The Dynamic Model for Cancer Relapse Based on Two-Stage Model of Carcinogenesis

In this article, the time from the start of chemotherapy randomization until cancer relapse is of primary interest. Here, cancer relapse refers to the appearance of the first observable malignant clone after therapy. A dynamic model for cancer relapse after chemotherapy is developed. The model differs from the traditional cure rate models in that it takes into consideration the growth kinetics of malignant tumors using a two-stage carcinogenesis model. The survival and hazard functions for cancer relapse time are derived, and a simulation study is performed to validate the underlying model.     

Bayesian dynamic models for survival data with a cure fraction

In this paper, we propose a new class of semi-parametric cure rate models. Specifically, we construct dynamic models for piecewise hazard functions over a finite partition of the time axis. Allowing the size of partition and the levels of baseline hazard to be random, our proposed models provide a great flexibility in controlling the degree of parametricity in the right tail of the survival distribution and the amount of correlations among the log-baseline hazard levels. Several properties of the proposed models are derived, and propriety of the implied posteriors with improper noninformative priors for regression coefficients based on the proposed models is established for the fixed partition of the time axis. In addition, an efficient reversible jump computational algorithm is developed for carrying out posterior computation. A real data set from a melanoma clinical trial is analyzed in detail to further demonstrate the proposed methodology.     

Bayesian D-Optimal Designs for Poisson Regression Models

By incorporating informative and/or historical knowledge of the unknown parameters, Bayesian experimental design under the decision-theory framework can combine all the information available to the experimenter so that a better design may be achieved. Bayesian optimal designs for generalized linear regression models, especially for the Poisson regression model, is of interest in this article. In addition, lack of an efficient computational method in dealing with the Bayesian design leads to development of a hybrid computational method that consists of the combination of a rough global optima search and a more precise local optima search. This approach can efficiently search for the optimal design for multi-variable generalized linear models. Furthermore, the equivalence theorem is used to verify whether the design is optimal or not.     

A dynamic hurdle model for zero-inflated count data

Excess zeros are encountered in many empirical count data applications. We provide a new explanation of extra zeros, related to the underlying stochastic process that generates events. The process has two rates: a lower rate until the first event and a higher one thereafter. We derive the corresponding distribution of the number of events during a fixed period and extend it to account for observed and unobserved heterogeneity. An application to the socioeconomic determinants of the individual number of doctor visits in Germany illustrates the usefulness of the new approach.     

Estimating the causal effects in randomized trials for survival data with a cure fraction and non compliance

We consider causal inference in randomized studies for survival data with a cure fraction and all-or-none treatment non compliance. To describe the causal effects, we consider the complier average causal effect (CACE) and the complier effect on survival probability beyond time t (CESP), where CACE and CESP are defined as the difference of cure rate and non cured subjects’ survival probability between treatment and control groups within the complier class. These estimands depend on the distributions of survival times in treatment and control groups. Given covariates and latent compliance type, we model these distributions with transformation promotion time cure model whose parameters are estimated by maximum likelihood. Both the infinite dimensional parameter in the model and the mixture structure of the problem create some computational difficulties which are overcome by an expectation-maximization (EM) algorithm. We show the estimators are consistent and asymptotically normal. Some simulation studies are conducted to assess the finite-sample performance of the proposed approach. We also illustrate our method by analyzing a real data from the Healthy Insurance Plan of Greater New York.     

Linear transformation models for survival analysis with tumor growth information in cancer screening study

The complication in analyzing tumor data is that the tumors detected in a screening program tend to be slowly progressive tumors, which is the so-called left-truncated sampling that is inherent in screening studies. Under the assumption that all subjects have the same tumor growth function, Ghosh (2008 Ghosh, D. (2008). Proportional hazards regression for cancer studies. Biometrics 64:141–148.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) developed estimation procedures for the Cox proportional hazards model. Shen (2011a Shen, P.-S. (2011a). Proportional hazards regression for cancer screening data. J. Stat. Comput. Simul. 18:367–377.[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar]) demonstrated that Ghosh (2008 Ghosh, D. (2008). Proportional hazards regression for cancer studies. Biometrics 64:141–148.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar])'s approach can be extended to the case when each subject has a specific growth function. In this article, under linear transformation model, we present a general framework to the analysis of data from cancer screening studies. We developed estimation procedures under linear transformation model, which includes Cox's model as a special case. A simulation study is conducted to demonstrate the potential usefulness of the proposed estimators.     

