Semiparametric estimation of the cumulative incidence function under competing risks and left-truncated sampling

In this article, we propose semiparametric methods to estimate the cumulative incidence function of two dependent competing risks for left-truncated and right-censored data. The proposed method is based on work by Huang and Wang (1995). We extend previous model by allowing for a general parametric truncation distribution and a third competing risk before recruitment. Based on work by Vardi (1989), several iterative algorithms are proposed to obtain the semiparametric estimates of cumulative incidence functions. The asymptotic properties of the semiparametric estimators are derived. Simulation results show that a semiparametric approach assuming the parametric truncation distribution is correctly specified produces estimates with smaller mean squared error than those obtained in a fully nonparametric model.     

Estimation of association parameters in copula models for bivariate left-truncated and right-censored data

We investigate the problem of estimating the association between two related survival variables when they follow a copula model and bivariate left-truncated and right-censored data are available. By expressing truncation probability as the functional of marginal survival functions, we propose a two-stage estimation procedure for estimating the parameters of Archimedean copulas. The asymptotic properties of the proposed estimators are established. Simulation studies are conducted to investigate the finite sample properties of the proposed estimators. The proposed method is applied to a bivariate RNA data.     

Nonparametric estimation of transition probabilities in a non-Markov illness–death model

In this paper we consider nonparametric estimation of transition probabilities for multi-state models. Specifically, we focus on the illness-death or disability model. The main novelty of the proposed estimators is that they do not rely on the Markov assumption, typically assumed to hold in a multi-state model. We investigate the asymptotic properties of the introduced estimators, such as their consistency and their convergence to a normal law. Simulations demonstrate that the new estimators may outperform Aalen–Johansen estimators (the classical nonparametric tool for estimating the transition probabilities) in non-Markov situation. An illustration through real data analysis is included.     

A maximum likelihood estimator for left-truncated lifetimes based on probabilistic prior information about time of occurrence

In forestry, many processes of interest are binary and they can be modeled using lifetime analysis. However, available data are often incomplete, being interval- and right-censored as well as left-truncated, which may lead to biased parameter estimates. While censoring can be easily considered in lifetime analysis, left truncation is more complicated when individual age at selection is unknown. In this study, we designed and tested a maximum likelihood estimator that deals with left truncation by taking advantage of prior knowledge about the time when the individuals enter the experiment. Whenever a model is available for predicting the time of selection, the distribution of the delayed entries can be obtained using Bayes' theorem. It is then possible to marginalize the likelihood function over the distribution of the delayed entries in the experiment to assess the joint distribution of time of selection and time to event. This estimator was tested with continuous and discrete Gompertz-distributed lifetimes. It was then compared with two other estimators: a standard one in which left truncation was not considered and a second estimator that implemented an analytical correction. Our new estimator yielded unbiased parameter estimates with empirical coverage of confidence intervals close to their nominal value. The standard estimator leaded to an overestimation of the long-term probability of survival.     

Dimension reduction in estimating equations with covariates missing at random

To estimate parameters defined by estimating equations with covariates missing at random, we consider three bias-corrected nonparametric approaches based on inverse probability weighting, regression and augmented inverse probability weighting. However, when the dimension of covariates is not low, the estimation efficiency will be affected due to the curse of dimensionality. To address this issue, we propose a two-stage estimation procedure by using the dimension-reduced kernel estimation in conjunction with bias-corrected estimating equations. We show that the resulting three estimators are asymptotically equivalent and achieve the desirable properties. The impact of dimension reduction in nonparametric estimation of parameters is also investigated. The finite-sample performance of the proposed estimators is studied through simulation, and an application to an automobile data set is also presented.     

Logspline Density Estimation under Censoring and Truncation

ABSTRACT. In this paper we consider logspline density estimation for data that may be left-truncated or right-censored. For randomly left-truncated and right-censored data the product-limit estimator is known to be a consistent estimator of the survivor function, having a faster rate of convergence than many density estimators. The product-limit estimator and B-splines are used to construct the logspline density estimate for possibly censored or truncated data. Rates of convergence are established when the log-density function is assumed to be in a Besov space. An algorithm involving a procedure similar to maximum likelihood, stepwise knot addition, and stepwise knot deletion is proposed for the estimation of the density function based upon sample data. Numerical examples are used to show the finite-sample performance of inference based on the logspline density estimation.     

Efficient inverse probability weighting method for quantile regression with nonignorable missing data

Quantitle regression (QR) is a popular approach to estimate functional relations between variables for all portions of a probability distribution. Parameter estimation in QR with missing data is one of the most challenging issues in statistics. Regression quantiles can be substantially biased when observations are subject to missingness. We study several inverse probability weighting (IPW) estimators for parameters in QR when covariates or responses are subject to missing not at random. Maximum likelihood and semiparametric likelihood methods are employed to estimate the respondent probability function. To achieve nice efficiency properties, we develop an empirical likelihood (EL) approach to QR with the auxiliary information from the calibration constraints. The proposed methods are less sensitive to misspecified missing mechanisms. Asymptotic properties of the proposed IPW estimators are shown under general settings. The efficiency gain of EL-based IPW estimator is quantified theoretically. Simulation studies and a data set on the work limitation of injured workers from Canada are used to illustrated our proposed methodologies.     

