Kueiyu Joshua Lin

Bowen Gu, Rishi J. Desai, Kueiyu Joshua Lin et al. · harvard

Large Language Models (LLMs) have shown promise in clinical applications through prompt engineering, allowing flexible clinical predictions. However, they struggle to produce reliable prediction probabilities, which are crucial for transparency and decision-making. While explicit prompts can lead LLMs to generate probability estimates, their numerical reasoning limitations raise concerns about reliability. We compared explicit probabilities from text generation to implicit probabilities derived from the likelihood of predicting the correct label token. Across six advanced open-source LLMs and five medical datasets, explicit probabilities consistently underperformed implicit probabilities in discrimination, precision, and recall. This discrepancy is more pronounced with smaller LLMs and imbalanced datasets, highlighting the need for cautious interpretation, improved probability estimation methods, and further research for clinical use of LLMs.

Jiageng Wu, Bowen Gu, Ren Zhou et al. · harvard, mit

Large language models (LLMs) hold great promise for medical applications and are evolving rapidly, with new models being released at an accelerated pace. However, benchmarking on large-scale real-world data such as electronic health records (EHRs) is critical, as clinical decisions are directly informed by these sources, yet current evaluations remain limited. Most existing benchmarks rely on medical exam-style questions or PubMed-derived text, failing to capture the complexity of real-world clinical data. Others focus narrowly on specific application scenarios, limiting their generalizability across broader clinical use. To address this gap, we present BRIDGE, a comprehensive multilingual benchmark comprising 87 tasks sourced from real-world clinical data sources across nine languages. It covers eight major task types spanning the entire continuum of patient care across six clinical stages and 20 representative applications, including triage and referral, consultation, information extraction, diagnosis, prognosis, and billing coding, and involves 14 clinical specialties. We systematically evaluated 95 LLMs (including DeepSeek-R1, GPT-4o, Gemini series, and Qwen3 series) under various inference strategies. Our results reveal substantial performance variation across model sizes, languages, natural language processing tasks, and clinical specialties. Notably, we demonstrate that open-source LLMs can achieve performance comparable to proprietary models, while medically fine-tuned LLMs based on older architectures often underperform versus updated general-purpose models. The BRIDGE and its corresponding leaderboard serve as a foundational resource and a unique reference for the development and evaluation of new LLMs in real-world clinical text understanding. The BRIDGE leaderboard: https://huggingface.co/spaces/YLab-Open/BRIDGE-Medical-Leaderboard

Yunying Zhu, Andrew R Weckstein, Kueiyu Joshua Lin et al.

Accurate disease trajectory prediction is critical for early intervention, resource allocation, and improving long-term outcomes. While electronic health records (EHRs) provide a rich longitudinal view of patient health in clinical environments, models trained on curated research cohorts may not reflect routine deployment settings, and those trained on single-hospital datasets capture only fragments of each patient's trajectory. This highlights the importance of leveraging large, multi-hospital health systems for training and validation to better reflect real-world clinical complexity. In this work, we develop DT-Transformer, a foundation model trained on 57.1M structured EHR entries over 1.7M patients from Mass General Brigham (MGB), spanning 11 hospitals and a broad network of outpatient clinics. DT-Transformer achieves strong discrimination in both held-out and prospective validation settings. Next-event prediction achieves a median age- and sex-stratified AUC of 0.871 across 896 disease categories, with all categories exceeding AUC 0.5. These results support health system-scale training as a path toward foundation models suited to real-world clinical forecasting.

