Semiparametric Likelihood Estimation in the Clayton–Oakes Failure Time Model

Multivariate failure time data arise when the sample consists of clusters and each cluster contains several possibly dependent failure times. The Clayton–Oakes model (Clayton, 1978; Oakes, 1982) for multivariate failure times characterizes the intracluster dependence parametrically but allows arbitrary specification of the marginal distributions. In this paper, we discuss estimation in the Clayton–Oakes model when the marginal distributions are modeled to follow the Cox (1972) proportional hazards regression model. Parameter estimation is based on an approximate generalized maximum likelihood estimator. We illustrate the model's application with example datasets.     

Marginal Likelihood Estimation for Proportional Odds Models with Right Censored Data

One majoraspect in medical research is to relate the survival times ofpatients with the relevant covariates or explanatory variables.The proportional hazards model has been used extensively in thepast decades with the assumption that the covariate effects actmultiplicatively on the hazard function, independent of time.If the patients become more homogeneous over time, say the treatmenteffects decrease with time or fade out eventually, then a proportionalodds model may be more appropriate. In the proportional oddsmodel, the odds ratio between patients can be expressed as afunction of their corresponding covariate vectors, in which,the hazard ratio between individuals converges to unity in thelong run. In this paper, we consider the estimation of the regressionparameter for a semiparametric proportional odds model at whichthe baseline odds function is an arbitrary, non-decreasing functionbut is left unspecified. Instead of using the exact survivaltimes, only the rank order information among patients is used.A Monte Carlo method is used to approximate the marginal likelihoodfunction of the rank invariant transformation of the survivaltimes which preserves the information about the regression parameter.The method can be applied to other transformation models withcensored data such as the proportional hazards model, the generalizedprobit model or others. The proposed method is applied to theVeteran's Administration lung cancer trial data.     

Estimating Survival Curves Under Proportional Hazards Model with Covariate Measurement Errors

For the Cox proportional hazards model with additive covariate measurement errors, we propose a corrected cumulative baseline hazard estimator that reduces the bias of the na]ve Breslow estimator. We also derive corresponding modified estimators for the hazard functions and the survival functions of individuals with particular covariate values. Using a Monte Carlo technique developed by Lin et al . (1994), we construct confidence bands for such hazard and survival functions.     

Proportional Hazards Model for Multivariate Failure Time Data

Multivariate failure time data also referred to as correlated or clustered failure time data, often arise in survival studies when each study subject may experience multiple events. Statistical analysis of such data needs to account for intracluster dependence. In this article, we consider a bivariate proportional hazards model using vector hazard rate, in which the covariates under study have different effect on two components of the vector hazard rate function. Estimation of the parameters as well as base line hazard function are discussed. Properties of the estimators are investigated. We illustrated the method using two real life data. A simulation study is reported to assess the performance of the estimator.     

Fitting Cox Models with Doubly Censored Data Using Spline‐Based Sieve Marginal Likelihood

In some applications, the failure time of interest is the time from an originating event to a failure event while both event times are interval censored. We propose fitting Cox proportional hazards models to this type of data using a spline‐based sieve maximum marginal likelihood, where the time to the originating event is integrated out in the empirical likelihood function of the failure time of interest. This greatly reduces the complexity of the objective function compared with the fully semiparametric likelihood. The dependence of the time of interest on time to the originating event is induced by including the latter as a covariate in the proportional hazards model for the failure time of interest. The use of splines results in a higher rate of convergence of the estimator of the baseline hazard function compared with the usual non‐parametric estimator. The computation of the estimator is facilitated by a multiple imputation approach. Asymptotic theory is established and a simulation study is conducted to assess its finite sample performance. It is also applied to analyzing a real data set on AIDS incubation time.     

Estimation in the Positive Stable Shared Frailty Cox Proportional Hazards Model

Shared frailty models are of interest when one has clustered survival data and when focus is on comparing the lifetimes within clusters and further on estimating the correlation between lifetimes from the same cluster. It is well known that the positive stable model should be preferred to the gamma model in situations where the correlated survival data show a decreasing association with time. In this paper, we devise a likelihood based estimation procedure for the positive stable shared frailty Cox model, which is expected to obtain high efficiency. The proposed estimator is provided with large sample properties and also a consistent estimator of standard errors is given. Simulation studies show that the estimation procedure is appropriate for practical use, and that it is much more efficient than a recently suggested procedure. The suggested methodology is applied to a dataset concerning time to blindness for patients with diabetic retinopathy.     

The Dantzig Selector in Cox's Proportional Hazards Model

Abstract. The Dantzig selector (DS) is a recent approach of estimation in high‐dimensional linear regression models with a large number of explanatory variables and a relatively small number of observations. As in the least absolute shrinkage and selection operator (LASSO), this approach sets certain regression coefficients exactly to zero, thus performing variable selection. However, such a framework, contrary to the LASSO, has never been used in regression models for survival data with censoring. A key motivation of this article is to study the estimation problem for Cox's proportional hazards (PH) function regression models using a framework that extends the theory, the computational advantages and the optimal asymptotic rate properties of the DS to the class of Cox's PH under appropriate sparsity scenarios. We perform a detailed simulation study to compare our approach with other methods and illustrate it on a well‐known microarray gene expression data set for predicting survival from gene expressions.     

