Structure-Aware Set Transformers: Temporal and Variable-Type Attention Biases for Asynchronous Clinical Time Series

Electronic Health Record (EHR) prediction models in the intensive care unit must learn from sparse and irregular measurements while preserving the clinical meaning of time and supporting transparent decision-making. We present INTERVenE, a family of Transformer architectures whose input is an interval-based, knowledge-based temporal abstraction (KBTA), a token stream of named clinical concepts (states, trends, events, contexts) drawn from a curated medical ontology, rather than an unnamed bin index or a raw measurement triplet. This naming layer is what we ask KBTA to do: it makes the model's per-token attributions resolve to clinical concepts by construction. INTERVenE offers two complementary variants: an auto-regressive decoder that generates future abstraction trajectories with a per-step risk readout (localizing when and after which events risk rises), and a bidirectional encoder for single-pass joint risk and time-to-event prediction. On 57,078 MIMIC-IV admissions, INTERVenE-Enc outperformed GRU-D, STraTS, and KarmaLego, reaching a support-weighted AUPRC of 0.672 ($+0.046$ over the strongest neural baseline, with non-overlapping 95% bootstrap CIs), AUROC of 0.901, and length-of-stay MAE of 44.4,h. INTERVenE-Ar complements these predictions with generated abstraction trajectories and evolving risk scores, achieving AUROC of 0.854 and AUPRC of 0.588 under the harder generative readout. An alternative-discretization ablation preserved predictive performance, supporting KBTA's role as a clinically named attribution substrate rather than a prerequisite for accuracy.

Foundation models for structured electronic health records (EHRs) are pretrained on longitudinal sequences of timestamped clinical events to learn adaptable patient representations. Tokenization -- how these timelines are converted into discrete model inputs -- determines what information is preserved, how efficiently it is encoded, and which relationships must be learned versus precomputed. Yet the impact of tokenization design choices on downstream performance and computational efficiency remains largely unexplored. Here, we pretrained a transformer on pediatric EHR data under a factorial design, varying tokenization along event encoding, time encoding, and workflow annotation. We evaluated area-under-the-receiver-operating-characteristic curve across 74 clinical prediction tasks. Joint event encoding and positional time encoding outperformed their alternatives (73/74 and 71/74 tasks) while requiring 39.5% and 9.6% fewer pretraining floating-point operations, respectively. Targeted ablations traced the joint encoding advantage to local binding efficiency, that is, code-attribute pairs are combined into single tokens, rather than split across tokens that the model must learn to associate during pretraining. External evaluation on an adult intensive care unit cohort demonstrated that this advantage generalizes despite substantial vocabulary mismatch, while temporal and workflow effects remain institution-specific. These results establish tokenization as a tractable lever for improving both the performance and efficiency of EHR foundation models.

Numerical time-series models effectively process irregular electronic health record (EHR) trajectories, but do not expose which temporal patterns support each prediction as readable evidence. Existing text-based interfaces either serialize observations, preserving source traceability but offering limited clinical interpretation, or generate patient-level summaries that improve readability but can obscure links to source measurements. We introduce STEP-CTS (Source-Traceable Evidence for Prediction from Clinical Time-Series), which learns to select source-traceable text evidence for a language-model predictor. Multi-scale window statistics of each trajectory are verbalized as sets of deterministic threshold predicates, each set linked to its source window (e.g., "[5-7 h]: last temperature at least 38C"). An offline LLM, run once per unique predicate set without access to patient records, the prediction task, or outcome labels, attaches clinical concepts such as "fever" to their supporting predicates and abstains when none applies. Each predicate set, together with its concepts, forms an evidence unit. A learned Evidence Selector selects a fixed-size subset of the evidence units, which a pretrained clinical language-model encoder reads to make the prediction, with no patient-level text generation. Across three ICU benchmarks, STEP-CTS outperforms evaluated text-based baselines, improving AUPRC over the strongest by 5.1, 3.7, and 11.7 percentage points on P2012, MIMIC-III, and P2019, respectively, and is competitive with dedicated numerical time-series models. Ablations show that clinical concepts and learned evidence selection each contribute to predictive performance. In a blinded clinician study, the selected evidence is rated as traceable as deterministic serialization, near the ceiling of the scale, and above generated summaries on clinical interpretation.