A Personalized Computational Framework for Assessing the Sufficiency of Partially Observed Data in Healthcare AI models

Achieving early and timely diagnosis and treatment for disease is a major challenge. Recent applications of machine learning (ML) algorithms trained on patient data have shown promise in many different settings for predicting the patient health state. A challenge often faced when applying these ML algorithms is that at any given time, not all clinical variables (features) needed as input to perform prediction tasks are available. We define the concept of full-feature-capacity (FFC) to refer to prediction performance when such algorithms make use of all features on which they were trained. We then introduce Feature Sufficiency Analysis (FSA) - an analysis for determining whether a subset of all clinical features needed by an AI model is sufficient to achieve FFC. FSA estimates the underlying distributions of missing variables conditioned on features that are available. FSA provides a patient-specific assessment of whether the existing set of measured features achieves FFC. If yes, then there is no need to acquire further inputs and a ML-based prediction. We provide two case studies: prediction of need for postoperative prolonged ventilation in patients recovering from heart surgery; 10-year mortality prediction in an outpatient cohort. We also demonstrate that FSA also provides a clinically interpretable feature-ranking methodology based on prediction sufficiency, identifies intrinsically hard-to-predict patient populations, and has the potential to perform cost-aware optimization for clinical data acquisition. FSA provides a generic computational approach for determining whether incomplete clinical information is sufficient to support trustworthy AI-assisted clinical decision-making, thereby facilitating the prospective deployment of healthcare AI systems across diverse clinical settings.

SHIFT: Survival Prediction from Incomplete and Heterogeneous Genomic Data

Genomic prediction models often fail to transfer across institutions because sequencing panels differ across sites, creating structural feature missingness at deployment. Existing approaches to this challenge typically restrict analysis to genes shared across cohorts, exclude patients with incomplete profiles, or rely on test-time imputation, all of which can reduce robustness and limit the use of multi-center data. We propose Survival prediction Handling Incomplete Features using Transformer (SHIFT), a missingness-aware survival model that directly predicts from incomplete genomic inputs without test-time imputation. SHIFT represents each genomic feature separately and uses masked self-attention, along with a feature-availability mask, so that predictions are based only on observed inputs. Further, we introduce variable-rate feature masking during training to improve robustness to heterogeneous missingness patterns. We evaluate the approach on glioblastoma and lung squamous cell carcinoma with external validation across multiple cohorts, including a challenging setting with severe cross-cohort panel mismatch. Across these settings, SHIFT shows strong generalization and compares favorably with standard survival baselines and imputation-based approaches, while using a single model across differing feature sets. We also find that incorporating patients from incomplete cohorts during development can improve performance on external data, suggesting that partially observed cohorts need not be excluded from model building. These results support missingness-aware modeling as a practical strategy for multi-center survival prediction in precision oncology.

Informative Missingness to Generate Irregular Clinical Time Series

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.

Multi-FRuGaL: Multimodal Flexible Redundancy-aware Decomposed Gated Learning for Cancer Diagnosis and Prognosis

Modern medicine relies on heterogeneous data sources spanning radiology, pathology, text reports, and structured clinical information. However, real-world patient data are frequently incomplete, with missing or sparsely acquired modalities, limiting the effectiveness of standard multimodal fusion approaches. To this end, we propose the Multimodal Flexible Redundancy-aware decomposed GAted Learning (Multi-FRuGaL) framework, a decomposition-aware, adaptive gated intermediate-fusion framework that performs modality-level representation learning under missing data. Multi-FRuGaL integrates per-modality encoders with a signal decomposition layer, an input-conditioned gating network, and an information-aware fusion objective to separate redundant from modality-specific complementary signals, selectively upweighting informative modalities and suppressing redundant or noisy inputs, and remaining well-defined even when multiple modalities are absent. We evaluate Multi-FRuGaL on two multimodal head and neck cancer cohorts: the HANCOCK challenge dataset (N = 763) comprising five modalities and two prognostic endpoints (5-year survival and 2-year recurrence), and the HECKTOR challenge dataset (N = 588) comprising three modalities for human papillomavirus (HPV) status classification. Multi-FRuGaL consistently achieves higher mean performance than the evaluated baselines across multiple tasks, improving AUC from 0.601 to 0.8496 for survival, from 0.672 to 0.8102 for recurrence, and achieving 0.975 AUC for HPV prediction on HECKTOR. For survival analysis, it further achieves a concordance index of 0.6814 for overall survival, 0.7421 for recurrence-free survival, and 0.7143 for progression-free survival on HANCOCK, and 0.7203 for recurrence-free survival on HECKTOR. Qualitative analyses further show that Multi-FRuGaL learns discriminative and robust multimodal representations, even under severe missing-modality conditions.

