A Nonparametric Frailty Model for Clustered Survival Data

Clayton-type counting process formulations for survival data and parametric gamma models for cluster-specific frailty quantities are now routinely applied in analyses of clustered survival data. On the other hand, although nonparametric frailty models have been studied, they are not used much in practice. In this article, the distribution of the frailty terms is assumed to be an unknown random variable. The unknown frailty distribution is then modelled completely with a Dirichlet process prior. This prior assigns cluster units into sub-classes whose members have the same random frailty effect. The Gibbs sampler algorithm is used for computing posterior parameter estimates of the fixed effect hazards regression and the frailty distribution. The methodology is used to analyze community-clustered child survival in sub-Saharan Africa. The results show that the communities could be separated into fewer distinct classes of risk of childhood mortality; the fewer classes could be studied easily in order to provide useful guidance on the more effective use of resources for child health intervention programmes.     

Checking the Grouped Data Version of the Cox Model for Interval-grouped Survival Data

Abstract.  Epidemiology research often entails the analysis of failure times subject to grouping. In large cohorts interval grouping also offers a feasible choice of data reduction to actually facilitate an analysis of the data. Based on an underlying Cox proportional hazards model for the exact failure times one may deduce a grouped data version of this model which may then be used to analyse the data. The model bears a lot of resemblance to a generalized linear model, yet due to the nature of data one also needs to incorporate censoring. In the case of non-trivial censoring this precludes model checking procedures based on ordinary residuals as calculation of these requires knowledge of the censoring distribution. In this paper, we represent interval grouped data in a dynamical way using a counting process approach. This enables us to identify martingale residuals which can be computed without knowledge of the censoring distribution. We use these residuals to construct graphical as well as numerical model checking procedures. An example from epidemiology is provided.     

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.     

Proportional hazards model for discrete data: Some new developments

ABSTRACT

Many times, a product lifetime can be described through a non negative integer valued random variable. In this article, we propose a proportional hazards model for discrete data analogous to the version for continuous data. Some ageing properties of the model are discussed. Stochastic comparison of pair of random variables that follow the model are also made. A new test based on U-statistics is developed for testing that the proportionality parameter in the proposed model is 1. The asymptotic properties of the proposed test are studied. We present some numerical results to asses the performance of the test procedure.     

Generalized Method of Moments for Additive Hazards Model with Clustered Dental Survival Data

For multivariate survival data, we study the generalized method of moments (GMM) approach to estimation and inference based on the marginal additive hazards model. We propose an efficient iterative algorithm using closed‐form solutions, which dramatically reduces the computational burden. Asymptotic normality of the proposed estimators is established, and the corresponding variance–covariance matrix can be consistently estimated. Inference procedures are derived based on the asymptotic chi‐squared distribution of the GMM objective function. Simulation studies are conducted to empirically examine the finite sample performance of the proposed method, and a real data example from a dental study is used for illustration.     

A Class of Parametric Dynamic Survival Models

A class of parametric dynamic survival models are explored in which only limited parametric assumptions are made, whilst avoiding the assumption of proportional hazards. Both the log-baseline hazard and covariate effects are modelled by piecewise constant and correlated processes. The method of estimation is to use Markov chain Monte Carlo simulations Gibbs sampling with a Metropolis–Hastings step. In addition to standard right censored data sets, extensions to accommodate interval censoring and random effects are included. The model is applied to two well known and illustrative data sets, and the dynamic variability of covariate effects investigated.     

A Generalized Time-Dependent Conditional Linear Model with Left-Truncated and Right-Censored Data

Consider the model φ(S(y | X)) = β(y) ^T X, where φ is a known link function, S(· | X) is the survival function of a response Y given a covariate X = (1, X, X ²,…, X ^p ), and β(y) is an unknown vector of time-dependent regression coefficients. The response Y is subject to left truncation and right censoring. We assume that given X, Y is independent of (C, T) where C and T are censoring and truncation variables with P(C ≥ T) = 1. In this article, with some modification of the assumptions in Lemmas 5 and 6 of Iglesias-Pérez and González-Manteiga (1999 Iglesias-Pérez , C. J. , González-Manteiga , W. G. ( 1999 ). Strong representation of a generalized product-limit estimator for truncated and censored data with some application . J. Nonparametric Statist. 10 : 213 – 244 .[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]), we present an almost sure representation for the generalized product-limit estimator (GPL) of S(y | X). Based on the GPL and the approach of Teodorescu et al. (2010 Teodorescu , B. , Keilegom , I. V. , Cao , R. ( 2010 ). Generalized time-dependent conditional linear models under left truncation and right censoring . Ann. Instit. Statist. Math. 62 : 465 – 485 .[Crossref], [Web of Science ®] , [Google Scholar]), a least squares estimator of β(y) is obtained and a bootstrap procedure is proposed to choose the optimum bandwidth.     

