Parameter estimation in regression for long-term survival rate from censored data

In recent years, regression models have been shown to be useful for predicting the long-term survival probabilities of patients in clinical trials. The importance of a regression model is that once the regression parameters are estimated information about the regressed quantity is immediate. A simple estimator is proposed for the regression parameters in a model for the long-term survival rate. The proposed estimator is seen to arise from an estimating function that has the missing information principle underlying its construction. When the covariate takes values in a finite set, the proposed estimating function is equivalent to an ad hoc estimating function proposed in the literature. However, in general, the two estimating functions lead to different estimators of the regression parameter. For discrete covariates, the asymptotic covariance matrix of the proposed estimator is simple to calculate using standard techniques involving the predictable covariation process of martingale transforms. An ad hoc extension to the case of a one-dimensional continuous covariate is proposed. Simplicity and generalizability are two attractive features of the proposed approach. The last mentioned feature is not enjoyed by the other estimator.     

Estimation of regression parameters in generalized linear models for cluster correlated data with measurement error

Liang and Zeger (1986) introduced a class of estimating equations that gives consistent estimates of regression parameters and of their asymptotic variances in the class of generalized linear models for cluster correlated data. When the independent variables or covariates in such models are subject to measurement errors, the parameter estimates obtained from these estimating equations are no longer consistent. To correct for the effect of measurement errors, an estimator with smaller asymptotic bias is constructed along the lines of Stefanski (1985), assuming that the measurement error variance is either known or estimable. The asymptotic distribution of the bias-corrected estimator and a consistent estimator of its asymptotic variance are also given. The special case of a binary logistic regression model is studied in detail. For this case, methods based on conditional scores and quasilikelihood are also extended to cluster correlated data. Results of a small simulation study on the performance of the proposed estimators and associated tests of hypotheses are reported.     

Sequential estimation for semiparametric models with application to the proportional hazards model

In this paper, we show that if the Euclidean parameter of a semiparametric model can be estimated through an estimating function, we can extend straightforwardly conditions by Dmitrienko and Govindarajulu [2000. Ann. Statist. 28 (5), 1472–1501] in order to prove that the estimator indexed by any regular sequence (sequential estimator), has the same asymptotic behavior as the non-sequential estimator. These conditions also allow us to obtain the asymptotic normality of the stopping rule, for the special case of sequential confidence sets. These results are applied to the proportional hazards model, for which we show that after slight modifications, the classical assumptions given by Andersen and Gill [1982. Ann. Statist. 10(4), 1100–1120] are sufficient to obtain the asymptotic behavior of the sequential version of the well-known [Cox, 1972. J. Roy. Statist. Soc. Ser. B (34), 187–220] partial maximum likelihood estimator. To prove this result we need to establish a strong convergence result for the regression parameter estimator, involving mainly exponential inequalities for both continuous martingales and some basic empirical processes. A typical example of a fixed-width confidence interval is given and illustrated by a Monte Carlo study.     

Cox regression with missing covariate data using a modified partial likelihood method

Missing covariate values is a common problem in survival analysis. In this paper we propose a novel method for the Cox regression model that is close to maximum likelihood but avoids the use of the EM-algorithm. It exploits that the observed hazard function is multiplicative in the baseline hazard function with the idea being to profile out this function before carrying out the estimation of the parameter of interest. In this step one uses a Breslow type estimator to estimate the cumulative baseline hazard function. We focus on the situation where the observed covariates are categorical which allows us to calculate estimators without having to assume anything about the distribution of the covariates. We show that the proposed estimator is consistent and asymptotically normal, and derive a consistent estimator of the variance–covariance matrix that does not involve any choice of a perturbation parameter. Moderate sample size performance of the estimators is investigated via simulation and by application to a real data example.     

Cox regression of clustered event times with covariates missing not at random

Motivated by a recent tuberculosis (TB) study, this paper is concerned with covariates missing not at random (MNAR) and models the potential intracluster correlation by a frailty. We consider the regression analysis of right‐censored event times from clustered subjects under a Cox proportional hazards frailty model and present the semiparametric maximum likelihood estimator (SPMLE) of the model parameters. An easy‐to‐implement pseudo‐SPMLE is then proposed to accommodate more realistic situations using readily available supplementary information on the missing covariates. Algorithms are provided to compute the estimators and their consistent variance estimators. We demonstrate that both the SPMLE and the pseudo‐SPMLE are consistent and asymptotically normal by the arguments based on the theory of modern empirical processes. The proposed approach is examined numerically via simulation and illustrated with an analysis of the motivating TB study data.     

