Estimation of the joint survival function for successive duration times

In incident cohort studies, survival data often include subjects who have experienced an initiate event but have not experienced a subsequent event at the calendar time of recruitment. During the follow-up periods, subjects may undergo a series of successive events. Since the second/third duration process becomes observable only if the first/second event has occurred, the data are subject to left-truncation and dependent censoring. In this article, using the inverse-probability-weighted (IPW) approach, we propose nonparametric estimators for the estimation of the joint survival function of three successive duration times. The asymptotic properties of the proposed estimators are established. The simple bootstrap methods are used to estimate standard deviations and construct interval estimators. A simulation study is conducted to investigate the finite sample properties of the proposed estimators.     

Estimation of the joint survival function for successive duration times under double-truncation and right-censoring

ABSTRACT

In incident cohort studies, survival data often include subjects who have had an initiate event at recruitment and may potentially experience two successive events (first and second) during the follow-up period. When disease registries or surveillance systems collect data based on incidence occurring within a specific calendar time interval, the initial event is usually subject to double truncation. Furthermore, since the second duration process is observable only if the first event has occurred, double truncation and dependent censoring arise. In this article, under the two sampling biases with an unspecified distribution of truncation variables, we propose a nonparametric estimator of the joint survival function of two successive duration times using the inverse-probability-weighted (IPW) approach. The consistency of the proposed estimator is established. Based on the estimated marginal survival functions, we also propose a two-stage estimation procedure for estimating the parameters of copula model. The bootstrap method is used to construct confidence interval. Numerical studies demonstrate that the proposed estimation approaches perform well with moderate sample sizes.     

Interval estimation of the joint survival function for successive duration times under left truncation and right censoring

In incident cohort studies, survival data often include subjects who have had an initiate event at recruitment and may potentially experience two successive events (first and second) during the follow-up period. Since the second duration process becomes observable only if the first event has occurred, left truncation and dependent censoring arise if the two duration times are correlated. To confront the two potential sampling biases, we propose two inverse-probability-weighted (IPW) estimators for the estimation of the joint survival function of two successive duration times. One of them is similar to the estimator proposed by Chang and Tzeng [Nonparametric estimation of sojourn time distributions for truncated serial event data – a weight adjusted approach, Lifetime Data Anal. 12 (2006), pp. 53–67]. The other is the extension of the nonparametric estimator proposed by Wang and Wells [Nonparametric estimation of successive duration times under dependent censoring, Biometrika 85 (1998), pp. 561–572]. The weak convergence of both estimators are established. Furthermore, the delete-one jackknife and simple bootstrap methods are used to estimate standard deviations and construct interval estimators. A simulation study is conducted to compare the two IPW approaches.     

Nonparametric Estimation of Sojourn Time Distributions for Truncated Serial Event Data—a Weight-adjusted Approach

In follow-up studies, survival data often include subjects who have had a certain event at recruitment and may potentially experience a series of subsequent events during the follow-up period. This kind of survival data collected under a cross-sectional sampling criterion is called truncated serial event data. The outcome variables of interest in this paper are serial sojourn times between successive events. To analyze the sojourn times in truncated serial event data, we need to confront two potential sampling biases arising simultaneously from a sampling criterion and induced informative censoring. In this study, nonparametric estimation of the joint probability function of serial sojourn times is developed by using inverse probabilities of the truncation and censoring times as weight functions to accommodate these two sampling biases under various situations of truncation and censoring. Relevant statistical properties of the proposed estimators are also discussed. Simulation studies and two real data are presented to illustrate the proposed methods.     

Estimating treatment effects on the marginal recurrent event mean in the presence of a terminating event

In biomedical studies where the event of interest is recurrent (e.g., hospitalization), it is often the case that the recurrent event sequence is subject to being stopped by a terminating event (e.g., death). In comparing treatment options, the marginal recurrent event mean is frequently of interest. One major complication in the recurrent/terminal event setting is that censoring times are not known for subjects observed to die, which renders standard risk set based methods of estimation inapplicable. We propose two semiparametric methods for estimating the difference or ratio of treatment-specific marginal mean numbers of events. The first method involves imputing unobserved censoring times, while the second methods uses inverse probability of censoring weighting. In each case, imbalances in the treatment-specific covariate distributions are adjusted out through inverse probability of treatment weighting. After the imputation and/or weighting, the treatment-specific means (then their difference or ratio) are estimated nonparametrically. Large-sample properties are derived for each of the proposed estimators, with finite sample properties assessed through simulation. The proposed methods are applied to kidney transplant data.     