Chong Shao, Douglas Snyder, Chiran Li et al. · harvard

Identifying medication discontinuations in electronic health records (EHRs) is vital for patient safety but is often hindered by information being buried in unstructured notes. This study aims to evaluate the capabilities of advanced open-sourced and proprietary large language models (LLMs) in extracting medications and classifying their medication status from EHR notes, focusing on their scalability on medication information extraction without human annotation. We collected three EHR datasets from diverse sources to build the evaluation benchmark. We evaluated 12 advanced LLMs and explored multiple LLM prompting strategies. Performance on medication extraction, medication status classification, and their joint task (extraction then classification) was systematically compared across all experiments. We found that LLMs showed promising performance on the medication extraction and discontinuation classification from EHR notes. GPT-4o consistently achieved the highest average F1 scores in all tasks under zero-shot setting - 94.0% for medication extraction, 78.1% for discontinuation classification, and 72.7% for the joint task. Open-sourced models followed closely, Llama-3.1-70B-Instruct achieved the highest performance in medication status classification on the MIV-Med dataset (68.7%) and in the joint task on both the Re-CASI (76.2%) and MIV-Med (60.2%) datasets. Medical-specific LLMs demonstrated lower performance compared to advanced general-domain LLMs. Few-shot learning generally improved performance, while CoT reasoning showed inconsistent gains. LLMs demonstrate strong potential for medication extraction and discontinuation identification on EHR notes, with open-sourced models offering scalable alternatives to proprietary systems and few-shot can further improve LLMs' capability.

Janick Weberpals, Pamela A. Shaw, Kueiyu Joshua Lin et al.

Multiple imputation (MI) models can be improved by including auxiliary covariates (AC), but their performance in high-dimensional data is not well understood. We aimed to develop and compare high-dimensional MI (HDMI) approaches using structured and natural language processing (NLP)-derived AC in studies with partially observed confounders. We conducted a plasmode simulation study using data from opioid vs. non-steroidal anti-inflammatory drug (NSAID) initiators (X) with observed serum creatinine labs (Z2) and time-to-acute kidney injury as outcome. We simulated 100 cohorts with a null treatment effect, including X, Z2, atrial fibrillation (U), and 13 other investigator-derived confounders (Z1) in the outcome generation. We then imposed missingness (MZ2) on 50% of Z2 measurements as a function of Z2 and U and created different HDMI candidate AC using structured and NLP-derived features. We mimicked scenarios where U was unobserved by omitting it from all AC candidate sets. Using LASSO, we data-adaptively selected HDMI covariates associated with Z2 and MZ2 for MI, and with U to include in propensity score models. The treatment effect was estimated following propensity score matching in MI datasets and we benchmarked HDMI approaches against a baseline imputation and complete case analysis with Z1 only. HDMI using claims data showed the lowest bias (0.072). Combining claims and sentence embeddings led to an improvement in the efficiency displaying the lowest root-mean-squared-error (0.173) and coverage (94%). NLP-derived AC alone did not perform better than baseline MI. HDMI approaches may decrease bias in studies with partially observed confounders where missingness depends on unobserved factors.

Jiageng Wu, Kevin Xie, Bowen Gu et al.

Large language models (LLMs) are increasingly being applied to clinical care, a domain where both accuracy and transparent reasoning are critical for safe and trustworthy deployment. Chain-of-thought (CoT) prompting, which elicits step-by-step reasoning, has demonstrated improvements in performance and interpretability across a wide range of tasks. However, its effectiveness in clinical contexts remains largely unexplored, particularly in the context of electronic health records (EHRs), the primary source of clinical documentation, which are often lengthy, fragmented, and noisy. In this work, we present the first large-scale systematic study of CoT for clinical text understanding. We assess 95 advanced LLMs on 87 real-world clinical text tasks, covering 9 languages and 8 task types. Contrary to prior findings in other domains, we observe that 86.3\% of models suffer consistent performance degradation in the CoT setting. More capable models remain relatively robust, while weaker ones suffer substantial declines. To better characterize these effects, we perform fine-grained analyses of reasoning length, medical concept alignment, and error profiles, leveraging both LLM-as-a-judge evaluation and clinical expert evaluation. Our results uncover systematic patterns in when and why CoT fails in clinical contexts, which highlight a critical paradox: CoT enhances interpretability but may undermine reliability in clinical text tasks. This work provides an empirical basis for clinical reasoning strategies of LLMs, highlighting the need for transparent and trustworthy approaches.