Maximum likelihood estimation for tied survival data under Cox regression model via EM-algorithm

We consider tied survival data based on Cox proportional regression model. The standard approaches are the Breslow and Efron approximations and various so called exact methods. All these methods lead to biased estimates when the true underlying model is in fact a Cox model. In this paper we review the methods and suggest a new method based on the missing-data principle using EM-algorithm that leads to a score equation that can be solved directly. This score has mean zero. We also show that all the considered methods have the same asymptotic properties and that there is no loss of asymptotic efficiency when the tie sizes are bounded or even converge to infinity at a given rate. A simulation study is conducted to compare the finite sample properties of the methods.     

Semi-parametric extended Poisson process models for count data

A general framework for the analysis of count data (with covariates) is proposed using formulations for the transition rates of a state-dependent birth process. The form for the transition rates incorporates covariates proportionally, with the residual distribution determined from a smooth non-parametric state-dependent form. Computation of the resulting probabilities is discussed, leading to model estimation using a penalized likelihood function. Two data sets are used as illustrative examples, one representing underdispersed Poisson-like data and the other overdispersed binomial-like data.     

Approximate Bayesian Inference for Survival Models

Abstract. Bayesian analysis of time‐to‐event data, usually called survival analysis, has received increasing attention in the last years. In Cox‐type models it allows to use information from the full likelihood instead of from a partial likelihood, so that the baseline hazard function and the model parameters can be jointly estimated. In general, Bayesian methods permit a full and exact posterior inference for any parameter or predictive quantity of interest. On the other side, Bayesian inference often relies on Markov chain Monte Carlo (MCMC) techniques which, from the user point of view, may appear slow at delivering answers. In this article, we show how a new inferential tool named integrated nested Laplace approximations can be adapted and applied to many survival models making Bayesian analysis both fast and accurate without having to rely on MCMC‐based inference.     

Robust estimation for functional coefficient regression models with spatial data

A global smoothing procedure is developed using B-spline function approximation for estimating the unknown functions of a functional coefficient regression model with spatial data. A general formulation is used to treat mean regression, median regression, quantile regression and robust mean regression in one setting. The global convergence rates of the estimators of unknown coefficient functions are established. Various applications of the main results, including estimating conditional quantile coefficient functions and robustifying the mean regression coefficient functions are given. Finite sample properties of our procedures are studied through Monte Carlo simulations. A housing data example is used to illustrate the proposed methodology.     

Regression for censored survival data with lag effects

We consider regression modeling of survival data subject to right censoring when the full effect of some covariates (e.g. treatment) may be delayed. Several models are proposed, and methods for computing the maximum likelihood estimates of the parameters are described. Consistency and asymptotic normality properties of the estimators are derived. Some numerical examples are used to illustrate the implementation of the modeling and estimation procedures. Finally we apply the theory to interim data from a large scale randomized clinical trial for the prevention of skin cancer.     

Overdispersed poisson regression models for studies of air pollution and human health

This paper presents results from a simulation study motivated by a recent study of the relationships between ambient levels of air pollution and human health in the community of Prince George, British Columbia. The simulation study was designed to evaluate the performance of methods based on overdispersed Poisson regression models for the analysis of series of count data. Aspects addressed include estimation of the dispersion parameter, estimation of regression coefficients and their standard errors, and the performance of model selection tests. The effects of varying amounts of overdispersion and differing underlying variance structure on this performance were of particular interest. This study is related to work reported by Breslow (1990) although the context is quite different. Preliminary work led to the conclusion that estimation of the dispersion parameter should be based on Pearson's chi-square statistic rather than the Poisson deviance. Regression coefficients are well estimated, even in the présence of substantial overdispersion and when the model for the variance function is incorrectly specified. Despite potential greater variability, the empirical estimator of the covariance matrix is preferred because the model-based estimator is unreliable in general. When the model for the variance function is incorrect, model-based test statistics may perform poorly, in sharp contrast to empirical test statistics, which performed very well in this study.     

