An Approach to Determine Sample Size and to Allocate Sample Size for a Specific Region in a Multiregional Trial for Survival (Time-to-Event) Data under Accelerated Failure Time Model

For the time-to-event outcome, current methods for sample determination are based on the proportional hazard model. However, if the proportionality assumption fails to capture the relationship between the hazard time and covariates, the proportional hazard model is not suitable to analyze survival data. The accelerated failure time (AFT) model is an alternative method to deal with survival data. In this paper, we address the issue that the relationship between the hazard time and the treatment effect is satisfied with the AFT model to design a multiregional trial. The log-rank test is employed to deal with the heterogeneous effect size among regions. The test statistic for the overall treatment effect is used to determine the total sample size for a multiregional trial, and the proposed criteria are used to rationalize partition sample size to each region.     

Bayesian analysis of generalized odds-rate hazards models for survival data

In the analysis of censored survival data Cox proportional hazards model (1972) is extremely popular among the practitioners. However, in many real-life situations the proportionality of the hazard ratios does not seem to be an appropriate assumption. To overcome such a problem, we consider a class of nonproportional hazards models known as generalized odds-rate class of regression models. The class is general enough to include several commonly used models, such as proportional hazards model, proportional odds model, and accelerated life time model. The theoretical and computational properties of these models have been re-examined. The propriety of the posterior has been established under some mild conditions. A simulation study is conducted and a detailed analysis of the data from a prostate cancer study is presented to further illustrate the proposed methodology.     

A semiparametric extended hazard regression model with time-dependent covariates

We introduce a general class of semiparametric hazard regression models, called extended hazard (EH) models, that are designed to accommodate various survival schemes with time-dependent covariates. The EH model contains both the Cox model and the accelerated failure time (AFT) model as its subclasses so that we can use this nested structure to perform model selection between the Cox model and the AFT model. A class of estimating equations using counting process and martingale techniques is developed to estimate the regression parameters of the proposed model. The performance of the estimating procedure and the impact of model misspecification are assessed through simulation studies. Two data examples, Stanford heart transplant data and Mediterranean fruit flies, egg-laying data, are used to demonstrate the usefulness of the EH model.     

Random partition models with regression on covariates

Many recent applications of nonparametric Bayesian inference use random partition models, i.e. probability models for clustering a set of experimental units. We review the popular basic constructions. We then focus on an interesting extension of such models. In many applications covariates are available that could be used to a priori inform the clustering. This leads to random clustering models indexed by covariates, i.e., regression models with the outcome being a partition of the experimental units. We discuss some alternative approaches that have been used in the recent literature to implement such models, with an emphasis on a recently proposed extension of product partition models. Several of the reviewed approaches were not originally intended as covariate-based random partition models, but can be used for such inference.     

Regression analysis of informative current status data with the semiparametric linear transformation model

Many methods have been developed in the literature for regression analysis of current status data with noninformative censoring and also some approaches have been proposed for semiparametric regression analysis of current status data with informative censoring. However, the existing approaches for the latter situation are mainly on specific models such as the proportional hazards model and the additive hazard model. Corresponding to this, in this paper, we consider a general class of semiparametric linear transformation models and develop a sieve maximum likelihood estimation approach for the inference. In the method, the copula model is employed to describe the informative censoring or relationship between the failure time of interest and the censoring time, and Bernstein polynomials are used to approximate the nonparametric functions involved. The asymptotic consistency and normality of the proposed estimators are established, and an extensive simulation study is conducted and indicates that the proposed approach works well for practical situations. In addition, an illustrative example is provided.     

A Smooth Test in Proportional Hazard Survival Models Using Local Partial Likelihood Fitting

Proportional hazard models for survival data, even though popular and numerically handy, suffer from the restrictive assumption that covariate effects are constant over survival time. A number of tests have been proposed to check this assumption. This paper contributes to this area by employing local estimates allowing to fit hazard models in which covariate effects are smoothly varying with time. A formal test is derived to check for proportional hazards against smooth hazards as alternative. The test proves to possess omnibus power in that it is powerful against arbitrary but smooth alternatives. Comparative simulations and two data examples accompany the presentation. Extensions are provided to multiple covariate settings, where the focus of interest is to decide which of the covariate effects vary with time.     

