for policy-risk differences included zero, and no comparison remained statistically significant after Holm adjustment. Bayesian pooling generally preserved ungated allocations, whereas Empirical Bernstein gating was more conservative. Policies with similar estimated utility could nevertheless prioritize different individuals. The findings should be interpreted as assumption-dependent decision-support evidence for hypothetical state contrasts rather than proof of intervention benefit.

Clinical risk models routinely achieve strong aggregate performance while producing materially different error rates across patient subgroups. Audit pipelines have been proposed to catch this, but their components are rarely stress-tested, so it is unclear which parts of an audit can be trusted and under what conditions. We present KAISEN, a five-phase audit pipeline covering subgroup stratification, disparity measurement, mechanism diagnostics, post-hoc mitigation, and drift monitoring, evaluated to the point of failure on a synthetic benchmark of 16 disease tasks, 15 social-determinant axes from Healthy People 2030, and three prespecified intersections. Four findings follow. (i) Significance tracks each axis's gap against its own minimum detectable effect: rank correlation between significance count and raw equalized-odds difference (EOD) across the 15 axes is rho = 0.56, rising to rho = 0.78 once EOD is standardized by that floor. (ii) Per-group threshold optimization reduces EOD in 48 of 48 held-out runs (paired delta = -0.285, 95% CI [-0.313, -0.252]), while group-wise Platt scaling -- the better calibrator -- behaves as a coin flip on EOD (19 of 48 runs improved, 95% CI [0.26, 0.55]) with mean effect near zero, so what an audit should report is the variance, not the average. (iii) The mechanism diagnostic classifies 144 of 144 controlled cases correctly but recovers none of 48 model-driven cases under proxy misspecification, with no signal that it failed. (iv) CUSUM failures and false alarms track cohort realization far more than disease: at the reference threshold, all 27 false alarms and 7 of 8 missed shifts come from different seeds (chi-squared p = 0.002), so a threshold tuned on one cohort fails to transfer. All results are synthetic with known ground truth and do not establish clinical validity. Code, artifacts, and scripts reproducing every number are released.