A risk set adjustment for proportional hazards modeling of combined cohort data

Sporting careers observed over a preset time interval can be partitioned into two distinct subsamples. These samples consist of individuals whose careers had already commenced at the start of the time interval (prevalent subsample) and individuals whose careers began during the time interval (incident subsample) as well the respective individual-level covariate data such as salary, height, weight, performance statistics, draft position, etc. Under the assumption of a proportional hazards model, we propose a partial likelihood estimator to model the effect of covariates on survival via an adjusted risk set sampling procedure for when the incident cohort data is used in conjunction with the prevalent cohort data. We use simulated failure time data to validate the combined cohort proportional hazards methodology and illustrate our model using an NBA data set for career durations measured between 1990 and 2008.     

A Weibull Regression Model with Gamma Frailties for Multivariate Survival Data

Frequently in the analysis of survival data, survival times within the same group are correlated due to unobserved co-variates. One way these co-variates can be included in the model is as frailties. These frailty random block effects generate dependency between the survival times of the individuals which are conditionally independent given the frailty. Using a conditional proportional hazards model, in conjunction with the frailty, a whole new family of models is introduced. By considering a gamma frailty model, often the issue is to find an appropriate model for the baseline hazard function. In this paper a flexible baseline hazard model based on a correlated prior process is proposed and is compared with a standard Weibull model. Several model diagnostics methods are developed and model comparison is made using recently developed Bayesian model selection criteria. The above methodologies are applied to the McGilchrist and Aisbett (1991) kidney infection data and the analysis is performed using Markov Chain Monte Carlo methods. This revised version was published online in July 2006 with corrections to the Cover Date.     

A Proportional Hazards Regression Model for the Subdistribution with Covariates‐adjusted Censoring Weight for Competing Risks Data

With competing risks data, one often needs to assess the treatment and covariate effects on the cumulative incidence function. Fine and Gray proposed a proportional hazards regression model for the subdistribution of a competing risk with the assumption that the censoring distribution and the covariates are independent. Covariate‐dependent censoring sometimes occurs in medical studies. In this paper, we study the proportional hazards regression model for the subdistribution of a competing risk with proper adjustments for covariate‐dependent censoring. We consider a covariate‐adjusted weight function by fitting the Cox model for the censoring distribution and using the predictive probability for each individual. Our simulation study shows that the covariate‐adjusted weight estimator is basically unbiased when the censoring time depends on the covariates, and the covariate‐adjusted weight approach works well for the variance estimator as well. We illustrate our methods with bone marrow transplant data from the Center for International Blood and Marrow Transplant Research. Here, cancer relapse and death in complete remission are two competing risks.     

Small Sample Bias in the Gamma Frailty Model for Univariate Survival

The gamma frailty model is a natural extension of the Cox proportional hazards model in survival analysis. Because the frailties are unobserved, an E-M approach is often used for estimation. Such an approach is shown to lead to finite sample underestimation of the frailty variance, with the corresponding regression parameters also being underestimated as a result. For the univariate case, we investigate the source of the bias with simulation studies and a complete enumeration. The rank-based E-M approach, we note, only identifies frailty through the order in which failures occur; additional frailty which is evident in the survival times is ignored, and as a result the frailty variance is underestimated. An adaption of the standard E-M approach is suggested, whereby the non-parametric Breslow estimate is replaced by a local likelihood formulation for the baseline hazard which allows the survival times themselves to enter the model. Simulations demonstrate that this approach substantially reduces the bias, even at small sample sizes. The method developed is applied to survival data from the North West Regional Leukaemia Register.     

A semiparametric regression cure model for interval-censored and left-truncated data

Medical advancements have made it possible for patients to be cured of certain types of diseases. In follow-up studies, the disease event time can be subject to left truncation and interval censoring. In this article, we propose a semiparametric nonmixture cure model for the regression analysis of left-truncated and interval-censored (LTIC) data. We develop semiparametric maximum likelihood estimation for the nonmixture cure model with LTIC data. A simulation study is conducted to investigate the performance of the proposed estimators.     

The random-effects proportional hazards model with grouped survival data: a comparison between the grouped continuous and continuation ratio versions

Summary.  When analysing grouped time survival data having a hierarchical structure it is often appropriate to assume a random-effects proportional hazards model for the latent continuous time and then to derive the corresponding grouped time model. There are two formally equivalent grouped time versions of the proportional hazards model obtained from different perspec-tives, known as the continuation ratio and the grouped continuous models. However, the two models require distinct estimation procedures and, more importantly, they differ substantially when extended to time-dependent covariates and/or non-proportional effects. The paper discusses these issues in the context of random-effects models, illustrating the main points with an application to a complex data set on job opportunities for a cohort of graduates.     

Calculating the power or sample size for the logistic and proportional hazards models

An algorithm is presented for calculating the power for the logistic and proportional hazards models in which some of the covariates are discrete and the remainders are multivariate normal. The mean and covariance matrix of the multivariate normal covariates may depend on the discrete covariates.

