Buckley–James Type Estimator for Censored Data with Covariates Missing by Design

Abstract. The Buckley–James estimator (BJE) is a well‐known estimator for linear regression models with censored data. Ritov has generalized the BJE to a semiparametric setting and demonstrated that his class of Buckley–James type estimators is asymptotically equivalent to the class of rank‐based estimators proposed by Tsiatis. In this article, we revisit such relationship in censored data with covariates missing by design. By exploring a similar relationship between our proposed class of Buckley–James type estimating functions to the class of rank‐based estimating functions recently generalized by Nan, Kalbfleisch and Yu, we establish asymptotic properties of our proposed estimators. We also conduct numerical studies to compare asymptotic efficiencies from various estimators.     

Proportional hazards model for competing risks data with missing cause of failure

We consider the semiparametric proportional hazards model for the cause-specific hazard function in analysis of competing risks data with missing cause of failure. The inverse probability weighted equation and augmented inverse probability weighted equation are proposed for estimating the regression parameters in the model, and their theoretical properties are established for inference. Simulation studies demonstrate that the augmented inverse probability weighted estimator is doubly robust and the proposed method is appropriate for practical use. The simulations also compare the proposed estimators with the multiple imputation estimator of Lu and Tsiatis (2001). The application of the proposed method is illustrated using data from a bone marrow transplant study.     

Rank Regression Analysis of Multivariate Failure Time Data Based on Marginal Linear Models

Abstract.  Multivariate failure time data arises when each study subject can potentially ex-perience several types of failures or recurrences of a certain phenomenon, or when failure times are sampled in clusters. We formulate the marginal distributions of such multivariate data with semiparametric accelerated failure time models (i.e. linear regression models for log-transformed failure times with arbitrary error distributions) while leaving the dependence structures for related failure times completely unspecified. We develop rank-based monotone estimating functions for the regression parameters of these marginal models based on right-censored observations. The estimating equations can be easily solved via linear programming. The resultant estimators are consistent and asymptotically normal. The limiting covariance matrices can be readily estimated by a novel resampling approach, which does not involve non-parametric density estimation or evaluation of numerical derivatives. The proposed estimators represent consistent roots to the potentially non-monotone estimating equations based on weighted log-rank statistics. Simulation studies show that the new inference procedures perform well in small samples. Illustrations with real medical data are provided.     

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.     

A comparison of doubly robust estimators of the mean with missing data

We consider data with a continuous outcome that is missing at random and a fully observed set of covariates. We compare by simulation a variety of doubly-robust (DR) estimators for estimating the mean of the outcome. An estimator is DR if it is consistent when either the regression model for the mean function or the propensity to respond is correctly specified. Performance of different methods is compared in terms of root mean squared error of the estimates and width and coverage of confidence intervals or posterior credibility intervals in repeated samples. Overall, the DR methods tended to yield better inference than the incorrect model when either the propensity or mean model is correctly specified, but were less successful for small sample sizes, where the asymptotic DR property is less consequential. Two methods tended to outperform the other DR methods: penalized spline of propensity prediction [Little RJA, An H. Robust likelihood-based analysis of multivariate data with missing values. Statist Sinica. 2004;14:949–968] and the robust method proposed in [Cao W, Tsiatis AA, Davidian M. Improving efficiency and robustness of the doubly robust estimator for a population mean with incomplete data. Biometrika. 2009;96:723–734].     

The Weibull Marshall–Olkin family: Regression model and application to censored data

We introduce a new class of distributions called the Weibull Marshall–Olkin-G family. We obtain some of its mathematical properties. The special models of this family provide bathtub-shaped, decreasing-increasing, increasing-decreasing-increasing, decreasing-increasing-decreasing, monotone, unimodal and bimodal hazard functions. The maximum likelihood method is adopted for estimating the model parameters. We assess the performance of the maximum likelihood estimators by means of two simulation studies. We also propose a new family of linear regression models for censored and uncensored data. The flexibility and importance of the proposed models are illustrated by means of three real data sets.     

Marginal regression models with a time to event outcome and discrete multiple source predictors

Information from multiple informants is frequently used to assess psychopathology. We consider marginal regression models with multiple informants as discrete predictors and a time to event outcome. We fit these models to data from the Stirling County Study; specifically, the models predict mortality from self report of psychiatric disorders and also predict mortality from physician report of psychiatric disorders. Previously, Horton et al. found little relationship between self and physician reports of psychopathology, but that the relationship of self report of psychopathology with mortality was similar to that of physician report of psychopathology with mortality. Generalized estimating equations (GEE) have been used to fit marginal models with multiple informant covariates; here we develop a maximum likelihood (ML) approach and show how it relates to the GEE approach. In a simple setting using a saturated model, the ML approach can be constructed to provide estimates that match those found using GEE. We extend the ML technique to consider multiple informant predictors with missingness and compare the method to using inverse probability weighted (IPW) GEE. Our simulation study illustrates that IPW GEE loses little efficiency compared with ML in the presence of monotone missingness. Our example data has non-monotone missingness; in this case, ML offers a modest decrease in variance compared with IPW GEE, particularly for estimating covariates in the marginal models. In more general settings, e.g., categorical predictors and piecewise exponential models, the likelihood parameters from the ML technique do not have the same interpretation as the GEE. Thus, the GEE is recommended to fit marginal models for its flexibility, ease of interpretation and comparable efficiency to ML in the presence of missing data.     

