OPTIMAL DESIGNS FOR FITTING A PROPORTIONAL HAZARDS REGRESSION MODEL TO DATA SUBJECT TO CENSORING

Suppose the probability model for failure time data, subject to censoring, is specified by the hazard function λ(t)exp(β_T x), where x is a vector of covariates. Analytical difficulties involved in finding the optimal design are avoided by assuming that λ is completely specified and by using D-optimality based on the information matrix for β Optimal designs are found to depend on β, but some results of practical consequence are obtained. It is found that censoring does not affect the choice of design appreciably when β^T x ≥ 0 for all points of the feasible region, but may have an appreciable effect when β_ix_i 0, for all i and all points in the feasible experimental region. The nature of the effect is discussed in detail for the cases of one and two parameters. It is argued that in practical biomedical situations the optimal design is almost always the same as for uncensored data.     

SADDLEPOINT METHODS FOR BOOTSTRAP CONFIDENCE BANDS IN NONPARAMETRIC REGRESSION

Bootstrap techniques have been used to construct confidence bands in nonparametric regression problems (Härdle & Bowman, 1988). Yet the required simulation is generally computationally intensive and therefore makes it difficult to conduct further investigations. In this paper, two saddlepoint methods are considered as alternatives to the naive simulation procedure. Some improvements to Härdle & Bowman's bootstrap method are suggested. The improvements are numerically verified using these efficient and accurate analytic methods.     

Reducing bias in parameter estimates from stepwise regression in proportional hazards regression with right-censored data

When variable selection with stepwise regression and model fitting are conducted on the same data set, competition for inclusion in the model induces a selection bias in coefficient estimators away from zero. In proportional hazards regression with right-censored data, selection bias inflates the absolute value of parameter estimate of selected parameters, while the omission of other variables may shrink coefficients toward zero. This paper explores the extent of the bias in parameter estimates from stepwise proportional hazards regression and proposes a bootstrap method, similar to those proposed by Miller (Subset Selection in Regression, 2nd edn. Chapman & Hall/CRC, 2002) for linear regression, to correct for selection bias. We also use bootstrap methods to estimate the standard error of the adjusted estimators. Simulation results show that substantial biases could be present in uncorrected stepwise estimators and, for binary covariates, could exceed 250% of the true parameter value. The simulations also show that the conditional mean of the proposed bootstrap bias-corrected parameter estimator, given that a variable is selected, is moved closer to the unconditional mean of the standard partial likelihood estimator in the chosen model, and to the population value of the parameter. We also explore the effect of the adjustment on estimates of log relative risk, given the values of the covariates in a selected model. The proposed method is illustrated with data sets in primary biliary cirrhosis and in multiple myeloma from the Eastern Cooperative Oncology Group.     

Analyzing Cohort Mortality Data

Several methods for analyzing data from mortality studies of occupationally or environmentally exposed cohorts are shown to be special cases of a single procedure. The procedure assumes a proportional hazards model for exposure effects and represents the log-likelihood kernel for the data as that of N independent Poisson variates, where N is the total number of person-units of mortality observation time in the study. It formalizes and justifies the epidemiological techniques of classifying deaths and person-months of study time into categories defined by exposure and other covariates, and of computing standardized mortality ratios and indirectly standardized death rates. Parameters representing exposure effects can be estimated by using standard software packages. Special cases and applications are described in the context of lung cancer mortality among U.S. uranium miners.     

BOOTSTRAP TESTS FOR THE ERROR DISTRIBUTION IN LINEAR AND NONPARAMETRIC REGRESSION MODELS

In this paper we investigate several tests for the hypothesis of a parametric form of the error distribution in the common linear and non‐parametric regression model, which are based on empirical processes of residuals. It is well known that tests in this context are not asymptotically distribution‐free and the parametric bootstrap is applied to deal with this problem. The performance of the resulting bootstrap test is investigated from an asymptotic point of view and by means of a simulation study. The results demonstrate that even for moderate sample sizes the parametric bootstrap provides a reliable and easy accessible solution to the problem of goodness‐of‐fit testing of assumptions regarding the error distribution in linear and non‐parametric regression models.     

Exponential tilt models for two-group comparison with censored data

We study application of the Exponential Tilt Model (ETM) to compare survival distributions in two groups. The ETM assumes a parametric form for the density ratio of the two distributions. It accommodates a broad array of parametric models such as the log-normal and gamma models and can be sufficiently flexible to allow for crossing hazard and crossing survival functions. We develop a nonparametric likelihood approach to estimate ETM parameters in the presence of censoring and establish related asymptotic results. We compare the ETM to the Proportional Hazards Model (PHM) in simulation studies. When the proportional hazards assumption is not satisfied but the ETM assumption is, the ETM has better power for testing the hypothesis of no difference between the two groups. And, importantly, when the ETM relation is not satisfied but the PHM assumption is, the ETM can still have power reasonably close to that of the PHM. Application of the ETM is illustrated by a gastrointestinal tumor study.     

