title: Estimation of vaccine efficacy in a repeated measures study under heterogeneity of exposure or susceptibility to infection.
abstract: Vaccine efficacy (VE) is commonly estimated through proportional hazards modelling of the time to first infection or disease, even when the event of interest can recur. These methods can result in biased estimates when VE is heterogeneous across levels of exposure and susceptibility in subjects. These two factors are important sources of unmeasured heterogeneity, since they vary within and across areas, and often cannot be individually quantified. We propose an estimator of VE per exposure that accounts for heterogeneous susceptibility and exposure for a repeated measures study with binary recurrent outcomes. The estimator requires only information about the probability distribution of environmental exposures. Through simulation studies, we compare the properties of this estimator with proportional hazards estimation under the heterogeneity of exposure. The methods are applied to a reanalysis of a malaria vaccine trial in Brazil.
authors.affiliation: Clinical Research Program, Children's Hospital Boston, 300 Longwood Ave. Boston, MA 02115, USA. clarissa.valim@childrens.harvard.edu
authors.forename: Clarissa
authors.initials: C
authors.lastname: Valim
authors.forename: Maura
authors.initials: M
authors.lastname: Mezzetti
authors.forename: James
authors.initials: J
authors.lastname: Maguire
authors.forename: Margarita
authors.initials: M
authors.lastname: Urdaneta
authors.forename: David
authors.initials: D
authors.lastname: Wypij
mesh_terms: D015982:Bias; D001699:Biometry; D001938:Brazil; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D006801:Humans; D017053:Infection Control / Q000706:statistics & numerical data; D016014:Linear Models; D008288:Malaria / Q000517:prevention & control; D017780:Malaria Vaccines / Q000494:pharmacology; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D014611:Vaccination / Q000706:statistics & numerical data*
chemical_list: D017780:Malaria Vaccines