A study of regression calibration in a partially observed stratified Cox model

Regression calibration is a simple method for estimating regression models when covariate data are missing for some study subjects. It consists in replacing an unobserved covariate by an estimator of its conditional expectation given available covariates. Regression calibration has recently been investigated in various regression models such as the linear, generalized linear, and proportional hazards models. The aim of this paper is to investigate the appropriateness of this method for estimating the stratified Cox regression model with missing values of the covariate defining the strata. Despite its practical relevance, this problem has not yet been discussed in the literature. Asymptotic distribution theory is developed for the regression calibration estimator in this setting. A simulation study is also conducted to investigate the properties of this estimator.     

A Generalization of Turnbull’s Estimator for Interval-Censored and Doubly Truncated Data

Nonparametric estimates of the conditional distribution of a response variable given a covariate are important for data exploration purposes. In this article, we propose a nonparametric estimator of the conditional distribution function in the case where the response variable is subject to interval censoring and double truncation. Using the approach of Dehghan and Duchesne (2011), the proposed method consists in adding weights that depend on the covariate value in the self-consistency equation of Turnbull (1976), which results in a nonparametric estimator. We demonstrate by simulation that the estimator, bootstrap variance estimation and bandwidth selection all perform well in finite samples.     

Uniform strong convergence results for the conditional kaplan-meier estimator and its quantiles

We consider a fixed design model in which the responses are possibly right censored. The aim of this paper is to establish some important almost sure convergence properties of the Kaplan-Meier type estimator for the lifetime distribution at a given covariate value. We also consider the corresponding quantile estimator and obtain a modulus of continuity result. Our rates of uniform strong convergence are obtained via exponential probability bounds.     

A generalization of Turnbull’s estimator for nonparametric estimation of the conditional survival function with interval-censored data

Simple nonparametric estimates of the conditional distribution of a response variable given a covariate are often useful for data exploration purposes or to help with the specification or validation of a parametric or semi-parametric regression model. In this paper we propose such an estimator in the case where the response variable is interval-censored and the covariate is continuous. Our approach consists in adding weights that depend on the covariate value in the self-consistency equation proposed by Turnbull (J R Stat Soc Ser B 38:290–295, 1976), which results in an estimator that is no more difficult to implement than Turnbull’s estimator itself. We show the convergence of our algorithm and that our estimator reduces to the generalized Kaplan–Meier estimator (Beran, Nonparametric regression with randomly censored survival data, 1981) when the data are either complete or right-censored. We demonstrate by simulation that the estimator, bootstrap variance estimation and bandwidth selection (by rule of thumb or cross-validation) all perform well in finite samples. We illustrate the method by applying it to a dataset from a study on the incidence of HIV in a group of female sex workers from Kinshasa.     

Local Estimation of the Conditional Stable Tail Dependence Function

We consider the local estimation of the stable tail dependence function when a random covariate is observed together with the variables of main interest. Our estimator is a weighted version of the empirical estimator adapted to the covariate framework. We provide the main asymptotic properties of our estimator, when properly normalized, in particular the convergence of the empirical process towards a tight centred Gaussian process. The finite sample performance of our estimator is illustrated on a small simulation study and on a dataset of air pollution measurements.     

Product-limit Estimators and Cox Regression with Missing Censoring Information

The Kaplan–Meier estimator of a survival function requires that the censoring indicator is always observed. A method of survival function estimation is developed when the censoring indicators are missing completely at random (MCAR). The resulting estimator is a smooth functional of the Nelson–Aalen estimators of certain cumulative transition intensities. The asymptotic properties of this estimator are derived. A simulation study shows that the proposed estimator has greater efficiency than competing MCAR-based estimators. The approach is extended to the Cox model setting for the estimation of a conditional survival function given a covariate.     

