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Published on: August 14, 2019
Methods and operational framework of GALFLU: Individually randomized pragmatic controlled trial of high- versus
Narmeen Mallah1, Jacobo Pardo-Seco2, Carmen Rodriguez-Tenreiro-Sánchez3
1Genetics, Vaccines and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Galicia, Spain; WHO Collaborating Centre for Vaccine Safety, Santiago de Compostela, Galicia, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBER-ESP), Madrid, Spain; Department of Preventive Medicine and Institute of Psychology (IPISUS), University of Santiago de Compostela (USC), Santiago de Compostela, Galicia, Spain.
Introduction:
Optimizing influenza vaccination in older adults is a public health priority. While high-dose inactivated influenza vaccines (HD-IIV) have shown superior immunogenicity and efficacy over standard-dose vaccines (SD-IIV), there is a shortage of large-scale, individually randomized data evaluating real-world effectiveness against severe outcomes-especially within publicly funded health systems.
Methods:
GALFLU is a pragmatic, individually randomized, open-label clinical trial comparing HD-IIV and SD-IIV in adults aged 65-79 years in Galicia, Spain, during the 2023-2024 and 2024-2025 influenza seasons. The trial embedded individual randomization into the regional vaccination program and exploited digital health registries for comprehensive, low-burden data collection under real-world conditions. The primary outcome is relative vaccine effectiveness (rVE) against a composite of influenza- or pneumonia-related hospitalizations. Secondary and exploratory outcomes include rVE against cardio-respiratory hospitalization, laboratory-confirmed influenza hospitalization, all-cause hospitalization, mortality, and healthcare utilization. The GALFLU protocol was approved by the Comité de ética de la investigación con medicamentos de Galicia (CEIm-G, code 2023/374). Participation was fully voluntary.
Results:
GALFLU demonstrated the feasibility of large-scale, pragmatic randomized controlled trials within routine clinical practice. Findings from GALFLU will be disseminated in peer-reviewed scientific journals and scientific meetings and shared with relevant authorities.
Conclusions:
GALFLU provides a reproducible blueprint for future pragmatic evaluations embedded in routine public health settings.
Trial Registration:
The trial was registered in EU Clinical Trials Register (2023-506,977-36-00); ClinicalTrials.gov (NCT06141655).
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