title: Flexible modeling of the effects of continuous prognostic factors in relative survival.
abstract: Relative survival methods permit separating the effects of prognostic factors on disease-related 'excess mortality' from their effects on other-causes 'natural mortality', even when individual causes of death are unknown. As in conventional 'crude' survival, accurate assessment of prognostic factors requires testing and possibly modeling of non-proportional effects and, for continuous covariates, of non-linear relationships with the hazard. We propose a flexible extension of the additive-hazards relative survival model, in which the observed all-causes mortality hazard is represented by a sum of disease-related 'excess' and natural mortality hazards. In our flexible model, the three functions representing (i) the baseline hazard for 'excess' mortality, (ii) the time-dependent effects, and (iii) for continuous covariates, non-linear effects, on the logarithm of this hazard, are all modeled by low-dimension cubic regression splines. Non-parametric likelihood ratio tests are proposed to test the time-dependent and non-linear effects. The accuracy of the estimated functions is evaluated in multivariable simulations. To illustrate the new insights offered by the proposed model, we apply it to re-assess the effects of patient age and of secular trends on disease-related mortality in colon cancer.
authors: Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada H3A 1A1.
authors: Amel
authors: A
authors: Mahboubi
authors: Michal
authors: M
authors: Abrahamowicz
authors: Roch
authors: R
authors: Giorgi
authors: Christine
authors: C
authors: Binquet
authors: Claire
authors: C
authors: Bonithon-Kopp
authors: Catherine
authors: C
authors: Quantin
mesh_terms: D015179:Colorectal Neoplasms / Q000401:mortality; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D016016:Proportional Hazards Models; D016019:Survival Analysis