The beta modified Weibull distribution

A five-parameter distribution so-called the beta modified Weibull distribution is defined and studied. The new distribution contains, as special submodels, several important distributions discussed in the literature, such as the generalized modified Weibull, beta Weibull, exponentiated Weibull, beta exponential, modified Weibull and Weibull distributions, among others. The new distribution can be used effectively in the analysis of survival data since it accommodates monotone, unimodal and bathtub-shaped hazard functions. We derive the moments and examine the order statistics and their moments. We propose the method of maximum likelihood for estimating the model parameters and obtain the observed information matrix. A real data set is used to illustrate the importance and flexibility of the new distribution.     

Estimation of conditional cumulative incidence functions under generalized semiparametric regression models with missing covariates,with application to analysis of biomarker correlates in vaccine trials

This article presents generalized semiparametric regression models for conditional cumulative incidence functions with competing risks data when covariates are missing by sampling design or happenstance. A doubly robust augmented inverse probability weighted (AIPW) complete-case approach to estimation and inference is investigated. This approach modifies IPW complete-case estimating equations by exploiting the key features in the relationship between the missing covariates and the phase-one data to improve efficiency. An iterative numerical procedure is derived to solve the nonlinear estimating equations. The asymptotic properties of the proposed estimators are established. A simulation study examining the finite-sample performances of the proposed estimators shows that the AIPW estimators are more efficient than the IPW estimators. The developed method is applied to the RV144 HIV-1 vaccine efficacy trial to investigate vaccine-induced IgG binding antibodies to HIV-1 as correlates of acquisition of HIV-1 infection while taking account of whether the HIV-1 sequences are near or far from the HIV-1 sequences represented in the vaccine construct.     

Fast accelerated failure time modeling for case-cohort data

Semiparametric accelerated failure time (AFT) models directly relate the expected failure times to covariates and are a useful alternative to models that work on the hazard function or the survival function. For case-cohort data, much less development has been done with AFT models. In addition to the missing covariates outside of the sub-cohort in controls, challenges from AFT model inferences with full cohort are retained. The regression parameter estimator is hard to compute because the most widely used rank-based estimating equations are not smooth. Further, its variance depends on the unspecified error distribution, and most methods rely on computationally intensive bootstrap to estimate it. We propose fast rank-based inference procedures for AFT models, applying recent methodological advances to the context of case-cohort data. Parameters are estimated with an induced smoothing approach that smooths the estimating functions and facilitates the numerical solution. Variance estimators are obtained through efficient resampling methods for nonsmooth estimating functions that avoids full blown bootstrap. Simulation studies suggest that the recommended procedure provides fast and valid inferences among several competing procedures. Application to a tumor study demonstrates the utility of the proposed method in routine data analysis.     

Bayesian analysis for monotone hazard ratio

We propose a Bayesian approach for estimating the hazard functions under the constraint of a monotone hazard ratio. We construct a model for the monotone hazard ratio utilizing the Cox’s proportional hazards model with a monotone time-dependent coefficient. To reduce computational complexity, we use a signed gamma process prior for the time-dependent coefficient and the Bayesian bootstrap prior for the baseline hazard function. We develope an efficient MCMC algorithm and illustrate the proposed method on simulated and real data sets.     

A doubly robust goodness-of-fit test in general linear models with missing covariates

In this article, we utilize a form of general linear model where missing data occurred randomly on the covariates. We propose a test function based on the doubly robust method to investigate goodness of fit of the model. For this aim, kernel method is used to estimate unknown functions under estimating equation method. Doubly robustness and asymptotic properties of the test function are obtained under local and alternative hypotheses. Furthermore, we investigate the power of the proposed test function by means of some simulation studies and finally we apply this method on analyzing a real dataset.     

A new algorithm to estimate monotone nonparametric link functions and a comparison with parametric approach

The generalized linear model (GLM) is a class of regression models where the means of the response variables and the linear predictors are joined through a link function. Standard GLM assumes the link function is fixed, and one can form more flexible GLM by either estimating the flexible link function from a parametric family of link functions or estimating it nonparametically. In this paper, we propose a new algorithm that uses P-spline for nonparametrically estimating the link function which is guaranteed to be monotone. It is equivalent to fit the generalized single index model with monotonicity constraint. We also conduct extensive simulation studies to compare our nonparametric approach for estimating link function with various parametric approaches, including traditional logit, probit and robit link functions, and two recently developed link functions, the generalized extreme value link and the symmetric power logit link. The simulation study shows that the link function estimated nonparametrically by our proposed algorithm performs well under a wide range of different true link functions and outperforms parametric approaches when they are misspecified. A real data example is used to illustrate the results.     

