Evaluating large language models as clinical decision support tools in primary healthcare settings: Protocol for a multi-country comparative validation study on expert-adjudicated hypothetical vignettes (hypMOOVE-PHC)
Introduction: Large language models (LLMs) have the potential to strengthen clinical decision-making in low-resource primary healthcare (PHC) settings. However, most LLMs are developed and benchmarked in high-resource settings and evidence on their safety and contextual appropriateness in Sub-Saharan Africa remains limited. The hypMOOVE-PHC study is the hypothetical vignette phase of the Massive Open Online Validation and Evaluation (MOOVE) initiative, implemented in Kenya, Malawi, and Tanzania. It aims to validate a pool of LLMs through clinical review of expert-generated vignettes. Methods and analysis: This is a fully crossed repeated-measures comparative evaluation study. In each country, experienced clinicians develop 200-250 hypothetical clinical vignettes reflecting realistic patient presentations and independently produce a human benchmark care plan for each. Vignettes are used to prompt a selection of six open-source and proprietary LLMs selected based on code availability, local hostability, and model size. During in-person workshops (valiDATAthons), independent clinical experts rate LLM- and human-generated responses in source-attribution masked side-by-side comparisons across five dimensions (clinical soundness, safety, contextual fit, clarity & completeness, and appropriate confidence). The primary endpoints are each LLM's overall performance profile and non-inferior safety profile, as compared to the human benchmark. At minimum, 358 evaluations per LLM (or 1,253 paired evaluations in total) are required per country. Ethics and dissemination: The study is approved by the EPFL Human Ethics Research Committee in Switzerland, Harvard T.H. Chan School of Public Health in the USA, KNH-UoN Ethics and Research Committee in Kenya, MUBAS Research Ethics Committee in Malawi, and MUHAS Research and Ethics Committee and National Institute for Medical Research in Tanzania. Findings will be reported according to the TRIPOD-LLM framework and shared with national ministries of health, disseminated at conferences and in peer-reviewed journals, and de-identified benchmark data will be released under FAIR principles.