Methods: A systematic review of studies that evaluated the economic impact of influenza vaccination was conducted. Studies were identified by searching Medline, Embase, and Econlit databases and also included some works-in-progress (n=39). Each study was assigned to 2 reviewers and underwent a structured data abstraction review process. The structured review included study characteristics such as appropriateness of model design, model inputs (including epidemiological and clinical inputs, cost inputs, and quality adjustments), method of analysis and sensitivity analysis. Reviewers presented summaries of each study to the entire group of reviewers who then decided on inclusion or exclusion based study characteristics. Subgroups for prioritization were stratified by age and the presence or absence of medical conditions associated with a high risk for influenza complications.

Results: Studies were excluded if they were identified as review papers (n=8) or as having significant limitations (n=17). The primary reasons for exclusions were inappropriate assumptions regarding key inputs, primarily influenza attack rates, vaccine effectiveness, and vaccination costs, paired with insufficient sensitivity analysis. The final ranking was based on 14 studies. Within age groups, vaccinating high-risk persons was more cost-effective than vaccinating non-high-risk individuals. Ranking across age groups was difficult due to the lack of studies that included persons of all ages, lack of transparency in methods, and the use of different endpoints and methods. The groups that consistently demonstrated the highest economic returns to vaccination were high-risk elderly and nursing home residents. The next highest priority group was the non-high-risk elderly. The next groups were high-risk children and adults. Several subgroups were not ranked because there were no economic data available.

Conclusions: Vaccinating the elderly was consistently cost-saving across a variety of studies using different methods, while younger age and non-high-risk groups were likely to require an investment for health benefits. Ranking by economic data yielded results similar to rankings by hospitalization and death rates. Lack of transparency in methods limited the ability to use results from a number of economic studies.