Key issues for estimating the impact and cost-effectiveness of seasonal influenza vaccination strategies.

Many countries have considered or are considering modifying their seasonal influenza immunization policies. Estimating the impact of such changes requires understanding the existing clinical and economic burden of influenza, as well as the potential impact of different vaccination options. Previous studies suggest that vaccinating clinical risk groups, health care workers, children and the elderly may be cost-effective. However, challenges in such estimation include: (1) potential cases are not usually virologically tested; (2) cases have non-specific symptoms and are rarely reported to surveillance systems; (3) endpoints for influenza proxies (such as influenza-like illness) need to be matched to case definitions for treatment costs, (4) disease burden estimates vary from year to year with strain transmissibility, virulence and prior immunity, (5) methods to estimate productivity losses due to influenza vary, (6) vaccine efficacy estimates from trials differ due to variation in subtype prevalence, vaccine match and case ascertainment, and (7) indirect (herd) protection from vaccination depends on setting-specific variables that are difficult to directly measure. Given the importance of knowing the impact of changes to influenza policy, such complexities need careful treatment using tools such as population-based trial designs, meta-analyses, time-series analyses and transmission dynamic models.