Making Cross-Continental Federated Learning Repeatable with FLIP: a Multi-Application Study

Federated learning enables collaborative training without sharing patient-level data, but most studies remain simulations. Based on five requirements derived from the literature, we analyzed 14 FL frameworks and found that none fully satisfied these requirements. We present FL-Net, a novel federated clinical research framework to fulfill all requirements. It integrates modular data harmonization, data discovery, disclosure control, securely built versioned FL-Net-Tools and containerized federated workflow execution into a persistent network. It enables the re-use of harmonized data and workflows across studies. FL-Net's end-to-end capabilities were evaluated through harmonization, cross-study patient discovery across MIMIC and US-130, and reproducible, audited federated workflows with up to 50 concurrent clients. FL-Net is being developed within the dAIbetes and Microb-AI-ome EU projects and will cover over 800,000 patients across 10 hospitals in 9 countries covering longitudinal and single point in time data, FL-Net provides a practical foundation for interoperable, reproducible, and privacy-preserving multicenter clinical research.

Federated learning lets institutions train shared models without moving their data, which makes it a natural fit for health and life sciences research under strict privacy regulation. The methods are maturing fast, but the practical barrier now comes earlier: a team starting a federated project meets a scattered mix of frameworks, governance obligations, and unfamiliar roles, with no structured place to begin that fits its own background. FLKit closes that gap. It is an open, community-maintained onboarding toolkit that takes a multidisciplinary team through the full federated learning lifecycle and gives every contributor, clinical, legal, governance, or technical, a role-aware entry point instead of assuming fluency across all four. We modeled it on the ELIXIR Research Data Management Kit and built it with a multidisciplinary core team, a wider consortium supplying milestone reviews and roadmap direction, and external practitioners interviewed to keep the content grounded in real practice. FLKit sits on four lifecycle stages, Governance, Infrastructure, Wrangling, and Analysis, and connects them through 11 role-specific entry points, a cross-disciplinary glossary, a reusable FAIR-aligned FL Story template for planning and documenting projects, and a curated directory of tools, frameworks, and communities. Since the December 2024 demo it has grown to 39 pages across eight sections, with seven FL Stories documenting completed and ongoing projects in multiple sclerosis disability prediction, inflammatory bowel disease, genomics, and brain-computer interfaces. It is openly available at https://uhasselt-biomedicaldatasciences.github.io/federated-learning-toolkit/ and welcomes contributions from across the life sciences.

Recent reviews find that the vast majority of published healthcare federated learning (FL) studies never reach real-world deployment. We developed an embedding-based FL pipeline for iron deficiency prediction from routine full blood count (FBC) data and deployed it across real institutional environments at Amsterdam University Medical Centre (AUMC) and NHS Blood and Transplant (NHSBT), two clinical environments that differ markedly in iron deficiency prevalence, ferritin distribution, and subject populations. A frozen domain-specific haematology foundation model, DeepCBC, performs site-local representation extraction, restricting federated training to a compact downstream classifier and substantially reducing recurrent communication relative to full-encoder federation. The two clinical datasets are structurally not independent and identically distributed (non-IID), with heterogeneity arising from distinct population differences rather than sampling artefacts. Runtime governance is enforced by FLA$^3$, a healthcare-oriented FL platform providing study-scoped execution, policy-based authorisation, and signed audit logging. Standard sample-size-weighted aggregation (FedAvg) reduced the area under the receiver operating characteristic curve (ROC-AUC) at both sites relative to local-only training, as the global update was biased towards the larger AUMC distribution. FedMAP, a personalised aggregation method, raised ROC-AUC from 0.9470 to 0.9594 at AUMC and from 0.8558 to 0.8671 at NHSBT relative to local-only training, achieving the highest macro ROC-AUC of 0.9133 and the best macro balanced accuracy overall. These results support personalised aggregation in clinical federations where client sample size and task relevance diverge substantially.