Graphical representation of survival curves in the presence of time-dependent categorical covariates with application to liver transplantation

Graphical representation of survival curves is often used to illustrate associations between exposures and time-to-event outcomes. However, when exposures are time-dependent, calculation of survival probabilities is not straightforward. Our aim was to develop a method to estimate time-dependent survival probabilities and represent them graphically. Cox models with time-dependent indicators to represent state changes were fitted, and survival probabilities were plotted using pre-specified times of state changes. Time-varying hazard ratios for the state change were also explored. The method was applied to data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Survival curves showing a ‘split’ at a pre-specified time t allow for the qualitative comparison of survival probabilities between patients with similar baseline covariates who do and do not experience a state change at time t. Time since state change interactions can be visually represented to reflect changing hazard ratios over time. A2ALL study results showed differences in survival probabilities among those who did not receive a transplant, received a living donor transplant, and received a deceased donor transplant. These graphical representations of survival curves with time-dependent indicators improve upon previous methods and allow for clinically meaningful interpretation.     

Fitting Weibull duration models with random effects

Duration time models often should include correlated failure times, due to clustered data. These random effects hierarchical models sometimes are called frailty models when used for survival analyses. The data analyzed here involve such correlations because patient level outcomes (the times until graft failure following kidney transplantation) are observed, but patients are clustered in different transplant centers. We describe fitting such models by combining two kinds of software, one for parametric survival regression models, and the other for doing Poisson regression in a hierarchical setting. The latter is implemented by using PRIMM (Poisson Regression and Interactive Multilevel Modeling) methods and software (Christiansen & Morris, 1994a). An illustrative example for profiling data is included withk=11 kidney transplant centers andN=412 patients.     

Weibull multi-state models with misclassification

It is often important to allow multi-state models (MSMs) to accommodate misclassification of states. We introduce Bayesian parametric MSMs with unknown misclassification of states and Weibull distributed waiting times between states. This allows transitions between states to depend on the time spent in the current state, a feature lacking in commonly used exponential waiting times model. To fit the proposed model, a MCMC algorithm was employed. An example on the progression of bipolar disorder is presented along with simulation results. There was evidence that Weibull waiting times are an improvement over exponential in the study of bipolar disorder.     

Bayesian longitudinal models for paediatric kidney transplant recipients

Chronic kidney disease is a progressive loss of renal function which results in the inability of the kidneys to properly filter waste from the blood. Renal function is usually estimated by the glomerular filtration rate (eGFR), which decreases with the worsening of the disease. Bayesian longitudinal models with covariates, random effects, serial correlation and measurement error are discussed to analyse the progression of eGFR in first transplanted children taken from a study in València, Spain.     

Adaptive truncated weighting for improving marginal structural model estimation of treatment effects informally censored by subsequent therapy

Randomized clinical trials are designed to estimate the direct effect of a treatment by randomly assigning patients to receive either treatment or control. However, in some trials, patients who discontinued their initial randomized treatment are allowed to switch to another treatment. Therefore, the direct treatment effect of interest may be confounded by subsequent treatment. Moreover, the decision on whether to initiate a second‐line treatment is typically made based on time‐dependent factors that may be affected by prior treatment history. Due to these time‐dependent confounders, traditional time‐dependent Cox models may produce biased estimators of the direct treatment effect. Marginal structural models (MSMs) have been applied to estimate causal treatment effects even in the presence of time‐dependent confounders. However, the occurrence of extremely large weights can inflate the variance of the MSM estimators. In this article, we proposed a new method for estimating weights in MSMs by adaptively truncating the longitudinal inverse probabilities. This method provides balance in the bias variance trade‐off when large weights are inevitable, without the ad hoc removal of selected observations. We conducted simulation studies to explore the performance of different methods by comparing bias, standard deviation, confidence interval coverage rates, and mean square error under various scenarios. We also applied these methods to a randomized, open‐label, phase III study of patients with nonsquamous non‐small cell lung cancer. Copyright © 2015 John Wiley & Sons, Ltd.     

Shared frailty models with baseline generalized Pareto distribution

Abstract

In this article, we have considered three different shared frailty models under the assumption of generalized Pareto Distribution as baseline distribution. Frailty models have been used in the survival analysis to account for the unobserved heterogeneity in an individual risks to disease and death. These three frailty models are with gamma frailty, inverse Gaussian frailty and positive stable frailty. Then we introduce the Bayesian estimation procedure using Markov chain Monte Carlo (MCMC) technique to estimate the parameters. We applied these three models to a kidney infection data and find the best fitted model for kidney infection data. We present a simulation study to compare true value of the parameters with the estimated values. Model comparison is made using Bayesian model selection criterion and a well-fitted model is suggested for the kidney infection data.     

