title: The effect of disease prior to an outbreak on estimates of vaccine efficacy following the outbreak.
abstract: A common source of bias in evaluating vaccine efficacy following a disease outbreak is the presence of persons who had the disease prior to the outbreak. This paper examines the effects of including and excluding pre-outbreak disease cases from the calculation of vaccine efficacy based on the cumulative incidence at the end of an outbreak. Using a five-stage model, the effects of the following factors on the bias of vaccine efficacy estimates are examined: the true protective efficacy of the vaccine, the prevaccination infection rate, differences in vaccine uptake among the previously diseased and nondiseased, differences in pre-outbreak exposure to infection between vaccinees and nonvaccinees, and differences in exposure during the outbreak between vaccinees and nonvaccinees. Numerical calculations of the bias are performed for a hypothetical outbreak of measles in a developing country. Exclusion of pre-outbreak disease cases requires accurate data on disease rates prior to the outbreak, and such data are often unreliable or nonexistent. Inclusion of pre-outbreak cases contributes to the bias of the estimated vaccine efficacy, especially when there is a high prevaccination infection rate and vaccine uptake among the previously diseased is considerably lower than that among the nondiseased. In most practical cases, however, this bias is not very large.
authors.affiliation: Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
authors.forename: M
authors.initials: M
authors.lastname: Haber
authors.forename: W A
authors.initials: WA
authors.lastname: Orenstein
authors.forename: M E
authors.initials: ME
authors.lastname: Halloran
authors.forename: I M
authors.initials: IM
authors.lastname: Longini
mesh_terms: D004196:Disease Outbreaks; D004341:Drug Evaluation; D004812:Epidemiologic Methods; D006801:Humans; D014611:Vaccination; D014612:Vaccines
chemical_list: D014612:Vaccines