From algorithmic innovation to clinical deployment: A systematic review of methodological gaps limiting federated learning in healthcare.

OBJECTIVE: Federated learning (FL) is a distributed machine learning paradigm designed to enable model training across decentralized data sources without requiring data centralization. This review critically examines FL as a methodological approach in biomedical informatics, summarizing its conceptual foundations, methodological variants, successes, and limitations, and identifying directions for future research. METHODS: We conducted a systematic methodological review following PRISMA 2020 guidelines. Searches were performed in PubMed, Web of Science, Scopus, IEEE Xplore, and Google Scholar for studies published between January 2017 and March 2025. Articles were included if they proposed, extended, or critically analyzed FL methods for biomedical or life science data. Methods were categorized by federation topology, optimization strategy, data heterogeneity handling, privacy mechanisms, evaluation design, and translational readiness. RESULTS: From 8,412 records, 97 articles met inclusion criteria. Rapid methodological innovation exists in optimization and privacy mechanisms, while support for design-time evaluation and governance remains limited. CONCLUSION: Federated learning represents a significant methodological advance in biomedical informatics but current implementations address only a subset of translational challenges. Future work must integrate study design, evaluation, interpretability, and governance into FL methods.