Global Partial Likelihood for Nonparametric Proportional Hazards Models

As an alternative to the local partial likelihood method of Tibshirani and Hastie and Fan, Gijbels, and King, a global partial likelihood method is proposed to estimate the covariate effect in a nonparametric proportional hazards model, λ(t|x) = exp{ψ(x)}λ(0)(t). The estimator, ψ?(x), reduces to the Cox partial likelihood estimator if the covariate is discrete. The estimator is shown to be consistent and semiparametrically efficient for linear functionals of ψ(x). Moreover, Breslow-type estimation of the cumulative baseline hazard function, using the proposed estimator ψ?(x), is proved to be efficient. The asymptotic bias and variance are derived under regularity conditions. Computation of the estimator involves an iterative but simple algorithm. Extensive simulation studies provide evidence supporting the theory. The method is illustrated with the Stanford heart transplant data set. The proposed global approach is also extended to a partially linear proportional hazards model and found to provide efficient estimation of the slope parameter. This article has the supplementary materials online.     

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.     

The mixed model for survey regression estimation

Estimation of the population mean under the regression model with random components is considered. Conditions under which the random components regression estimator is design consistent are given. It is shown that consistency holds when incorrect values are used for the variance components. The regression estimator constructed with model parameters that differ considerably from the true parameters performed well in a Monte Carlo study. Variance estimators for the regression predictor are suggested. A variance estimator appropriate for estimators constructed with a biased estimator for the between-group variance component performed well in the Monte Carlo study.     

Semiparametric estimation in single index Poisson regression: a practical approach

In a single index Poisson regression model with unknown link function, the index parameter can be root- n consistently estimated by the method of pseudo maximum likelihood. In this paper, we study, by simulation arguments, the practical validity of the asymptotic behaviour of the pseudo maximum likelihood index estimator and of some associated cross-validation bandwidths. A robust practical rule for implementing the pseudo maximum likelihood estimation method is suggested, which uses the bootstrap for estimating the variance of the index estimator and a variant of bagging for numerically stabilizing its variance. Our method gives reasonable results even for moderate sized samples; thus, it can be used for doing statistical inference in practical situations. The procedure is illustrated through a real data example.     

A note on the asymptotic relative efficiency of estimators from the additive hazards model

In this note, the asymptotic variance formulas are explicitly derived and compared between the parametric and semiparametric estimators of a regression parameter and survival probability under the additive hazards model. To obtain explicit formulas, it is assumed that the covariate term including a regression coefficient follows a gamma distribution and the baseline hazard function is constant. The results show that the semiparametric estimator of the regression coefficient parameter is fully efficient relative to the parametric counterpart when the survival time and a covariate are independent, as in the proportional hazards model. Relative to a more realistic case of the parametric additive hazards model with a Weibull baseline, the loss of efficiency of the semiparametric estimator of survival probability is moderate.     

A class of semiparametric transformation models for survival data with a cured proportion

We propose a new class of semiparametric regression models based on a multiplicative frailty assumption with a discrete frailty, which may account for cured subgroup in population. The cure model framework is then recast as a problem with a transformation model. The proposed models can explain a broad range of nonproportional hazards structures along with a cured proportion. An efficient and simple algorithm based on the martingale process is developed to locate the nonparametric maximum likelihood estimator. Unlike existing expectation-maximization based methods, our approach directly maximizes a nonparametric likelihood function, and the calculation of consistent variance estimates is immediate. The proposed method is useful for resolving identifiability features embedded in semiparametric cure models. Simulation studies are presented to demonstrate the finite sample properties of the proposed method. A case study of stage III soft-tissue sarcoma is given as an illustration.     

Generation of pseudo random numbers and estimation under Cox models with time-dependent covariates

ABSTRACT

We study the method for generating pseudo random numbers under various special cases of the Cox model with time-dependent covariates when the baseline hazard function may not be constant and the random variable may equal infinity with a positive probability. During our simulation studies in computing the partial likelihood estimates, in between 3% and 20% of the time with a moderate sample size, it happens that the partial likelihood estimate of the regression coefficient is ∞ for the data from the Cox model. We propose a semi-parametric estimator as a modification for such a case. We present simulation results on the asymptotic properties of the semi-parametric estimator.     