Monte Carlo methods for nonparametric survival model determination

In the causal analysis of survival data a time-based response is related to a set of explanatory variables. Definition of the relation between the time and the covariates may become a difficult task, particularly in the preliminary stage, when the information is limited. Through a nonparametric approach, we propose to estimate the survival function allowing to evaluate the relative importance of each potential explanatory variable, in a simple and explanatory fashion. To achieve this aim, each of the explanatory variables is used to partition the observed survival times. The observations are assumed to be partially exchangeable according to such partition. We then consider, conditionally on each partition, a hierarchical nonparametric Bayesian model on the hazard functions. We define and compare different prior distribution for the hazard functions.     

Fitting and testing the Marshall–Olkin extended Weibull model with randomly censored data

The random censorship model (RCM) is commonly used in biomedical science for modeling life distributions. The popular non-parametric Kaplan–Meier estimator and some semiparametric models such as Cox proportional hazard models are extensively discussed in the literature. In this paper, we propose to fit the RCM with the assumption that the actual life distribution and the censoring distribution have a proportional odds relationship. The parametric model is defined using Marshall–Olkin's extended Weibull distribution. We utilize the maximum-likelihood procedure to estimate model parameters, the survival distribution, the mean residual life function, and the hazard rate as well. The proportional odds assumption is also justified by the newly proposed bootstrap Komogorov–Smirnov type goodness-of-fit test. A simulation study on the MLE of model parameters and the median survival time is carried out to assess the finite sample performance of the model. Finally, we implement the proposed model on two real-life data sets.     

On additive-multiplicative hazards model

In survival analysis and reliability theory, a fundamental problem is the study of lifetime properties of a live organism or system. In this regard, there have been considered and studied several models based on different concepts of ageing such as hazard rate and mean residual life. In this paper, we consider an additive-multiplicative hazard model (AMHM) and study some reliability and ageing properties of the proposed model. We then specify the bivariate models whose conditionals satisfy AMHM. Several properties of the proposed bivariate model are investigated and adequacy of the model is evaluated based on a real data set.     

Survival and lifetime data analysis with a flexible class of distributions

We introduce a general class of continuous univariate distributions with positive support obtained by transforming the class of two-piece distributions. We show that this class of distributions is very flexible, easy to implement, and contains members that can capture different tail behaviours and shapes, producing also a variety of hazard functions. The proposed distributions represent a flexible alternative to the classical choices such as the log-normal, Gamma, and Weibull distributions. We investigate empirically the inferential properties of the proposed models through an extensive simulation study. We present some applications using real data in the contexts of time-to-event and accelerated failure time models. In the second kind of applications, we explore the use of these models in the estimation of the distribution of the individual remaining life.     

A Statistical Issue About a Phase III Multi-regional Trial for the Survival Data under Accelerated Failure Time Model with Unrecognized Heterogeneity

For the time-to-event outcome, current methods for sample size determination are based on the proportional hazard model. However, if the proportionality assumption fails to capture the relationship between the hazard time and covariates, the proportional hazard model is not suitable to analyze survival data. The accelerated failure time model is an alternative method to deal with survival data. In this article, we address the issue that the relationship between the hazard time and the treatment effect is satisfied with the accelerated failure time model to design a multi-regional trial for a phase III clinical trial. The log-rank test is employed to deal with the heterogeneous effect size among regions. The test statistic for the overall treatment effect is used to determine the total sample size for a multi-regional trial and the consistent trend is used to rationalize partition sample size to each region.     

Graphical Tests for the Assumption of Gamma and Inverse Gaussian Frailty Distributions

The common choices of frailty distribution in lifetime data models include the Gamma and Inverse Gaussian distributions. We present diagnostic plots for these distributions when frailty operates in a proportional hazards framework. Firstly, we present plots based on the form of the unconditional survival function when the baseline hazard is assumed to be Weibull. Secondly, we base a plot on a closure property that applies for any baseline hazard, namely, that the frailty distribution among survivors at time t has the same form as the original distribution, with the same shape parameter but different scale parameter. We estimate the shape parameter at different values of t and examine whether it is constant, that is, whether plotted values form a straight line parallel to the time axis. We provide simulation results assuming Weibull baseline hazard and an example to illustrate the methods.     

