Evaluating Large Language Models for Evidence-Based Clinical Question Answering

Abstract

Large Language Models (LLMs) have demonstrated substantial progress in biomedical and clinical applications, motivating rigorous evaluation of their ability to answer nuanced, evidence-based questions. We curate a multi-source benchmark drawing from Cochrane systematic reviews and clinical guidelines, including structured recommendations from the American Heart Association and narrative guidance used by insurers. Using GPT-4o-mini and GPT-5, we observe consistent performance patterns across sources and clinical domains: accuracy is highest on structured guideline recommendations (90%) and lower on narrative guideline and systematic review questions (60--70%). We also find a strong correlation between accuracy and the citation count of the underlying systematic reviews, where each doubling of citations is associated with roughly a 30% increase in the odds of a correct answer. Models show moderate ability to reason about evidence quality when contextual information is supplied. When we incorporate retrieval-augmented prompting, providing the gold-source abstract raises accuracy on previously incorrect items to 0.79; providing top 3 PubMed abstracts (ranked by semantic relevance) improves accuracy to 0.23, while random abstracts reduce accuracy (0.10, within temperature variation). These effects are mirrored in GPT-4o-mini, underscoring that source clarity and targeted retrieval -- not just model size -- drive performance. Overall, our results highlight both the promise and current limitations of LLMs for evidence-based clinical question answering. Retrieval-augmented prompting emerges as a useful strategy to improve factual accuracy and alignment with source evidence, while stratified evaluation by specialty and question type remains essential to understand current knowledge access and to contextualize model performance.