title: Robust non-parametric one-sample tests for the analysis of recurrent events.
abstract: One-sample non-parametric tests are proposed here for inference on recurring events. The focus is on the marginal mean function of events and the basis for inference is the standardized distance between the observed and the expected number of events under a specified reference rate. Different weights are considered in order to account for various types of alternative hypotheses on the mean function of the recurrent events process. A robust version and a stratified version of the test are also proposed. The performance of these tests was investigated through simulation studies under various underlying event generation processes, such as homogeneous and nonhomogeneous Poisson processes, autoregressive and renewal processes, with and without frailty effects. The robust versions of the test have been shown to be suitable in a wide variety of event generating processes. The motivating context is a study on gene therapy in a very rare immunodeficiency in children, where a major end-point is the recurrence of severe infections. Robust non-parametric one-sample tests for recurrent events can be useful to assess efficacy and especially safety in non-randomized studies or in epidemiological studies for comparison with a standard population.
authors.affiliation: Department of Clinical Medicine and Prevention, Center of Biostatistics for Clinical Epidemiology, University of Milano-Bicocca, Via Cadore 48-20052, Monza, Italy. paola.rebora@unimib.it
authors.forename: Paola
authors.initials: P
authors.lastname: Rebora
authors.forename: Stefania
authors.initials: S
authors.lastname: Galimberti
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency; D000361:Agammaglobulinemia / Q000628:therapy; D002986:Clinical Trials as Topic / Q000379:methods*; D003198:Computer Simulation; D015316:Genetic Therapy / Q000379:methods / Q000592:standards; D006801:Humans; D007239:Infections / Q000453:epidemiology; D015233:Models, Statistical; D012008:Recurrence; D012016:Reference Values; D016511:Severe Combined Immunodeficiency / Q000628:therapy; D018709:Statistics, Nonparametric
chemical_list: D000243:Adenosine Deaminase