Analysis of eligibility criteria clusters based on large language models for clinical trial design.

Abstract

Clinical trials (CTs) are essential for improving patient care by evaluating new treatments' safety and efficacy. A key component in CT protocols is the study population defined by the eligibility criteria. This study aims to evaluate the effectiveness of large language models (LLMs) in encoding eligibility criterion information to support CT-protocol design. We extracted eligibility criterion sections, phases, conditions, and interventions from CT protocols available in the ClinicalTrials.gov registry. Eligibility sections were split into individual rules using a criterion tokenizer and embedded using LLMs. The obtained representations were clustered. The quality and relevance of the clusters for protocol design was evaluated through 3 experiments: intrinsic alignment with protocol information and human expert cluster coherence assessment, extrinsic evaluation through CT-level classification tasks, and eligibility section generation. Sentence embeddings fine-tuned using biomedical corpora produce clusters with the highest alignment to CT-level information. Human expert evaluation confirms that clusters are well structured and coherent. Despite the high information compression, clusters retain significant CT information, up to 97% of the classification performance obtained with raw embeddings. Finally, eligibility sections automatically generated using clusters achieve 95% of the ROUGE scores obtained with a generative LLM prompted with CT-protocol details, suggesting that clusters encapsulate information useful to CT-protocol design. Clusters derived from sentence-level LLM embeddings effectively summarize complex eligibility criterion data while retaining relevant CT-protocol details. Clustering-based approaches provide a scalable enhancement in CT design that balances information compression with accuracy. Clustering eligibility criteria using LLM embeddings provides a practical and efficient method to summarize critical protocol information. We provide an interactive visualization of the pipeline here.