Statistical Analysis Of Interval Censored Failure Time Data

This book collects and unifies statistical models and methods that have been proposed for analyzing interval-censored failure time data. It provides the first comprehensive coverage of the topic of interval-censored data and complements the books on right-censored data. The focus of the book is on nonparametric and semiparametric inferences, but it also describes parametric and imputation approaches. This book provides an up-to-date reference for people who are conducting research on the analysis of interval-censored failure time data as well as for those who need to analyze interval-censored data to answer substantive questions.

Interval-Censored Time-to-Event Data: Methods and Applications collects the most recent techniques, models, and computational tools for interval-censored time-to-event data. Top biostatisticians from academia, biopharmaceutical industries, and government agencies discuss how these advances are impacting clinical trials and biomedical research.Divid

In this thesis, we will examine the statistical methods used in survival analysis applied to interval-censored failure time data. Interval-censored data is not widely used due to the fact that it is more difficult to work with. However, the same methods commonly used for random- censoring can be applied to interval-censoring as well. This includes finding the basic quantities, survival curves, regression analysis, Bayesian regression analysis and a comparison between interval-censored data and random-censored data.

Survival Analysis with Interval-Censored Data: A Practical Approach with Examples in R, SAS, and BUGS provides the reader with a practical introduction into the analysis of interval-censored survival times. Although many theoretical developments have appeared in the last fifty years, interval censoring is often ignored in practice. Many are unaware of the impact of inappropriately dealing with interval censoring. In addition, the necessary software is at times difficult to trace. This book fills in the gap between theory and practice. Features: -Provides an overview of frequentist as well as Bayesian methods. -Include a focus on practical aspects and applications. -Extensively illustrates the methods with examples using R, SAS, and BUGS. Full programs are available on a supplementary website. The authors: Kris Bogaerts is project manager at I-BioStat, KU Leuven. He received his PhD in science (statistics) at KU Leuven on the analysis of interval-censored data. He has gained expertise in a great variety of statistical topics with a focus on the design and analysis of clinical trials. Arnošt Komárek is associate professor of statistics at Charles University, Prague. His subject area of expertise covers mainly survival analysis with the emphasis on interval-censored data and classification based on longitudinal data. He is past chair of the Statistical Modelling Society and editor of Statistical Modelling: An International Journal. Emmanuel Lesaffre is professor of biostatistics at I-BioStat, KU Leuven. His research interests include Bayesian methods, longitudinal data analysis, statistical modelling, analysis of dental data, interval-censored data, misclassification issues, and clinical trials. He is the founding chair of the Statistical Modelling Society, past-president of the International Society for Clinical Biostatistics, and fellow of ISI and ASA.

A voluminous literature on right-censored failure time data has been developed in the past 30 years. Due to advances in biomedical research, interval censoring has become increasingly common in medical follow-up studies. In these cases, each study subject is examined or observed periodically, thus the observed failure time falls into a certain interval. Additional problems arise in the analysis of multivariate interval-censored failure time data. These include the estimating the correlation among failure times. The first part of this dissertation considers regression analysis of multivariate interval-censored failure time data using the proportional odds model. One situation in which the proportional odds model is preferred is when the covariate effects diminish over time. In contrast, if the proportional hazards model is applied for the situation, one may have to deal with time-dependent covariates. We present an inference approach for fitting the model to multivariate interval-censored failure time data. Simulation studies are conducted and an AIDS clinical trial is analyzed by using this methodology. The second part of this dissertation is devoted to the additive hazards model for multivariate interval-censored failure time data. In many applications, the proportional hazards model may not be appropriate and the additive hazards model provides an important and useful alternative. The presented estimates of regression parameters are consistent and asymptotically normal and a robust estimate of their covariance matrix is given that takes into account the correlation of the survival variables. Simulation studies are conducted for practical situations. The third part of this dissertation discusses regression analysis of multivariate interval censored failure time data using the frailty model approach. Based on the most commonly used regression model, the proportional hazards model, the frailty model approach considers the random effect directly models the correlation between multivariate failure times. For the analysis, we will focus on current status or case I interval-censored data and the maximum likelihood approach is developed for inference. The simulation studies are conducted to asses and compare the finite-sample behaviors of the estimators and we apply the proposed method to an animal tumorigenicity experiment.

