%0 Journal Article
%T smoothHR: An R Package for Pointwise Nonparametric Estimation of Hazard Ratio Curves of Continuous Predictors
%A Lu¨ªs Meira-Machado
%A Carmen Cadarso-Su¨¢rez
%A Francisco Gude
%A Artur Ara¨²jo
%J Computational and Mathematical Methods in Medicine
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/745742
%X The Cox proportional hazards regression model has become the traditional choice for modeling survival data in medical studies. To introduce flexibility into the Cox model, several smoothing methods may be applied, and approaches based on splines are the most frequently considered in this context. To better understand the effects that each continuous covariate has on the outcome, results can be expressed in terms of splines-based hazard ratio (HR) curves, taking a specific covariate value as reference. Despite the potential advantages of using spline smoothing methods in survival analysis, there is currently no analytical method in the R software to choose the optimal degrees of freedom in multivariable Cox models (with two or more nonlinear covariate effects). This paper describes an R package, called smoothHR, that allows the computation of pointwise estimates of the HRs¡ªand their corresponding confidence limits¡ªof continuous predictors introduced nonlinearly. In addition the package provides functions for choosing automatically the degrees of freedom in multivariable Cox models. The package is available from the R homepage. We illustrate the use of the key functions of the smoothHR package using data from a study on breast cancer and data on acute coronary syndrome, from Galicia, Spain. 1. Introduction An important aim in longitudinal medical studies is to study the possible effect of a set of prognostic factors on the course of a disease. In many of these studies, some of the prognostic factors may be continuous and their effects can be unknown. A classical approach for studying these effects is through the Cox regression model (Cox [1], Kalbfleisch and Prentice [2]). One possible approach allowing for nonlinear effects in the Cox model is to express the hazard as an additive Cox model (see, e.g., Hastie and Tibshirani [3], Gray [4], Huang et al. [5], and Huang and Liu [6]). In this paper, we use natural cubic regression splines (de Boor [7]) and penalized splines (P-splines, Eilers, and Marx [8]) to reflect the nature of continuous covariate effects in the additive Cox model. One of the most commonly used measures of this effect is the hazard ratio (HR) function. Cadarso-Su¨¢rez et al. [9] proposed a flexible method for constructing smoothing hazard ratio curves with confidence limits, which facilitates the expression of the results in a manner that is standard in clinical survival studies. The authors suggest the use of an additive Cox model where the effects of continuous predictors on log hazards are modeled nonlinearly using P-splines. This paper
%U http://www.hindawi.com/journals/cmmm/2013/745742/