Alert-List Concordance for Evaluating Imputation Strategies in ICU Sepsis Prediction

Clinical care often relies on key laboratory indicators, yet real-world patient visits are sparse and tests are ordered irregularly, leading to pervasive missingness. While many imputation methods improve average accuracy, they provide limited guidance on which imputed values are reliable enough for high-stakes downstream use. In this work, we study reliable clinical imputation, aiming to produce accurate imputations while selectively releasing the reliable results, with statistical control over clinically unacceptable errors. To achieve this goal, we propose SafeImpute, a reliable imputation framework for irregular and sparse clinical longitudinal records. SafeImpute constructs an event graph that captures both intra-patient temporal trajectories and inter-patient clinical similarity, and learns imputations with a two-relation GNN and adaptive fusion, regularized by an auxiliary masked reconstruction objective. For reliability guarantees, SafeImpute converts a proxy risk score into conformal p-values and applies the Benjamini--Hochberg procedure to control the false discovery rate (FDR) of unacceptable errors among released imputations at a user-specified tolerance. Experiments on our Mayo Clinic data, the public MIMIC-III and MIMIC-IV datasets show that SafeImpute achieves strong imputation accuracy while providing reliable error control, outperforming diverse baselines in both standard imputation evaluation and FDR-controlled selective-release evaluation.

Early sepsis prediction from electronic health records is challenged by irregular sampling, high missingness, and class imbalance. We systematically compare four modeling paradigms -- self-supervised Joint Embedding Predictive Architecture (JEPA) via masked latent prediction, self-supervised VICReg (variance-invariance-covariance regularization) with two-view augmentation, semi-supervised fine-tuning of a VICReg-pretrained encoder, and supervised Temporal Convolutional Network (TCN) -- alongside raw-feature baselines. All models share a common preprocessing pipeline of hourly binning with forward-fill imputation applied to 7 biomarkers selected via sparsity analysis from the MIMIC-III dataset. Our best model (JEPA + XGBoost + mean pooling) achieves AUPRC 0.636 at the time of onset (H0), approaching the SupMix benchmark (0.667) while using 83% fewer biomarkers. The Tier 1 pipeline -- VICReg pretraining followed by semi-supervised fine-tuning and XGBoost -- achieves AUPRC 0.510 at H0, a 3.1$\times$ improvement over the raw-feature baseline (0.165) and a 7.6% improvement over the end-to-end supervised TCN (0.474). Crucially, the fine-tuned VICReg encoder exhibits the most temporally persistent representations, degrading only 16.8% from H0 to H10 compared to 47.5% for supervised TCN and 65.3% for JEPA, demonstrating that self-supervised pretraining with task-aware fine-tuning yields features that are both sharp near onset and robust across prediction horizons.

Imputing physiological time series (arterial blood pressure, blood glucose, etc.) is essential for addressing the missingness that pervades clinical data. Yet modern imputation methods perform poorly in this domain: a recent benchmark found that simple linear interpolation outperformed every learned imputer on real-world clinical signals with realistic gaps. We show that this reflects two properties of physiological missingness that generic imputers ignore: gaps may occur when the signal is clinically extreme rather than typical, and gap lengths can easily span orders of magnitude. To this end, we introduce Curriculum-Aware Interpolate-then-Refine (CAIR), a two-stage framework for physiological time-series imputation. Our key motivation is to learn a coarse base curve and then repeatedly correct it toward physiological realism, rather than predict a gap in a single pass. Consequently, CAIR couples a bidirectional-GRU interpolator with a Transformer refiner that corrects its own estimate over three successive passes, trained jointly under a broad, signal-agnostic random-gap curriculum. We evaluate imputers stratified by gap length and missingness mechanism (MCAR, MAR, NMAR) rather than by a single average, and CAIR is the most accurate under every mechanism on continuous glucose monitoring (AI-READI) and arterial pressure in intensive care (MIMIC-III). Its margin over the strongest baseline grows with difficulty, from 9% under MCAR to 19% under value-dependent dropout, where generic learned imputers are weakest. We further show low reconstruction error alone does not recover the burden metrics clinicians act on: interpolants matching CAIR's error fail to preserve those metrics, imputers that recover them are far less accurate, and CAIR alone ranks among the best on both axes.