Maximum Likelihood Estimations and EM Algorithms with Length-biased Data

Length-biased sampling has been well recognized in economics, industrial reliability, etiology applications, epidemiological, genetic and cancer screening studies. Length-biased right-censored data have a unique data structure different from traditional survival data. The nonparametric and semiparametric estimations and inference methods for traditional survival data are not directly applicable for length-biased right-censored data. We propose new expectation-maximization algorithms for estimations based on full likelihoods involving infinite dimensional parameters under three settings for length-biased data: estimating nonparametric distribution function, estimating nonparametric hazard function under an increasing failure rate constraint, and jointly estimating baseline hazards function and the covariate coefficients under the Cox proportional hazards model. Extensive empirical simulation studies show that the maximum likelihood estimators perform well with moderate sample sizes and lead to more efficient estimators compared to the estimating equation approaches. The proposed estimates are also more robust to various right-censoring mechanisms. We prove the strong consistency properties of the estimators, and establish the asymptotic normality of the semi-parametric maximum likelihood estimators under the Cox model using modern empirical processes theory. We apply the proposed methods to a prevalent cohort medical study. Supplemental materials are available online.     

Conditional maximum likelihood estimation in semiparametric transformation model with LTRC data

Left-truncated data often arise in epidemiology and individual follow-up studies due to a biased sampling plan since subjects with shorter survival times tend to be excluded from the sample. Moreover, the survival time of recruited subjects are often subject to right censoring. In this article, a general class of semiparametric transformation models that include proportional hazards model and proportional odds model as special cases is studied for the analysis of left-truncated and right-censored data. We propose a conditional likelihood approach and develop the conditional maximum likelihood estimators (cMLE) for the regression parameters and cumulative hazard function of these models. The derived score equations for regression parameter and infinite-dimensional function suggest an iterative algorithm for cMLE. The cMLE is shown to be consistent and asymptotically normal. The limiting variances for the estimators can be consistently estimated using the inverse of negative Hessian matrix. Intensive simulation studies are conducted to investigate the performance of the cMLE. An application to the Channing House data is given to illustrate the methodology.     

Identity for the NPMLE in Censored Data Models

We derive an identity for nonparametric maximum likelihood estimators (NPMLE) and regularized MLEs in censored data models which expresses the standardized maximum likelihood estimator in terms of the standardized empirical process. This identity provides an effective starting point in proving both consistency and efficiency of NPMLE and regularized MLE. The identity and corresponding method for proving efficiency is illustrated for the NPMLE in the univariate right-censored data model, the regularized MLE in the current status data model and for an implicit NPMLE based on a mixture of right-censored and current status data. Furthermore, a general algorithm for estimation of the limiting variance of the NPMLE is provided. This revised version was published online in July 2006 with corrections to the Cover Date.     

Absolute error criteria for bandwidth selection in density estimation from censored data

In Kernel density estimation, a criticism of bandwidth selection techniques which minimize squared error expressions is that they perform poorly when estimating tails of probability density functions. Techniques minimizing absolute error expressions are thought to result in more uniform performance and be potentially superior. An asympotic mean absolute error expression for nonparametric kernel density estimators from right-censored data is developed here. This expression is used to obtain local and global bandwidths that are optimal in the sense that they minimize asymptotic mean absolute error and integrated asymptotic mean absolute error, respectively. These estimators are illustrated fro eight data sets from known distributions. Computer simulation results are discussed, comparing the estimation methods with squared-error-based bandwidth selection for right-censored data.     

Median regression model with left truncated and right censored data

We study the problem of fitting a heteroscedastic median regression model from left-truncated and right-censored data. It is demonstrated that the adapted Efron's self-consistency equation of McKeague et al. (2001) can be extended to analyze left-truncated and right-censored data. We evaluate the finite sample performance of the proposed estimators through simulation studies.     

A comparison study of nonparametric imputation methods

Consider estimation of a population mean of a response variable when the observations are missing at random with respect to the covariate. Two common approaches to imputing the missing values are the nonparametric regression weighting method and the Horvitz-Thompson (HT) inverse weighting approach. The regression approach includes the kernel regression imputation and the nearest neighbor imputation. The HT approach, employing inverse kernel-estimated weights, includes the basic estimator, the ratio estimator and the estimator using inverse kernel-weighted residuals. Asymptotic normality of the nearest neighbor imputation estimators is derived and compared to kernel regression imputation estimator under standard regularity conditions of the regression function and the missing pattern function. A comprehensive simulation study shows that the basic HT estimator is most sensitive to discontinuity in the missing data patterns, and the nearest neighbors estimators can be insensitive to missing data patterns unbalanced with respect to the distribution of the covariate. Empirical studies show that the nearest neighbor imputation method is most effective among these imputation methods for estimating a finite population mean and for classifying the species of the iris flower data.     