Testing for Linear Regression Relationships in Randomly Right-Censored Varying-Coefficient Models

A test statistic is constructed to test linear relationships in randomly right-censored varying-coefficient models. A residual-based bootstrap procedure is employed to derive the p-value of the test. The performance of the test is examined by extensive simulations. The simulation results show that the bootstrap estimate of the null distribution of the test statistic is approximately valid and the test method with the residual-based bootstrap works satisfactorily for at least moderate censoring rates of the response. Furthermore, the proposed test is applied to the Stanford heart transplant data for exploring a linear regression relationship between the logrithm of the survival time and the age of the patients.     

Intermediate clinical events,surrogate markers and survival

This paper investigates one- and two-sample problems comparing survival times when an individual may experience an intermediate event prior to death or reaching some well defined endpoint. The intermediate event may be polychotomous. Patients experiencing the intermediate event may have an altered survival distribution after the intermediate event. Score tests are derived for testing if the occurrence of the intermediate event actually alters survival. These models have implications for evaluating therapies without randomization as well as strengthening the log rank test for comparing two survival distributions. The exact distribution of the score tests can be found by conditioning on both the waiting time and occurrence of the intermedate event.Deceased     

Longitudinal data analysis of mean passage time among malnutrition states: an application of Markov chains

Clinical prognosis of patients can be best described from a longitudinal study and a Markov regression model is an appropriate way of analyzing the prognosis of disease when the outcomes are serially dependent. Mean first passage time (MFPT) is a method to estimate the average number of transitions between the states of a Markov chain. The present study used the secondary data from a longitudinal study which was done during 1982–1986. This study was to illustrate the MFPT among the states of malnutrition, which were classified as Normal, Mild/Moderate and Severe among children aged 5–7 years, in South India. The 95% confidence interval (CI) for the MFPT was calculated using Monte Carlo simulation. Markov regression models were used to test for the association of state transitions across the risk factors. The average time taken for an underweight child to transit from Severe state of malnutrition to become Normal was nearly 2.73 (95% CI 2.60–2.86) years and 3.41 (95% CI 3.25–3.58) years in Rural area and 2.31(95% CI 2.20–2.42) in Urban area. The significant difference between the MFPT for some risk factors are useful to plan interventions. It will especially be useful to find the impact of duration among school-going children on their cognitive disorders.     

The analysis of transition times in multistate stochastic processes using proportional hazard regression models

Extensions to Cox's proportional hazards regression model (Cox, 1972) for the analysis of survival data are considered for a more general multistate framework. This framework allows several transient disease states between initial entry state and death as well as incorporating possible competing causes of death. Methods for parameter and function estimation within this extension are presented and applied to the analysis of data from the Stanford Heart Transplantation Program (Crowley and Hu,1977).     

Reliability Evaluation for a Multi-State System Under Stress-Strength Setup

The two most commonly used reliability models in engineering applications are binary k-out-of-n:G and consecutive k-out-of-n:G systems. Multi-state k-out-of-n:G and multi-state consecutive k-out-of-n:G systems have been proposed as an extension of these systems and they have been found to be more flexible tool for modeling engineering systems. In this article, multi-state systems, in particular, multi-state k-out-of-n:G and multi-state consecutive k-out-of-n:G, are considered in a stress-strength setup. The states of the system are classified considering the number of components whose strengths above (below) the multiple stresses available in an environment. The exact state probabilities are provided and the results are illustrated for various stress-strength distributions. Maximum likelihood estimators of state probabilities are also presented.     

Testing Heterogeneity for Frailty Distribution in Shared Frailty Model

Abstract

The frailties, representing extra variations due to unobserved measurements, are often assumed to be iid in shared frailty models. In medical applications, however, a speculation can arise that a data set might violate the iid assumption. In this paper we investigate this conjecture through an analysis of the kidney infection data in McGilchrist and Aisbett (McGilchrist, C. A., Aisbett, C. W. (1991). Regression with frailty in survival analysis. Biometrics 47:461–466). As a test procedure, we consider the cusum of squares test which is frequently used for monitoring a variance change in statistical models. Our result strongly sustains the heterogeneity of the frailty distribution.     

Semiparametric inference for survival models with step process covariates

The authors consider Bayesian methods for fitting three semiparametric survival models, incorporating time‐dependent covariates that are step functions. In particular, these are models due to Cox [Cox ( 1972 ) Journal of the Royal Statistical Society, Series B, 34, 187–208], Prentice & Kalbfleisch and Cox & Oakes [Cox & Oakes ( 1984 ) Analysis of Survival Data, Chapman and Hall, London]. The model due to Prentice & Kalbfleisch [Prentice & Kalbfleisch ( 1979 ) Biometrics, 35, 25–39], which has seen very limited use, is given particular consideration. The prior for the baseline distribution in each model is taken to be a mixture of Polya trees and posterior inference is obtained through standard Markov chain Monte Carlo methods. They demonstrate the implementation and comparison of these three models on the celebrated Stanford heart transplant data and the study of the timing of cerebral edema diagnosis during emergency room treatment of diabetic ketoacidosis in children. An important feature of their overall discussion is the comparison of semi‐parametric families, and ultimate criterion based selection of a family within the context of a given data set. The Canadian Journal of Statistics 37: 60–79; © 2009 Statistical Society of Canada     

