# 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

## TL;DR

Newer influenza vaccines show better relative efficacy than standard vaccines, but their absolute benefit in preventing cases is small when measured at the population level.

## Contribution

The paper introduces risk difference and number needed to vaccinate as alternative metrics to assess the real-world impact of newer influenza vaccines.

## Key findings

- Newer vaccines like HD-IIV, rIV, cIV, and aIV have higher relative vaccine efficacy than standard-dose vaccines.
- The absolute benefit of newer vaccines is modest, preventing fewer than 10 additional cases per 1000 vaccinations.
- Standard-dose vaccines remain highly relevant for public health despite incremental improvements in newer vaccines.

## Abstract

What are the main findings?
Novel influenza vaccines—including HD-IIV, rIV, cIV, and aIV—show superior relative vaccine efficacy (rVE) compared with standard-dose inactivated influenza vaccines (SD-IIV).However, when examined through the risk difference (ΔRD) and the number needed to vaccinate (ΔNNV), the absolute benefit at the population level is modest, with fewer than 10 additional cases prevented per 1000 vaccinations.

Novel influenza vaccines—including HD-IIV, rIV, cIV, and aIV—show superior relative vaccine efficacy (rVE) compared with standard-dose inactivated influenza vaccines (SD-IIV).

However, when examined through the risk difference (ΔRD) and the number needed to vaccinate (ΔNNV), the absolute benefit at the population level is modest, with fewer than 10 additional cases prevented per 1000 vaccinations.

What are the implications of the main findings?
Although newer influenza vaccines offer improved relative efficacy, the modest absolute benefit highlights that standard-dose influenza vaccines remain highly relevant and valuable for public health.This suggests that while enhanced vaccines provide incremental improvements, broadening immunization continues to be an important and effective strategy, irrespective of vaccine type, especially when considering cost, availability, and overall impact at the population level.

Although newer influenza vaccines offer improved relative efficacy, the modest absolute benefit highlights that standard-dose influenza vaccines remain highly relevant and valuable for public health.

This suggests that while enhanced vaccines provide incremental improvements, broadening immunization continues to be an important and effective strategy, irrespective of vaccine type, especially when considering cost, availability, and overall impact at the population level.

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.