A Cost-Effective Multimodal LLM Reasoning Framework for Question Answering over Irregular Clinical Time Series

Question answering (QA) over irregular clinical time series (ICTS) plays a pivotal role in a wide range of healthcare applications. Although recent multimodal time-series large language models (LLMs) have shown considerable promise in general-purpose time-series QA, they remain poorly equipped to model the sparsity, asynchrony, and irregular sampling patterns of clinical observations. To fill this gap, we propose ClinPRISM, a cost-effective multimodal LLM reasoning framework for question answering over ICTS data. First, we devise an irregularity-aware multi-scale encoder to capture sparse clinical evidence at diverse temporal scales. Then, we propose a temporal evidence distiller to integrate representations across these scales and compress them into a small number of LLM-compatible tokens. Moreover, we introduce a progressive alignment strategy that sequentially aligns the irregular trajectories with the LLM's textual embedding space. To facilitate training, we construct 30,000 clinical time series paired with multi-scale descriptions, together with 41,000 instruction-tuning instances spanning 11 tasks. Using a 4-billion-parameter LLM backbone, ClinPRISM achieves state-of-the-art performance on the held-out evaluation benchmark while using only 16 time-series tokens and achieving an average inference latency of 0.15 seconds per question.

MissHyper: Restoring Clinical Synchronicity in Missingness-Guided Hypergraph Forecasting

Clinical irregular multivariate time series are shaped not only by physiological dynamics but also by the measurement process that determines when and what to observe. In event-centric models, however, co-timestamp structure can be flattened too early: measurements acquired at the same timestamp are embedded as isolated nodes, leaving local patient-state context unavailable until later message-passing layers. We study this pre-propagation representation bottleneck and address it by restoring co-timestamp context before message passing begins. We propose MissHyper, a missingness-guided hypergraph forecasting model with pre-propagation synchronicity restoration. MissHyper augments each event with a local support-density cue, aggregates co-timestamp records to recover patient-state context, and uses a missingness-guided gate to adaptively fuse node-specific evidence with the recovered context. Across PhysioNet 2012, MIMIC-III, and MIMIC-IV, MissHyper achieves consistent gains in multi-step forecasting and outperforms a strong hypergraph baseline. These results suggest that improving event initialization can benefit sparse clinical forecasting without requiring a redesigned downstream propagation architecture. Ablations indicate that snapshot restoration, adaptive fusion, and support-density encoding all contribute, pointing to event initialization as a critical design axis for sparse clinical forecasting.

CLIR-Bench: Benchmarking Multimodal Question Answering over Irregular Clinical Time Series

Clinical time series are central to patient monitoring, risk assessment, and clinical decision support. However, they are often sparse, irregularly sampled, and asynchronous, making it difficult for models to identify the temporal evidence required for clinical Question Answering (QA). Existing benchmarks primarily focus on regularly sampled time-series QA or medical QA over static data, and therefore rarely assess whether models can faithfully ground their answers in irregular temporal observations. To fill this gap, we introduce CLIR-Bench, a benchmark for irregular clinical time series QA constructed from de-identified ICU records through a principled four-stage pipeline. CLIR-Bench contains 6,600 QA instances spanning 11 clinical variables, organized into four capability dimensions and 11 tasks. Each question is linked to explicit temporal evidence and task-specific answer derivation rules, enabling evaluation of both answer accuracy and evidence use. Experiments show that existing generalist models struggle to retrieve and reason over sparse clinical evidence, highlighting the need for stronger irregular time-series reasoning methods. Our code and data are available at https://huggingface.co/datasets/winall/CLIR-Bench.

Missingness as Signal: Channel-Independent Spectrogram Learning for Clinical Time Series Prediction

Clinical time series prediction in intensive care units remains challenging due to heterogeneous physiological variables and informative missingness. The presence or absence of a measurement can reflect clinical decisions and patient severity, and thus missingness can serve as a predictive signal rather than a simple data artifact. This work presents CISM, a Channel-Independent Spectrogram framework with a Missingness stream for clinical multivariate time series prediction. CISM converts each clinical variable into a variable-wise time-frequency spectrogram, preserves variable identity through variable-aligned encoding, and aligns an explicit missingness stream with the spectrogram representation. Experiments on an in-hospital mortality task derived from MIMIC-IV show that CISM achieves the highest mean AUROC (0.7225), AUPRC (0.3308), and F1 (0.3808) among the compared time series, missingness-aware, vision, and time-frequency baselines. Ablation studies further show that observation patterns provide a meaningful informative signal. Pixel-level mask injection improves performance over plain spectrogram inputs and recovers much of this predictive value. The aligned missingness stream contributes a further, complementary gain in both AUROC and AUPRC. These results highlight the importance of modeling observation patterns as structured signals in clinical time series prediction.

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.

Differentiable latent structure discovery for interpretable forecasting in clinical time series

Background: Timely, uncertainty-aware forecasting from irregular electronic health records (EHR) can support critical-care decisions, yet most approaches either impute to a grid or sacrifice interpretability. We introduce StructGP, a continuous-time multi-task Gaussian process that couples process convolutions with differentiable structure learning to uncover a sparse, ordered directed acyclic graph (DAG) of inter-variable dependencies while preserving principled uncertainty. We further propose LP-StructGP, which augments StructGP with latent pathways-shared, temporally shifted trajectories inferred via subject-specific coupling filters and a softmax gating mechanism-to capture cross-patient progression patterns. Both models are trained under sparsity and acyclicity constraints (augmented Lagrangian, Adam) using scalable low-rank updates. Results: In simulations, the approach reliably recovers ground-truth graphs (Structural Hamming Distance approaching 0 as cohorts grow) and pathway assignments (high Adjusted Rand Index). On a MIMIC-IV septic shock cohort (n=1,008; norepinephrine, creatinine, mean arterial pressure), StructGP improves short-horizon (6 h) forecasting over independent-task baselines (average RMSE 0.68 [95%CI: 0.63--0.74] vs. 0.88 [0.83-0.94]) and, with 15 additional inputs, markedly outperforms unstructured kernels (0.63 [0.58-0.69] vs. 3.02 [2.85-3.18]) with superior calibration (coverage 0.96 vs. 0.84). On the PhysioNet Challenge (12k patients, 41 variables), StructGP attains competitive accuracy (MAE 3.72e-2) relative to a state-of-the-art graph neural model while maintaining calibrated uncertainty. Conclusion: These results show that structured process convolutions with latent pathways deliver interpretable, scalable, and well-calibrated forecasting for irregular clinical time series.