Our analysis suggests that Ontario's UIIP is economically attractive. UIIP reduces the number of influenza cases and deaths and reduces health services resource use. The additional costs of UIIP are partly (39%) offset by savings in health care costs. Compared to TIIP, UIIP is cost-effective at an ICUR of $10,797 per QALY gained.
The main limitation in determining the impact of UIIP is the ecologic study design of the underlying effectiveness study. Causality cannot be established with this type of study design. The effect size may be exaggerated if there are province-specific epidemiological or health service factors that have in more recent years reduced influenza events in Ontario or increased it in other provinces. Similarly, since the outcome measure is influenza-like illness rather than confirmed influenza, it is possible that this could make estimates of outcomes sensitive to changes in the epidemiology of non-influenza respiratory illness. However, this design is appropriate for assessing the public health impact of a population-wide intervention 
. The results of Kwong's analysis of observational ecologic data in four provinces over 7 y are congruent with the results of randomized controlled trial data in targeted groups. Targeted immunization has been shown to be effective in preventing laboratory-confirmed influenza infection in healthy children 2 y and older 
, in healthy adults, especially when there is a good match and virus circulation is high 
, and older adults (65 y and older), especially in long-term care facilities 
. The weight of evidence seems to support the hypothesis that UIIP has been responsible for the decrease in cases and deaths in Ontario, in the absence of other obvious causal mechanisms. Stronger randomised clinical trial evidence of the effectiveness of universal vaccination in large populations is unlikely to be available in the future. Finally, to test whether the disproportionate decrease in influenza events from a 9% difference in coverage improvement may be attributable to herd immunity, we analyzed a simple Susceptible-Infected-Removed (SIR) compartmental model (for a description of the model and results, see Figures S1
, Tables S7
, and Text S3
). This basic analysis suggests that the 40%–60% decrease in influenza events is plausible.
Other study limitations relate to the definition of cases and quality of life estimates used. Cases were defined based on health care resource use for pneumonia and influenza and therefore represent influenza-like illness cases. Symptomatic cases not requiring health care contacts are not included, potentially underestimating the benefit of the program. Utility weights to estimate QALYs were obtained from an analysis of clinical trial data from influenza patients in Europe and North America 
. While these data are not Canada-specific, the populations are similar. Furthermore, sensitivity analysis was performed and reported for utility weights used in the analysis.
This study has several strengths. The model is robust and is based on administrative health care resource use and cost data covering all residents of Ontario. Data were extracted and analyzed in detail to estimate influenza-associated events and costs as accurately as possible to assess the impact of this intervention on the population of interest rather than estimating parameter values from other, smaller subpopulations that may not be representative. Finally, extensive sensitivity analyses demonstrated the program to be effective and cost-effective under very conservative assumptions.
The cost-effectiveness of influenza immunization programs has been demonstrated by numerous economic evaluations of TIIPs, many of which are directly based on clinical trial data. TIIPs have been shown to be cost-effective in children 6 mo and older 
, adults 50 y and older 
, working adults 
, working adult cancer patients 
, pregnant women 
, health care workers 
, high-risk individuals 
, and older adults (65 y and older) 
from a health care payer perspective. Most economic evaluations found TIIPs to be not only cost-effective but cost-saving from a societal perspective.
Policy makers in many jurisdictions considering the implementation of universal immunization have expressed interest in an economic evaluation of Ontario's program. The program appears to offer some health benefits, but the relationship between cost and health benefits of universal immunization had not been evaluated. Our study provides evidence that a universal program is economically attractive in jurisdictions with influenza epidemiology and health care costs that are broadly similar to that of Ontario.
A UIIP may be an appealing intervention in high-income jurisdictions with comparable demographic characteristics (age distribution, risk profile, density) where influenza transmission can be expected to be reasonably similar to the population analyzed. A health care system similar to Ontario's (i.e., health care systems with one major payer), where the costs of the immunization program and the costs of treating influenza cases are both in the payer's budget, will enable the universal program costs to be partly offset by savings in health care cost.
This analysis indicates that compared to a TIIP, Ontario's UIIP reduces influenza illness attack rates, morbidity, and mortality at reasonable cost to the health care payer.