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This study introduces a framework to structure and analyze eligibility criteria across three real-world trial protocols, aiming to inform more granular AI-driven trial matching strategies. Trial criteria from three protocols were decomposed into individual variables and evaluated based on data type, scope, and dependency. Complexity was assessed using a novel formula incorporating the number of independent and dependent variables, alongside the Flesch-Kincaid reading grade level. Quantitative analysis explored variation across trials. Protocols contained between 22\u2013160 eligibility variables, with 4\u201322% showing interdependence. Reading grade levels ranged from sixth grade to first-year college. Complexity scores varied significantly, with some trials exhibiting particularly high cognitive and logical burdens. Recursive and hierarchical structures were prevalent in high-complexity protocols. This study reveals the substantial variability and structural complexity of clinical trial criteria, highlighting challenges for AI matching systems. A standardized approach to measuring trial complexity can enhance algorithm transparency, scalability, and interpretability. These findings underscore the need for structured, computable frameworks to improve equity and efficiency in clinical trial recruitment.<\/jats:p>","DOI":"10.1007\/s10916-025-02303-y","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T06:44:19Z","timestamp":1763793859000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Computational Framework for Structuring and Analyzing Clinical Trial Criteria for AI-Guided Fine-grained Matching"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0504-9076","authenticated-orcid":false,"given":"Daniel R. 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