Local Linear Regression in Proportional Hazards Model with Censored Data

In this article we study the method of nonparametric regression based on a transformation model, under which an unknown transformation of the survival time is nonlinearly, even more, nonparametrically, related to the covariates with various error distributions, which are parametrically specified with unknown parameters. Local linear approximations and locally weighted least squares are applied to obtain estimators for the effects of covariates with censored observations. We show that the estimators are consistent and asymptotically normal. This transformation model, coupled with local linear approximation techniques, provides many alternatives to the more general proportional hazards models with nonparametric covariates.     

Estimating the causal effects in randomized trials for survival data with a cure fraction and non compliance

We consider causal inference in randomized studies for survival data with a cure fraction and all-or-none treatment non compliance. To describe the causal effects, we consider the complier average causal effect (CACE) and the complier effect on survival probability beyond time t (CESP), where CACE and CESP are defined as the difference of cure rate and non cured subjects’ survival probability between treatment and control groups within the complier class. These estimands depend on the distributions of survival times in treatment and control groups. Given covariates and latent compliance type, we model these distributions with transformation promotion time cure model whose parameters are estimated by maximum likelihood. Both the infinite dimensional parameter in the model and the mixture structure of the problem create some computational difficulties which are overcome by an expectation-maximization (EM) algorithm. We show the estimators are consistent and asymptotically normal. Some simulation studies are conducted to assess the finite-sample performance of the proposed approach. We also illustrate our method by analyzing a real data from the Healthy Insurance Plan of Greater New York.     

Block and Basu bivariate lifetime distribution in the presence of cure fraction

This paper presents estimates for the parameters included in the Block and Basu bivariate lifetime distributions in the presence of covariates and cure fraction, applied to analyze survival data when some individuals may never experience the event of interest and two lifetimes are associated with each unit. A Bayesian procedure is used to get point and confidence intervals for the unknown parameters. Posterior summaries of interest are obtained using standard Markov Chain Monte Carlo methods in rjags package for R software. An illustration of the proposed methodology is given for a Diabetic Retinopathy Study data set.     

Modeling categorical covariates for lifetime data in the presence of cure fraction by Bayesian partition structures

In this paper, we propose a Bayesian partition modeling for lifetime data in the presence of a cure fraction by considering a local structure generated by a tessellation which depends on covariates. In this modeling we include information of nominal qualitative variables with more than two categories or ordinal qualitative variables. The proposed modeling is based on a promotion time cure model structure but assuming that the number of competing causes follows a geometric distribution. It is an alternative modeling strategy to the conventional survival regression modeling generally used for modeling lifetime data in the presence of a cure fraction, which models the cure fraction through a (generalized) linear model of the covariates. An advantage of our approach is its ability to capture the effects of covariates in a local structure. The flexibility of having a local structure is crucial to capture local effects and features of the data. The modeling is illustrated on two real melanoma data sets.     

Sample size calculation for a proportional hazards mixture cure model with nonbinary covariates

Sample size calculation is a critical issue in clinical trials because a small sample size leads to a biased inference and a large sample size increases the cost. With the development of advanced medical technology, some patients can be cured of certain chronic diseases, and the proportional hazards mixture cure model has been developed to handle survival data with potential cure information. Given the needs of survival trials with potential cure proportions, a corresponding sample size formula based on the log-rank test statistic for binary covariates has been proposed by Wang et al. [25]. However, a sample size formula based on continuous variables has not been developed. Herein, we presented sample size and power calculations for the mixture cure model with continuous variables based on the log-rank method and further modified it by Ewell's method. The proposed approaches were evaluated using simulation studies for synthetic data from exponential and Weibull distributions. A program for calculating necessary sample size for continuous covariates in a mixture cure model was implemented in R.     

On computing estimates of a change-point in the Weibull regression hazard model

The hazard function describes the instantaneous rate of failure at a time t, given that the individual survives up to t. In applications, the effect of covariates produce changes in the hazard function. When dealing with survival analysis, it is of interest to identify where a change point in time has occurred. In this work, covariates and censored variables are considered in order to estimate a change-point in the Weibull regression hazard model, which is a generalization of the exponential model. For this more general model, it is possible to obtain maximum likelihood estimators for the change-point and for the parameters involved. A Monte Carlo simulation study shows that indeed, it is possible to implement this model in practice. An application with clinical trial data coming from a treatment of chronic granulomatous disease is also included.     

Bayesian Semiparametric Cure Rate Model with an Unknown Threshold

Abstract.  We propose a Bayesian semiparametric model for survival data with a cure fraction. We explicitly consider a finite cure time in the model, which allows us to separate the cured and the uncured populations. We take a mixture prior of a Markov gamma process and a point mass at zero to model the baseline hazard rate function of the entire population. We focus on estimating the cure threshold after which subjects are considered cured. We can incorporate covariates through a structure similar to the proportional hazards model and allow the cure threshold also to depend on the covariates. For illustration, we undertake simulation studies and a full Bayesian analysis of a bone marrow transplant data set.     