Estimation and Prediction in the Presence of Spatial Confounding for Spatial Linear Models

In studies that produce data with spatial structure, it is common that covariates of interest vary spatially in addition to the error. Because of this, the error and covariate are often correlated. When this occurs, it is difficult to distinguish the covariate effect from residual spatial variation. In an i.i.d. normal error setting, it is well known that this type of correlation produces biased coefficient estimates, but predictions remain unbiased. In a spatial setting, recent studies have shown that coefficient estimates remain biased, but spatial prediction has not been addressed. The purpose of this paper is to provide a more detailed study of coefficient estimation from spatial models when covariate and error are correlated and then begin a formal study regarding spatial prediction. This is carried out by investigating properties of the generalized least squares estimator and the best linear unbiased predictor when a spatial random effect and a covariate are jointly modelled. Under this setup, we demonstrate that the mean squared prediction error is possibly reduced when covariate and error are correlated.     

Correlation curve estimation for multiplicative distortion measurement errors data

A correlation curve measures the strength of the association between two variables locally at different values of covariate. This paper studies how to estimate the correlation curve under the multiplicative distortion measurement errors setting. The unobservable variables are both distorted in a multiplicative fashion by an observed confounding variable. We obtain asymptotic normality results for the estimated correlation curve. We conduct Monte Carlo simulation experiments to examine the performance of the proposed estimator. The estimated correlation curve is applied to analyze a real dataset for an illustration.     

Proportional hazards estimate of the conditional survival function

We introduce a new estimator of the conditional survival function given some subset of the covariate values under a proportional hazards regression. The new estimate does not require estimating the base-line cumulative hazard function. An estimate of the variance is given and is easy to compute, involving only those quantities that are routinely calculated in a Cox model analysis. The asymptotic normality of the new estimate is shown by using a central limit theorem for Kaplan–Meier integrals. We indicate the straightforward extension of the estimation procedure under models with multiplicative relative risks, including non-proportional hazards, and to stratified and frailty models. The estimator is applied to a gastric cancer study where it is of interest to predict patients' survival based only on measurements obtained before surgery, the time at which the most important prognostic variable, stage, becomes known.     

Auxiliary covariate in additive hazards regression for survival data

We consider the additive hazards regression analysis by utilising auxiliary covariate information to improve the efficiency of the statistical inference when the primary covariate is ascertained only for a randomly selected subsample. We construct a martingale-based estimating equation for the regression parameter and establish the asymptotic consistency and normality of the resultant estimator. Simulation study shows that our proposed method can improve the efficiency compared with the estimator which discards the auxiliary covariate information. A real example is also analysed as an illustration.     

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.     

Nonstationary nonlinear quantile regression

This study examines estimation and inference based on quantile regression for parametric nonlinear models with an integrated time series covariate. We first derive the limiting distribution of the nonlinear quantile regression estimator and then consider testing for parameter restrictions, when the regression function is specified as an asymptotically homogeneous function. We also study linear-in-parameter regression models when the regression function is given by integrable regression functions as well as asymptotically homogeneous regression functions. We, furthermore, propose a fully modified estimator to reduce the bias in the original estimator under a certain set of conditions. Finally, simulation studies show that the estimators behave well, especially when the regression error term has a fat-tailed distribution.     

Estimation of odds of concordance based on the Aalen additive model

The Cox regression model is often used when analyzing survival data as it provides a convenient way of summarizing covariate effects in terms of relative risks. The proportional hazards assumption may not hold, however. A typical violation of the assumption is time-changing covariate effects. Under such scenarios one may use more flexible models but the results from such models may be complicated to communicate and it is desirable to have simple measures of a treatment effect, say. In this paper we focus on the odds-of-concordance measure that was recently studied by Schemper et al. (Stat Med 28:2473?C2489, 2009). They suggested to estimate this measure using weighted Cox regression (WCR). Although WCR may work in many scenarios no formal proof can be established. We suggest an alternative estimator of the odds-of-concordance measure based on the Aalen additive hazards model. In contrast to the WCR, one may derive the large sample properties for this estimator making formal inference possible. The estimator also allows for additional covariate effects.     

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.     