The heteroscedastic odd log-logistic generalized gamma regression model for censored data

We propose a four-parameter extended generalized gamma model, which includes as special cases some important distributions and it is very useful for modeling lifetime data. A advantage is that it can represent the error distribution for a new heteroscedastic log-odd log-logistic generalized gamma regression model. The proposed heteroscedastic regression model can be used more effectively in the analysis of survival data since it includes as special models several widely-known regression models. Further, for different parameter settings, sample sizes and censoring percentages, various simulations are performed. Overall, the new regression model is very useful to the analysis of real data.     

Some recent developments for regression analysis of multivariate failure time data

Cox's seminal 1972 paper on regression methods for possibly censored failure time data popularized the use of time to an event as a primary response in prospective studies. But one key assumption of this and other regression methods is that observations are independent of one another. In many problems, failure times are clustered into small groups where outcomes within a group are correlated. Examples include failure times for two eyes from one person or for members of the same family.This paper presents a survey of models for multivariate failure time data. Two distinct classes of models are considered: frailty and marginal models. In a frailty model, the correlation is assumed to derive from latent variables (frailties) common to observations from the same cluster. Regression models are formulated for the conditional failure time distribution given the frailties. Alternatively, marginal models describe the marginal failure time distribution of each response while separately modelling the association among responses from the same cluster.We focus on recent extensions of the proportional hazards model for multivariate failure time data. Model formulation, parameter interpretation and estimation procedures are considered.     

Estimation of dependence between paired correlated failure times in the presence of covariate measurement error

Summary. In many biomedical studies, covariates are subject to measurement error. Although it is well known that the regression coefficients estimators can be substantially biased if the measurement error is not accommodated, there has been little study of the effect of covariate measurement error on the estimation of the dependence between bivariate failure times. We show that the dependence parameter estimator in the Clayton–Oakes model can be considerably biased if the measurement error in the covariate is not accommodated. In contrast with the typical bias towards the null for marginal regression coefficients, the dependence parameter can be biased in either direction. We introduce a bias reduction technique for the bivariate survival function in copula models while assuming an additive measurement error model and replicated measurement for the covariates, and we study the large and small sample properties of the dependence parameter estimator proposed.     

Estimation of Survival Function in Cox Regression Model Under Random Censoring From Both Sides

In this article we present three types of parametric–non parametric estimators for conditional survival function in Cox proportional hazards regression model when the lifetime of interest is subjected to random censorship from both sides. We prove consistency and asymptotic normality of estimators.     

Estimation in a model for a semi-Markov process with covariates under right-censoring

A semi-Markov model with covariates is proposed for a multi-state process with a finite number of states such that the transition probabilities between the states and the distribution functions of the duration times between the occurrence of two states depend on a discrete covariate. The hazard rates for the time elapsed between two successive states depend on the covariate through a proportional hazards model involving a set of regression parameters, while the transition probabilities depend on the covariate in an unspecified way. We propose estimators for these parameters and for the cumulative hazard functions of the sojourn times. A difficulty comes from the fact that when a sojourn time in a state is right-censored, the next state is unknown. We prove that our estimators are consistent and asymptotically Gaussian under the model constraints.     

Testing for overdispersion in a censored Poisson regression model

In this article, we investigate the efficiency of score tests for testing a censored Poisson regression model against censored negative binomial regression alternatives. Based on the results of a simulation study, score tests using the normal approximation, underestimate the nominal significance level. To remedy this problem, bootstrap methods are proposed. We find that bootstrap methods keep the significance level close to the nominal one and have greater power uniformly than does the normal approximation for testing the hypothesis.     

