Citation reliability of frontier large language models in medical writing and its automated verification

Abstract

Large language models (LLMs) are increasingly used to draft medical manuscripts, yet their citations are unreliable and clinicians lack a validated way to verify them. We evaluated three frontier LLMs, Claude Opus 4.8, GPT-5.5, and Gemini 3.5 Flash, generating 270 cardiology narrative reviews with web search enabled, and verified all 8,050 references against PubMed. Problematic references accounted for 11.5% of GPT-5.5 output, 29.2% of Claude output, and 29.6% of Gemini output (P < 0.001), with no significant gradient across topics of differing publication volume (P = 0.052). Misattribution, a valid PubMed identifier that resolves to a different article, made up 77% of errors, whereas fabrication was rare (0.6%). Against an expert-adjudicated set of 270 references, an LLM-based Chain-of-Verification (CoVe) detected 60 of 62 problematic references (sensitivity 96.8%, specificity 98.6%), including every misattribution and fabrication. LLM-generated citations require identifier-level verification, and CoVe provides it at expert-level accuracy.