The feasibility of pragmatic influenza vaccine randomized controlled real-world trials in Denmark and England
Joshua Nealon,
Daniel Modin,
Rebecca E. Ghosh,
Deborah Rudin,
Gunnar Gislason,
Helen P. Booth,
Jens Ulrik Stæhr Jensen,
Rachael Williams,
Hilary Shepherd,
Eleanor Yelland,
Helene Bricout,
Sandra S. Chaves,
Tor Biering-Sørensen
Affiliations
Joshua Nealon
Sanofi Pasteur Medical Evidence Generation
Daniel Modin
Department of Cardiology, Copenhagen University Hospital—Herlev and Gentofte
Rebecca E. Ghosh
Clinical Practice Research Datalink, Medicines and Healthcare products Regulatory Agency
Deborah Rudin
Sanofi Pasteur Global Medical Affairs
Gunnar Gislason
Department of Cardiology, Copenhagen University Hospital—Herlev and Gentofte
Helen P. Booth
Clinical Practice Research Datalink, Medicines and Healthcare products Regulatory Agency
Jens Ulrik Stæhr Jensen
Department of Pulmonology, Copenhagen University Hospital—Herlev and Gentofte & Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen
Rachael Williams
Clinical Practice Research Datalink, Medicines and Healthcare products Regulatory Agency
Hilary Shepherd
Clinical Practice Research Datalink, Medicines and Healthcare products Regulatory Agency
Eleanor Yelland
Clinical Practice Research Datalink, Medicines and Healthcare products Regulatory Agency
Helene Bricout
Sanofi Pasteur Medical Evidence Generation
Sandra S. Chaves
Modelling, Epidemiology and Data Science, Sanofi Pasteur
Tor Biering-Sørensen
Department of Cardiology, Copenhagen University Hospital—Herlev and Gentofte
Abstract We estimated the frequency of non-specific influenza-associated clinical endpoints to inform the feasibility of pragmatic randomized controlled trials (RCT) assessing relative vaccine effectiveness (rVE). Hospitalization rates of respiratory, cardiovascular and diabetic events were estimated from Denmark and England’s electronic databases and stratified by age, comorbidity and influenza vaccination status. We included a seasonal average of 4.5 million Danish and 7.2 million English individuals, 17 and 32% with comorbidities. Annually, approximately 1% of Danish and 0.5% of English individuals were hospitalized for selected events, ~50% of them respiratory. Hospitalization rates were 40–50-fold and 2–10-fold higher in those >50 years and with comorbidities, respectively. Our findings suggest that a pragmatic RCT using non-specific endpoints is feasible. However, for outcomes with rates <2.5%, it would require randomization of ~100,000 participants to have the power to detect a rVE difference of ~13%. Targeting selected groups (older adults, those with comorbidities) where frequency of events is high would improve trial efficiency.
