Methods for Bivariate Survival Data with Mismeasured Covariates Under an Accelerated Failure Time Model

Accelerated failure time models are useful in survival data analysis, but such models have received little attention in the context of measurement error. In this paper we discuss an accelerated failure time model for bivariate survival data with covariates subject to measurement error. In particular, methods based on the marginal and joint models are considered. Consistency and efficiency of the resultant estimators are investigated. Simulation studies are carried out to evaluate the performance of the estimators as well as the impact of ignoring the measurement error of covariates. As an illustration we apply the proposed methods to analyze a data set arising from the Busselton Health Study (Knuiman et al., 1994 Knuiman , M. W. , Cullent , K. J. , Bulsara , M. K. , Welborn , T. A. , Hobbs , M. S. T. ( 1994 ). Mortality trends, 1965 to 1989, in Busselton, the site of repeated health surveys and interventions . Austral. J. Public Health 18 : 129 – 135 . [CSA] [Crossref], [PubMed] , [Google Scholar]).     

An Alternative Estimation Method for the Semiparametric Accelerated Failure Time Mixture Cure Model

We propose an alternative estimation method for the semiparametric accelerated failure time mixture cure model by incorporating the profile likelihood into the M-step of the EM algorithm. The proposed method performs as well as the existing methods when the censoring is light and better than the existing methods when the censoring is moderate from the simulation studies. Regarding to the computational time, the proposed method runs faster than the existing methods.     

Calibration of Proportional Hazards and Accelerated Failure Time Models

Given a prognostic model based on one population, one may ask: Can this model be used to accurately predict disease in a different population? When the underlying rate of disease differs in the new population, the model must be calibrated. van Houwelingen (2000 van Houwelingen , H. ( 2000 ). Validation, calibration, revision and combination of prognostic survival models . Statistics in Medicine 19 : 3401 – 3415 .[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) considered this calibration problem focusing on proportional hazards models. We extend the validation by calibration to the log-logistic accelerated failure time model. We use calibration of proportional hazards models and log-logistic accelerated failure time models to examine whether a survival model based on the Framingham Heart Study can be applied to diverse studies around the world.     

Chi-Squared Goodness-of-Fit Tests for Parametric Accelerated Failure Time Models

We give chi-squared goodness-of fit tests for parametric regression models such as accelerated failure time, proportional hazards, generalized proportional hazards, frailty models, transformation models, and models with cross-effects of survival functions. Random right censored data are used. Choice of random grouping intervals as data functions is considered.     

Robust Smoothed Rank Estimation Methods for Accelerated Failure Time Model Allowing Clusters

Smoothed Gehan rank estimation methods are widely used in accelerated failure time (AFT) models with/without clusters. However, most methods are sensitive to outliers in the covariates. In order to solve this problem, we propose robust approaches based on the smoothed Gehan rank estimation methods for the AFT model, allowing for clusters by employing two different weight functions. Simulation studies show that the proposed methods outperform existing smoothed rank estimation methods regarding their biases and standard deviations when there are outliers in the covariates. The proposed methods are also applied to a real dataset from the “Major cardiovascular interventions” study.     

A Corrected Pseudo-score Approach for Additive Hazards Model with Longitudinal Covariates Measured with Error

In medical studies, it is often of interest to characterize the relationship between a time-to-event and covariates, not only time-independent but also time-dependent. Time-dependent covariates are generally measured intermittently and with error. Recent interests focus on the proportional hazards framework, with longitudinal data jointly modeled through a mixed effects model. However, approaches under this framework depend on the normality assumption of the error, and might encounter intractable numerical difficulties in practice. This motivates us to consider an alternative framework, that is, the additive hazards model, about which little research has been done when time-dependent covariates are measured with error. We propose a simple corrected pseudo-score approach for the regression parameters with no assumptions on the distribution of the random effects and the error beyond those for the variance structure of the latter. The estimator has an explicit form and is shown to be consistent and asymptotically normal. We illustrate the method via simulations and by application to data from an HIV clinical trial.     

Estimated Generalized Estimating Equation for Correlated Failure Time Data with Auxiliary Covariates

In this article, we study a marginal hazard model with common baseline hazard for correlated failure time data. We assume that the true covariate is measured precisely in a subset of the whole study cohort, whereas an auxiliary information for the true covariate is available for the whole cohort. We first estimate the relative risk function empirically. Then we obtain the estimator for the regression parameter by replacing the relative risk function with its estimator in a generalized estimating equation (GEE) proposed by Cai (1992 Cai , J. ( 1992 ). Generalized estimation equations for censored multivariate failure time data. Ph.D. thesis, University of Washington, Seattle, Washington . [Google Scholar]). A key feature of this method is that it is nonparametric with respect to the association between the missing covariate and the observed auxiliary covariate. The proposed estimator is shown to be consistent and asymptotically normal. Furthermore, we present a corrected Breslow-type estimator for the cumulative hazard function. Simulation studies are conducted to evaluate the proposed method.     

