Shifting Perspective in Influenza Vaccines Efficacy: How Risk Difference Shows an Alternative View of the Comparative Efficacy Profile of Newer and Enhanced Influenza Vaccines Compared to Standard, Egg-Based Vaccines

Annual influenza vaccination remains critical for mitigating severe illness and reducing healthcare strain, particularly among high-risk populations. Despite advancements in vaccine platforms, the comparative efficacy of novel vaccines—such as high-dose (HD-IIV), recombinant (rIV), cell-based (cIV), and adjuvanted (aIV) influenza vaccines—versus standard-dose non-adjuvanted (SD-IIV) vaccines remains a public health concern. Traditional Relative Vaccine Efficacy (rVE) metrics, though robust, may overestimate population-level benefits. This short communication explores alternative comparative efficacy measures: risk difference (ΔRD) and number needed to vaccinate (ΔNNV). Analysis of data derived from randomized controlled trials (RCTs), or robust pragmatic trials, shows that while rVE values for newer vaccines often indicate superior efficacy, ΔRD and ΔNNV highlight the limits in incremental protection at the population level, with ΔRD generally below 10 cases per 1000 vaccinated. These findings underline the sustained relevance of SD-IIV in immunization programs and emphasize the need for broader vaccine coverage to highlight the benefits of vaccination and enhance population health outcomes.