Evaluating the Clinical Evidence for Influenza Vaccine Target Population Recommendations

Background: Yearly vaccination is the best defense against influenza infection and resulting complications. A well-matched influenza vaccine can have efficacy (the prevention of laboratory confirmed influenza infection) of up to eighty percent- providing protections against a significant number of infections thus has the potential to have a significant public health impact. The World Health Organization publishes position papers regarding the use of influenza virus vaccination and recommendations of target populations. Although non-binding on member states, the position of the WHO has a ripple effect that impacts standards of care worldwide. Target populations for influenza vaccination should be based upon high-quality clinical evidence due not only to the yearly burden of seasonal influenza but also the public health risks of pandemic influenza. Methods:The methods for this project merge policy analysis and a systematic review of influenza vaccine efficacy trials with traditional humanist methods of literature analysis and comparison. Results:The historical review of target population recommendation show that recommendations have been based on deduction and fear as opposed to high quality clinical research evidence.  Of 3,494 articles identified with the systematic review search criteria, 59 articles were eligible for inclusion in this review. The majority (43) of the trials were conducted in high-income countries with the United States being the most common location. Of the 59 studies, only one included influenza associated pneumonia, hospitalization or death as a primary endpoint and four included these severe outcomes as secondary endpoint. 39 of the 59 studies used laboratory confirmed influenza as the primary endpoint, 11 required symptomatic laboratory confirmed influenza. The remaining 9 studies had endpoints based upon serological responses (6) or other clinical, i.e. safety influenza outcomes (3).  Most studies reported specimen collection criteria for a range of respiratory and systemic symptoms (28) with influenza like illness triggering a collection in 15 studies and any respiratory symptom in 8. Symptoms combined with physician discretion occurred in 6 studies.  Any visit to the physician’s office triggered a specimen collection in 2 trials. One study randomly samples hospital patients, another collected blood samples from all patients. Only one did not report any specimen collection criteria. Conclusion: Randomized, controlled clinical trials studying influenza vaccine efficacy focus on mild outcomes in high resource areas which does not reflect the target population recommendation of pregnant women, the elderly and young children. Ethical and financial barriers exist to utilizing high quality clinical research evidence in making recommendations.