Semiparametric estimation method for accelerated failure time model with dependent censoring

Independent censoring is commonly assumed in survival analysis. However, it may be questionable when censoring is related to event time. We model the event and censoring time marginally through accelerated failure time models, and model their association by a known copula. An iteration algorithm is proposed to estimate the regression parameters. Simulation results show the improvement of the proposed method compared to the naive method under independent censoring. Sensitivity analysis gives the evidences that the proposed method can obtain reasonable estimates even when the forms of copula are misspecified. We illustrate its application by analyzing prostate cancer data.     

Estimating Marginal Effects in Accelerated Failure Time Models for Serial Sojourn Times Among Repeated Events

Recurrent event data are commonly encountered in longitudinal studies when events occur repeatedly over time for each study subject. An accelerated failure time (AFT) model on the sojourn time between recurrent events is considered in this article. This model assumes that the covariate effect and the subject-specific frailty are additive on the logarithm of sojourn time, and the covariate effect maintains the same over distinct episodes, while the distributions of the frailty and the random error in the model are unspecified. With the ordinal nature of recurrent events, two scale transformations of the sojourn times are derived to construct semiparametric methods of log-rank type for estimating the marginal covariate effects in the model. The proposed estimation approaches/inference procedures also can be extended to the bivariate events, which alternate themselves over time. Examples and comparisons are presented to illustrate the performance of the proposed methods.     

Semiparametric Inference Methods for General Time Scale Models

In this paper we consider semiparametric inference methods for the time scale parameters in general time scale models (Oakes, 1995, Duchesne and Lawless, 2000). We use the results of Robins and Tsiatis (1992) and Lin and Ying (1995) to derive a rank-based estimator that is more efficient and robust than the traditional minimum coefficient of variation (min CV) estimator of Kordonsky and Gerstbakh (1993) for many underlying models. Moreover, our estimator can readily handle censored samples, which is not the case with the min CV method.     

Semiparametric Regression Models with Applications to Scoring: A Review

Semiparametric regression models have been proposed in the econometric literature as a trade-off between the simple but easily implementable and interpretable parametric models and the flexible but structure free smoothing techniques. Some semiparametric models for binary response with possible application to scoring data are reviewed: single-index models, generalized partially linear models, generalized partially linear single-index models, and multiple-index models. All these models are extensions of the classical logistic regression.     

Locally Efficient Semiparametric Estimators for Proportional Hazards Models with Measurement Error

We propose a new class of semiparametric estimators for proportional hazards models in the presence of measurement error in the covariates, where the baseline hazard function, the hazard function for the censoring time, and the distribution of the true covariates are considered as unknown infinite dimensional parameters. We estimate the model components by solving estimating equations based on the semiparametric efficient scores under a sequence of restricted models where the logarithm of the hazard functions are approximated by reduced rank regression splines. The proposed estimators are locally efficient in the sense that the estimators are semiparametrically efficient if the distribution of the error‐prone covariates is specified correctly and are still consistent and asymptotically normal if the distribution is misspecified. Our simulation studies show that the proposed estimators have smaller biases and variances than competing methods. We further illustrate the new method with a real application in an HIV clinical trial.     

A Semiparametric Estimation Approach for Linear Mixed Models

Maximum likelihood approach is the most frequently employed approach for the inference of linear mixed models. However, it relies on the normal distributional assumption of the random effects and the within-subject errors, and it is lack of robustness against outliers. This article proposes a semiparametric estimation approach for linear mixed models. This approach is based on the first two marginal moments of the response variable, and does not require any parametric distributional assumptions of random effects or error terms. The consistency and asymptotically normality of the estimator are derived under fairly general conditions. In addition, we show that the proposed estimator has a bounded influence function and a redescending property so it is robust to outliers. The methodology is illustrated through an application to the famed Framingham cholesterol data. The finite sample behavior and the robustness properties of the proposed estimator are evaluated through extensive simulation studies.     

Variable Selection for Semiparametric Varying Coefficient Partially Linear Errors-in-Variables (EV) Model with Missing Response

This paper focuses on the variable selection for semiparametric varying coefficient partially linear model when the covariates are measured with additive errors and the response is missing. An adaptive lasso estimator and the smoothly clipped absolute deviation estimator as a comparison for the parameters are proposed. With the proper selection of regularization parameter, the sampling properties including the consistency of the two procedures and the oracle properties are established. Furthermore, the algorithms and corresponding standard error formulas are discussed. A simulation study is carried out to assess the finite sample performance of the proposed methods.     

