Training LLMs for EHR-Based Reasoning Tasks via Reinforcement Learning

We present EHRMIND, a practical recipe for adapting large language models (LLMs) to complex clinical reasoning tasks using reinforcement learning with verifiable rewards (RLVR). While RLVR has succeeded in mathematics and coding, its application to healthcare contexts presents unique challenges due to the specialized knowledge and reasoning required for electronic health record (EHR) interpretation. Our pilot study on the MEDCALC benchmark reveals two key failure modes: (1) misapplied knowledge, where models possess relevant medical knowledge but apply it incorrectly, and (2) missing knowledge, where models lack essential domain knowledge. To address these cases, EHRMIND applies a two-stage solution: a lightweight supervised fine-tuning (SFT) warm-up that injects missing domain knowledge, stabilizes subsequent training, and encourages structured, interpretable outputs; followed by RLVR, which reinforces outcome correctness and refines the model's decision-making. We demonstrate the effectiveness of our method across diverse clinical applications, including medical calculations (MEDCALC), patient-trial matching (TREC CLINICAL TRIALS), and disease diagnosis (EHRSHOT). EHRMIND delivers consistent gains in accuracy, interpretability, and cross-task generalization. These findings offer practical guidance for applying RLVR to enhance LLM capabilities in healthcare settings.

Reinforcement Learning for Out-of-Distribution Reasoning in LLMs: An Empirical Study on Diagnosis-Related Group Coding

Diagnosis-Related Group (DRG) codes are essential for hospital reimbursement and operations but require labor-intensive assignment. Large Language Models (LLMs) struggle with DRG coding due to the out-of-distribution (OOD) nature of the task: pretraining corpora rarely contain private clinical or billing data. We introduce DRG-Sapphire, which uses large-scale reinforcement learning (RL) for automated DRG coding from clinical notes. Built on Qwen2.5-7B and trained with Group Relative Policy Optimization (GRPO) using rule-based rewards, DRG-Sapphire introduces a series of RL enhancements to address domain-specific challenges not seen in previous mathematical tasks. Our model achieves state-of-the-art accuracy on the MIMIC-IV benchmark and generates physician-validated reasoning for DRG assignments, significantly enhancing explainability. Our study further sheds light on broader challenges of applying RL to knowledge-intensive, OOD tasks. We observe that RL performance scales approximately linearly with the logarithm of the number of supervised fine-tuning (SFT) examples, suggesting that RL effectiveness is fundamentally constrained by the domain knowledge encoded in the base model. For OOD tasks like DRG coding, strong RL performance requires sufficient knowledge infusion prior to RL. Consequently, scaling SFT may be more effective and computationally efficient than scaling RL alone for such tasks.

TrialPanorama: Database and Benchmark for Systematic Review and Design of Clinical Trials

Developing artificial intelligence (AI) for vertical domains requires a solid data foundation for both training and evaluation. In this work, we introduce TrialPanorama, a large-scale, structured database comprising 1,657,476 clinical trial records aggregated from 15 global sources. The database captures key aspects of trial design and execution, including trial setups, interventions, conditions, biomarkers, and outcomes, and links them to standard biomedical ontologies such as DrugBank and MedDRA. This structured and ontology-grounded design enables TrialPanorama to serve as a unified, extensible resource for a wide range of clinical trial tasks, including trial planning, design, and summarization. To demonstrate its utility, we derive a suite of benchmark tasks directly from the TrialPanorama database. The benchmark spans eight tasks across two categories: three for systematic review (study search, study screening, and evidence summarization) and five for trial design (arm design, eligibility criteria, endpoint selection, sample size estimation, and trial completion assessment). The experiments using five state-of-the-art large language models (LLMs) show that while general-purpose LLMs exhibit some zero-shot capability, their performance is still inadequate for high-stakes clinical trial workflows. We release TrialPanorama database and the benchmark to facilitate further research on AI for clinical trials.

