A New Estimator for Cox Proportional Hazard Regression Model in Presence of Collinearity

We propose a new approach to estimate the parameters of the Cox proportional hazards model in the presence of collinearity. Generally, a maximum partial likelihood estimator is used to estimate parameters for the Cox proportional hazards model. However, the maximum partial likelihood estimators can be seriously affected by the presence of collinearity since the parameter estimates result in large variances.

In this study, we develop a Liu-type estimator for Cox proportional hazards model parameters and compare it with a ridge regression estimator based on the scalar mean squared error (MSE). Finally, we evaluate its performance through a simulation study.     

An Asymptotic Linear Representation for the Breslow Estimator

We provide an asymptotic linear representation for the Breslow estimator of the baseline cumulative hazard function in the Cox model. Our representation consists of an average of independent random variables and a term involving the difference between the maximum partial likelihood estimator and the underlying regression parameter. The order of the remainder term is arbitrarily close to n ^?1.     

Survival Estimation with Missing Censoring Times for the Generalized Koziol–Green Model

ABSTRACT

When analyzing time-to-event data, there are various situations in which right censoring times for unfailed units are missing. In that context, by taking a supplementary sample of a convenient percentage of unfailed units, we propose a semi-parametric method for estimating a survival function under the natural extension of the Koziol–Green model to double random censoring. Some large sample properties of this estimator are derived. We prove uniform strong consistency and asymptotic weak convergence to a Gaussian process. A simulation study is also presented in order to analyze the behavior of the proposed estimator.     

Estimation and Inference Based on Neumann Series Approximation to Locally Efficient Score in Missing Data Problems

Abstract.  Theory on semi-parametric efficient estimation in missing data problems has been systematically developed by Robins and his coauthors. Except in relatively simple problems, semi-parametric efficient scores cannot be expressed in closed forms. Instead, the efficient scores are often expressed as solutions to integral equations. Neumann series was proposed in the form of successive approximation to the efficient scores in those situations. Statistical properties of the estimator based on the Neumann series approximation are difficult to obtain and as a result, have not been clearly studied. In this paper, we reformulate the successive approximation in a simple iterative form and study the statistical properties of the estimator based on the reformulation. We show that a doubly robust locally efficient estimator can be obtained following the algorithm in robustifying the likelihood score. The results can be applied to, among others, parametric regression, marginal regression and Cox regression when data are subject to missing values and the data are missing at random. A simulation study is conducted to evaluate the performance of the approach and a real data example is analysed to demonstrate the use of the approach.     

Piecewise Cox models with right-censored data

We study a general class of piecewise Cox models. We discuss the computation of the semi-parametric maximum likelihood estimates (SMLE) of the parameters, with right-censored data, and a simplified algorithm for the maximum partial likelihood estimates (MPLE). Our simulation study suggests that the relative efficiency of the PMLE of the parameter to the SMLE ranges from 96% to 99.9%, but the relative efficiency of the existing estimators of the baseline survival function to the SMLE ranges from 3% to 24%. Thus, the SMLE is much better than the existing estimators.     

Full likelihood inference in the Cox model with LTRC data when covariates are discrete

For the regression parameter β in the Cox model, there have been several estimates based on different types of approximated likelihood. For right-censored data, Ren and Zhou [Full likelihood inferences in the Cox model: an empirical approach. Ann Inst Statist Math. 2011;63:1005–1018] derive the full likelihood function for (β, F₀), where F₀ is the baseline distribution function in the Cox model. In this article, we extend their results to left-truncated and right-censored data with discrete covariates. Using the empirical likelihood parameterization, we obtain the full-profile likelihood function for β when covariates are discrete. Simulation results indicate that the maximum likelihood estimator outperforms Cox's partial likelihood estimator in finite samples.     

Comparison Between Two Partial Likelihood Approaches for the Competing Risks Model with Missing Cause of Failure

In many clinical studies where time to failure is of primary interest, patients may fail or die from one of many causes where failure time can be right censored. In some circumstances, it might also be the case that patients are known to die but the cause of death information is not available for some patients. Under the assumption that cause of death is missing at random, we compare the Goetghebeur and Ryan (1995, Biometrika, 82, 821–833) partial likelihood approach with the Dewanji (1992, Biometrika, 79, 855–857)partial likelihood approach. We show that the estimator for the regression coefficients based on the Dewanji partial likelihood is not only consistent and asymptotically normal, but also semiparametric efficient. While the Goetghebeur and Ryan estimator is more robust than the Dewanji partial likelihood estimator against misspecification of proportional baseline hazards, the Dewanji partial likelihood estimator allows the probability of missing cause of failure to depend on covariate information without the need to model the missingness mechanism. Tests for proportional baseline hazards are also suggested and a robust variance estimator is derived.     