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.     

Additive hazards model with truncated and doubly censored data

In longitudinal studies, the additive hazard model is often used to analyze covariate effects on the duration time, defined as the elapsed time between the first and the second event. In this article, we consider the situation when the first event suffers partly interval censoring and the second event suffers left truncation and right-censoring. We proposed a two-step estimation procedure for estimating the regression coefficients of the additive hazards model. A simulation study is conducted to investigate the performance of the proposed estimator. The proposed method is applied to the Centers for Disease Control acquired immune deficiency syndrome blood transfusion data.     

Analysis of transformation models with right-truncated data

In many applications, statistical data are frequently observed subject to a retrospective sampling criterion resulting in right-truncated data. In this article, a general class of semiparametric transformation models that include proportional hazards model and proportional odds model as special cases is studied for the analysis of right-truncated data. We proposed two estimators for regression coefficients. The first estimator is based on martingale estimating equations. The second estimator is based on the conditional likelihood function given the truncation times. The asymptotic properties of both estimators are derived. The finite sample performance is examined through a simulation study.     

A study of grouped failure time data and the misapplication of recurrent event modeling

Clinical trials often assess whether or not subjects have a disease at predetermined follow-up times. When the response of interest is a recurrent event, a subject may respond at multiple follow-up times over the course of the study. Alternatively, when the response of interest is an irreversible event, a subject is typically only observed until the time at which the response is first detected. However, some recent studies have recorded subjects responses at follow-up times after an irreversible event is initially observed. This study compares how existing models perform when failure time data are treated as recurrent events.     

Non parametric analysis of gap times for bivariate recurrent event data with cure fraction

Recurrent event data often arise in longitudinal studies. In many applications, subjects may experience two different types of events alternatively over time or a pair of subjects may experience recurrent events of the same type. Medical advances have made it possible for some patients to be cured such that the disease of interest does not recur. In this article, we consider non parametric analysis of bivariate recurrent event data with cure fraction. Using the inverse-probability weighted (IPW) approach, we propose non parametric estimators for the proportion of cured patients and for the joint distribution functions of bivariate recurrence times of the uncured ones. The asymptotic properties of the proposed estimators are established. Simulation study indicates that the proposed estimators perform well in finite samples.     

Joint modeling approach for semicompeting risks data with missing nonterminal event status

Semicompeting risks data, where a subject may experience sequential non-terminal and terminal events, and the terminal event may censor the non-terminal event but not vice versa, are widely available in many biomedical studies. We consider the situation when a proportion of subjects’ non-terminal events is missing, such that the observed data become a mixture of “true” semicompeting risks data and partially observed terminal event only data. An illness–death multistate model with proportional hazards assumptions is proposed to study the relationship between non-terminal and terminal events, and provide covariate-specific global and local association measures. Maximum likelihood estimation based on semiparametric regression analysis is used for statistical inference, and asymptotic properties of proposed estimators are studied using empirical process and martingale arguments. We illustrate the proposed method with simulation studies and data analysis of a follicular cell lymphoma study.     

Nonparametric estimators for a survivor function of paired recurrent events

Recurrent event data arise in longitudinal studies where each study subject may experience multiple events during the follow-up. In many situations in survival studies, pairs of individuals can potentially experience recurrent events. The analysis of such data is not straightforward as it involves two kinds of dependences, namely, dependence between the individuals in the same pair and dependence among a sequence of pairs. In the present paper, we introduce a new stochastic model for the analysis of such recurrent event data. Nonparametric estimators for a bivariate survivor function are developed. Asymptotic properties of the estimators are discussed. Simulation studies are carried out to assess the finite sample properties of the estimator. We illustrate the procedure with real life data on eye disease.     

