Work

Use of composite outcomes in cluster randomized control trials of influenza vaccines

Year: 2026

Type: article

Abstract: Despite being widely used in other fields, composite outcomes are seldom used in influenza vaccine randomized trials. Vaccine trialists may benefit from the increased event rates and power of composite outcomes. We explored the use of a composite outcome on a series of randomized control trials conducted within Canadian Hutterite communities. Using data from three blinded, cluster randomized control trials of pediatric influenza vaccination, we assessed the use of a composite outcome of antimicrobial prescription, school or work-related absenteeism, and medically attended visits for respiratory illness. Key comparisons between component outcomes and the composite included odds reduction, frequency, and confidence intervals. In Trial 1, 65 Hutterite colonies were randomly assigned to receive either the influenza vaccine or the hepatitis A vaccine. Among all season 1 and 3 participants in Trial 1, the composite outcome yielded a greater event rate, significance, precision, and a greater protective effect than its components. Within participants across all seasons in Trial 2, the composite yielded a greater event rate, lower significance, a null protective effect, and greater precision than two out of three of its components. Among all participants across all seasons in Trial 3, the composite outcome yielded a greater event rate and a weaker protective effect than its components, with no notable differences in precision or significance. Composite outcomes can be a viable approach to raise event rates and increase the precision of estimates in influenza vaccine trials and should be explored further within this field. • This paper used composite outcomes of clinical endpoints in influenza trials. • Composite estimates tend to be more precise than their component estimates. • Estimates tend to be more precise regardless of changes to statistical significance. • Composite effect sizes can exceed the range of their components in either direction. • Influenza vaccine trials may benefit from the use of composite clinical outcomes.

Source: Vaccine

DOI: 10.1016/j.vaccine.2026.128224

Authors: Kingsley Cheng, Eleanor Pullenayegum, Pardeep Singh, Mark Loeb

Institutions: McMaster University, University of Toronto, Hospital for Sick Children

Language: English

Topic: Statistical Methods in Clinical Trials

Subfield: Statistics and Probability

Field: Mathematics

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,620