Modelling population-based cancer survival trends using join point models for grouped survival data

Summary.  In the USA cancer as a whole is the second leading cause of death and a major burden to health care; thus medical progress against cancer is a major public health goal. There are many individual studies to suggest that cancer treatment breakthroughs and early diagnosis have significantly improved the prognosis of cancer patients. To understand better the relationship between medical improvements and the survival experience for the patient population at large, it is useful to evaluate cancer survival trends on the population level, e.g. to find out when and how much the cancer survival rates changed. We analyse population-based grouped cancer survival data by incorporating join points into the survival models. A join point survival model facilitates the identification of trends with significant change-points in cancer survival, when related to cancer treatments or interventions. The Bayesian information criterion is used to select the number of join points. The performance of the join point survival models is evaluated with respect to cancer prognosis, join point locations, annual percentage changes in death rates by year of diagnosis and sample sizes through intensive simulation studies. The model is then applied to grouped relative survival data for several major cancer sites from the 'Surveillance, epidemiology and end results' programme of the National Cancer Institute. The change-points in the survival trends for several major cancer sites are identified and the potential driving forces behind such change-points are discussed.     

Joint modelling of pre-randomisation event counts and multiple post-randomisation survival times with cure rates: application to data for early epilepsy and single seizures

In this paper, we consider the analysis of recurrent event data that examines the differences between two treatments. The outcomes that are considered in the analysis are the pre-randomisation event count and post-randomisation times to first and second events with associated cure fractions. We develop methods that allow pre-randomisation counts and two post-randomisation survival times to be jointly modelled under a Poisson process framework, assuming that outcomes are predicted by (unobserved) event rates. We apply these methods to data that examine the difference between immediate and deferred treatment policies in patients presenting with single seizures or early epilepsy. We find evidence to suggest that post-randomisation seizure rates change at randomisation and following a first seizure after randomisation. We also find that there are cure rates associated with the post-randomisation times to first and second seizures. The increase in power over standard survival techniques, offered by the joint models that we propose, resulted in more precise estimates of the treatment effect and the ability to detect interactions with covariate effects.     

EM algorithm-based likelihood estimation for a generalized Gompertz regression model in presence of survival data with long-term survivors: an application to uterine cervical cancer data

In this paper we develop a regression model for survival data in the presence of long-term survivors based on the generalized Gompertz distribution introduced by El-Gohary et al. [The generalized Gompertz distribution. Appl Math Model. 2013;37:13–24] in a defective version. This model includes as special case the Gompertz cure rate model proposed by Gieser et al. [Modelling cure rates using the Gompertz model with covariate information. Stat Med. 1998;17:831–839]. Next, an expectation maximization algorithm is then developed for determining the maximum likelihood estimates (MLEs) of the parameters of the model. In addition, we discuss the construction of confidence intervals for the parameters using the asymptotic distributions of the MLEs and the parametric bootstrap method, and assess their performance through a Monte Carlo simulation study. Finally, the proposed methodology was applied to a database on uterine cervical cancer.     

Conditional Akaike Information Criteria for a Class of Poisson Mixture Models with Random Effects

Focusing on the model selection problems in the family of Poisson mixture models (including the Poisson mixture regression model with random effects and zero‐inflated Poisson regression model with random effects), the current paper derives two conditional Akaike information criteria. The criteria are the unbiased estimators of the conditional Akaike information based on the conditional log‐likelihood and the conditional Akaike information based on the joint log‐likelihood, respectively. The derivation is free from the specific parametric assumptions about the conditional mean of the true data‐generating model and applies to different types of estimation methods. Additionally, the derivation is not based on the asymptotic argument. Simulations show that the proposed criteria have promising estimation accuracy. In addition, it is found that the criterion based on the conditional log‐likelihood demonstrates good model selection performance under different scenarios. Two sets of real data are used to illustrate the proposed method.     

Stationary state space models for longitudinal data

The authors consider a class of state space models for the analysis of non‐normal longitudinal data whose latent process follows a stationary AR(1) model with exponential dispersion model margins. They propose to estimate parameters through an estimating equation approach based on the Kalman smoother. This allows them to carry out a straightforward analysis of a wide range of non‐normal data. They illustrate their approach via a simulation study and through analyses of Brazilian precipitation and US polio infection data.     

Tree-structured subgroup analysis for censored survival data: Validation of computationally inexpensive model selection criteria

The performance of computationally inexpensive model selection criteria in the context of tree-structured subgroup analysis is investigated. It is shown through simulation that no single model selection criterion exhibits a uniformly superior performance over a wide range of scenarios. Therefore, a two-stage approach for model selection is proposed and shown to perform satisfactorily. Applied example of subgroup analysis is presented. Problems associated with tree-structured subgroup analysis are discussed and practical solutions are suggested.