SafeImpute: Reliable Clinical Data Imputation via Conformal Selection
Authors: Xinrui He, Mengting Ai, Junting Wang, Curtiss B. Cook, Jingrui He
Abstract
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.
Missing value imputation is a fundamental task in machine learning, with most existing methods assuming that all missing entries correspond to unobserved regular values. In many real-world datasets, however, missingness may arise from two distinct sources: some entries are meaningfully missing (intrinsically absent and semantically valid), while others are missing due to the observation process and should be imputed. We formalize this distinction as a selective imputation problem, where the goal is to jointly infer which missing entries should be preserved and which should be recovered. To address this challenge, we propose Diff-Joint, a diffusion-based framework that jointly models tabular data together with a latent missingness mask. The method alternates between conditional sampling and uncertainty-aware aggregation to iteratively refine both imputed values and missingness labels. Empirical results on synthetic and real-world datasets demonstrate that Diff-Joint effectively identifies meaningfully missing entries while achieving competitive imputation accuracy and improved downstream task performance.
Laboratory tests in electronic health records are collected irregularly, and the absence of a test order can be as informative as the measurement itself. Such missingness reflects clinicians' decisions and patient physiology, making it important to model it directly rather than treat it as a preprocessing artifact. Here we present a diffusion-based approach for generating clinical time series that jointly models laboratory values and their observation patterns using the public Data Analytics Challenge on Missing Data Imputation (DACMI) benchmark derived from MIMIC-III. To preserve realistic sampling, we align chart times into 4-hour intervals and segment admissions into 7-day windows, producing trajectories that pair each lab value with a corresponding observation indicator. Standard transformations and normalization are applied to stabilize training. Our method extends the TimeDiff framework to learn continuous lab values and discrete missingness patterns through complementary diffusion objectives. Experiments show that the generated data closely match real patient trajectories across individual lab distributions and joint value-missingness embeddings, demonstrating that diffusion models can capture clinically meaningful dependencies between patient physiology and clinicians' testing behavior under MNAR-like (missing-not-at-random) missingness. These preliminary results indicate that our model can serve as an initial component toward developing clinical foundation models. By producing synthetic priors that preserve key physiology-missingness relationships, this work motivates the subsequent training of Prior-Data Fitted Networks capable of leveraging informative missingness, which we will investigate in the extended work.
Hadi Mehdizavareh, Gabriele Santangelo, Giovanna Nicora +4
Missing data imputation remains a fundamental challenge in modern data science, especially when uncertainty quantification is essential. In this work, we propose MissBGM, an AI-powered missing data imputation method via Bayesian generative modeling that bridges the expressive flexibility of neural networks with the statistical rigor of Bayesian inference. Unlike existing methods that often focus on point estimates or treat the missingness mechanism implicitly, MissBGM explicitly and jointly models the data-generating and missingness mechanisms, providing principled posterior uncertainty over imputations rather than a single point estimate. We develop a stochastic optimization framework with alternating updates among missing values, model parameters, and latent variables until convergence. Our theoretical analysis shows that estimates of missing values from MissBGM converge consistently under mild assumptions. Empirically, we demonstrate that MissBGM achieves superior performance over traditional imputers and recent neural network-based methods across extensive experimental settings. These results establish MissBGM as a principled and scalable solution for modern missing data imputation. The code for MissBGM is open sourced at https://github.com/liuq-lab/MissBGM.