The algorithm, which finds the power of the Wald test, uses the result that the information matrix can be calculated using univariate numerical integration even when there are several continuous covariates. The algorithm is checked using simulation and in certain situations gives more accurate results than current methods which are based on simple formulae. The algorithm is used to explore properties of these models, in particular, the power gain from a prognostic covariate in the analysis of a clinical trial or observational study. The methods can be extended to determine power for other generalized linear models.     

A New Survival Model for the Diffusion Pattern of TV Programs

The study of television audience viewing behavior is very important. The results can provide broadcasters and advertisers useful information to increase the effectiveness of television programming and advertising. Based on hazard rate analysis for survival model, this research develops a new statistical model to fit the diffusion pattern of TV programs, which is a measure of the overall popularity of the program and is used as a criterion to sell the television time. The model helps the decision makers at the networks better understand the acceptance of the show and the underlying behavioral patterns of the viewers. It fits the empirical data in Hong Kong very well and outperforms the existing models. This basic model is then extended to the proportional hazard model to study the covariate effects on the likelihood of an individual watching the program at an earlier stage. Advertisers can benefit from these results in targeting their desired customers.     

Parametric Analysis for Matched Pair Survival Data

Hougaard's (1986) bivariate Weibull distribution with positive stable frailties is applied to matched pairs survival data when either or both components of the pair may be censored and covariate vectors may be of arbitrary fixed length. When there is no censoring, we quantify the corresponding gain in Fisher information over a fixed-effects analysis. With the appropriate parameterization, the results take a simple algebraic form. An alternative marginal (independence working model) approach to estimation is also considered. This method ignores the correlation between the two survival times in the derivation of the estimator, but provides a valid estimate of standard error. It is shown that when both the correlation between the two survival times is high, and the ratio of the within-pair variability to the between-pair variability of the covariates is high, the fixed-effects analysis captures most of the information about the regression coefficient but the independence working model does badly. When the correlation is low, and/or most of the variability of the covariates occurs between pairs, the reverse is true. The random effects model is applied to data on skin grafts, and on loss of visual acuity among diabetics. In conclusion some extensions of the methods are indicated and they are placed in a wider context of Generalized Estimating Equation methodology.     

Choice of Parametric Accelerated Life and Proportional Hazards Models for Survival Data: Asymptotic Results

We discuss the impact of misspecifying fully parametric proportional hazards and accelerated life models. For the uncensored case, misspecified accelerated life models give asymptotically unbiased estimates of covariate effect, but the shape and scale parameters depend on the misspecification. The covariate, shape and scale parameters differ in the censored case. Parametric proportional hazards models do not have a sound justification for general use: estimates from misspecified models can be very biased, and misleading results for the shape of the hazard function can arise. Misspecified survival functions are more biased at the extremes than the centre. Asymptotic and first order results are compared. If a model is misspecified, the size of Wald tests will be underestimated. Use of the sandwich estimator of standard error gives tests of the correct size, but misspecification leads to a loss of power. Accelerated life models are more robust to misspecification because of their log-linear form. In preliminary data analysis, practitioners should investigate proportional hazards and accelerated life models; software is readily available for several such models.     

Bayesian Transformation Models for Multivariate Survival Data

In this paper, we propose a general class of Gamma frailty transformation models for multivariate survival data. The transformation class includes the commonly used proportional hazards and proportional odds models. The proposed class also includes a family of cure rate models. Under an improper prior for the parameters, we establish propriety of the posterior distribution. A novel Gibbs sampling algorithm is developed for sampling from the observed data posterior distribution. A simulation study is conducted to examine the properties of the proposed methodology. An application to a data set from a cord blood transplantation study is also reported.     

Rank Tests for Clustered Survival Data

In a clinical trial, we may randomize subjects (called clusters) to different treatments (called groups), and make observations from multiple sites (called units) of each subject. In this case, the observations within each subject could be dependent, whereas those from different subjects are independent. If the outcome of interest is the time to an event, we may use the standard rank tests proposed for independent survival data, such as the logrank and Wilcoxon tests, to test the equality of marginal survival distributions, but their standard error should be modified to accommodate the possible intracluster correlation. In this paper we propose a method of calculating the standard error of the rank tests for two-sample clustered survival data. The method is naturally extended to that for K-sample tests under dependence.     

A Simulation Study Comparing Modeling Approaches in an Illness-Death Multi-State Model

In many medical studies, there are covariates that change their values over time and their analysis is most often modeled using the Cox regression model. However, many of these time-dependent covariates can be expressed as an intermediate event, which can be modeled using a multi-state model. Using the relationship of time-dependent (discrete) covariates and multi-state models, we compare (via simulation studies) the Cox model with time-dependent covariates with the most frequently used multi-state regression models. This article also details the procedures for generating survival data arising from all approaches, including the Cox model with time-dependent covariates.