Tipping the Balance: Impact of Class Imbalance Correction on the Performance of Clinical Risk Prediction Models

Resampling methods such as SMOTE and random under/over-sampling are standard tools for class-imbalanced classification, almost always evaluated by minority-class accuracy or F1. Prior work has established that undersampling degrades probability calibration by distorting the training prior [1]. We extend this lens to synthetic oversampling (SMOTE) and provide a practical, evidence-based guide to when calibration damage matters and how to fix it. Across five public datasets (imbalance ratio 1.9-70) and two ensemble models (random forest, gradient boosting), with ten seeds and paired statistics, we find: (1) SMOTE's calibration cost is real but small (ECE +0.009; Cliff's delta = +0.27, small-to-moderate) across the studied imbalance range (IR 1.9-70) and its discrimination gains typically outweigh the calibration penalty; (2) random undersampling is the genuine danger -- its damage grows sharply with imbalance, inflating ECE from 0.008 to 0.395 on a dataset with ratio 70, largely because the resulting training sets are too small to estimate probabilities reliably; (3) a single post-hoc recalibration step (Platt or isotonic) eliminates the damage, reducing ECE by up to 66% at a negligible ranking-power cost (AUC -0.002, Cliff's delta = -0.07); and (4) the analytic prior-shift correction that repairs undersampling does not transfer to SMOTE, because SMOTE distorts the class-conditional density rather than only the prior -- so data-driven recalibration remains necessary. We recommend that imbalanced-learning studies report calibration alongside discrimination, and that practitioners recalibrate after resampling whenever predicted probabilities drive decisions.

Clinical language models (LMs) are increasingly applied to support clinical risk prediction from free-text notes, yet their uncertainty estimates often remain poorly calibrated and clinically unreliable. In this work, we propose Clinical Uncertainty Risk Alignment (CURA), a framework that aligns clinical LM-based risk estimates and uncertainty with both individual error likelihoods and cohort-level ambiguities. CURA first fine-tunes domain-specific clinical LMs to obtain task-adapted patient embeddings, and then performs uncertainty fine-tuning of a multi-head classifier using a bi-level uncertainty objective. Specifically, an individual-level calibration term aligns predictive uncertainty with each patient's likelihood of error, while a cohort-aware regularizer pulls risk estimates toward event rates in their local neighborhoods in the embedding space and places extra weight on ambiguous cohorts near the decision boundary. We further show that this cohort-aware term can be interpreted as a cross-entropy loss with neighborhood-informed soft labels, providing a label-smoothing view of our method. Extensive experiments on MIMIC-IV clinical risk prediction tasks across various clinical LMs show that CURA consistently improves calibration metrics without substantially compromising discrimination. Further analysis illustrates that CURA reduces overconfident false reassurance and yields more trustworthy uncertainty estimates for downstream clinical decision support.

Background. Selective prediction systems improve the safety of clinical artificial intelligence by deferring ambiguous cases to human experts while automating high-confidence decisions. However, this safety mechanism relies entirely on the premise that uncertainty scores accurately reflect clinical ambiguity. In prognostic tasks characterized by severe class imbalance, where the clinical outcome of interest is a minority, this assumption breaks down. Standard uncertainty measures cease to capture clinically aligned ambiguity; instead, they become a proxy for class membership, systematically penalizing minority patients regardless of their individual predictive clarity. Results. Across 56 synthetic conditions and three neurodegenerative cohorts spanning severe class imbalance to near-balanced conditions (multiple sclerosis, Parkinson's Disease, Alzheimer's Disease), our framework consistently maintained bounded, balanced risk across trajectories. In contrast, global metrics either collapsed minority Sensitivity or protected the minority at the expense of majority patients. Applying CCR with standard entropy fails to protect the minority because it breaks within-class monotonicity when tau=0.5. Combining CCR with threshold-aware metrics restores strict monotonicity, correctly identifies ambiguous patients, and safely mitigates minority exclusion. Conclusions. Under clinical class imbalance, standard uncertainty quantification measures dataset sparsity rather than clinical ambiguity, creating a systemic illusion of safety. This bias is a correctable structural flaw. Clinical pipelines deploying selective prediction under imbalance should adopt threshold-aligned uncertainty measures and class-stratified evaluation. This reduces class-specific risk imbalance, supporting safer selective prediction under the evaluated conditions without silently excluding the most vulnerable patients.