Likelihood methods for missing covariate data in highly stratified studies

Summary. The paper considers canonical link generalized linear models with stratum-specific nuisance intercepts and missing covariate data. This family includes the conditional logistic regression model. Existing methods for this problem, each of which uses a conditioning argu- ment to eliminate the nuisance intercept, model either the missing covariate data or the missingness process. The paper compares these methods under a common likelihood framework. The semiparametric efficient estimator is identified, and a new estimator, which reduces dependence on the model for the missing covariate, is proposed. A simulation study compares the methods with respect to efficiency and robustness to model misspecification.     

Three estimators for the poisson regression model with measurement errors

We consider two consistent estimators for the parameters of the linear predictor in the Poisson regression model, where the covariate is measured with errors. The measurement errors are assumed to be normally distributed with known error variance σ _u ² . The SQS estimator, based on a conditional mean-variance model, takes the distribution of the latent covariate into account, and this is here assumed to be a normal distribution. The CS estimator, based on a corrected score function, does not use the distribution of the latent covariate. Nevertheless, for small σ _u ² , both estimators have identical asymptotic covariance matrices up to the order of σ _u ² . We also compare the consistent estimators to the naive estimator, which is based on replacing the latent covariate with its (erroneously) measured counterpart. The naive estimator is biased, but has a smaller covariance matrix than the consistent estimators (at least up to the order of σ _u ² ).     

Finite-Sample Properties of the Maximum Likelihood Estimator for the Poisson Regression Model With Random Covariates

We examine the small-sample behaviour of the maximum likelihood estimator for the Poisson regression model with random covariates. Analytic expressions for the second-order bias and mean squared error are derived, and we undertake some numerical evaluations to illustrate these results for the single covariate case. The properties of the bias-adjusted maximum likelihood estimator are investigated in a Monte Carlo experiment. Correcting the estimator for its second-order bias is found to be effective in the cases considered, and we recommend its use when the Poisson regression model is estimated by maximum likelihood with small samples.     

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.     

Penalized angular regression for personalized predictions

Personalization is becoming an important aspect of many predictive applications. We introduce a penalized regression method which inherently implements personalization. Personalized angle (PAN) regression constructs regression coefficients that are specific to the covariate vector for which one is producing a prediction, thus personalizing the regression model itself. This is achieved by penalizing the normalized prediction for a given covariate vector. The method therefore penalizes the normalized regression coefficients, or the angles of the regression coefficients in a hyperspherical parametrization, introducing a new angle-based class of penalties. PAN hence combines two novel concepts: penalizing the normalized coefficients and personalization. For an orthogonal design matrix, we show that the PAN estimator is the solution to a low-dimensional eigenvector equation. Based on the hyperspherical parametrization, we construct an efficient algorithm to calculate the PAN estimator. We propose a parametric bootstrap procedure for selecting the tuning parameter, and simulations show that PAN regression can outperform ordinary least squares, ridge regression and other penalized regression methods in terms of prediction error. Finally, we demonstrate the method in a medical application.     

On Confounding, Prediction and Efficiency in the Analysis of Longitudinal and Cross-sectional Clustered Data

Abstract.  In the analysis of clustered and/or longitudinal data, it is usually desirable to ignore covariate information for other cluster members as well as future covariate information when predicting outcome for a given subject at a given time. This can be accomplished through con-ditional mean models which merely condition on the considered subject's covariate history at each time. Pepe & Anderson (Commun. Stat. Simul. Comput. 23, 1994 , 939) have shown that ordinary generalized estimating equations may yield biased estimates for the parameters in such models, but that valid inferences can be guaranteed by using a diagonal working covariance matrix in the equations. In this paper, we provide insight into the nature of this problem by uncovering substantive data-generating mechanisms under which such biases will result. We then propose a class of asymptotically unbiased estimators for the parameters indexing the suggested conditional mean models. In addition, we provide a representation for the efficient estimator in our class, which attains the semi-parametric efficiency bound under the model, along with an efficient algorithm for calculating it. This algorithm is easy to apply and may realize major efficiency improvements as demonstrated through simulation studies. The results suggest ways to improve the efficiency of inverse-probability-of-treatment estimators which adjust for time-varying confounding, and are used to estimate the effect of discontinuing highly active anti-retroviral therapy (HAART) on viral load in HIV-infected patients.