A Log-Linear Regression Model for the Beta-Weibull Distribution

We introduce the log-beta Weibull regression model based on the beta Weibull distribution (Famoye et al., 2005 Famoye , F. , Lee , C. , Olumolade , O. ( 2005 ). The beta-Weibull distribution . Journal of Statistical Theory and Applications 4 : 121 – 136 . [Google Scholar]; Lee et al., 2007 Lee , C. , Famoye , F. , Olumolade , O. ( 2007 ). Beta-Weibull distribution: Some properties and applications to censored data . Journal of Modern Applied Statistical Methods 6 : 173 – 186 .[Crossref] , [Google Scholar]). We derive expansions for the moment generating function which do not depend on complicated functions. The new regression model represents a parametric family of models that includes as sub-models several widely known regression models that can be applied to censored survival data. We employ a frequentist analysis, a jackknife estimator, and a parametric bootstrap for the parameters of the proposed model. We derive the appropriate matrices for assessing local influences on the parameter estimates under different perturbation schemes and present some ways to assess global influences. Further, for different parameter settings, sample sizes, and censoring percentages, several simulations are performed. In addition, the empirical distribution of some modified residuals are displayed and compared with the standard normal distribution. These studies suggest that the residual analysis usually performed in normal linear regression models can be extended to a modified deviance residual in the proposed regression model applied to censored data. We define martingale and deviance residuals to evaluate the model assumptions. The extended regression model is very useful for the analysis of real data and could give more realistic fits than other special regression models.     

The generalized log-gamma mixture model with covariates: local influence and residual analysis

In a sample of censored survival times, the presence of an immune proportion of individuals who are not subject to death, failure or relapse, may be indicated by a relatively high number of individuals with large censored survival times. In this paper the generalized log-gamma model is modified for the possibility that long-term survivors may be present in the data. The model attempts to separately estimate the effects of covariates on the surviving fraction, that is, the proportion of the population for which the event never occurs. The logistic function is used for the regression model of the surviving fraction. Inference for the model parameters is considered via maximum likelihood. Some influence methods, such as the local influence and total local influence of an individual are derived, analyzed and discussed. Finally, a data set from the medical area is analyzed under the log-gamma generalized mixture model. A residual analysis is performed in order to select an appropriate model. The authors would like to thank the editor and referees for their helpful comments. This work was supported by CNPq, Brazil.     

IMPROVED SCORE TESTS FOR VON MISES REGRESSION MODELS

We present, in matrix notation, a finite-sample correction formula to improve score tests in von Mises regression models with concentration covariates. The formula only requires simple operations on matrices and can be used to obtain analytically closed-form corrections for score test statistics in a variety of special von Mises models. The paper also provides a numerical comparison of the size of two score test statistics with bootstrap-based critical values.     

Comparing Two Survival Time Distributions: An Investigation of Several Weight Functions for the Weighted Logrank Statistic

In survival analysis, it is often of interest to test whether or not two survival time distributions are equal, specifically in the presence of censored data. One very popular test statistic utilized in this testing procedure is the weighted logrank statistic. Much attention has been focused on finding flexible weight functions to use within the weighted logrank statistic, and we propose yet another. We demonstrate our weight function to be more stable than one of the most popular, which is given by Fleming and Harrington, by means of asymptotic normal tests, bootstrap tests and permutation tests performed on two datasets with a variety of characteristics.     

INFLUENCE DIAGNOSTICS FOR THE NORMAL LINEAR MODEL WITH CENSORED DATA

Methods of detecting influential observations for the normal model for censored data are proposed. These methods include one-step deletion methods, deletion of observations and the empirical influence function. Emphasis is placed on assessing the impact that a single observation has on the estimation of coefficients of the model. Functions of the coefficients such as the median lifetime are also considered. Results are compared when applied to two sets of data.     

INFERENCE FOR CENSORED MATCHED PAIRS USING SIGNED RANKS

Using the marginal likelihood based on the signed ranks derived from matched pairs data, inferences are made for regression parameters. Both members of a given pair are subject to the same censoring time, while different pairs are subject to different censoring times. Censoring is independent of the response and on the right. Easily calculated logistic density scores are used to provide an approximate analysis so that inferences can be made about a regression parameter in the presence of a difference within the matched pairs. Inference for the survival times of matched skin grafts is considered.     

On the Breslow estimator

In his discussion of Cox’s (1972) paper on proportional hazards regression, Breslow (1972) provided the maximum likelihood estimator for the cumulative baseline hazard function. This estimator is commonly used in practice. The estimator has also been highly valuable in the further development of Cox regression and semiparametric inference with censored data. The present paper describes the Breslow estimator and its tremendous impact on the theory and practice of survival analysis.     

Discrete Nonparametric Kernel and Parametric Methods for the Modeling of Pavement Deterioration

This article is concerned with one discrete nonparametric kernel and two parametric regression approaches for providing the evolution law of pavement deterioration. The first parametric approach is a survival data analysis method; and the second is a nonlinear mixed-effects model. The nonparametric approach consists of a regression estimator using the discrete associated kernels. Some asymptotic properties of the discrete nonparametric kernel estimator are shown as, in particular, its almost sure consistency. Moreover, two data-driven bandwidth selection methods are also given, with a new theoretical explicit expression of optimal bandwidth provided for this nonparametric estimator. A comparative simulation study is realized with an application of bootstrap methods to a measure of statistical accuracy.