SafeImpute: Reliable Clinical Data Imputation via Conformal Selection

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.

Multi-center clinical studies and biomedical research collaborations increasingly seek to utilize data across centers to build models that generalize beyond any single center. This creates two distinct challenges: data protection regulations may restrict the sharing of raw patient data across institutions, while centers may collect only partially overlapping sets of features under different protocols. Federated learning enables collaborative model training without centralizing raw data. However, existing federated imputation methods rarely evaluate feature-level missingness, in which entire features are unobserved at some centers. To address this setting, we adapt the ReMasker masked autoencoder to federated learning (Fed-ReMasker), enabling centers to impute features never observed locally by leveraging knowledge learned across collaborating centers. We evaluate Fed-ReMasker in a benchmark spanning synthetic datasets with linear and nonlinear relationships and real-world tabular datasets, including clinical data. The benchmark varies the number of centers, the missingness ratios, and client heterogeneity. Fed-ReMasker achieves the lowest imputation error in 93.2% of value-level and 96.7% of feature-level scenarios in the homogeneous benchmark. It also remains robust to client heterogeneity using simple federated averaging, outperforming all baselines in all 36 value-level scenarios and each baseline in at least 35 of 36 feature-level scenarios, and comes within 3.0% on average of a centralized model trained on the pooled data.

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.