Double robust estimation in longitudinal marginal structural models

In this article we consider estimation of causal parameters in a marginal structural model for the discrete intensity of the treatment specific counting process (e.g. hazard of a treatment specific survival time) based on longitudinal observational data on treatment, covariates and survival. We define three estimators: the inverse probability of treatment weighted (IPTW) estimator, the maximum likelihood estimator (MLE), and a double robust (DR) estimator. The DR estimator is obtained by following a general methodology for constructing double robust estimating functions in censored data models as described in van der Laan and Robins (Unified Methods for Censored Longitudinal Data and Causality, 2002). The double-robust estimator is consistent and asymptotically linear when either the treatment mechanism or the partial likelihood of the observed data is consistently estimated. We illustrate the superiority of the DR estimator relative to the IPTW and ML estimators in a simulation study. The proposed methodology is also applied to estimate the causal effect of exercise on physical functioning in a longitudinal study of seniors in Sonoma County.     

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.     

A protective estimator for longitudinal binary data subject to non-ignorable non-monotone missingness

Summary.  In longitudinal studies missing data are the rule not the exception. We consider the analysis of longitudinal binary data with non-monotone missingness that is thought to be non-ignorable. In this setting a full likelihood approach is complicated algebraically and can be computationally prohibitive when there are many measurement occasions. We propose a 'protective' estimator that assumes that the probability that a response is missing at any occasion depends, in a completely unspecified way, on the value of that variable alone. Relying on this 'protectiveness' assumption, we describe a pseudolikelihood estimator of the regression parameters under non-ignorable missingness, without having to model the missing data mechanism directly. The method proposed is applied to CD4 cell count data from two longitudinal clinical trials of patients infected with the human immunodeficiency virus.     

Adjusted Hazard Rate Estimator Based on a Known Censoring Probability

In most reliability studies involving censoring, one assumes that censoring probabilities are unknown. We derive a nonparametric estimator for the survival function when information regarding censoring frequency is available. The estimator is constructed by adjusting the Nelson–Aalen estimator to incorporate censoring information. Our results indicate significant improvements can be achieved if available information regarding censoring is used. We compare this model to the Koziol–Green model, which is also based on a form of proportional hazards for the lifetime and censoring distributions. Two examples of survival data help to illustrate the differences in the estimation techniques.     

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.     

Optimal Estimator for Logistic Model with Distribution‐free Random Intercept

Logistic models with a random intercept are prevalent in medical and social research where clustered and longitudinal data are often collected. Traditionally, the random intercept in these models is assumed to follow some parametric distribution such as the normal distribution. However, such an assumption inevitably raises concerns about model misspecification and misleading inference conclusions, especially when there is dependence between the random intercept and model covariates. To protect against such issues, we use a semiparametric approach to develop a computationally simple and consistent estimator where the random intercept is distribution‐free. The estimator is revealed to be optimal and achieve the efficiency bound without the need to postulate or estimate any latent variable distributions. We further characterize other general mixed models where such an optimal estimator exists.     

Weak Instrumental Variables Models for Longitudinal Data

This article considers the estimation and testing of a within-group two-stage least squares (TSLS) estimator for instruments with varying degrees of weakness in a longitudinal (panel) data model. We show that adding the repeated cross-sectional information into a regression model can improve the estimation in weak instruments. Moreover, the consistency and limiting distribution of the TSLS estimator are established when both N and T tend to infinity. Some asymptotically pivotal tests are extended to a longitudinal data model and their asymptotic properties are examined. A Monte Carlo experiment is conducted to evaluate the finite sample performance of the proposed estimators.     

The estimation of treatment effect for the censored bivariate data under the univariate censoring

This paper establishes a nonparametric estimator for the treatment effect on censored bivariate data under unvariate censoring. This proposed estimator is based on the one from Lin and Ying(1993)'s nonparametric bivariate survival function estimator, which is itself a generalized version of Park and Park(1995)' quantile estimator. A Bahadur type representation of quantile functions were obtained from the marginal survival distribution estimator of Lin and Ying' model. The asymptotic property of this estimator is shown below and the simulation studies are also given     

A Simple Approach to Inference in Random Coefficient Models

Random coefficient regression models have been used to analyze cross-sectional and longitudinal data in economics and growth-curve data from biological and agricultural experiments. In the literature several estimators, including the ordinary least squares and the estimated generalized least squares (EGLS), have been considered for estimating the parameters of the mean model. Based on the asymptotic properties of the EGLS estimators, test statistics have been proposed for testing linear hypotheses involving the parameters of the mean model. An alternative estimator, the simple mean of the individual regression coefficients, provides estimation and hypothesis-testing procedures that are simple to compute and teach. The large sample properties of this simple estimator are shown to be similar to that of the EGLS estimator. The performance of the proposed estimator is compared with that of the existing estimators by Monte Carlo simulation.     

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.     