Vertical modeling: analysis of competing risks data with a cure fraction

In this paper, we extend the vertical modeling approach for the analysis of survival data with competing risks to incorporate a cure fraction in the population, that is, a proportion of the population for which none of the competing events can occur. The proposed method has three components: the proportion of cure, the risk of failure, irrespective of the cause, and the relative risk of a certain cause of failure, given a failure occurred. Covariates may affect each of these components. An appealing aspect of the method is that it is a natural extension to competing risks of the semi-parametric mixture cure model in ordinary survival analysis; thus, causes of failure are assigned only if a failure occurs. This contrasts with the existing mixture cure model for competing risks of Larson and Dinse, which conditions at the onset on the future status presumably attained. Regression parameter estimates are obtained using an EM-algorithm. The performance of the estimators is evaluated in a simulation study. The method is illustrated using a melanoma cancer data set.

     

Estimation of parameters for the truncated exponential distribution

We consider the right truncated exponential distribution where the truncation point is unknown and show that the ML equation has a unique solution over an extended parameter space. In the case of the estimation of the truncation point T we show that the asymptotic distribution of the MLE is not centered at T. A modified MLE is introduced which outperforms all other considered estimators including the minimum variance unbiased estimator. Asymptotic as well as small sample properties of different estimators are investigated and compared. The truncated exponential distribution has an increasing failure rate, ideally suited for use as a survival distribution for biological and industrial data.     

Semiparametric multiparameter regression survival modeling

We consider a log-linear model for survival data, where both the location and scale parameters depend on covariates, and the baseline hazard function is completely unspecified. This model provides the flexibility needed to capture many interesting features of survival data at a relatively low cost in model complexity. Estimation procedures are developed, and asymptotic properties of the resulting estimators are derived using empirical process theory. Finally, a resampling procedure is developed to estimate the limiting variances of the estimators. The finite sample properties of the estimators are investigated by way of a simulation study, and a practical application to lung cancer data is illustrated.     

Penalized inverse probability weighted estimators for weighted rank regression with missing covariates

Abstract

In this article, we study the variable selection and estimation for linear regression models with missing covariates. The proposed estimation method is almost as efficient as the popular least-squares-based estimation method for normal random errors and empirically shown to be much more efficient and robust with respect to heavy tailed errors or outliers in the responses and covariates. To achieve sparsity, a variable selection procedure based on SCAD is proposed to conduct estimation and variable selection simultaneously. The procedure is shown to possess the oracle property. To deal with the covariates missing, we consider the inverse probability weighted estimators for the linear model when the selection probability is known or unknown. It is shown that the estimator by using estimated selection probability has a smaller asymptotic variance than that with true selection probability, thus is more efficient. Therefore, the important Horvitz-Thompson property is verified for penalized rank estimator with the covariates missing in the linear model. Some numerical examples are provided to demonstrate the performance of the estimators.     

A class of semiparametric cure models with current status data

Current status data occur in many biomedical studies where we only know whether the event of interest occurs before or after a particular time point. In practice, some subjects may never experience the event of interest, i.e., a certain fraction of the population is cured or is not susceptible to the event of interest. We consider a class of semiparametric transformation cure models for current status data with a survival fraction. This class includes both the proportional hazards and the proportional odds cure models as two special cases. We develop efficient likelihood-based estimation and inference procedures. We show that the maximum likelihood estimators for the regression coefficients are consistent, asymptotically normal, and asymptotically efficient. Simulation studies demonstrate that the proposed methods perform well in finite samples. For illustration, we provide an application of the models to a study on the calcification of the hydrogel intraocular lenses.

     

Inverse probability weighted estimators for single-index models with missing covariates

Abstract

In this article, we consider the inverse probability weighted estimators for a single-index model with missing covariates when the selection probabilities are known or unknown. It is shown that the estimator for the index parameter by using estimated selection probabilities has a smaller asymptotic variance than that with true selection probabilities, thus is more efficient. Therefore, the important Horvitz-Thompson property is verified for the index parameter in single index model. However, this difference disappears for the estimators of the link function. Some numerical examples and a real data application are also conducted to illustrate the performances of the estimators.     

Generalized Proportional Hazards Model Based on Modified Partial Likelihood

The proportional hazards (Cox) model is generalized by assuming that at any moment the ratio of hazard rates is depending not only on values of covariates but also on resources used until this moment. Relations with generalized multiplicative, frailty and linear transformation models are considered. A modified partial likelihood function is proposed, and properties of the estimators are investigated.     

