Cochrane re-arranged: support for policies to vaccinate elderly people against influenza.

The 2010 Cochrane review on efficacy, effectiveness and safety of influenza vaccination in the elderly by Jefferson et al. covering dozens of clinical studies over a period of four decades, confirmed vaccine safety, but found no convincing evidence for vaccine effectiveness (VE) against disease thus challenging the ongoing efforts to vaccinate the elderly. However, the Cochrane review analyzed and presented the data in a way that may itself have hampered the desired separation of real vaccine benefits from inevitable 'background noise'. The data are arranged in more than one hundred stand-alone meta-analyses, according to various vaccine types, study designs, populations, and outcome case definitions, and then further subdivided according to virus circulation and antigenic match. In this way, general vaccine effects could not be separated from an abundance of environmental and operational, non vaccine-related variation. Furthermore, expected impacts of changing virus circulation and antigenic drift on VE could not be demonstrated. We re-arranged the very same data according to a biological and conceptual framework based on the basic sequence of events throughout the 'patient journey' (exposure, infection, clinical outcome, observation) and using broad outcome definitions and simple frequency distributions of VE values. This approach produced meaningful predictions for VE against influenza-related fatal and non-fatal complications (average ~30% with large dispersion), typical influenza-like illness (~40%), disease with confirmed virus infection (~50%), and biological vaccine efficacy against infection (~60%), under conditions of virus circulation. We could also demonstrate a VE average around zero in the absence of virus circulation, and decreasing VE values with decreasing virus circulation and increasing antigenic drift. We regard these findings as substantial evidence for the ability of influenza vaccine to reduce the risk of influenza infection and influenza-related disease and death in the elderly.