This book primarily aims to discuss emerging topics in statistical methods and to booster research, education, and training to advance statistical modeling on interval-censored survival data. Commonly collected from public health and biomedical research, among other sources, interval-censored survival data can easily be mistaken for typical right-censored survival data, which can result in erroneous statistical inference due to the complexity of this type of data. The book invites a group of internationally leading researchers to systematically discuss and explore the historical development of the associated methods and their computational implementations, as well as emerging topics related to interval-censored data. It covers a variety of topics, including univariate interval-censored data, multivariate interval-censored data, clustered interval-censored data, competing risk interval-censored data, data with interval-censored covariates, interval-censored data from electric medical records, and misclassified interval-censored data. Researchers, students, and practitioners can directly make use of the state-of-the-art methods covered in the book to tackle their problems in research, education, training and consultation.

Interval-censored failure time data arises when the failure time of interest is known only to lie within an interval or window instead of being observed exactly. Many clinical trials and longitudinal studies may generate interval-censored data. One common area that often produces such data is medical or health studies with periodic follow-ups, in which the medical condition of interest such as the onset of a disease is only known to occur between two adjacent examination times. An important special case of interval-censored data is the so-called current status data when each study subject is observed only once for the status of the event of interest. That is, instead of observing the survival endpoint directly, we will only know the observation time and whether or not the event of interest has occurred by that time. Such data may occur in many fields as cross-sectional studies and tumorigenicity experiments. Sometimes we also refer current status data as case I interval-censored data and the general case as case II interval-censored data. Recently the semi-parametric statistical analysis of both case I and case II intervalcensored failure time data has attracted a great deal of attention. Many procedures have been proposed for their regression analysis under various models. We will describe the structure of interval-censored data in Chapter 1 and provides two specific examples. Also some special situations like informative censoring and failure time data with missing covariates are discussed. Besides, a brief review of the literature on some important topics, including nonparametric estimation and regression analysis are performed. However, there are still a number of problems that remain unsolved or lack approaches that are simpler, more efficient and could apply to more general situations compared to the existing ones. For regression analysis of interval-censored data, many approaches have been proposed and more specifically most of them are developed for the widely used proportional hazards model. The research in this dissertation focuses on the statistical analysis on non-proportional hazards models. In Chapter 2 we will discuss the regression analysis of interval-censored failure time data with possibly crossing hazards. For the problem of crossing hazards, people assume that the hazard functions with two samples considered may cross each other where most of the existing approaches cannot deal with such situation. Many authors has provided some efficient methods on right-censored failure time data, but little articles could be found on interval-censored data. By applying the short-term and long-term hazard ratio model, we develop a spline-based maximum likelihood estimation procedure to deal with this specific situation. In the method, a splined-based sieve estimation are used to approximate the underlying unknown function. The proposed estimators are shown to be strongly consistent and the asymptotic normality of the estimators of regression parameters are also shown to be true. In addition, we also provided a Cramer-Raw type of criterion to do the model validation. Simulation study was conducted for the assessment of the finite sample properties of the presented procedure and suggests that the method seems to work well for practical situations. Also an illustrative example using a data set from a tumor study is provided. As we discussed in Chapter 1, several semi-parametric and non-parametric methods have been proposed for the analysis of current status data. However, most of them only deal with the situation where observation time is independent of the underlying survival time. In Chapter 3, we consider regression analysis of current status data with informative observation times in additive hazards model. In many studies, the observation time may be correlated to the underlying failure time of interest, which is often referred to as informative censoring. Several authors have discussed the problem and in particular, an estimating equation-based approach for fitting current status data to additive hazards model has been proposed previously when informative censoring occurs. However, it is well known that such procedure may not be efficient and to address this, we propose a sieve maximum likelihood procedure. In particular, an EM algorithm is developed and the resulting estimators of regression parameters are shown to be consistent and asymptotically normal. An extensive simulation study was conducted for the assessment of the finite sample properties of the presented procedure and suggests that it seems to work well for practical situations. An application to a tumorigenicity experiment is also provided. In Chapter 4, we considered another special case under the additive hazards model, case II interval-censored data with possibly missing covariates. In many areas like demographical, epidemiological, medical and sociological studies, a number of nonparametric or semi-parametric methods have been developed for interval-censored data when the covariates are complete. However, it is well-known that in reality some covariates may suffer missingness due to various reasons, data with missing covariates could be very common in these areas. In the case of missing covariates, a naive method is clearly the complete-case analysis, which deletes the cases or subjects with missing covariates. However, it's apparent that such analysis could result in loss of efficiency and furthermore may lead to biased estimation. To address this, we propose the inverse probability weighted method and reweighting approach to estimate the regression parameters under the additive hazards model when some of the covariates are missing at random. The resulting estimators of regression parameters are shown to be consistent and asymptotically normal. Several numerical results suggest that the proposed method works well in practical situations. Also an application to a health survey is provided. Several directions for future research are discussed in Chapter 5.