Efficient Rank Regression with Wavelet Estimated Scores

We provide an estimate of the score function for rank regression using compactly supported wavelets. This estimate is then used to find a rank-based asymptotically efficient estimator for the slope parameter of a linear model. We also provide a consistent estimator of the asymptotic variance of the rank estimator. For related mixed models, the asymptotic relative efficiency is also discussed     

A multivariate non-parametric kernel estimator for global sensitivity analysis

The fact of estimating how a model output is influenced by the variations of inputs has become an important problematic in reliability and sensitivity analysis. This article is interested in estimating sensitivity indices useful to quantify the contribution of inputs to the variance of model output. A multivariate mixed kernel estimator is investigated since, until now, discrete and continuous inputs have been separately considered in kernel estimation of sensitivity indices. To illustrate the differences between the influence of mixed, discrete, and continuous inputs, analytical expressions of Sobol sensitivity indices are expressed in these three cases for the Ishigami test function. Besides, the performance of the mixed kernel estimator is illustrated through simulations in which the Bayesian procedure is applied for bandwidth parameter choice. An application is also realized on a real example. Finally, the use of an appropriate kernel estimator according to the type of inputs is found to be influential on the accuracy of sensitivity indices estimates.     

Fast Censored Linear Regression

Weighted log‐rank estimating function has become a standard estimation method for the censored linear regression model, or the accelerated failure time model. Well established statistically, the estimator defined as a consistent root has, however, rather poor computational properties because the estimating function is neither continuous nor, in general, monotone. We propose a computationally efficient estimator through an asymptotics‐guided Newton algorithm, in which censored quantile regression methods are tailored to yield an initial consistent estimate and a consistent derivative estimate of the limiting estimating function. We also develop fast interval estimation with a new proposal for sandwich variance estimation. The proposed estimator is asymptotically equivalent to the consistent root estimator and barely distinguishable in samples of practical size. However, computation time is typically reduced by two to three orders of magnitude for point estimation alone. Illustrations with clinical applications are provided.     

The relative efficiency of the restricted estimators in linear regression models

This paper deals with the problem of multicollinearity in a multiple linear regression model with linear equality restrictions. The restricted two parameter estimator which was proposed in case of multicollinearity satisfies the restrictions. The performance of the restricted two parameter estimator over the restricted least squares (RLS) estimator and the ordinary least squares (OLS) estimator is examined under the mean square error (MSE) matrix criterion when the restrictions are correct and not correct. The necessary and sufficient conditions for the restricted ridge regression, restricted Liu and restricted shrunken estimators, which are the special cases of the restricted two parameter estimator, to have a smaller MSE matrix than the RLS and the OLS estimators are derived when the restrictions hold true and do not hold true. Theoretical results are illustrated with numerical examples based on Webster, Gunst and Mason data and Gorman and Toman data. We conduct a final demonstration of the performance of the estimators by running a Monte Carlo simulation which shows that when the variance of the error term and the correlation between the explanatory variables are large, the restricted two parameter estimator performs better than the RLS estimator and the OLS estimator under the configurations examined.     

Multivariate regression models for discrete and continuous repeated measurements

A general class of multivariate regression models is considered for repeated measurements with discrete and continuous outcome variables. The proposed model is based on the seemingly unrelated regression model (Zellner, 1962) and an extension of the model of Park and Woolson(1992). The regression parameters of the model are consistently estimated using the two-stage least squares method. When the out come variables are multivariate normal, the two-stage estimator reduces to Zellner’s two-stage estimator. As a special case, we consider the marginal distribution described by Liang and Zeger (1986). Under this this distributional assumption, we show that the two-stage estimator has similar asymptotic properties and comparable small sample properties to Liang and Zeger's estimator. Since the proposed approach is based on the least squares method, however, any distributional assumption is not required for variables outcome variables. As a result, the proposed estimator is more robust to the marginal distribution of outcomes.     

Semiparametric regression estimation for longitudinal data in models with martingale difference error's structure

An inherent characteristic of longitudinal data is the dependence among the observations within the same subject. For exhibiting dependencies among the observations within the same subject, this paper considers a semiparametric partially linear regression model for longitudinal data based on martingale difference error's structure. We establish a strong consistency for the least squares estimator of a parametric component and the estimator of a non-parametric function under some mild conditions. A simulation study shows the performance of the proposed estimator in finite samples.     

SEMIPARAMETRIC ESTIMATION OF THE ERROR DISTRIBUTION IN MULTIVARIATE REGRESSION USING COPULAS

A semiparametric method is developed to estimate the dependence parameter and the joint distribution of the error term in the multivariate linear regression model. The nonparametric part of the method treats the marginal distributions of the error term as unknown, and estimates them using suitable empirical distribution functions. Then the dependence parameter is estimated by either maximizing a pseudolikelihood or solving an estimating equation. It is shown that this estimator is asymptotically normal, and a consistent estimator of its large sample variance is given. A simulation study shows that the proposed semiparametric method is better than the parametric ones available when the error distribution is unknown, which is almost always the case in practice. It turns out that there is no loss of asymptotic efficiency as a result of the estimation of regression parameters. An empirical example on portfolio management is used to illustrate the method.