title: Magnitude of potential biases in a simulated case-control study of the effectiveness of influenza vaccination.
abstract: BACKGROUND
  Many influenza vaccine effectiveness estimates have been made using case-control methods. Although several forms of bias may distort estimates of vaccine effectiveness derived from case-control studies, there have been few attempts to quantify the magnitude of these biases.
  
  
  METHODS
  We estimated the magnitude of potential biases in influenza vaccine effectiveness values derived from case-control studies from several factors, including bias from differential use of diagnostic testing based on influenza vaccine status, imperfect diagnostic test characteristics, and confounding. A decision tree model was used to simulate an influenza vaccine effectiveness case-control study in children. Using probability distributions, we varied the value of factors that influence vaccine effectiveness estimates, including diagnostic test characteristics, vaccine coverage, likelihood of receiving a diagnostic test for influenza, likelihood that a child hospitalized with acute respiratory infection had influenza, and others. Bias was measured as the difference between the effectiveness observed in the simulated case-control study and a true underlying effectiveness value.
  
  
  CONCLUSIONS
  We found an average difference between observed and true vaccine effectiveness of -11.9%. Observed vaccine effectiveness underestimated the true effectiveness in 88% of model iterations. Diagnostic test specificity exhibited the strongest association with observed vaccine effectiveness, followed by the likelihood of receiving a diagnostic test based on vaccination status and the likelihood that a child hospitalized with acute respiratory infection had influenza. Our findings suggest that the potential biases in case-control studies that we examined tend to result in underestimates of true influenza vaccine effects.
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. jferdinands@cdc.gov
authors.forename: Jill M
authors.initials: JM
authors.lastname: Ferdinands
authors.forename: David K
authors.initials: DK
authors.lastname: Shay
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood*; D015982:Bias; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D006801:Humans; D007223:Infant; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines