Variable selection strategies in survival models with multiple imputations

In this paper, the variable selection strategies (criteria) are thoroughly discussed and their use in various survival models is investigated. The asymptotic efficiency property, in the sense of Shibata Ann Stat 8: 147-164, 1980, of a class of variable selection strategies which includes the AIC and all criteria equivalent to it, is established for a general class of survival models, such as parametric frailty or transformation models and accelerated failure time models, under minimum conditions. Furthermore, a multiple imputations method is proposed which is found to successfully handle censored observations and constitutes a competitor to existing methods in the literature. A number of real and simulated data are used for illustrative purposes.     

Multilevel models for longitudinal variables prognostic for survival

The issue of modelling the joint distribution of survival time and of prognostic variables measured periodically has recently become of interest in the AIDS literature but is of relevance in other applications. The focus of this paper is on clinical trials where follow-up measurements of potentially prognostic variables are often collected but not routinely used. These measurements can be used to study the biological evolution of the disease of interest; in particular the effect of an active treatment can be examined by comparing the time profiles of patients in the active and placebo group. It is proposed to use multilevel regression analysis to model the individual repeated observations as function of time and, possibly, treatment. To address the problem of informative drop-out—which may arise if deaths (or any other censoring events) are related to the unobserved values of the prognostic variables—we analyse sequentially overlapping portions of the follow-up information. An example arising from a randomized clinical trial for the treatment of primary biliary cirrhosis is examined in detail.     

An individual measure of relative survival

Summary.  Relative survival techniques are used to compare survival experience in a study cohort with that expected if background population rates apply. The techniques are especially useful when cause-specific death information is not accurate or not available as they provide a measure of excess mortality in a group of patients with a certain disease. Whereas these methods are based on group comparisons, we present here a transformation approach which instead gives for each individual an outcome measure relative to the appropriate background population. The new outcome measure is easily interpreted and can be analysed by using standard survival analysis techniques. It provides additional information on relative survival and gives new options in regression analysis. For example, one can estimate the proportion of patients who survived longer than a given percentile of the respective general population or compare survival experience of individuals while accounting for the population differences. The regression models for the new outcome measure are different from existing models, thus providing new possibilities in analysing relative survival data. One distinctive feature of our approach is that we adjust for expected survival before modelling. The paper is motivated by a study into the survival of patients after acute myocardial infarction.     

Mixture models in survival analysis: Are they worth the risk?

There has been a recurring interest in models for survival data which hypothesize subpopulations of individuals highly susceptible to some type of adverse event. Other individuals are assumed to be at much less risk. Most commonly, in clinical trials, these models attempt to estimate the fraction of patients cured of disease. The use of such models is examined, and the likelihood function is advocated as an informative inference tool.     

Profile likelihood approaches for semiparametric copula and frailty models for clustered survival data

ABSTRACT

In clustered survival data, the dependence among individual survival times within a cluster has usually been described using copula models and frailty models. In this paper we propose a profile likelihood approach for semiparametric copula models with different cluster sizes. We also propose a likelihood ratio method based on profile likelihood for testing the absence of association parameter (i.e. test of independence) under the copula models, leading to the boundary problem of the parameter space. For this purpose, we show via simulation study that the proposed likelihood ratio method using an asymptotic chi-square mixture distribution performs well as sample size increases. We compare the behaviors of the two models using the profile likelihood approach under a semiparametric setting. The proposed method is demonstrated using two well-known data sets.     

A New lifetime model for multivariate survival data with a surviving fraction

In this paper we propose a new lifetime model for multivariate survival data with a surviving fraction. We develop this model assuming that there are m types of unobservable competing risks, where each risk is related to a time of the occurrence of an event of interest. We explore the use of Markov chain Monte Carlo methods to develop a Bayesian analysis for the proposed model. We also perform a simulation study in order to analyse the frequentist coverage probabilities of credible interval derived from posteriors. Our modelling is illustrated through a real data set.     

Fully exponential Laplace approximations for the joint modelling of survival and longitudinal data

Summary.  A common objective in longitudinal studies is the joint modelling of a longitudinal response with a time-to-event outcome. Random effects are typically used in the joint modelling framework to explain the interrelationships between these two processes. However, estimation in the presence of random effects involves intractable integrals requiring numerical integration. We propose a new computational approach for fitting such models that is based on the Laplace method for integrals that makes the consideration of high dimensional random-effects structures feasible. Contrary to the standard Laplace approximation, our method requires much fewer repeated measurements per individual to produce reliable results.     

Bounds on the covariate-time transformation for competing-risks survival analysis

A fundamental problem with the latent-time framework in competing risks is the lack of identifiability of the joint distribution. Given observed covariates along with assumptions as to the form of their effect, then identifiability may obtain. However it is difficult to check any assumptions about form since a more general model may lose identifiability. This paper considers a general framework for modelling the effect of covariates, with the single assumption that the copula dependency structure of the latent times is invariant to the covariates. This framework consists of a set of functions: the covariate-time transformations. The main result produces bounds on these functions, which are derived solely from the crude incidence functions. These bounds are a useful model checking tool when considering the covariate-time transformation resulting from any particular set of further assumptions. An example is given where the widely-used assumption of independent competing risks is checked.     

Dynamic survival models with spatial frailty

In many survival studies, covariates effects are time-varying and there is presence of spatial effects. Dynamic models can be used to cope with the variations of the effects and spatial components are introduced to handle spatial variation. This paper proposes a methodology to simultaneously introduce these components into the model. A number of specifications for the spatial components are considered. Estimation is performed via a Bayesian approach through Markov chain Monte Carlo methods. Models are compared to assess relevance of their components. Analysis of a real data set is performed, showing the relevance of both time-varying covariate effects and spatial components. Extensions to the methodology are proposed along with concluding remarks.     

