Training Large Language Models to Predict Clinical Events

Predicting future clinical outcomes from electronic health records (EHR) remains challenging due to the complexity and heterogeneity of patient data. LLMs have shown strong potential for such predictive tasks, yet existing approaches mainly focus on enhancing medical knowledge through distillation or RAG while relying on the model's internal ability to interpret contextual information. In this work, we present ReMedi (Reasoner for Medical Clinical Prediction), a framework for improving clinical outcome prediction from EHR. ReMedi generates rationale-answer pairs using a challenging sample regeneration mechanism for complex clinical questions, which leverages ground-truth answers as hints to enhance reasoning for further fine-tuning and preference tuning. ReMedi integrates ground-truth outcome guidance into the preference data construction loop, regenerating rationale-answer variants. By tuning on these rationale-answer pairs, the model improves its predictive performance. Experiments on multiple EHR prediction tasks demonstrate substantial gains of up to 19.9 percent over state-of-the-art baselines in terms of F1 score, underscoring ReMedi's effectiveness in real-world clinical prediction.

Clinical language models (LMs) are increasingly applied to support clinical risk prediction from free-text notes, yet their uncertainty estimates often remain poorly calibrated and clinically unreliable. In this work, we propose Clinical Uncertainty Risk Alignment (CURA), a framework that aligns clinical LM-based risk estimates and uncertainty with both individual error likelihoods and cohort-level ambiguities. CURA first fine-tunes domain-specific clinical LMs to obtain task-adapted patient embeddings, and then performs uncertainty fine-tuning of a multi-head classifier using a bi-level uncertainty objective. Specifically, an individual-level calibration term aligns predictive uncertainty with each patient's likelihood of error, while a cohort-aware regularizer pulls risk estimates toward event rates in their local neighborhoods in the embedding space and places extra weight on ambiguous cohorts near the decision boundary. We further show that this cohort-aware term can be interpreted as a cross-entropy loss with neighborhood-informed soft labels, providing a label-smoothing view of our method. Extensive experiments on MIMIC-IV clinical risk prediction tasks across various clinical LMs show that CURA consistently improves calibration metrics without substantially compromising discrimination. Further analysis illustrates that CURA reduces overconfident false reassurance and yields more trustworthy uncertainty estimates for downstream clinical decision support.

Large language models (LLMs) can generate or synthesize clinical text for a wide range of applications, from improving clinical documentation to augmenting clinical text analytics. Yet evaluations typically focus on a narrow aspect -- such as similarity or utility comparisons -- even though these aspects are complementary and best viewed in parallel. In this study, we aim to conduct a systematic evaluation of LLM-generated clinical text, which includes intrinsic, extrinsic, and factuality evaluations of synthetic clinical notes rephrased from MIMIC databases at million-note scale. Our analysis demonstrates that synthetic notes preserve core clinical information and predictive utility for coarse-grained tasks despite substantial linguistic changes, but lose fine-grained details for task like ICD coding. We show this loss of detail can be substantially mitigated by rephrasing notes by chunks rather than by the whole note, but at the cost of reduced factual precision under incomplete context. Through fact-checking and error analysis, we further find that synthesis errors are dominated by misinterpretation of clinical context, alongside temporal confusion, measurement errors, and fabricated claims. Finally, we show that the synthetic notes -- despite their task-agnostic nature -- can effectively augment task-specific training for rare ICD codes.