TRACE: A Temporal Conditional Estimation for Multimodal Time Series Foundation Models

Time series foundation models (TS-FMs) aim to learn generalizable temporal representations that can be adapted to a wide range of downstream tasks. In real-world multimodal settings, time series are frequently affected by temporal misalignment and partial modality missingness, where different modalities are observed at heterogeneous time scales or are partially absent. Existing approaches typically rely on naive imputation or masking strategies, which fail to account for cross-modal dependencies and often lead to misaligned or degraded representations. We propose TRACE, a conditional estimation paradigm for multimodal time series foundation model pipelines under missingness and irregular sampling, allowing incomplete target modalities to be systematically inferred from available auxiliary modalities. We evaluate TRACE on diverse multimodal benchmarks spanning healthcare and affective computing, including the MIMIC-IV clinical dataset and the CMU-MOSI and CMU-MOSEI benchmarks for multimodal sentiment analysis. Across a range of downstream prediction tasks and missing-modality settings, TRACE consistently outperforms prior multimodal fusion approaches, demonstrating improved robustness to severe modality missingness and more reliable cross-modal representations.

MambaGaze: Bidirectional Mamba with Explicit Missing Data Modeling for Cognitive Load Assessment from Eye-Gaze Tracking Data

Real-time cognitive load assessment from eye-tracking signals could potentially enable adaptive human-centered-AI such as safety-critical applications such as driver vigilance monitoring or automated flight deck assistance, yet two challenges persist: handling frequent data missingness from blinks and tracking failures, and efficiently modeling long-range temporal dependencies. We propose MambaGaze, a framework that addresses these challenges through 1) XMD encoding, which augments raw features with observation masks and time-deltas to explicitly model data uncertainty, and 2) bidirectional Mamba-2, which captures temporal dependencies with linear computational complexity. Experiments on CLARE and CL-Drive datasets under leave-one-subject-out evaluation show that MambaGaze achieves 76.8% and 73.1% accuracy, respectively, outperforming CNN, Transformer, ResNet, and VGG baselines by 4-12 percentage points. Edge deployment benchmarks on NVIDIA Jetson platforms demonstrate real-time inference at 43-68 FPS with power consumption below 7.5W, confirming feasibility for wearable cognitive load monitoring.

Joint Treatment Effect Estimation from Incomplete Healthcare Data: Temporal Causal Normalizing Flows with LLM-driven Evolutionary MNAR Imputation

Target trial emulation (TTE) enables causal questions to be studied with observational data when randomized controlled trials (RCTs) are infeasible. Yet treatment-effect methods often address causal estimation, missingness, and temporal structure separately, limiting their robustness in electronic health records (EHRs), where time-varying confounding and missing-not-at-random (MNAR) biomarkers can reach 50%--80%. We propose a two-stage pipeline for treatment effect estimation from incomplete longitudinal EHRs. First, CausalFlow-T, a directed acyclic graph (DAG)-constrained normalizing flow with long short-term memory (LSTM)-encoded patient history, performs exact invertible counterfactual inference, avoiding approximation errors from variational inference and separating confounding through explicit causal structure. Ablations on four synthetic and one semi-synthetic benchmark with known counterfactuals show that DAG constraints and exact inference address distinct failure modes: neither compensates for the other. Second, because CausalFlow-T requires completed inputs, we introduce an LLM-driven evolutionary imputer that proposes executable imputation operators rather than individual entries, and evaluate it with three large language model (LLM) backends, including two open-source models. Across 30%--80% MNAR missingness, this imputer achieves the best pooled rank over biomarker and causal metrics, leading in point-wise accuracy and temporal extrapolation while preserving average treatment effect (ATE) recovery as statistical baselines degrade. On Swiss primary-care EHRs from adults with type 2 diabetes initiating a GLP-1 receptor agonist or SGLT-2 inhibitor, the pipeline estimates a per-protocol weight-loss difference of -0.98 kg [95% CI -1.01, -0.96] favoring GLP-1 receptor agonists, consistent with randomized evidence and obtained from realistically incomplete real-world EHRs.