title: A joint frailty model to estimate the recurrence process and the disease-specific mortality process without needing the cause of death.
abstract: In chronic diseases, such as cancer, recurrent events (such as relapses) are commonly observed; these could be interrupted by death. With such data, a joint analysis of recurrence and mortality processes is usually conducted with a frailty parameter shared by both processes. We examined a joint modeling of these processes considering death under two aspects: 'death due to the disease under study' and 'death due to other causes', which enables estimating the disease-specific mortality hazard. The excess hazard model was used to overcome the difficulties in determining the causes of deaths (unavailability or unreliability); this model allows estimating the disease-specific mortality hazard without needing the cause of death but using the mortality hazards observed in the general population. We propose an approach to model jointly recurrence and disease-specific mortality processes within a parametric framework. A correlation between the two processes is taken into account through a shared frailty parameter. This approach allows estimating unbiased covariate effects on the hazards of recurrence and disease-specific mortality. The performance of the approach was evaluated by simulations with different scenarios. The method is illustrated by an analysis of a population-based dataset on colon cancer with observations of colon cancer recurrences and deaths. The benefits of the new approach are highlighted by comparison with the 'classical' joint model of recurrence and overall mortality. Moreover, we assessed the goodness of fit of the proposed model. Comparisons between the conditional hazard and the marginal hazard of the disease-specific mortality are shown, and differences in interpretation are discussed.
authors.affiliation: Service de Biostatistique, Hospices Civils de Lyon, F-69495 Pierre-Bénite Cedex, France; Université de Lyon, F-69000 Lyon, France; Université Lyon I, Villeurbanne, F-69622, France; CNRS ; UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique Santé, Pierre-Bénite, F-69495, France; Département des Maladies Chroniques et Traumatismes, Institut de Veille Sanitaire, Saint-Maurice, F-94415, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Belot
authors.forename: Virginie
authors.initials: V
authors.lastname: Rondeau
authors.forename: Laurent
authors.initials: L
authors.lastname: Remontet
authors.forename: Roch
authors.initials: R
authors.lastname: Giorgi
mesh_terms: D000465:Algorithms; D056808:Biostatistics; D002423:Cause of Death; D003110:Colonic Neoplasms / Q000401:mortality; D003198:Computer Simulation; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D009026:Mortality; D016016:Proportional Hazards Models; D012008:Recurrence
keywords: excess hazard; joint model; recurrent events; shared frailty