It has been difficult to demonstrate an improvement in survival after influenza vaccination in elderly patients in randomized controlled trials because mortality is a rare end-point. The systematic review cited above found a significant reduction in death from influenza or pneumonia , but some have suggested that frailty selection bias in cohort studies has led to an overestimation of any mortality benefit of influenza vaccination in elderly adults .
A pooled cohort study published after the systematic review demonstrated a small but significant reduction in mortality in vaccinated elderly individuals (1.0 versus 1.6 percent in unvaccinated individuals) . A sensitivity analysis was performed to detect unmeasured confounders. Even when a higher rate of confounders was assumed, there was still a significant reduction in mortality. Other studies have supported this finding . Any mortality benefit in elderly patients is increased with annual vaccination . (See 'Need for annual vaccination' below.)
The difficulty of using observational data to evaluate the effect of influenza vaccine on mortality is further illustrated by a prospective case-control study of patients (mostly over the age of 65) with community-acquired pneumonia (CAP). The study assessed the impact of influenza vaccination on in-hospital mortality in patients admitted during the off-season for influenza . A significant mortality reduction was observed in vaccinated patients (OR 0.49; 95% CI 0.30-0.79). However, when adjustments were made to address confounding factors (eg, functional and socioeconomic status), the mortality benefit became nonsignificant (adjusted OR 0.81; 95% CI 0.35-1.85). This study shows that the presence of bias may overestimate the mortality benefit of influenza vaccination .
In contrast to the studies described above, a large cohort study of community-dwelling elderly individuals did not detect a mortality benefit from influenza vaccination . An important limitation of this study was the likely underreporting of vaccination status, which could have contributed to the vaccine appearing ineffective .