Further Evidence for Bias in Observational Studies of Influenza Vaccine Effectiveness: The 2009 Influenza A(H1N1) Pandemic

• Published in: American journal of epidemiology 2013-10, Vol.178 (8), p.1327-1336
• Main Authors: JACKSON, Michael L, ONCHEE YU, NELSON, Jennifer C, NALEWAY, Allison, BELONGIA, Edward A, BAXTER, Roger, NARWANEY, Komal, JACOBSEN, Steven J, SHAY, David K, JACKSON, Lisa A
• Format: Article
• Language: English
• Subjects: Aged; Bias; Biological and medical sciences; Confounding Factors (Epidemiology); Epidemiologic Methods; Epidemiology; Female; General aspects; Human viral diseases; Humans; Immunization; Infectious diseases; Influenza; Influenza A Virus, H1N1 Subtype; Influenza Vaccines - immunology; Influenza, Human - epidemiology; Influenza, Human - prevention & control; Male; Medical research; Medical sciences; Miscellaneous; Mortality; Observation; Pandemics; Practice of Epidemiology; Prevention and actions; Proportional Hazards Models; Public health. Hygiene; Public health. Hygiene-occupational medicine; Retrospective Studies; Seasons; United States - epidemiology; Viral diseases; Viral diseases of the respiratory system and ent viral diseases
• ISSN: 0002-9262; 1476-6256
• DOI: 10.1093/aje/kwt124

Preinfluenza periods have been used to test for uncontrolled confounding in studies of influenza vaccine effectiveness, but some authors have claimed that confounding differs in preinfluenza and influenza periods. We tested this claim by comparing estimates of the vaccine-mortality association during the 2009/2010 influenza year, when there was essentially no circulation of seasonal influenza in the United States, and 2007/2008, a typical influenza year. We pooled data on seniors (adults aged ≥65 years) from 7 US managed care organizations that participated in the Vaccine Safety Datalink Project. We defined influenza vaccination, all-cause mortality, and potential confounders from administrative databases. We quantified the vaccine-mortality association using Cox regression. During 2007/2008, the adjusted hazard ratio was 0.44 prior to influenza season, 0.62 during influenza season, and 0.71 after influenza season. A similar pattern was observed during 2009/2010, when any effect of seasonal influenza vaccine observed during all time periods must have resulted from confounding: 0.65 during the autumn, 0.80 during the winter, and 0.84 during the summer. In a year with minimal seasonal influenza, we found no evidence that confounding in autumn preinfluenza periods is qualitatively different from confounding in winter. This supports the use of preinfluenza periods as control time periods in studies of influenza vaccine effectiveness.