title: Structural accelerated failure time models for the effects of observed exposures on repeated events in a clinical trial.
abstract: Structural accelerated failure time models form a unique tool for the analysis of causal effects of observed exposures in randomized trials. When actual exposure levels are not completely controlled they may be selective, i.e. depend on unmeasured prognostic factors. Nevertheless, consistent randomization-based estimators have been derived for the effect of such exposures on a right-censored survival outcome. In this paper, we extend the methodology to allow for estimation of the structural effect of an experimental vaginal gel on repeated occurrences of genital lesions. The marginal distribution of each ordered event is modelled assuming a common treatment effect. Estimation is possible by inverting alpha-level tests using a robust variance estimator to allow for correlated repeated events. We discuss the logical constraints imposed by this model choice as well as new challenges posed on recensoring.
authors.affiliation: Department of Applied Mathematics and Computer Science, Ghent University, Krijgslaan 281-S9, B-9000 Ghent, Belgium. an.vandebosch@ugent.be
authors.forename: An
authors.initials: A
authors.lastname: Vandebosch
authors.forename: Els
authors.initials: E
authors.lastname: Goetghebeur
authors.forename: Lut
authors.initials: L
authors.lastname: Van Damme
mesh_terms: D000282:Administration, Intravaginal; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D005260:Female; D005782:Gels / Q000008:administration & dosage; D015658:HIV Infections / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D015233:Models, Statistical; D011477:Sex Work; D013019:South Africa; D016019:Survival Analysis
chemical_list: D005782:Gels