A Class of Weighted Estimating Equations for Semiparametric Transformation Models with Missing Covariates

In survival analysis, covariate measurements often contain missing observations; ignoring this feature can lead to invalid inference. We propose a class of weighted estimating equations for right‐censored data with missing covariates under semiparametric transformation models. Time‐specific and subject‐specific weights are accommodated in the formulation of the weighted estimating equations. We establish unified results for estimating missingness probabilities that cover both parametric and non‐parametric modelling schemes. To improve estimation efficiency, the weighted estimating equations are augmented by a new set of unbiased estimating equations. The resultant estimator has the so‐called ‘double robustness’ property and is optimal within a class of consistent estimators.     

A Class of Semiparametric Transformation Models for Doubly Censored Failure Time Data

Doubly censored failure time data occur in many areas including demographical studies, epidemiology studies, medical studies and tumorigenicity experiments, and correspondingly some inference procedures have been developed in the literature (Biometrika, 91, 2004, 277; Comput. Statist. Data Anal., 57, 2013, 41; J. Comput. Graph. Statist., 13, 2004, 123). In this paper, we discuss regression analysis of such data under a class of flexible semiparametric transformation models, which includes some commonly used models for doubly censored data as special cases. For inference, the non‐parametric maximum likelihood estimation will be developed and in particular, we will present a novel expectation–maximization algorithm with the use of subject‐specific independent Poisson variables. In addition, the asymptotic properties of the proposed estimators are established and an extensive simulation study suggests that the proposed methodology works well for practical situations. The method is applied to an AIDS study.     

Weighted Estimator for the Linear Transformation Models with Multivariate Failure Time Data

In this article, a simple and efficient weighted method is proposed to improve the estimation efficiency for the linear transformation models with multivariate failure time data. Asymptotic properties of the estimators with a closed-form variance-covariance matrix are established. In addition, a goodness-of-fit test is developed to evaluate the adequacy of the model. The performance of proposed method and the comparison on the efficiency between the proposed method and the working independence method (Lu, 2005) are conducted in finite-sample situation by simulation studies. Finally a real data set from the Busselton Population Health Surveys is illustrated to validate the proposed methodology. The related proofs of the theorems are given in the Appendix.     

A Profile Conditional Likelihood Approach for the Semiparametric Transformation Regression Model with Missing Covariates

We propose a profile conditional likelihood approach to handle missing covariates in the general semiparametric transformation regression model. The method estimates the marginal survival function by the Kaplan-Meier estimator, and then estimates the parameters of the survival model and the covariate distribution from a conditional likelihood, substituting the Kaplan-Meier estimator for the marginal survival function in the conditional likelihood. This method is simpler than full maximum likelihood approaches, and yields consistent and asymptotically normally distributed estimator of the regression parameter when censoring is independent of the covariates. The estimator demonstrates very high relative efficiency in simulations. When compared with complete-case analysis, the proposed estimator can be more efficient when the missing data are missing completely at random and can correct bias when the missing data are missing at random. The potential application of the proposed method to the generalized probit model with missing continuous covariates is also outlined.     

Objective Priors for Parameters in a Normal Linear Regression with Measurement Error

We investigate certain objective priors for the parameters in a normal linear regression models with one of the explanatory variables subject to measurement error. We first show that the use of the standard non informative prior for normal linear regression without measurement error leads to an improper posterior in the measurement error model. We then derive the Jeffreys prior and reference priors, and show that they lead to proper posteriors. We use simulation study to compare the frequentist performance of the estimates derived using these priors, and the MLE.     

Empirical Bayes Estimation of Small Area Means under a Nested Error Linear Regression Model with Measurement Errors in the Covariates

Abstract.  Previously, small area estimation under a nested error linear regression model was studied with area level covariates subject to measurement error. However, the information on observed covariates was not used in finding the Bayes predictor of a small area mean. In this paper, we first derive the fully efficient Bayes predictor by utilizing all the available data. We then estimate the regression and variance component parameters in the model to get an empirical Bayes (EB) predictor and show that the EB predictor is asymptotically optimal. In addition, we employ the jackknife method to obtain an estimator of mean squared prediction error (MSPE) of the EB predictor. Finally, we report the results of a simulation study on the performance of our EB predictor and associated jackknife MSPE estimators. Our results show that the proposed EB predictor can lead to significant gain in efficiency over the previously proposed EB predictor.