Nonparametric hypothesis testing in clustered survival model

A nonparametric test for the presence of clustering in survival data is proposed. Assuming a model that incorporates the clustering effect into the Cox Proportional Hazards model, simulation studies indicate that the procedure is correctly sized and powerful in a reasonably wide range of scenarios. The test for the presence of clustering over time is also robust to model misspecification. With large number of clusters, the test is powerful even if the data is highly heterogeneous.     

Unified multivariate survival model with a surviving fraction: an application to a Brazilian customer churn data

In this paper we propose a new lifetime model for multivariate survival data in presence of surviving fractions and examine some of its properties. Its genesis is based on situations in which there are m types of unobservable competing causes, where each cause is related to a time of occurrence of an event of interest. Our model is a multivariate extension of the univariate survival cure rate model proposed by Rodrigues et al. [37 J. Rodrigues, V.G. Cancho, M. de Castro, and F. Louzada-Neto, On the unification of long-term survival models, Statist. Probab. Lett. 79 (2009), pp. 753–759. doi: 10.1016/j.spl.2008.10.029[Crossref], [Web of Science ®] , [Google Scholar]]. The inferential approach exploits the maximum likelihood tools. We perform a simulation study in order to verify the asymptotic properties of the maximum likelihood estimators. The simulation study also focus on size and power of the likelihood ratio test. The methodology is illustrated on a real data set on customer churn data.     

The effect of classification errors in survival data analysis

Survival data analysis aims at collecting data on durations spent in a state by a sample of units, in order to analyse the process of transition to a different state. Survival analysis applied to social and economic phenomena typically relies upon data on transitions collected, for a sample of units, in one or more follow-up surveys. We explore the effect of misclassification of the transition indicator on parameter estimates in an appropriate statistical model for the duration spent in an origin state. Some empirical investigations about the bias induced when ignoring misclassification are reported, extending the model to include the possibility that the rate of misclassification can vary across units according to the value of some covariates. Finally it is shown how a Bayesian approach can lead to parameter estimates.     

Nonparametric modeling of clustered customer survival data

We incorporate a random clustering effect into the nonparametric version of Cox Proportional Hazards model to characterize clustered survival data. The simulation studies provide evidence that clustered survival data can be better characterized through a nonparametric model. Predictive accuracy of the nonparametric model is affected by number of clusters and distribution of the random component accounting for clustering effect. As the functional form of the covariate departs from linearity, the nonparametric model is becoming more advantageous over the parametric counterpart. Finally, nonparametric is better than parametric model when data are highly heterogenous and/or there is misspecification error.     

Bayesian significance test for discriminating between survival distributions

An evaluation of FBST, Fully Bayesian Significance Test, restricted to survival models is the main objective of the present paper. A Survival distribution should be chosen among the tree celebrated ones, lognormal, gamma, and Weibull. For this discrimination, a linear mixture of the three distributions is an important tool: the FBST is used to test the hypotheses defined on the mixture weights space. Another feature of the paper is that all three distributions are reparametrized in that all the six parameters are written as functions of the mean and the variance of the population been studied. Some numerical results from simulations with some right-censored data are considered.     

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.     

A flexible model for survival data with a cure rate: a Bayesian approach

In this paper we deal with a Bayesian analysis for right-censored survival data suitable for populations with a cure rate. We consider a cure rate model based on the negative binomial distribution, encompassing as a special case the promotion time cure model. Bayesian analysis is based on Markov chain Monte Carlo (MCMC) methods. We also present some discussion on model selection and an illustration with a real data set.     

Spatially explicit survival modeling for small area cancer data

In this paper we propose a novel Bayesian statistical methodology for spatial survival data. Our methodology broadens the definition of the survival, density and hazard functions by explicitly modeling the spatial dependency using direct derivations of these functions and their marginals and conditionals. We also derive spatially dependent likelihood functions. Finally we examine the applications of these derivations with geographically augmented survival distributions in the context of the Louisiana Surveillance, Epidemiology, and End Results registry prostate cancer data.     

Jointly modeling skew longitudinal survival data with missingness and mismeasured covariates

Jointly modeling longitudinal and survival data has been an active research area. Most researches focus on improving the estimating efficiency but ignore many data features frequently encountered in practice. In the current study, we develop the joint models that concurrently accounting for longitudinal and survival data with multiple features. Specifically, the proposed model handles skewness, missingness and measurement errors in covariates which are typically observed in the collection of longitudinal survival data from many studies. We employ a Bayesian inferential method to make inference on the proposed model. We applied the proposed model to an real data study. A few alternative models under different conditions are compared. We conduct extensive simulations in order to evaluate how the method works.     

Testing equality of survival distributions when the population marks are missing

This paper introduces a nonparametric approach for testing the equality of two or more survival distributions based on right censored failure times with missing population marks for the censored observations. The standard log-rank test is not applicable here because the population membership information is not available for the right censored individuals. We propose to use the imputed population marks for the censored observations leading to fractional at-risk sets that can be used in a two sample censored data log-rank test. We demonstrate with a simple example that there could be a gain in power by imputing population marks (the proposed method) for the right censored individuals compared to simply removing them (which also would maintain the right size). Performance of the imputed log-rank tests obtained this way is studied through simulation. We also obtain an asymptotic linear representation of our test statistic. Our testing methodology is illustrated using a real data set.