Jenelle Jindal

Scott L. Fleming, Alejandro Lozano, William J. Haberkorn et al. · stanford

The ability of large language models (LLMs) to follow natural language instructions with human-level fluency suggests many opportunities in healthcare to reduce administrative burden and improve quality of care. However, evaluating LLMs on realistic text generation tasks for healthcare remains challenging. Existing question answering datasets for electronic health record (EHR) data fail to capture the complexity of information needs and documentation burdens experienced by clinicians. To address these challenges, we introduce MedAlign, a benchmark dataset of 983 natural language instructions for EHR data. MedAlign is curated by 15 clinicians (7 specialities), includes clinician-written reference responses for 303 instructions, and provides 276 longitudinal EHRs for grounding instruction-response pairs. We used MedAlign to evaluate 6 general domain LLMs, having clinicians rank the accuracy and quality of each LLM response. We found high error rates, ranging from 35% (GPT-4) to 68% (MPT-7B-Instruct), and an 8.3% drop in accuracy moving from 32k to 2k context lengths for GPT-4. Finally, we report correlations between clinician rankings and automated natural language generation metrics as a way to rank LLMs without human review. We make MedAlign available under a research data use agreement to enable LLM evaluations on tasks aligned with clinician needs and preferences.

Alejandro Lozano, Keiko Ihara, Ping-Hao Yang et al.

Summarizing the latest medical literature to guide clinical decision-making is essential for evidence-based medicine and high-quality patient care. Yet clinicians face increasing challenges due to limited time with patients and a rapidly growing volume of published articles. Although retrieval-augmented large language models (LLMs) have shown promise in clinical summarization, human evaluations of their effectiveness in synthesizing broader scientific literature and direct comparisons to expert-written syntheses remain scarce. We constructed a RAG-based agentic AI framework using three state-of-the-art LLMs: Sonnet, GPT-4o, and Llama 3.1. A headache specialist created 13 questions, three for prompt optimization and ten for evaluation. Ten headache specialists across the United States and Canada each wrote a summary for one question, yielding four summaries per question (expert, Sonnet, GPT-4o, and Llama). The experts, blinded to authorship, critically evaluated the summaries, excluding the topic for which they wrote a summary, based on correctness, completeness, conciseness, and clinical utility, scoring each from 1 to 10 using standardized rubrics. They also ranked the summaries by preference and indicated whether they believed each summary was written by an expert or an LLM. Our study, comparing LLM- and expert-written literature summaries evaluated by headache specialists, showed that expert-written summaries were preferred, although experts sometimes found it challenging to distinguish between human- and AI-generated summaries. We also identified key expert-valued features beyond standard evaluation metrics that can guide future refinement of both human and AI literature summarization pipelines.

Michael Wornow, Alejandro Lozano, Dev Dash et al.

Matching patients to clinical trials is a key unsolved challenge in bringing new drugs to market. Today, identifying patients who meet a trial's eligibility criteria is highly manual, taking up to 1 hour per patient. Automated screening is challenging, however, as it requires understanding unstructured clinical text. Large language models (LLMs) offer a promising solution. In this work, we explore their application to trial matching. First, we design an LLM-based system which, given a patient's medical history as unstructured clinical text, evaluates whether that patient meets a set of inclusion criteria (also specified as free text). Our zero-shot system achieves state-of-the-art scores on the n2c2 2018 cohort selection benchmark. Second, we improve the data and cost efficiency of our method by identifying a prompting strategy which matches patients an order of magnitude faster and more cheaply than the status quo, and develop a two-stage retrieval pipeline that reduces the number of tokens processed by up to a third while retaining high performance. Third, we evaluate the interpretability of our system by having clinicians evaluate the natural language justifications generated by the LLM for each eligibility decision, and show that it can output coherent explanations for 97% of its correct decisions and 75% of its incorrect ones. Our results establish the feasibility of using LLMs to accelerate clinical trial operations.

David Wu, Fateme Nateghi Haredasht, Saloni Kumar Maharaj et al.

Large language models (LLMs) are routinely used by physicians and patients for medical advice, yet their clinical safety profiles remain poorly characterized. We present NOHARM (Numerous Options Harm Assessment for Risk in Medicine), a benchmark using 100 real primary-care-to-specialist consultation cases to measure harm frequency and severity from LLM-generated medical recommendations. NOHARM covers 10 specialties, with 12,747 expert annotations for 4,249 clinical management options. Across 31 LLMs, severe harm occurs in up to 22.2% (95% CI 21.6-22.8%) of cases, with harms of omission accounting for 76.6% (95% CI 76.4-76.8%) of errors. Safety performance is only moderately correlated (r = 0.61-0.64) with existing AI and medical knowledge benchmarks. The best models outperform generalist physicians on safety (mean difference 9.7%, 95% CI 7.0-12.5%), and a diverse multi-agent approach reduces harm compared to solo models (mean difference 8.0%, 95% CI 4.0-12.1%). Therefore, despite strong performance on existing evaluations, widely used AI models can produce severely harmful medical advice at nontrivial rates, underscoring clinical safety as a distinct performance dimension necessitating explicit measurement.

Monica Munnangi, Akshay Swaminathan, Jason Alan Fries et al.

Verifying and attributing factual claims is essential for the safe and effective use of large language models (LLMs) in healthcare. A core component of factuality evaluation is fact decomposition, the process of breaking down complex clinical statements into fine-grained atomic facts for verification. Recent work has proposed fact decomposition, which uses LLMs to rewrite source text into concise sentences conveying a single piece of information, to facilitate fine-grained fact verification. However, clinical documentation poses unique challenges for fact decomposition due to dense terminology and diverse note types and remains understudied. To address this gap and explore these challenges, we present FactEHR, an NLI dataset consisting of document fact decompositions for 2,168 clinical notes spanning four types from three hospital systems, resulting in 987,266 entailment pairs. We assess the generated facts on different axes, from entailment evaluation of LLMs to a qualitative analysis. Our evaluation, including review by the clinicians, reveals substantial variability in LLM performance for fact decomposition. For example, Gemini-1.5-Flash consistently generates relevant and accurate facts, while Llama-3 8B produces fewer and less consistent outputs. The results underscore the need for better LLM capabilities to support factual verification in clinical text.