Nonparametric Bayesian estimation of survival function under random left truncation

Several observational studies give rise to randomly left truncated data. In a nonparametric model for such data X denotes a variable of interest, T denotes the truncation variable and the distributions of both X and T are left unspecified. For this model, the product-limit estimator, which is also the maximum likelihood estimator of the survival curve, has been widely discussed. In this article, a nonparametric Bayes estimator of the survival function based on randomly left truncated data and Dirichlet process prior is presented. Some new results on the mixtures of Dirichlet processes in the context of truncated data are obtained. These results are then used to derive the Bayes estimator of the survival function under squared error loss. The weak convergence of the Bayes estimator is studied. An example using transfusion related AIDS data quoted in Kalbfleisch and Lawless (1989) is considered.     

Bayesian quantile regression for parametric nonlinear mixed effects models

We propose quantile regression (QR) in the Bayesian framework for a class of nonlinear mixed effects models with a known, parametric model form for longitudinal data. Estimation of the regression quantiles is based on a likelihood-based approach using the asymmetric Laplace density. Posterior computations are carried out via Gibbs sampling and the adaptive rejection Metropolis algorithm. To assess the performance of the Bayesian QR estimator, we compare it with the mean regression estimator using real and simulated data. Results show that the Bayesian QR estimator provides a fuller examination of the shape of the conditional distribution of the response variable. Our approach is proposed for parametric nonlinear mixed effects models, and therefore may not be generalized to models without a given model form.     

Mixed Discrete and Continuous Cox Regression Model

The Cox (1972) regression model is extended to include discrete and mixed continuous/discrete failure time data by retaining the multiplicative hazard rate form of the absolutely continuous model. Application of martingale arguments to the regression parameter estimating function show the Breslow (1974) estimator to be consistent and asymptotically Gaussian under this model. A computationally convenient estimator of the variance of the score function can be developed, again using martingale arguments. This estimator reduces to the usual hypergeometric form in the special case of testing equality of several survival curves, and it leads more generally to a convenient consistent variance estimator for the regression parameter. A small simulation study is carried out to study the regression parameter estimator and its variance estimator under the discrete Cox model special case and an application to a bladder cancer recurrence dataset is provided.     

Expected estimating equations to accommodate covariate measurement error

Estimating equations which are not necessarily likelihood-based score equations are becoming increasingly popular for estimating regression model parameters. This paper is concerned with estimation based on general estimating equations when true covariate data are missing for all the study subjects, but surrogate or mismeasured covariates are available instead. The method is motivated by the covariate measurement error problem in marginal or partly conditional regression of longitudinal data. We propose to base estimation on the expectation of the complete data estimating equation conditioned on available data. The regression parameters and other nuisance parameters are estimated simultaneously by solving the resulting estimating equations. The expected estimating equation (EEE) estimator is equal to the maximum likelihood estimator if the complete data scores are likelihood scores and conditioning is with respect to all the available data. A pseudo-EEE estimator, which requires less computation, is also investigated. Asymptotic distribution theory is derived. Small sample simulations are conducted when the error process is an order 1 autoregressive model. Regression calibration is extended to this setting and compared with the EEE approach. We demonstrate the methods on data from a longitudinal study of the relationship between childhood growth and adult obesity.     

第三类Tobit模型的半参数估计方法

本文给出第三类Tobit模型的一种新的半参数估计方法。在独立性假设下,利用主方程和选择方程中可观察受限因变量的条件生存函数所满足的关系式,构造第三类Tobit模型参数的一步联立估计量。在已知选择方程中参数一致性估计量的条件下,这种方法也可用于构造主方程模型参数 的两步估计量。本文证明了所提出的一步联立估计量和两步估计量的一致性和渐近正态性。实验模拟表明,我们提出的估计量在有限样本下具有良好表现,且一步联立估计量的有限样本表现优于或接近于Chen（1997）的估计量。     

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.     

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.     

Robust variance estimators for fixed-effect estimates with hierarchical-likelihood

In longitudinal studies, robust sandwich variance estimators are often used, and are especially useful when model assumptions are in doubt. However, the usual sandwich estimator does not allow for models with crossed random effects. The hierarchical likelihood extends the idea of the sandwich estimator to models not currently covered. By simulation studies, we show that the new sandwich estimator is robust against heteroscedastic errors and against misspecification of overdispersion in the y | v component.     

Nonparametric estimators for a survivor function of paired recurrent events

Recurrent event data arise in longitudinal studies where each study subject may experience multiple events during the follow-up. In many situations in survival studies, pairs of individuals can potentially experience recurrent events. The analysis of such data is not straightforward as it involves two kinds of dependences, namely, dependence between the individuals in the same pair and dependence among a sequence of pairs. In the present paper, we introduce a new stochastic model for the analysis of such recurrent event data. Nonparametric estimators for a bivariate survivor function are developed. Asymptotic properties of the estimators are discussed. Simulation studies are carried out to assess the finite sample properties of the estimator. We illustrate the procedure with real life data on eye disease.