Nonparametric estimation of the cumulative intensities in an interval censored competing risks model

The nonparametric maximum likelihood estimation (NPMLE) of the distribution function from the interval censored (IC) data has been extensively studied in the extant literature. The NPMLE was also developed for the subdistribution functions in an IC competing risks model and in an illness-death model under various interval-censoring scenarios. But the important problem of estimation of the cumulative intensities (CIs) in the interval-censored models has not been considered previously. We develop the NPMLE of the CI in a simple alive/dead model and of the CIs in a competing risks model. Assuming that data are generated by a discrete and finite mixed case interval censoring mechanism we provide a discussion and the simulation study of the asymptotic properties of the NPMLEs of the CIs. In particular we show that they are asymptotically unbiased; in contrast the ad hoc estimators presented in extant literature are substantially biased. We illustrate our methods with the data from a prospective cohort study on the longevity of dental veneers.     

Maximum Penalized Likelihood Estimation in a Gamma-Frailty Model

The shared frailty models allow for unobserved heterogeneity or for statistical dependence between observed survival data. The most commonly used estimation procedure in frailty models is the EM algorithm, but this approach yields a discrete estimator of the distribution and consequently does not allow direct estimation of the hazard function. We show how maximum penalized likelihood estimation can be applied to nonparametric estimation of a continuous hazard function in a shared gamma-frailty model with right-censored and left-truncated data. We examine the problem of obtaining variance estimators for regression coefficients, the frailty parameter and baseline hazard functions. Some simulations for the proposed estimation procedure are presented. A prospective cohort (Paquid) with grouped survival data serves to illustrate the method which was used to analyze the relationship between environmental factors and the risk of dementia.     

Quantile regression methods for left-truncated and right-censored data

Left-truncated and right-censored (LTRC) data are encountered frequently due to a prevalent cohort sampling in follow-up studies. Because of the skewness of the distribution of survival time, quantile regression is a useful alternative to the Cox's proportional hazards model and the accelerated failure time model for survival analysis. In this paper, we apply the quantile regression model to LTRC data and develops an unbiased estimating equation for regression coefficients. The proposed estimation methods use the inverse probabilities of truncation and censoring weighting technique. The resulting estimator is uniformly consistent and asymptotically normal. The finite-sample performance of the proposed estimation methods is also evaluated using extensive simulation studies. Finally, analysis of real data is presented to illustrate our proposed estimation methods.     

Handling missing data by deleting completely observed records

When data are missing, analyzing records that are completely observed may cause bias or inefficiency. Existing approaches in handling missing data include likelihood, imputation and inverse probability weighting. In this paper, we propose three estimators inspired by deleting some completely observed data in the regression setting. First, we generate artificial observation indicators that are independent of outcome given the observed data and draw inferences conditioning on the artificial observation indicators. Second, we propose a closely related weighting method. The proposed weighting method has more stable weights than those of the inverse probability weighting method (Zhao, L., Lipsitz, S., 1992. Designs and analysis of two-stage studies. Statistics in Medicine 11, 769–782). Third, we improve the efficiency of the proposed weighting estimator by subtracting the projection of the estimating function onto the nuisance tangent space. When data are missing completely at random, we show that the proposed estimators have asymptotic variances smaller than or equal to the variance of the estimator obtained from using completely observed records only. Asymptotic relative efficiency computation and simulation studies indicate that the proposed weighting estimators are more efficient than the inverse probability weighting estimators under wide range of practical situations especially when the missingness proportion is large.     

The Cox–Aalen model for left-truncated and right-censored data

We analyze left-truncated and right-censored (LTRC) data using an additive-multiplicative Cox–Aalen model proposed by Scheike and Zhang (2002), which extends the Cox regression model as well as the additive Aalen model. Based on the conditional likelihood function, we derive the weighted least-squared (WLS) estimators for the regression parameters and cumulative intensity functions of the model. The estimators are shown to be consistent and asymptotically normal. A simulation study is conducted to investigate the performance of the proposed estimators.     

Presmoothed Estimation with Left-Truncated and Right-Censored Data

We propose a new method to estimate the cumulative hazard function and the corresponding distribution function of survival times under randomly left-truncated and right-censored observations (LTRC). The new estimators are based on presmoothing ideas, the estimation of the conditional expectation m of the censoring indicator. An almost sure representation for both estimators is established, from which a strong consistency rate and asymptotic normality are derived. It is shown that the presmoothed modification leads to a gain in terms of asymptotic mean squared error. This efficiency with respect to the classical estimators is also shown in a simulation study. Finally, an application to a real data set is provided.     

For censored and truncated data

In this paper we develop nonparametric methods for regression analysis when the response variable is subject to censoring and/or truncation. The development is based on a data completion princple that enables us to apply, via an iterative scheme, nonparametric regression techniques to iteratively com¬pleted data from a given sample with censored and/or truncated observations. In particular, locally weighted regression smoothers and additive regression models are extended to left-truncated and right-censored data Nonparamet¬ric regression analysis is applied to the Stanford heart transplant data, which have been analyzed by previous authors using semiparametric regression meth¬ods. and provides new insights into the relationship between expected survival time after a heart transplant and explanatory variables.