Regularization for Cox's proportional hazards model with NP-dimensionality

High throughput genetic sequencing arrays with thousands of measurements per sample and a great amount of related censored clinical data have increased demanding need for better measurement specific model selection. In this paper we establish strong oracle properties of nonconcave penalized methods for nonpolynomial (NP) dimensional data with censoring in the framework of Cox's proportional hazards model. A class of folded-concave penalties are employed and both LASSO and SCAD are discussed specifically. We unveil the question under which dimensionality and correlation restrictions can an oracle estimator be constructed and grasped. It is demonstrated that nonconcave penalties lead to significant reduction of the "irrepresentable condition" needed for LASSO model selection consistency. The large deviation result for martingales, bearing interests of its own, is developed for characterizing the strong oracle property. Moreover, the nonconcave regularized estimator, is shown to achieve asymptotically the information bound of the oracle estimator. A coordinate-wise algorithm is developed for finding the grid of solution paths for penalized hazard regression problems, and its performance is evaluated on simulated and gene association study examples.Comment: Published in at http://dx.doi.org/10.1214/11-AOS911 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

An Interval-Censored Proportional Hazards Model

We fit a Cox proportional hazards (PH) model to interval-censored survival data by first subdividing each individual\u27s failure interval into non-overlapping sub-intervals. Using the set of all interval endpoints in the data set, those that fall into the individual\u27s interval are then used as the cut points for the sub-intervals. Each sub-interval has an accompanying weight calculated from a parametric Weibull model based on the current parameter estimates. A weighted PH model is then fit with multiple lines of observations corresponding to the sub-intervals for each individual, where the lower end of each sub-interval is used as the observed failure time with the accompanying weights incorporated. Right-censored observations are handled in the usual manner. We iterate between estimating the baseline Weibull distribution and fitting the weighted PH model until the regression parameters of interest converge. The regression parameter estimates are fixed as an offset when we update the estimates of the Weibull distribution and recalculate the weights. Our approach is similar to Satten et al.\u27s (1998) method for interval-censored survival analysis that used imputed failure times generated from a parametric model in a PH model. Simulation results demonstrate apparently unbiased parameter estimation for the correctly specified Weibull model and little to no bias for a mis-specified log-logistic model. Breast cosmetic deterioration data and ICU hyperlactemia data are analyzed

joineR: Joint modelling of repeated measurements and time-to-event data

The joineR package implements methods for analysing data from longitudinal studies in which the response from each subject consists of a time-sequence of repeated measurements and a possibly censored time-toevent outcome. The modelling framework for the repeated measurements is the linear model with random effects and/or correlated error structure. The model for the time-to-event outcome is a Cox proportional hazards model with log-Gaussian frailty. Stochastic dependence is captured by allowing the Gaussian random effects of the linear model to be correlated with the frailty term of the Cox proportional hazards model

Statistical estimation in the proportional hazards model with risk set sampling

Thomas' partial likelihood estimator of regression parameters is widely used in the analysis of nested case-control data with Cox's model. This paper proposes a new estimator of the regression parameters, which is consistent and asymptotically normal. Its asymptotic variance is smaller than that of Thomas' estimator away from the null. Unlike some other existing estimators, the proposed estimator does not rely on any more data than strictly necessary for Thomas' estimator and is easily computable from a closed form estimating equation with a unique solution. The variance estimation is obtained as minus the inverse of the derivative of the estimating function and therefore the inference is easily available. A numerical example is provided in support of the theory.Comment: Published by the Institute of Mathematical Statistics (http://www.imstat.org) in the Annals of Statistics (http://www.imstat.org/aos/) at http://dx.doi.org/10.1214/00905360400000051

Proportional hazards models with continuous marks

For time-to-event data with finitely many competing risks, the proportional hazards model has been a popular tool for relating the cause-specific outcomes to covariates [Prentice et al. Biometrics 34 (1978) 541--554]. This article studies an extension of this approach to allow a continuum of competing risks, in which the cause of failure is replaced by a continuous mark only observed at the failure time. We develop inference for the proportional hazards model in which the regression parameters depend nonparametrically on the mark and the baseline hazard depends nonparametrically on both time and mark. This work is motivated by the need to assess HIV vaccine efficacy, while taking into account the genetic divergence of infecting HIV viruses in trial participants from the HIV strain that is contained in the vaccine, and adjusting for covariate effects. Mark-specific vaccine efficacy is expressed in terms of one of the regression functions in the mark-specific proportional hazards model. The new approach is evaluated in simulations and applied to the first HIV vaccine efficacy trial.Comment: Published in at http://dx.doi.org/10.1214/07-AOS554 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Regularization Paths for Cox's Proportional Hazards Model via Coordinate Descent

We introduce a pathwise algorithm for the Cox proportional hazards model, regularized by convex combinations of l_1 and l_2 penalties (elastic net). Our algorithm fits via cyclical coordinate descent, and employs warm starts to find a solution along a regularization path. We demonstrate the efficacy of our algorithm on real and simulated data sets, and find considerable speedup between our algorithm and competing methods.

Semiparametric estimation of a panel data proportional hazards model with fixed effects

This paper considers a panel duration model that has a proportional hazards specification with fixed effects. The paper shows how to estimate the baseline and integrated baseline hazard functions without assuming that they belong to known, finitedimensional families of functions. Existing estimators assume that the baseline hazard function belongs to a known parametric family. Therefore, the estimators presented here are more general than existing ones. This paper also presents a method for estimating the parametric part of the proportional hazards model with dependent right censoring, under which the partial likelihood estimator is inconsistent. The paper presents some Monte Carlo evidence on the small sample performance of the new estimators