Operationalizing Large Language Models for Clinical Research Data Extraction: Methods, Quality Control, and Governance

Checked 30 Sept 2026. Open license (CC-BY, CC-BY-SA, CC0, public domain): full text indexed and used in synthesis.

MethodsThis narrative review drew on targeted searches of PubMed/MEDLINE and arXiv (January 2020–October 2025), verification of peer-reviewed versions via ACL Anthology for selected preprints, and citation tracking of seminal literature. In this review, we trace the methodological evolution from rules to encoder-based models and LLMs, propose a multidimensional evaluation framework for real-world deployment—which includes accuracy, structural quality, human-in-the-loop effort, stability, and compliance—and develop an operational governance checklist to support auditable and reproducible implementations. Using representative tasks—diagnosis extraction, medication records, clinical trial data, and phenotype integration—we summarize the improvements and failure modes of LLM-based extraction and analyze key challenges, including domain shift, factual “hallucinations,” privacy and regulatory constraints, and cost/latency trade-offs. Finally, we outline future directions through which multimodal and cross-lingual extensions, human–machine collaborative annotation, and standardized reporting practices can advance precision medicine and sustainable, high-quality clinical research.

• Chen et al. 2026 argue that keyword- and rule-based clinical text extraction breaks down on negation, temporal reasoning, and cross-paragraph dependencies, and that LLMs paired with retrieval augmentation and structured output constraints enable a "generation-as-structured-output" paradigm—though they hedge that RAG only "may improve" factual errors and inconsistencies. Trace →
• Liu et al. 2025 identify integrating RAG systems within electronic health records as a key future direction, which speaks directly to the persistent "last-mile" bottleneck in preparing research-grade clinical datasets that Chen et al. 2026 describe. Trace →

• RAG reliability and evaluation