Generalized Proportional Hazards Model Based on Modified Partial Likelihood

The proportional hazards (Cox) model is generalized by assuming that at any moment the ratio of hazard rates is depending not only on values of covariates but also on resources used until this moment. Relations with generalized multiplicative, frailty and linear transformation models are considered. A modified partial likelihood function is proposed, and properties of the estimators are investigated.     

Model Selection Criterion Based on the Multivariate Quasi‐Likelihood for Generalized Estimating Equations

The generalized estimating equations (GEE) approach has attracted considerable interest for the analysis of correlated response data. This paper considers the model selection criterion based on the multivariate quasi‐likelihood (MQL) in the GEE framework. The GEE approach is closely related to the MQL. We derive a necessary and sufficient condition for the uniqueness of the risk function based on the MQL by using properties of differential geometry. Furthermore, we establish a formal derivation of model selection criterion as an asymptotically unbiased estimator of the prediction risk under this condition, and we explicitly take into account the effect of estimating the correlation matrix used in the GEE procedure.     

Empirical Likelihood for the Additive Hazards Model with Current Status Data

We investigate empirical likelihood for the additive hazards model with current status data. An empirical log-likelihood ratio for a vector or subvector of regression parameters is defined and its limiting distribution is shown to be a standard chi-squared distribution. The proposed inference procedure enables us to make empirical likelihood-based inference for the regression parameters. Finite sample performance of the proposed method is assessed in simulation studies to compare with that of a normal approximation method, it shows that the empirical likelihood method provides more accurate inference than the normal approximation method. A real data example is used for illustration.     

Bayesian Analysis of the Proportional Hazards Model with Time‐Varying Coefficients

We study a Bayesian analysis of the proportional hazards model with time‐varying coefficients. We consider two priors for time‐varying coefficients – one based on B‐spline basis functions and the other based on Gamma processes – and we use a beta process prior for the baseline hazard functions. We show that the two priors provide optimal posterior convergence rates (up to the term) and that the Bayes factor is consistent for testing the assumption of the proportional hazards when the two priors are used for an alternative hypothesis. In addition, adaptive priors are considered for theoretical investigation, in which the smoothness of the true function is assumed to be unknown, and prior distributions are assigned based on B‐splines.     

A Proportional Hazards Regression Model for the Subdistribution with Covariates‐adjusted Censoring Weight for Competing Risks Data

With competing risks data, one often needs to assess the treatment and covariate effects on the cumulative incidence function. Fine and Gray proposed a proportional hazards regression model for the subdistribution of a competing risk with the assumption that the censoring distribution and the covariates are independent. Covariate‐dependent censoring sometimes occurs in medical studies. In this paper, we study the proportional hazards regression model for the subdistribution of a competing risk with proper adjustments for covariate‐dependent censoring. We consider a covariate‐adjusted weight function by fitting the Cox model for the censoring distribution and using the predictive probability for each individual. Our simulation study shows that the covariate‐adjusted weight estimator is basically unbiased when the censoring time depends on the covariates, and the covariate‐adjusted weight approach works well for the variance estimator as well. We illustrate our methods with bone marrow transplant data from the Center for International Blood and Marrow Transplant Research. Here, cancer relapse and death in complete remission are two competing risks.     

Empirical Likelihood Inference for the Cox Model with Time-dependent Coefficients via Local Partial Likelihood

Abstract.  The Cox model with time-dependent coefficients has been studied by a number of authors recently. In this paper, we develop empirical likelihood (EL) pointwise confidence regions for the time-dependent regression coefficients via local partial likelihood smoothing. The EL simultaneous confidence bands for a linear combination of the coefficients are also derived based on the strong approximation methods. The EL ratio is formulated through the local partial log-likelihood for the regression coefficient functions. Our numerical studies indicate that the EL pointwise/simultaneous confidence regions/bands have satisfactory finite sample performances. Compared with the confidence regions derived directly based on the asymptotic normal distribution of the local constant estimator, the EL confidence regions are overall tighter and can better capture the curvature of the underlying regression coefficient functions. Two data sets, the gastric cancer data and the Mayo Clinic primary biliary cirrhosis data, are analysed using the proposed method.     

On Estimation and Tests of Time-Varying Effects in the Proportional Hazards Model

Abstract.  Cox's proportional hazards model is routinely used in many applied fields, some times, however, with too little emphasis on the fit of the model. In this paper, we suggest some new tests for investigating whether or not covariate effects vary with time. These tests are a natural and integrated part of an extended version of the Cox model. An important new feature of the suggested test is that time constancy for a specific covariate is examined in a model, where some effects of other covariates are allowed to vary with time and some are constant; thus making successive testing of time-dependency possible. The proposed techniques are illustrated with the well-known Mayo liver disease data, and a small simulation study investigates the finite sample properties of the tests.     