BioDSA-1K: Benchmarking Data Science Agents for Biomedical Research

Validating scientific hypotheses is a central challenge in biomedical research, and remains difficult for artificial intelligence (AI) agents due to the complexity of real-world data analysis and evidence interpretation. In this work, we present BioDSA-1K, a benchmark designed to evaluate AI agents on realistic, data-driven biomedical hypothesis validation tasks. BioDSA-1K consists of 1,029 hypothesis-centric tasks paired with 1,177 analysis plans, curated from over 300 published biomedical studies to reflect the structure and reasoning found in authentic research workflows. Each task includes a structured hypothesis derived from the original study's conclusions, expressed in the affirmative to reflect the language of scientific reporting, and one or more pieces of supporting evidence grounded in empirical data tables. While these hypotheses mirror published claims, they remain testable using standard statistical or machine learning methods. The benchmark enables evaluation along four axes: (1) hypothesis decision accuracy, (2) alignment between evidence and conclusion, (3) correctness of the reasoning process, and (4) executability of the AI-generated analysis code. Importantly, BioDSA-1K includes non-verifiable hypotheses: cases where the available data are insufficient to support or refute a claim, reflecting a common yet underexplored scenario in real-world science. We propose BioDSA-1K as a foundation for building and evaluating generalizable, trustworthy AI agents for biomedical discovery.

s3: You Don't Need That Much Data to Train a Search Agent via RL

Retrieval-augmented generation (RAG) systems empower large language models (LLMs) to access external knowledge during inference. Recent advances have enabled LLMs to act as search agents via reinforcement learning (RL), improving information acquisition through multi-turn interactions with retrieval engines. However, existing approaches either optimize retrieval using search-only metrics (e.g., NDCG) that ignore downstream utility or fine-tune the entire LLM to jointly reason and retrieve-entangling retrieval with generation and limiting the real search utility and compatibility with frozen or proprietary models. In this work, we propose s3, a lightweight, model-agnostic framework that decouples the searcher from the generator and trains the searcher using a Gain Beyond RAG reward: the improvement in generation accuracy over naive RAG. s3 requires only 2.4k training samples to outperform baselines trained on over 70x more data, consistently delivering stronger downstream performance across six general QA and five medical QA benchmarks.

SECRET: Semi-supervised Clinical Trial Document Similarity Search

Clinical trials are vital for evaluation of safety and efficacy of new treatments. However, clinical trials are resource-intensive, time-consuming and expensive to conduct, where errors in trial design, reduced efficacy, and safety events can result in significant delays, financial losses, and damage to reputation. These risks underline the importance of informed and strategic decisions in trial design to mitigate these risks and improve the chances of a successful trial. Identifying similar historical trials is critical as these trials can provide an important reference for potential pitfalls and challenges including serious adverse events, dosage inaccuracies, recruitment difficulties, patient adherence issues, etc. Addressing these challenges in trial design can lead to development of more effective study protocols with optimized patient safety and trial efficiency. In this paper, we present a novel method to identify similar historical trials by summarizing clinical trial protocols and searching for similar trials based on a query trial's protocol. Our approach significantly outperforms all baselines, achieving up to a 78% improvement in recall@1 and a 53% improvement in precision@1 over the best baseline. We also show that our method outperforms all other baselines in partial trial similarity search and zero-shot patient-trial matching, highlighting its superior utility in these tasks.

Integration of Large Language Models and Traditional Deep Learning for Social Determinants of Health Prediction

Social Determinants of Health (SDoH) are economic, social and personal circumstances that affect or influence an individual's health status. SDoHs have shown to be correlated to wellness outcomes, and therefore, are useful to physicians in diagnosing diseases and in decision-making. In this work, we automatically extract SDoHs from clinical text using traditional deep learning and Large Language Models (LLMs) to find the advantages and disadvantages of each on an existing publicly available dataset. Our models outperform a previous reference point on a multilabel SDoH classification by 10 points, and we present a method and model to drastically speed up classification (12X execution time) by eliminating expensive LLM processing. The method we present combines a more nimble and efficient solution that leverages the power of the LLM for precision and traditional deep learning methods for efficiency. We also show highly performant results on a dataset supplemented with synthetic data and several traditional deep learning models that outperform LLMs. Our models and methods offer the next iteration of automatic prediction of SDoHs that impact at-risk patients.