Estimating the Expectation of the Log-Likelihood with Censored Data for Estimator Selection

A criterion for choosing an estimator in a family of semi-parametric estimators from incomplete data is proposed. This criterion is the expected observed log-likelihood (ELL). Adapted versions of this criterion in case of censored data and in presence of explanatory variables are exhibited. We show that likelihood cross-validation (LCV) is an estimator of ELL and we exhibit three bootstrap estimators. A simulation study considering both families of kernel and penalized likelihood estimators of the hazard function (indexed on a smoothing parameter) demonstrates good results of LCV and a bootstrap estimator called ELL_bboot . We apply the ELL_bboot criterion to compare the kernel and penalized likelihood estimators to estimate the risk of developing dementia for women using data from a large cohort study.     

A semi-parametric cox’s regression model for zero-inflated left-censored time to event data

Abstract

In some clinical, environmental, or economical studies, researchers are interested in a semi-continuous outcome variable which takes the value zero with a discrete probability and has a continuous distribution for the non-zero values. Due to the measuring mechanism, it is not always possible to fully observe some outcomes, and only an upper bound is recorded. We call this left-censored data and observe only the maximum of the outcome and an independent censoring variable, together with an indicator. In this article, we introduce a mixture semi-parametric regression model. We consider a parametric model to investigate the influence of covariates on the discrete probability of the value zero. For the non-zero part of the outcome, a semi-parametric Cox’s regression model is used to study the conditional hazard function. The different parameters in this mixture model are estimated using a likelihood method. Hereby the infinite dimensional baseline hazard function is estimated by a step function. As results, we show the identifiability and the consistency of the estimators for the different parameters in the model. We study the finite sample behaviour of the estimators through a simulation study and illustrate this model on a practical data example.     

Estimation and Simulation of the Riesz-Bessel Distribution

ABSTRACT

In this article, further properties of the Riesz-Bessel distribution are provided. These properties allow for the simulation of random variables from the Riesz-Bessel distribution. Estimation is addressed by nonlinear generalized least squares regression on the empirical characteristic function. The estimator is seen to approximate the maximum likelihood estimator. The distribution is illustrated with financial data.     

Bias evaluation in the proportional hazards model

We consider two approaches for bias evaluation and reduction in the proportional hazards model proposed by Cox. The first one is an analytical approach in which we derive the n^-1 bias term of the maximum partial likelihood estimator. The second approach consists of resampling methods, namely the jackknife and the bootstrap. We compare all methods through a comprehensive set of Monte Carlo simulations. The results suggest that bias-corrected estimators have better finite-sample performance than the standard maximum partial likelihood estimator. There is some evidence oithe bootstrap-correction superiority over the jackknife-correction but its performance is similar to the analytical estimator. Finaily an application iliustrates the proposed approaches.     

Estimation Under the Lehmann Regression Model with Interval-Censored Data

We consider the estimation problem under the Lehmann model with interval-censored data, but focus on the computational issues. There are two methods for computing the semi-parametric maximum likelihood estimator (SMLE) under the Lehmann model (or called Cox model): the Newton-Raphson (NR) method and the profile likelihood (PL) method. We show that they often do not get close to the SMLE. We propose several approach to overcome the computational difficulty and apply our method to a breast cancer research data set.     

Mimicking Cox-Regression

Abstract

A class of objective functions, related to the Cox partial likelihood, that generates unbiased estimating equations is proposed. These equations allow for estimation of interest parameters when nuisance parameters are proportional to expectations. Examples of the objective functions are applied to binary data with a log-link in three situations: independent observations, independent groups of observations with common random intercept and discrete survival data. It is pointed out that the Peto–Breslow approximation to the partial likelihood with discrete failure times fits a conditional model with a log-link.     

Inference for proportional hazard model with propensity score

Since the publication of the seminal paper by Cox (1972), proportional hazard model has become very popular in regression analysis for right censored data. In observational studies, treatment assignment may depend on observed covariates. If these confounding variables are not accounted for properly, the inference based on the Cox proportional hazard model may perform poorly. As shown in Rosenbaum and Rubin (1983), under the strongly ignorable treatment assignment assumption, conditioning on the propensity score yields valid causal effect estimates. Therefore we incorporate the propensity score into the Cox model for causal inference with survival data. We derive the asymptotic property of the maximum partial likelihood estimator when the model is correctly specified. Simulation results show that our method performs quite well for observational data. The approach is applied to a real dataset on the time of readmission of trauma patients. We also derive the asymptotic property of the maximum partial likelihood estimator with a robust variance estimator, when the model is incorrectly specified.     

