Serina Applebaum

Hyunjae Kim, Jiwoong Sohn, Aidan Gilson et al.

Large language models (LLMs) are transforming the landscape of medicine, yet two fundamental challenges persist: keeping up with rapidly evolving medical knowledge and providing verifiable, evidence-grounded reasoning. Retrieval-augmented generation (RAG) has been widely adopted to address these limitations by supplementing model outputs with retrieved evidence. However, whether RAG reliably achieves these goals remains unclear. Here, we present the most comprehensive expert evaluation of RAG in medicine to date. Eighteen medical experts contributed a total of 80,502 annotations, assessing 800 model outputs generated by GPT-4o and Llama-3.1-8B across 200 real-world patient and USMLE-style queries. We systematically decomposed the RAG pipeline into three components: (i) evidence retrieval (relevance of retrieved passages), (ii) evidence selection (accuracy of evidence usage), and (iii) response generation (factuality and completeness of outputs). Contrary to expectation, standard RAG often degraded performance: only 22% of top-16 passages were relevant, evidence selection remained weak (precision 41-43%, recall 27-49%), and factuality and completeness dropped by up to 6% and 5%, respectively, compared with non-RAG variants. Retrieval and evidence selection remain key failure points for the model, contributing to the overall performance drop. We further show that simple yet effective strategies, including evidence filtering and query reformulation, substantially mitigate these issues, improving performance on MedMCQA and MedXpertQA by up to 12% and 8.2%, respectively. These findings call for re-examining RAG's role in medicine and highlight the importance of stage-aware evaluation and deliberate system design for reliable medical LLM applications.

Nicholas Wan, Qiao Jin, Joey Chan et al.

Although large language models (LLMs) have been assessed for general medical knowledge using licensing exams, their ability to support clinical decision-making, such as selecting medical calculators, remains uncertain. We assessed nine LLMs, including open-source, proprietary, and domain-specific models, with 1,009 multiple-choice question-answer pairs across 35 clinical calculators and compared LLMs to humans on a subset of questions. While the highest-performing LLM, OpenAI o1, provided an answer accuracy of 66.0% (CI: 56.7-75.3%) on the subset of 100 questions, two human annotators nominally outperformed LLMs with an average answer accuracy of 79.5% (CI: 73.5-85.0%). Ultimately, we evaluated medical trainees and LLMs in recommending medical calculators across clinical scenarios like risk stratification and diagnosis. With error analysis showing that the highest-performing LLMs continue to make mistakes in comprehension (49.3% of errors) and calculator knowledge (7.1% of errors), our findings highlight that LLMs are not superior to humans in calculator recommendation.

Nikhil Khandekar, Qiao Jin, Guangzhi Xiong et al.

As opposed to evaluating computation and logic-based reasoning, current benchmarks for evaluating large language models (LLMs) in medicine are primarily focused on question-answering involving domain knowledge and descriptive reasoning. While such qualitative capabilities are vital to medical diagnosis, in real-world scenarios, doctors frequently use clinical calculators that follow quantitative equations and rule-based reasoning paradigms for evidence-based decision support. To this end, we propose MedCalc-Bench, a first-of-its-kind dataset focused on evaluating the medical calculation capability of LLMs. MedCalc-Bench contains an evaluation set of over 1000 manually reviewed instances from 55 different medical calculation tasks. Each instance in MedCalc-Bench consists of a patient note, a question requesting to compute a specific medical value, a ground truth answer, and a step-by-step explanation showing how the answer is obtained. While our evaluation results show the potential of LLMs in this area, none of them are effective enough for clinical settings. Common issues include extracting the incorrect entities, not using the correct equation or rules for a calculation task, or incorrectly performing the arithmetic for the computation. We hope our study highlights the quantitative knowledge and reasoning gaps in LLMs within medical settings, encouraging future improvements of LLMs for various clinical calculation tasks.