Interpretation of Relative Efficacy and Effectiveness for Influenza Vaccines

Background Relative vaccine effectiveness (rVE) are metrics commonly reported to compare absolute VE (aVE) of 2 vaccine products. Methods Estimates of rVE for enhanced influenza vaccines (eIV) vs standard inactivated influenza vaccine (IIV) have been assessed across different seasons, influenza-specific endpoints, and nonspecific endpoints (eg, all-cause cardiovascular hospitalizations). To illustrate the challenges of comparability across studies, we conducted a scenario analysis to evaluate the effects of varying absolute VE (aVE) of IIV (ie, as compared with placebo) on the interpretation of rVE of eIV vs IIV. Results We show that estimates of rVE might not be comparable across studies because additional benefits commensurate with a given estimate of rVE are dependent on the aVE for the comparator vaccine, which can depend on factors such as host response to vaccine, virus type, and clinical endpoint evaluated. Conclusions These findings have implications for interpretation of rVE across studies and for sample size considerations in future trials. This scenario analysis demonstrates challenges in interpreting relative vaccine efficacy and effectiveness measures for influenza vaccines, and provides onward implications for data reporting and study design.