title: A multilevel excess hazard model to estimate net survival on hierarchical data allowing for non-linear and non-proportional effects of covariates.
abstract: The excess hazard regression model is an approach developed for the analysis of cancer registry data to estimate net survival, that is, the survival of cancer patients that would be observed if cancer was the only cause of death. Cancer registry data typically possess a hierarchical structure: individuals from the same geographical unit share common characteristics such as proximity to a large hospital that may influence access to and quality of health care, so that their survival times might be correlated. As a consequence, correct statistical inference regarding the estimation of net survival and the effect of covariates should take this hierarchical structure into account. It becomes particularly important as many studies in cancer epidemiology aim at studying the effect on the excess mortality hazard of variables, such as deprivation indexes, often available only at the ecological level rather than at the individual level. We developed here an approach to fit a flexible excess hazard model including a random effect to describe the unobserved heterogeneity existing between different clusters of individuals, and with the possibility to estimate non-linear and time-dependent effects of covariates. We demonstrated the overall good performance of the proposed approach in a simulation study that assessed the impact on parameter estimates of the number of clusters, their size and their level of unbalance. We then used this multilevel model to describe the effect of a deprivation index defined at the geographical level on the excess mortality hazard of patients diagnosed with cancer of the oral cavity. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.|Service de Biostatistique, Hospices Civils de Lyon, F-69003, Lyon, France.|Université de Lyon, F-69000, Lyon, France.|Université Lyon 1, F-69100, Villeurbanne, France.|CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, F-69100, Villeurbanne, France.
authors.forename: Hadrien
authors.initials: H
authors.lastname: Charvat
authors.affiliation: Service de Biostatistique, Hospices Civils de Lyon, F-69003, Lyon, France.|Université de Lyon, F-69000, Lyon, France.|Université Lyon 1, F-69100, Villeurbanne, France.|CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, F-69100, Villeurbanne, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Remontet
authors.affiliation: Service de Biostatistique, Hospices Civils de Lyon, F-69003, Lyon, France.|Université de Lyon, F-69000, Lyon, France.|Université Lyon 1, F-69100, Villeurbanne, France.|CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, F-69100, Villeurbanne, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Bossard
authors.affiliation: Service de Biostatistique, Hospices Civils de Lyon, F-69003, Lyon, France.|Université de Lyon, F-69000, Lyon, France.|Université Lyon 1, F-69100, Villeurbanne, France.|CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, F-69100, Villeurbanne, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Roche
authors.affiliation: Cancers & Preventions, U1086 INSERM, Avenue du Général Harris, F-14076, Caen, France.|Centre Hospitalier Universitaire, Avenue de la Côte de Nacre, F-14000, Caen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dejardin
authors.affiliation: Cancer Research UK Cancer Survival Group, Faculty of Epidemiology and Population Health, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, U.K.
authors.forename: Bernard
authors.initials: B
authors.lastname: Rachet
authors.affiliation: Cancers & Preventions, U1086 INSERM, Avenue du Général Harris, F-14076, Caen, France.|Centre Hospitalier Universitaire, Avenue de la Côte de Nacre, F-14000, Caen, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Launoy
authors.affiliation: Service de Biostatistique, Hospices Civils de Lyon, F-69003, Lyon, France.|Université de Lyon, F-69000, Lyon, France.|Université Lyon 1, F-69100, Villeurbanne, France.|CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, F-69100, Villeurbanne, France.|Département des maladies chroniques et traumatismes, Institut de Veille Sanitaire, F-94410, Saint-Maurice, France.|Cancer Research UK Cancer Survival Group, Faculty of Epidemiology and Population Health, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, U.K.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Belot
mesh_terms: D005843:Geography; D006801:Humans; D009369:Neoplasms / Q000401:mortality*; D016016:Proportional Hazards Models; D012042:Registries; D016019:Survival Analysis
keywords: adaptive quadrature; deprivation index; excess hazard model; net survival; shared frailty