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.     

Inference on proportional hazard rate model parameter under Type-I progressively hybrid censoring scheme

ABSTRACT

In this paper, under Type-I progressive hybrid censoring sample, we obtain maximum likelihood estimator of unknown parameter when the parent distribution belongs to proportional hazard rate family. We derive the conditional probability density function of the maximum likelihood estimator using moment-generating function technique. The exact confidence interval is obtained and compared by conducting a Monte Carlo simulation study for burr Type XII distribution. Finally, we obtain the Bayes and posterior regret gamma minimax estimates of the parameter under a precautionary loss function with precautionary index k = 2 and compare their behavior via a Monte Carlo simulation study.     

Improved likelihood inference for the shape parameter in Weibull regression

We obtain adjustments to the profile likelihood function in Weibull regression models with and without censoring. Specifically, we consider two different modified profile likelihoods: (i) the one proposed by Cox and Reid [Cox, D.R. and Reid, N., 1987, Parameter orthogonality and approximate conditional inference. Journal of the Royal Statistical Society B, 49, 1–39.], and (ii) an approximation to the one proposed by Barndorff–Nielsen [Barndorff–Nielsen, O.E., 1983, On a formula for the distribution of the maximum likelihood estimator. Biometrika, 70, 343–365.], the approximation having been obtained using the results by Fraser and Reid [Fraser, D.A.S. and Reid, N., 1995, Ancillaries and third-order significance. Utilitas Mathematica, 47, 33–53.] and by Fraser et al. [Fraser, D.A.S., Reid, N. and Wu, J., 1999, A simple formula for tail probabilities for frequentist and Bayesian inference. Biometrika, 86, 655–661.]. We focus on point estimation and likelihood ratio tests on the shape parameter in the class of Weibull regression models. We derive some distributional properties of the different maximum likelihood estimators and likelihood ratio tests. The numerical evidence presented in the paper favors the approximation to Barndorff–Nielsen's adjustment.     

Computationally simple estimation and improved efficiency for special cases of double truncation

Doubly truncated survival data arise when event times are observed only if they occur within subject specific intervals of times. Existing iterative estimation procedures for doubly truncated data are computationally intensive (Turnbull 38:290–295, 1976; Efron and Petrosian 94:824–825, 1999; Shen 62:835–853, 2010a). These procedures assume that the event time is independent of the truncation times, in the sample space that conforms to their requisite ordering. This type of independence is referred to as quasi-independence. In this paper we identify and consider two special cases of quasi-independence: complete quasi-independence and complete truncation dependence. For the case of complete quasi-independence, we derive the nonparametric maximum likelihood estimator in closed-form. For the case of complete truncation dependence, we derive a closed-form nonparametric estimator that requires some external information, and a semi-parametric maximum likelihood estimator that achieves improved efficiency relative to the standard nonparametric maximum likelihood estimator, in the absence of external information. We demonstrate the consistency and potentially improved efficiency of the estimators in simulation studies, and illustrate their use in application to studies of AIDS incubation and Parkinson’s disease age of onset.     

Flexible Modeling in the Koziol-Green Model by a Copula Function

In survival analysis, the classical Koziol-Green random censorship model is commonly used to describe informative censoring. Hereby, it is assumed that the distribution of the censoring time is a power of the distribution of the survival time. In this article, we extend this model by assuming a general function between these distributions. We determine this function from a relationship between the observable random variables which is described by a copula family that depends on an unknown parameter θ. For this setting, we develop a semi-parametric estimator for the distribution of the survival time in which we propose a pseudo-likelihood estimator for the copula parameter θ. As results, we show first the consistency and asymptotic normality of the estimator for θ. Afterwards, we prove the weak convergence of the process associated to the semi-parametric distribution estimator. Furthermore, we investigate the finite sample performance of these estimators through a simulation study and finally apply it to a practical data set on survival with malignant melanoma.     

Adjusting regression attenuation in the Cox proportional hazards model

In the measurement error Cox proportional hazards model, the naive maximum partial likelihood estimator (MPLE) is asymptotically biased. In this paper, we give the formula of the asymptotic bias for the additive measurement error Cox model. By adjusting for this error, we derive an adjusted MPLE that is less biased. The bias can be further reduced by adjusting for the estimator second and even third time. This estimator has the advantage of being easy to apply. The performance of the proposed estimator is evaluated through a simulation study.