Evaluating Retrieval-Augmented Generation vs. Long-Context Input for Clinical Reasoning over EHRs

Electronic health records (EHRs) are long, noisy, and often redundant, posing a major challenge for the clinicians who must navigate them. Large language models (LLMs) offer a promising solution for extracting and reasoning over this unstructured text, but the length of clinical notes often exceeds even state-of-the-art models' extended context windows. Retrieval-augmented generation (RAG) offers an alternative by retrieving task-relevant passages from across the entire EHR, potentially reducing the amount of required input tokens. In this work, we propose three clinical tasks designed to be replicable across health systems with minimal effort: 1) extracting imaging procedures, 2) generating timelines of antibiotic use, and 3) identifying key diagnoses. Using EHRs from actual hospitalized patients, we test three state-of-the-art LLMs with varying amounts of provided context, using either targeted text retrieval or the most recent clinical notes. We find that RAG closely matches or exceeds the performance of using recent notes, and approaches the performance of using the models' full context while requiring drastically fewer input tokens. Our results suggest that RAG remains a competitive and efficient approach even as newer models become capable of handling increasingly longer amounts of text.

MoMA: A Mixture-of-Multimodal-Agents Architecture for Enhancing Clinical Prediction Modelling

Multimodal electronic health record (EHR) data provide richer, complementary insights into patient health compared to single-modality data. However, effectively integrating diverse data modalities for clinical prediction modeling remains challenging due to the substantial data requirements. We introduce a novel architecture, Mixture-of-Multimodal-Agents (MoMA), designed to leverage multiple large language model (LLM) agents for clinical prediction tasks using multimodal EHR data. MoMA employs specialized LLM agents ("specialist agents") to convert non-textual modalities, such as medical images and laboratory results, into structured textual summaries. These summaries, together with clinical notes, are combined by another LLM ("aggregator agent") to generate a unified multimodal summary, which is then used by a third LLM ("predictor agent") to produce clinical predictions. Evaluating MoMA on three prediction tasks using real-world datasets with different modality combinations and prediction settings, MoMA outperforms current state-of-the-art methods, highlighting its enhanced accuracy and flexibility across various tasks.

An Information-Theoretic Perspective on Multi-LLM Uncertainty Estimation

Large language models (LLMs) often behave inconsistently across inputs, indicating uncertainty and motivating the need for its quantification in high-stakes settings. Prior work on calibration and uncertainty quantification often focuses on individual models, overlooking the potential of model diversity. We hypothesize that LLMs make complementary predictions due to differences in training and the Zipfian nature of language, and that aggregating their outputs leads to more reliable uncertainty estimates. To leverage this, we propose MUSE (Multi-LLM Uncertainty via Subset Ensembles), a simple information-theoretic method that uses Jensen-Shannon Divergence to identify and aggregate well-calibrated subsets of LLMs. Experiments on binary prediction tasks demonstrate improved calibration and predictive performance compared to single-model and naive ensemble baselines.

Position Paper On Diagnostic Uncertainty Estimation from Large Language Models: Next-Word Probability Is Not Pre-test Probability

Large language models (LLMs) are being explored for diagnostic decision support, yet their ability to estimate pre-test probabilities, vital for clinical decision-making, remains limited. This study evaluates two LLMs, Mistral-7B and Llama3-70B, using structured electronic health record data on three diagnosis tasks. We examined three current methods of extracting LLM probability estimations and revealed their limitations. We aim to highlight the need for improved techniques in LLM confidence estimation.