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.     

Concordance-based estimation approaches for the optimal sufficient dimension reduction score

To characterize the dependence of a response on covariates of interest, a monotonic structure is linked to a multivariate polynomial transformation of the central subspace (CS) directions with unknown structural degree and dimension. Under a very general semiparametric model formulation, such a sufficient dimension reduction (SDR) score is shown to enjoy the existence, optimality, and uniqueness up to scale and location in the defined concordance probability function. In light of these properties and its single-index representation, two types of concordance-based generalized Bayesian information criteria are constructed to estimate the optimal SDR score and the maximum concordance index. The estimation criteria are further carried out by effective computational procedures. Generally speaking, the outer product of gradients estimation in the first approach has an advantage in computational efficiency and the parameterization system in the second approach greatly reduces the number of parameters in estimation. Different from most existing SDR approaches, only one CS direction is required to be continuous in the proposals. Moreover, the consistency of structural degree and dimension estimators and the asymptotic normality of the optimal SDR score and maximum concordance index estimators are established under some suitable conditions. The performance and practicality of our methodology are also investigated through simulations and empirical illustrations.     

The odd log-logistic Lindley Poisson model for lifetime data

We define two new lifetime models called the odd log-logistic Lindley (OLL-L) and odd log-logistic Lindley Poisson (OLL-LP) distributions with various hazard rate shapes such as increasing, decreasing, upside-down bathtub, and bathtub. Various structural properties are derived. Certain characterizations of OLL-L distribution are presented. The maximum likelihood estimators of the unknown parameters are obtained. We propose a flexible cure rate survival model by assuming that the number of competing causes of the event of interest has a Poisson distribution and the time to event has an OLL-L distribution. The applicability of the new models is illustrated by means real datasets.     

A Comparison of REML and Covariance Adjustment Method in the Estimation of Growth Curve Models

The classical growth curve model is considered when one continuous characteristic is measured at q time points. The covariance adjusted estimator of growth curve parameters is the OLS estimator adjusted using analysis of covariance. The covariates are obtained from functions of within individuals error contrasts. On the other hand, REML estimators emerge from maximization of the likelihood of OLS residuals. We compare the efficiency of estimators of growth curve parameters obtained by REML with that of covariance-adjusted least squares estimators with covariates selected via CAIC.     

Bayesian Methods for Missing Covariates in Cure Rate Models

We propose methods for Bayesian inference for missing covariate data with a novel class of semi-parametric survival models with a cure fraction. We allow the missing covariates to be either categorical or continuous and specify a parametric distribution for the covariates that is written as a sequence of one dimensional conditional distributions. We assume that the missing covariates are missing at random (MAR) throughout. We propose an informative class of joint prior distributions for the regression coefficients and the parameters arising from the covariate distributions. The proposed class of priors are shown to be useful in recovering information on the missing covariates especially in situations where the missing data fraction is large. Properties of the proposed prior and resulting posterior distributions are examined. Also, model checking techniques are proposed for sensitivity analyses and for checking the goodness of fit of a particular model. Specifically, we extend the Conditional Predictive Ordinate (CPO) statistic to assess goodness of fit in the presence of missing covariate data. Computational techniques using the Gibbs sampler are implemented. A real data set involving a melanoma cancer clinical trial is examined to demonstrate the methodology.     

A marginal regression model for multivariate failure time data with a surviving fraction

A marginal regression approach for correlated censored survival data has become a widely used statistical method. Examples of this approach in survival analysis include from the early work by Wei et al. (J Am Stat Assoc 84:1065–1073, 1989) to more recent work by Spiekerman and Lin (J Am Stat Assoc 93:1164–1175, 1998). This approach is particularly useful if a covariate’s population average effect is of primary interest and the correlation structure is not of interest or cannot be appropriately specified due to lack of sufficient information. In this paper, we consider a semiparametric marginal proportional hazard mixture cure model for clustered survival data with a surviving or “cure” fraction. Unlike the clustered data in previous work, the latent binary cure statuses of patients in one cluster tend to be correlated in addition to the possible correlated failure times among the patients in the cluster who are not cured. The complexity of specifying appropriate correlation structures for the data becomes even worse if the potential correlation between cure statuses and the failure times in the cluster has to be considered, and thus a marginal regression approach is particularly attractive. We formulate a semiparametric marginal proportional hazards mixture cure model. Estimates are obtained using an EM algorithm and expressions for the variance–covariance are derived using sandwich estimators. Simulation studies are conducted to assess finite sample properties of the proposed model. The marginal model is applied to a multi-institutional study of local recurrences of tonsil cancer patients who received radiation therapy. It reveals new findings that are not available from previous analyses of this study that ignored the potential correlation between patients within the same institution.