tetano
Editor, Senior Moderator
Vaccine
. 2026 Mar 9:79:128435.
doi: 10.1016/j.vaccine.2026.128435. Online ahead of print.
Methods and operational framework of GALFLU: Individually randomized pragmatic controlled trial of high- versus standard-dose influenza vaccination in older adults
Narmeen Mallah[SUP] 1 [/SUP], Jacobo Pardo-Seco[SUP] 2 [/SUP], Carmen Rodriguez-Tenreiro-Sánchez[SUP] 3 [/SUP], Iago Giné-Vázquez[SUP] 3 [/SUP], Susana Mirás-Carballal[SUP] 4 [/SUP], Marta Piñeiro-Sotelo[SUP] 4 [/SUP], Martín Cribeiro-González[SUP] 5 [/SUP], Mónica Conde-Pájaro[SUP] 6 [/SUP], Juan-Manuel González-Pérez[SUP] 7 [/SUP], Josefina Lorena Razzini[SUP] 3 [/SUP], Irene Rivero-Calle[SUP] 8 [/SUP], Ana Isabel Dacosta-Urbieta[SUP] 8 [/SUP], Rebecca C Harris[SUP] 9 [/SUP], Matthew M Loiacono[SUP] 10 [/SUP], Robertus van Aalst[SUP] 11 [/SUP], Joan Manel Farre[SUP] 12 [/SUP], Marine Dufournet[SUP] 13 [/SUP], Niklas Dyrby Johansen[SUP] 14 [/SUP], Daniel Modin[SUP] 14 [/SUP], Tor Biering-Sørensen[SUP] 15 [/SUP], Carmen Duran-Parrondo[SUP] 16 [/SUP], Federico Martinón-Torres[SUP] 17 [/SUP]; GALFLU trial team
Affiliations
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).
Keywords: High-dose; Individually-randomized controlled trial; Influenza vaccine; Older adults; Pragmatic trial; Standard-dose.
. 2026 Mar 9:79:128435.
doi: 10.1016/j.vaccine.2026.128435. Online ahead of print.
Methods and operational framework of GALFLU: Individually randomized pragmatic controlled trial of high- versus standard-dose influenza vaccination in older adults
Narmeen Mallah[SUP] 1 [/SUP], Jacobo Pardo-Seco[SUP] 2 [/SUP], Carmen Rodriguez-Tenreiro-Sánchez[SUP] 3 [/SUP], Iago Giné-Vázquez[SUP] 3 [/SUP], Susana Mirás-Carballal[SUP] 4 [/SUP], Marta Piñeiro-Sotelo[SUP] 4 [/SUP], Martín Cribeiro-González[SUP] 5 [/SUP], Mónica Conde-Pájaro[SUP] 6 [/SUP], Juan-Manuel González-Pérez[SUP] 7 [/SUP], Josefina Lorena Razzini[SUP] 3 [/SUP], Irene Rivero-Calle[SUP] 8 [/SUP], Ana Isabel Dacosta-Urbieta[SUP] 8 [/SUP], Rebecca C Harris[SUP] 9 [/SUP], Matthew M Loiacono[SUP] 10 [/SUP], Robertus van Aalst[SUP] 11 [/SUP], Joan Manel Farre[SUP] 12 [/SUP], Marine Dufournet[SUP] 13 [/SUP], Niklas Dyrby Johansen[SUP] 14 [/SUP], Daniel Modin[SUP] 14 [/SUP], Tor Biering-Sørensen[SUP] 15 [/SUP], Carmen Duran-Parrondo[SUP] 16 [/SUP], Federico Martinón-Torres[SUP] 17 [/SUP]; GALFLU trial team
Affiliations
- PMID: 41806760
- DOI: 10.1016/j.vaccine.2026.128435
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).
Keywords: High-dose; Individually-randomized controlled trial; Influenza vaccine; Older adults; Pragmatic trial; Standard-dose.