Transient Analysis of Large Markov Models with Absorbing States Using Regenerative Randomization

ABSTRACT

In this article, we develop a new method, called regenerative randomization, for the transient analysis of continuous time Markov models with absorbing states. The method has the same good properties as standard randomization: numerical stability, well-controlled computation error, and ability to specify the computation error in advance. The method has a benign behavior for large t and is significantly less costly than standard randomization for large enough models and large enough t. For a class of models, class C, including typical failure/repair reliability models with exponential failure and repair time distributions and repair in every state with failed components, stronger theoretical results are available assessing the efficiency of the method in terms of “visible” model characteristics. A large example belonging to that class is used to illustrate the performance of the method and to show that it can indeed be much faster than standard randomization.     

Correlated gamma frailty models for bivariate survival data

Frailty models are used in the survival analysis to account for the unobserved heterogeneity in individual risks to disease and death. To analyze the bivariate data on related survival times (e.g., matched pairs experiments, twin or family data) the shared frailty models were suggested. Shared frailty models are used despite their limitations. To overcome their disadvantages correlated frailty models may be used. In this article, we introduce the gamma correlated frailty models with two different baseline distributions namely, the generalized log logistic, and the generalized Weibull. We introduce the Bayesian estimation procedure using Markov chain Monte Carlo (MCMC) technique to estimate the parameters involved in these models. We present a simulation study to compare the true values of the parameters with the estimated values. Also we apply these models to a real life bivariate survival dataset related to the kidney infection data and a better model is suggested for the data.     

The additive hazard estimator is consistent for continuous-time marginal structural models

Lifetime Data Analysis - Marginal structural models (MSMs) allow for causal analysis of longitudinal data. The standard MSM is based on discrete time models, but the continuous-time MSM is a...     

A joint latent class changepoint model to improve the prediction of time to graft failure

Summary.  The reciprocal of serum creatinine concentration, RC, is often used as a biomarker to monitor renal function. It has been observed that RC trajectories remain relatively stable after transplantation until a certain moment, when an irreversible decrease in the RC levels occurs. This decreasing trend commonly precedes failure of a graft. Two subsets of individuals can be distinguished according to their RC trajectories: a subset of individuals having stable RC levels and a subset of individuals who present an irrevocable decrease in their RC levels. To describe such data, the paper proposes a joint latent class model for longitudinal and survival data with two latent classes. RC trajectories within latent class one are modelled by an intercept-only random-effects model and RC trajectories within latent class two are modelled by a segmented random changepoint model. A Bayesian approach is used to fit this joint model to data from patients who had their first kidney transplantation in the Leiden University Medical Center between 1983 and 2002. The resulting model describes the kidney transplantation data very well and provides better predictions of the time to failure than other joint and survival models.     

Switching nonparametric regression models

We propose a methodology to analyse data arising from a curve that, over its domain, switches among J states. We consider a sequence of response variables, where each response y depends on a covariate x according to an unobserved state z. The states form a stochastic process and their possible values are j=1,?…?, J. If z equals j the expected response of y is one of J unknown smooth functions evaluated at x. We call this model a switching nonparametric regression model. We develop an Expectation–Maximisation algorithm to estimate the parameters of the latent state process and the functions corresponding to the J states. We also obtain standard errors for the parameter estimates of the state process. We conduct simulation studies to analyse the frequentist properties of our estimates. We also apply the proposed methodology to the well-known motorcycle dataset treating the data as coming from more than one simulated accident run with unobserved run labels.     

Analysis of cure rate survival data under proportional odds model

Due to significant progress in cancer treatments and management in survival studies involving time to relapse (or death), we often need survival models with cured fraction to account for the subjects enjoying prolonged survival. Our article presents a new proportional odds survival models with a cured fraction using a special hierarchical structure of the latent factors activating cure. This new model has same important differences with classical proportional odds survival models and existing cure-rate survival models. We demonstrate the implementation of Bayesian data analysis using our model with data from the SEER (Surveillance Epidemiology and End Results) database of the National Cancer Institute. Particularly aimed at survival data with cured fraction, we present a novel Bayes method for model comparisons and assessments, and demonstrate our new tool’s superior performance and advantages over competing tools.     

Costing Mixed Coxian Phase-type Systems with Poisson Arrivals

Previously, we developed a modeling framework which classifies individuals with respect to their length of stay (LOS) in the transient states of a continuous-time Markov model with a single absorbing state; phase-type models are used for each class of the Markov model. We here add costs and obtain results for moments of total costs in (0, t], for an individual, a cohort arriving at time zero and when arrivals are Poisson. Based on stroke patient data from the Belfast City Hospital we use the overall modelling framework to obtain results for total cost in a given time interval.