A Spline‐Based Semiparametric Maximum Likelihood Estimation Method for the Cox Model with Interval‐Censored Data

Abstract. We propose a spline‐based semiparametric maximum likelihood approach to analysing the Cox model with interval‐censored data. With this approach, the baseline cumulative hazard function is approximated by a monotone B‐spline function. We extend the generalized Rosen algorithm to compute the maximum likelihood estimate. We show that the estimator of the regression parameter is asymptotically normal and semiparametrically efficient, although the estimator of the baseline cumulative hazard function converges at a rate slower than root‐n. We also develop an easy‐to‐implement method for consistently estimating the standard error of the estimated regression parameter, which facilitates the proposed inference procedure for the Cox model with interval‐censored data. The proposed method is evaluated by simulation studies regarding its finite sample performance and is illustrated using data from a breast cosmesis study.     

Cox模型和寿险退保研究中的比例危险性

利用生存分析研究寿险退保问题是一个很好的工具，因为可以将寿险保单的持续期（persistency duration）视为生存期长，而将保单的退保或失效看作一个“保单生命”的结束，这其中的保单退保或失效就成为生存研究的目标事件。而导致保单失效的因素会有很多，只有通过利用Cox比例危险模型拟合寿险退保数据以分析影响客户退保的原因，并在对Cox模型的比例危险假设进行检验时，发现部分影响因素并不遵守此前提条件，从而推理得到这些影响因素在不同的时间段对客户退保的影响方式不同。也就是说，其影响有短期效应和长期效应之分。     

The Cox Proportional Hazards Model with a Partly Linear Relative Risk Function

The conventional Cox proportional hazards regression model contains a loglinear relative risk function, linking the covariate information to the hazard ratio with a finite number of parameters. A generalization, termed the partly linear Cox model, allows for both finite dimensional parameters and an infinite dimensional parameter in the relative risk function, providing a more robust specification of the relative risk function. In this work, a likelihood based inference procedure is developed for the finite dimensional parameters of the partly linear Cox model. To alleviate the problems associated with a likelihood approach in the presence of an infinite dimensional parameter, the relative risk is reparameterized such that the finite dimensional parameters of interest are orthogonal to the infinite dimensional parameter. Inference on the finite dimensional parameters is accomplished through maximization of the profile partial likelihood, profiling out the infinite dimensional nuisance parameter using a kernel function. The asymptotic distribution theory for the maximum profile partial likelihood estimate is established. It is determined that this estimate is asymptotically efficient; the orthogonal reparameterization enables employment of profile likelihood inference procedures without adjustment for estimation of the nuisance parameter. An example from a retrospective analysis in cancer demonstrates the methodology.     

A Smooth Test in Proportional Hazard Survival Models Using Local Partial Likelihood Fitting

Proportional hazard models for survival data, even though popular and numerically handy, suffer from the restrictive assumption that covariate effects are constant over survival time. A number of tests have been proposed to check this assumption. This paper contributes to this area by employing local estimates allowing to fit hazard models in which covariate effects are smoothly varying with time. A formal test is derived to check for proportional hazards against smooth hazards as alternative. The test proves to possess omnibus power in that it is powerful against arbitrary but smooth alternatives. Comparative simulations and two data examples accompany the presentation. Extensions are provided to multiple covariate settings, where the focus of interest is to decide which of the covariate effects vary with time.     

Bayesian Model Selection and Averaging in Additive and Proportional Hazards Models

Although Cox proportional hazards regression is the default analysis for time to event data, there is typically uncertainty about whether the effects of a predictor are more appropriately characterized by a multiplicative or additive model. To accommodate this uncertainty, we place a model selection prior on the coefficients in an additive-multiplicative hazards model. This prior assigns positive probability, not only to the model that has both additive and multiplicative effects for each predictor, but also to sub-models corresponding to no association, to only additive effects, and to only proportional effects. The additive component of the model is constrained to ensure non-negative hazards, a condition often violated by current methods. After augmenting the data with Poisson latent variables, the prior is conditionally conjugate, and posterior computation can proceed via an efficient Gibbs sampling algorithm. Simulation study results are presented, and the methodology is illustrated using data from the Framingham heart study.     

A Cox‐Aalen Model for Interval‐censored Data

The Cox‐Aalen model, obtained by replacing the baseline hazard function in the well‐known Cox model with a covariate‐dependent Aalen model, allows for both fixed and dynamic covariate effects. In this paper, we examine maximum likelihood estimation for a Cox‐Aalen model based on interval‐censored failure times with fixed covariates. The resulting estimator globally converges to the truth slower than the parametric rate, but its finite‐dimensional component is asymptotically efficient. Numerical studies show that estimation via a constrained Newton method performs well in terms of both finite sample properties and processing time for moderate‐to‐large samples with few covariates. We conclude with an application of the proposed methods to assess risk factors for disease progression in psoriatic arthritis.