Jenelle Jindal

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.

Edward Kim, Yuri Cho, Jose Eduardo E. Lima et al.

Digital health interventions increasingly deliver home exercise programs via sensor-equipped devices such as smartphones, enabling remote monitoring of adherence and performance. However, current software is usually authored before clinical encounters as libraries of modules for broad impairment categories. At the point of care, clinicians can only choose from these modules and adjust a few parameters (for example, duration or repetitions). As a result, individual limitations, goals, and environmental constraints are often not reflected, limiting personalization and benefit. We propose a paradigm in which large language models (LLMs) act as constrained translators that convert clinicians' exercise prescriptions into intervention software. Clinicians remain the decision makers: they design exercises during the encounter, tailored to each patient's impairments, goals, and environment, and the LLM generates matching software. We conducted a prospective single-arm feasibility study with 20 licensed physical and occupational therapists who created 40 individualized upper extremity programs for a standardized patient; 100% of prescriptions were translated into executable software, compared with 55% under a representative template-based digital health intervention (p < 0.01). LLM-generated software correctly delivered 99.7% of instructions and monitored performance with 88.4% accuracy (95% confidence interval, 0.843-0.915). Overall, 90% of therapists judged the system safe for patient interaction and 75% expressed willingness to adopt it in practice. To our knowledge, this is the first prospective evaluation of clinician-directed intervention software generation with an LLM in health care, demonstrating feasibility and motivating larger trials in real patient populations.

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.