OmniV-Med: Scaling Medical Vision-Language Model for Universal Visual Understanding

The practical deployment of medical vision-language models (Med-VLMs) necessitates seamless integration of textual data with diverse visual modalities, including 2D/3D images and videos, yet existing models typically employ separate encoders for different modalities. To address this limitation, we present OmniV-Med, a unified framework for multimodal medical understanding. Our technical contributions are threefold: First, we construct OmniV-Med-Instruct, a comprehensive multimodal medical dataset containing 252K instructional samples spanning 14 medical image modalities and 11 clinical tasks. Second, we devise a rotary position-adaptive encoder that processes multi-resolution 2D/3D images and videos within a unified architecture, diverging from conventional modality-specific encoders. Third, we introduce a medical-aware token pruning mechanism that exploits spatial-temporal redundancy in volumetric data (e.g., consecutive CT slices) and medical videos, effectively reducing 60\% of visual tokens without performance degradation. Empirical evaluations demonstrate that OmniV-Med-7B achieves state-of-the-art performance on 7 benchmarks spanning 2D/3D medical imaging and video understanding tasks. Notably, our lightweight variant (OmniV-Med-1.5B) attains comparable performance while requiring only 8 RTX3090 GPUs for training and supporting efficient long-video inference. Data, code and model will be released.

InformGen: An AI Copilot for Accurate and Compliant Clinical Research Consent Document Generation

Leveraging large language models (LLMs) to generate high-stakes documents, such as informed consent forms (ICFs), remains a significant challenge due to the extreme need for regulatory compliance and factual accuracy. Here, we present InformGen, an LLM-driven copilot for accurate and compliant ICF drafting by optimized knowledge document parsing and content generation, with humans in the loop. We further construct a benchmark dataset comprising protocols and ICFs from 900 clinical trials. Experimental results demonstrate that InformGen achieves near 100% compliance with 18 core regulatory rules derived from FDA guidelines, outperforming a vanilla GPT-4o model by up to 30%. Additionally, a user study with five annotators shows that InformGen, when integrated with manual intervention, attains over 90% factual accuracy, significantly surpassing the vanilla GPT-4o model's 57%-82%. Crucially, InformGen ensures traceability by providing inline citations to source protocols, enabling easy verification and maintaining the highest standards of factual integrity.

ExPath: Towards Explaining Targeted Pathways for Biological Knowledge Bases

Biological knowledge bases provide systemically functional pathways of cells or organisms in terms of molecular interaction. However, recognizing more targeted pathways, particularly when incorporating wet-lab experimental data, remains challenging and typically requires downstream biological analyses and expertise. In this paper, we frame this challenge as a solvable graph learning and explaining task and propose a novel pathway inference framework, ExPath, that explicitly integrates experimental data, specifically amino acid sequences (AA-seqs), to classify various graphs (bio-networks) in biological databases. The links (representing pathways) that contribute more to classification can be considered as targeted pathways. Technically, ExPath comprises three components: (1) a large protein language model (pLM) that encodes and embeds AA-seqs into graph, overcoming traditional obstacles in processing AA-seq data, such as BLAST; (2) PathMamba, a hybrid architecture combining graph neural networks (GNNs) with state-space sequence modeling (Mamba) to capture both local interactions and global pathway-level dependencies; and (3) PathExplainer, a subgraph learning module that identifies functionally critical nodes and edges through trainable pathway masks. We also propose ML-oriented biological evaluations and a new metric. The experiments involving 301 bio-networks evaluations demonstrate that pathways inferred by ExPath maintain biological meaningfulness. We will publicly release curated 301 bio-network data soon.