Objectives: This study aimed to determine the cost-effectiveness of influenza vaccination in people 65–74 years of age in the absence of comorbidity.

Design: Primary research: randomized controlled trial.

Setting: Primary care.

Participants: People without risk factors for influenza or contraindications to vaccination were identified from twenty general practitioner (GP) practices in Liverpool in September 1999 and invited to participate in the study. There were 5,875 of 9,727 (60.4 percent) people 65–74 years of age identified as potentially eligible, and of these, 729 (12 percent) were randomized.

Intervention: Participants were randomized to receive either influenza vaccine or placebo (ratio, 3:1), with all individuals receiving pneumococcal vaccine unless administered in the previous 10 years. Of the 729 people randomized, 552 received vaccine and 177 received placebo; 726 individuals were administered pneumococcal vaccine.

Main outcome measures and methodology of economic evaluation: GP attendance with influenza-like illness (ILI) or pneumonia (primary outcome measure); or any respiratory symptoms; hospitalization with a respiratory illness; death; participant self-reported ILI; quality of life (QoL) measures at 2, 4, and 6 months poststudy vaccination; adverse reactions 3 days after vaccination. A cost-effectiveness analysis was undertaken to identify the incremental cost associated with the avoidance of episodes of influenza in the vaccination population, and an impact model was used to extrapolate the cost-effectiveness results obtained from the trial to assess their generalizability throughout the National Health Service (NHS).

Results: In England and Wales, weekly consultations for influenza and ILI remained at baseline levels (less than 50 per 100,000 population) until week 50/1999 and then increased rapidly, peaking during week 2/2000 with a rate of 231/100,000. This rate fell within the range of “higher than expected seasonal activity” of 200–400/100,000. Rates then quickly declined, returning to baseline levels by week 5/2000. The predominant circulating strain during this period was influenza A (H3N2). Five (0.9 percent) people in the vaccine group were diagnosed by their GP with an ILI compared with two (1.1 percent) in the placebo group [relative risk (RR), 0.8; 95 percent confidence interval (CI) = 0.16 to 4.1]. No participants were diagnosed with pneumonia by their GP, and there were no hospitalizations for respiratory illness in either group. Significantly fewer vaccinated individuals self-reported a single ILI (4.6 percent vs 8.9 percent, RR, 0.51; 95 percent CI for RR, 0.28 to 0.96). There was no significant difference in any of the QoL measurements over time between the two groups. Reported systemic side-effects showed no significant differences between groups. Local side-effects occurred with a significantly increased incidence in the vaccine group (11.3 percent vs 5.1 percent, P = 0.02). Each GP consultation avoided by vaccination was estimated from trial data to generate a net NHS cost of £174.

Conclusions: No difference was seen between groups for the primary outcome measure, although the trial was underpowered to demonstrate a true difference. Vaccination had no significant effect on any of the QoL measures used, although vaccinated individuals were less likely to self-report ILI. The analysis did not suggest that influenza vaccination in healthy people 65–74 years of age would lead to lower NHS costs. Future research should look at ways to maximize vaccine uptake in people at greatest risk from influenza and also the level of vaccine protection afforded to people from different age and socioeconomic populations.