A nonparametric test for the association between longitudinal covariates and censored survival data. 2020

Ramon Oller, and Guadalupe Gómez Melis
Departament d'Economia i Empresa, Universitat de Vic-Universitat Central de Catalunya, Sagrada Família 7, 08500 Vic, Spain.

Many biomedical studies focus on the association between a longitudinal measurement and a time-to-event outcome while quantifying this association by means of a longitudinal-survival joint model. In this article we propose using the $LLR$ test - a longitudinal extension of the log-rank test statistic given by Peto and Peto (1972) - to provide evidence of a plausible association between a time-to-event outcome (right- or interval-censored) and a time-dependent covariate. As joint model methods are complex and hard to interpret, it is wise to conduct a preliminary test such as $LLR$ for checking the association between both processes. The $LLR$ statistic can be expressed in the form of a weighted difference of hazards, yielding a broad class of weighted log-rank test statistics known as $LWLR$, which allow a specific emphasis along the time axis of the effects of the time-dependent covariate on the survival. The asymptotic distribution of $LLR$ is derived by means of a permutation approach under the assumption that the censoring mechanism is independent of the survival time and the longitudinal covariate. A simulation study is conducted to evaluate the performance of the test statistics $LLR$ and $LWLR$, showing that the empirical size is close to the nominal significance level and that the power of the test depends on the association between the covariates and the survival time. A data set together with a toy example are used to illustrate the $LLR$ test. The data set explores the study Epidemiology of Diabetes Interventions and Complications (Sparling and others, 2006) which includes interval-censored data. A software implementation of our method is available on github (https://github.com/RamonOller/LWLRtest).

UI MeSH Term Description Entries
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012984 Software Sequential operating programs and data which instruct the functioning of a digital computer. Computer Programs,Computer Software,Open Source Software,Software Engineering,Software Tools,Computer Applications Software,Computer Programs and Programming,Computer Software Applications,Application, Computer Software,Applications Software, Computer,Applications Softwares, Computer,Applications, Computer Software,Computer Applications Softwares,Computer Program,Computer Software Application,Engineering, Software,Open Source Softwares,Program, Computer,Programs, Computer,Software Application, Computer,Software Applications, Computer,Software Tool,Software, Computer,Software, Computer Applications,Software, Open Source,Softwares, Computer Applications,Softwares, Open Source,Source Software, Open,Source Softwares, Open,Tool, Software,Tools, Software
D016019 Survival Analysis A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. Analysis, Survival,Analyses, Survival,Survival Analyses

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