Estimation of the cumulative baseline hazard function for dependently right-censored failure time data

In this paper, we study the properties of a special class of frailty models when the frailty is common to several failure times. The models are closely linked to Archimedean copula models. We establish a useful formula for cumulative baseline hazard functions and develop a new estimator for cumulative baseline hazard functions in bivariate frailty regression models. Based on our proposed estimator, we present a graphical model checking procedure. We fit a leukemia data set using our model and end our paper with some discussions.     

Modelling Survival Events with Longitudinal Covariates Measured with Error

In survival analysis, time-dependent covariates are usually present as longitudinal data collected periodically and measured with error. The longitudinal data can be assumed to follow a linear mixed effect model and Cox regression models may be used for modelling of survival events. The hazard rate of survival times depends on the underlying time-dependent covariate measured with error, which may be described by random effects. Most existing methods proposed for such models assume a parametric distribution assumption on the random effects and specify a normally distributed error term for the linear mixed effect model. These assumptions may not be always valid in practice. In this article, we propose a new likelihood method for Cox regression models with error-contaminated time-dependent covariates. The proposed method does not require any parametric distribution assumption on random effects and random errors. Asymptotic properties for parameter estimators are provided. Simulation results show that under certain situations the proposed methods are more efficient than the existing methods.     

A Semi-parametric Bayesian Analysis of Survival Data Based on Lévy-driven Processes

In the presence of covariate information, the proportional hazards model is one of the most popular models. In this paper, in a Bayesian nonparametric framework, we use a Markov (Lévy-driven) process to model the baseline hazard rate. Previous Bayesian nonparametric models have been based on neutral to the right processes, which have a number of drawbacks, such as discreteness of the cumulative hazard function. We allow the covariates to be time dependent functions and develop a full posterior analysis via substitution sampling. A detailed illustration is presented.     

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.     

An additive subdistribution hazard model for competing risks data

The cumulative incidence function plays an important role in assessing its treatment and covariate effects with competing risks data. In this article, we consider an additive hazard model allowing the time-varying covariate effects for the subdistribution and propose the weighted estimating equation under the covariate-dependent censoring by fitting the Cox-type hazard model for the censoring distribution. When there exists some association between the censoring time and the covariates, the proposed coefficients’ estimations are unbiased and the large-sample properties are established. The finite-sample properties of the proposed estimators are examined in the simulation study. The proposed Cox-weighted method is applied to a competing risks dataset from a Hodgkin's disease study.     

Marginal Likelihood Estimation for Proportional Odds Models with Right Censored Data

One majoraspect in medical research is to relate the survival times ofpatients with the relevant covariates or explanatory variables.The proportional hazards model has been used extensively in thepast decades with the assumption that the covariate effects actmultiplicatively on the hazard function, independent of time.If the patients become more homogeneous over time, say the treatmenteffects decrease with time or fade out eventually, then a proportionalodds model may be more appropriate. In the proportional oddsmodel, the odds ratio between patients can be expressed as afunction of their corresponding covariate vectors, in which,the hazard ratio between individuals converges to unity in thelong run. In this paper, we consider the estimation of the regressionparameter for a semiparametric proportional odds model at whichthe baseline odds function is an arbitrary, non-decreasing functionbut is left unspecified. Instead of using the exact survivaltimes, only the rank order information among patients is used.A Monte Carlo method is used to approximate the marginal likelihoodfunction of the rank invariant transformation of the survivaltimes which preserves the information about the regression parameter.The method can be applied to other transformation models withcensored data such as the proportional hazards model, the generalizedprobit model or others. The proposed method is applied to theVeteran's Administration lung cancer trial data.     

Estimation in proportional hazard and log-linear models

Proportional hazard models and models where the dependent variables follow a linear model are shown to be equivalent if and only if the hazard rate is the product of a non-negative periodic function and a Weibull factor. Estimates based on rank statistics are proposed for the parameters in the proportional hazard model.