This dissertation, "Analysis of Interval-censored Failure Time Data With Long-term Survivors" by Kin-yau, Wong, 黃堅祐, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Failure time data analysis, or survival analysis, is involved in various research fields, such as medicine and public health. One basic assumption in standard survival analysis is that every individual in the study population will eventually experience the event of interest. However, this assumption is usually violated in practice, for example when the variable of interest is the time to relapse of a curable disease resulting in the existence of long-term survivors. Also, presence of unobservable risk factors in the group of susceptible individuals may introduce heterogeneity to the population, which is not properly addressed in standard survival models. Moreover, the individuals in the population may be grouped in clusters, where there are associations among observations from a cluster. There are methodologies in the literature to address each of these problems, but there is yet no natural and satisfactory way to accommodate the coexistence of a non-susceptible group and the heterogeneity in the susceptible group under a univariate setting. Also, various kinds of associations among survival data with a cure are not properly accommodated. To address the above-mentioned problems, a class of models is introduced to model univariate and multivariate data with long-term survivors. A semiparametric cure model for univariate failure time data with long-term survivors is introduced. It accommodates a proportion of non-susceptible individuals and the heterogeneity in the susceptible group using a compound- Poisson distributed random effect term, which is commonly called a frailty. It is a frailty-Cox model which does not place any parametric assumption on the baseline hazard function. An estimation method using multiple imputation is proposed for right-censored data, and the method is naturally extended to accommodate interval-censored data. The univariate cure model is extended to a multivariate setting by introducing correlations among the compound- Poisson frailties for individuals from the same cluster. This multivariate cure model is similar to a shared frailty model where the degree of association among each pair of observations in a cluster is the same. The model is further extended to accommodate repeated measurements from a single individual leading to serially correlated observations. Similar estimation methods using multiple imputation are developed for the multivariate models. The univariate model is applied to a breast cancer data and the multivariate models are applied to the hypobaric decompression sickness data from National Aeronautics and Space Administration, although the methodologies are applicable to a wide range of data sets. DOI: 10.5353/th_b4819947 Subjects: Failure time data analysis Survival analysis (Biometry)

Data from clinical trials and epidemiological studies are often incomplete due to interval censoring and truncation. In this thesis, we will discuss the statistical analysis of survival data with interval-censoring and truncation. First, we consider the problem of comparing two failure time distributions based on interval-censored data. We propose three classes of nonparametric test procedures, which include most existing methods as special cases. To evaluate and compare the proposed and existing tests and to draw a guideline for selecting an appropriate test for a given situation, an extensive simulation study is conducted. Secondly, we consider the problem of estimating a survival function when there exists a change point. To obtain the maximum likelihood estimator of a survival function in this case, an EM algorithm is developed when the survival function is completely unknown before the change point and known up to a vector of unknown parameters after the change point. We evaluate the performance of the proposed algorithm and illustrate it using a set of survival data arising from an AIDS study. Thirdly, we consider a regression analysis of survival data with interval-censored covariates. To estimate regression parameters, methods based on estimating equations are developed. An extensive simulation study is performed to evaluate the proposed method.

Panel count data occur in studies that concern recurrent events, or event history studies, when study subjects are observed only at discrete time points. By recurrent events, we mean the event that can occur or happen multiple times or repeatedly. Examples of recurrent events include disease infections, hospitalizations in medical studies, warranty claims of automobiles or system break-downs in reliability studies. In fact, many other fields yield event history data too such as demographic studies, economic studies and social sciences. For the cases where the study subjects are observed continuously, the resulting data are usually referred to as recurrent event data. This book collects and unifies statistical models and methods that have been developed for analyzing panel count data. It provides the first comprehensive coverage of the topic. The main focus is on methodology, but for the benefit of the reader, the applications of the methods to real data are also discussed along with numerical calculations. There exists a great deal of literature on the analysis of recurrent event data. This book fills the void in the literature on the analysis of panel count data. This book provides an up-to-date reference for scientists who are conducting research on the analysis of panel count data. It will also be instructional for those who need to analyze panel count data to answer substantive research questions. In addition, it can be used as a text for a graduate course in statistics or biostatistics that assumes a basic knowledge of probability and statistics.