Estimation and variable selection in single-index composite quantile regression

In this article, a new composite quantile regression estimation approach is proposed for estimating the parametric part of single-index model. We use local linear composite quantile regression (CQR) for estimating the nonparametric part of single-index model (SIM) when the error distribution is symmetrical. The weighted local linear CQR is proposed for estimating the nonparametric part of SIM when the error distribution is asymmetrical. Moreover, a new variable selection procedure is proposed for SIM. Under some regularity conditions, we establish the large sample properties of the proposed estimators. Simulation studies and a real data analysis are presented to illustrate the behavior of the proposed estimators.     

Rank repeated measures analysis of covariance

When analyzing a response variable at the presence of both factors and covariates, with potentially correlated responses and violated assumptions of the normal residual or the linear relationship between the response and the covariates, rank-based tests can be an option for inferential procedures instead of the parametric repeated measures analysis of covariance (ANCOVA) models. This article derives a rank-based method for multi-way ANCOVA models with correlated responses. The generalized estimating equations (GEE) technique is employed to construct the proposed rank tests. Asymptotic properties of the proposed tests are derived. Simulation studies confirmed the performance of the proposed tests.     

The exponentiated generalized gamma distribution with application to lifetime data

A four-parameter extension of the generalized gamma distribution capable of modelling a bathtub-shaped hazard rate function is defined and studied. The beauty and importance of this distribution lies in its ability to model monotone and non-monotone failure rate functions, which are quite common in lifetime data analysis and reliability. The new distribution has a number of well-known lifetime special sub-models, such as the exponentiated Weibull, exponentiated generalized half-normal, exponentiated gamma and generalized Rayleigh, among others. We derive two infinite sum representations for its moments. We calculate the density of the order statistics and two expansions for their moments. The method of maximum likelihood is used for estimating the model parameters and the observed information matrix is obtained. Finally, a real data set from the medical area is analysed.     

ROBUST NON-PARAMETRIC ESTIMATION OF GENOTYPE–PHENOTYPE RELATIONSHIPS IN HUMAN PEDIGREES

Non‐parametric estimation of functional relationships is an important part of data analysis, particularly in the exploratory stages. This paper considers non‐parametric estimation of the mean functions in family studies using weighted robust estimating equations while retaining a fully parametric model for the covariance structure. The proposed procedure allows an exploratory examination of complex pedigree data that is an invaluable aid in determining appropriate models. This is illustrated by an examination of the relationship between IQ and the level of a particular protein in individuals collected as part of a large family study.     

On Semiparametric EV Models with Serially Correlated Errors in Both Regression Models and Mismeasured Covariates

Abstract.  We consider inference for a semiparametric regression model where some covariates are measured with errors, and the errors in both the regression model and the mismeasured covariates are serially correlated. We propose a weighted estimating equations-based estimator (WEEBE) for the regression coefficients. We show that the WEEBE is asymptotically more efficient than the estimators that neglect the serial correlations. This is an interesting new finding since earlier results in the statistical literature have shown that the weighted estimation is not as efficient as the unweighted estimation when the measurement errors and serially correlated errors of the regression models exist simultaneously (Biometrics, 49, 1993, 1262; Technometrics, 42, 2000, 137). The proposed WEEBE does not require undersmoothing the regressor functions in order to make it attain the root- n consistency. Simulation studies show that the proposed estimator has nice finite sample properties. A real data set is used to illustrate the proposed method.     

Nonparametric tests for left-truncated and interval-censored data

This paper considers two-sample nonparametric comparison of survival function when data are subject to left truncation and interval censoring. We propose a class of rank-based tests, which are generalization of weighted log-rank tests for right-censored data. Simulation studies indicate that the proposed tests are appropriate for practical use.     

An R package for model fitting,model selection and the simulation for longitudinal data with dropout missingness

Abstract

Missing data arise frequently in clinical and epidemiological fields, in particular in longitudinal studies. This paper describes the core features of an R package wgeesel, which implements marginal model fitting (i.e., weighted generalized estimating equations, WGEE; doubly robust GEE) for longitudinal data with dropouts under the assumption of missing at random. More importantly, this package comprehensively provide existing information criteria for WGEE model selection on marginal mean or correlation structures. Also, it can serve as a valuable tool for simulating longitudinal data with missing outcomes. Lastly, a real data example and simulations are presented to illustrate and validate our package.