Structural Accelerated Failure Time Models for the Effects of Observed Exposures on Repeated Events in a Clinical Trial An Vandebosch 1*† , Els Goetghebeur 1 , Lut Van Damme 2 1 Dept. of Applied Mathematics and Computer Science, Ghent University 2 Conrad, Arlington, USA SUMMARY Structural accelerated failure time models form a unique tool for the analysis of causal effects of observed exposures in randomised trials. When actual exposure levels are not completely controlled they may be selective, i.e. depend on unmeasured prognostic factors. Nevertheless, consistent randomisation 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 α-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 the new challenges posed on recensoring. Key words: causal inference, compliance, prevention, randomised clinical trial, recurrent events, structural accelerated failure time model * Correspondence to: An Vandebosch, Dept of Applied Mathematics and Computer Science, Ghent Univer- sity. Krijgslaan 281, S9; B-9000 Ghent; Belgium. Tel +32-(0)9-264 47 56. Fax +32-(0)9-264 49 95. Email: An.Vandebosch@rug.ac.be † Contract/Grant Sponsor: BOF, Ghent University. Contract/Grant Number: 011D3001 1