Leveraging generative AI to transform statistical analysis plan authoring in clinical trials.

Abstract

BackgroundStatistical analysis plans are critical regulatory documents that define the statistical methodology, objectives, and data-handling procedures for clinical trials. The traditional process of statistical analysis plan development is resource-intensive, typically spanning 4-6 weeks, and is increasingly complicated by evolving regulatory requirements and complex trial designs such as adaptive studies and real-world evidence investigations. The emergence of generative artificial intelligence presents an opportunity to streamline this workflow; however, applying AI in regulated environments requires rigorous control over accuracy and consistency.MethodsTo address these challenges, we designed and implemented a generative artificial intelligence-based solution tailored to the automated drafting of statistical analysis plans. The system utilizes a knowledge graph and vector database architecture to parse clinical protocols and map content to study-specific templates. We employed a hybrid generation strategy featuring four distinct modes: verbatim copying, summarization, standard text with dynamic variable insertion, and de novo text generation via prompt engineering. The solution was deployed as both a web application and a Microsoft Word add-in and was evaluated across a diverse portfolio of trial designs, including interventional, non-interventional, clinical pharmacology, and oncology studies.ResultsThe deployment of the solution yielded a transformative reduction in drafting time, creating first drafts in an average of 1.0-3.4 min across 71 statistical analysis plans, compared to the traditional timeline of 1-2 days. Subject matter expert evaluations rated the outputs between 3.6 and 4.2 on a five-point Likert-type scale, indicating moderate to high quality. Furthermore, in comparisons against manually authored statistical analysis plans, a Large Language Model-assisted evaluation demonstrated substantial preservation of meaning across corresponding sections, yielding an average semantic similarity score of 0.75. Automated standardization features ensured a high degree of consistency across diverse statistical analysis plan documents. This approach enables the management of expansive statistical analysis plan portfolios and supports a broad spectrum of trial designs, including adaptive studies and real-world evidence investigations.ConclusionThe application of generative artificial intelligence to statistical analysis plan authoring represents a substantive advancement for clinical research operations, delivering marked improvements in drafting speed and documentation consistency. Beyond immediate efficiency gains, standardized automated text generation may benefit downstream processes such as statistical programming and clinical study report drafting. Future work should focus on strengthening automated quality assurance, supporting amendments with auditable revision handling, and further integrating artificial intelligence-assisted authoring into end-to-end clinical trial documentation workflows.