BACKWARD ESTIMATION OF STOCHASTIC PROCESSES WITH FAILURE EVENTS AS TIME ORIGINS

Stochastic processes often exhibit sudden systematic changes in pattern a short time before certain failure events. Examples include increase in medical costs before death and decrease in CD4 counts before AIDS diagnosis. To study such terminal behavior of stochastic processes, a natural and direct way is to align the processes using failure events as time origins. This paper studies backward stochastic processes counting time backward from failure events, and proposes one-sample nonparametric estimation of the mean of backward processes when follow-up is subject to left truncation and right censoring. We will discuss benefits of including prevalent cohort data to enlarge the identifiable region and large sample properties of the proposed estimator with related extensions. A SEER-Medicare linked data set is used to illustrate the proposed methodologies.     

Marginal Means/Rates Models for Multiple Type Recurrent Event Data

Recurrent events are frequently observed in biomedical studies, and often more than one type of event is of interest. Follow-up time may be censored due to loss to follow-up or administrative censoring. We propose a class of semi-parametric marginal means/rates models, with a general relative risk form, for assessing the effect of covariates on the censored event processes of interest. We formulate estimating equations for the model parameters, and examine asymptotic properties of the parameter estimators. Finite sample properties of the regression coefficients are examined through simulations. The proposed methods are applied to a retrospective cohort study of risk factors for preschool asthma.     

Nonparametric estimation with left-truncated and right-censored data when the sample size before truncation is known

In this article, we consider nonparametric estimation of the survival function when the data are subject to left-truncation and right-censoring and the sample size before truncation is known. We propose two estimators. The first estimator is derived based on a self-consistent estimating equation. The second estimator is obtained by using the constrained expectation-maximization algorithm. Simulation results indicate that both estimators are more efficient than the product-limit estimator. When there is no censoring, the performance of the proposed estimators is compared with that of the estimator proposed by Li and Qin [Semiparametric likelihood-based inference for biased and truncated data when total sample size is known, J. R. Stat. Soc. B 60 (1998), pp. 243–254] via simulation study.     

Estimation of discrete survival function for error‐prone diagnostic tests

The product limit or Kaplan‐Meier (KM) estimator is commonly used to estimate the survival function in the presence of incomplete time to event. Application of this method assumes inherently that the occurrence of an event is known with certainty. However, the clinical diagnosis of an event is often subject to misclassification due to assay error or adjudication error, by which the event is assessed with some uncertainty. In the presence of such errors, the true distribution of the time to first event would not be estimated accurately using the KM method. We develop a method to estimate the true survival distribution by incorporating negative predictive values and positive predictive values, into a KM‐like method of estimation. This allows us to quantify the bias in the KM survival estimates due to the presence of misclassified events in the observed data. We present an unbiased estimator of the true survival function and its variance. Asymptotic properties of the proposed estimators are provided, and these properties are examined through simulations. We demonstrate our methods using data from the Viral Resistance to Antiviral Therapy of Hepatitis C study.     

Recurrent Events Analysis in the Presence of Terminal Event and Zero-recurrence Subjects

Recurrent event data are often encountered in longitudinal follow-up studies related to biomedical science, econometrics, reliability, and demography. In many situations, a terminal event such as death can happen during the follow-up period that precludes further recurrences. In this article, we will review some existing models for recurrent event with information censoring, and then extend them to allow zero-recurrence subjects as well as a terminal event. Estimating equations and partial likelihood are employed to estimate the coefficients of covariates, accumulative rate functions and the proportions of zero-recurrence subjects. The large-sample properties ofthe estimators are established as well. Simulations are performed to evaluate the estimationprocedure and an example of application on a set of migration data is provided to illustrateour proposed models and methods.     

Nonparametric analysis of recurrent gap time data

Abstract

Recurrent event data are frequently encountered in longitudinal studies. In many applications, the times between successive recurrent events (gap times) are often of interest and lead to problems that have received much attention recently. In this article, using the approach of inverse probability-of-censoring weights (IPCW), we propose nonparametric estimators for the estimation of the bivariate distribution and survival functions for gap times of recurrent event data. We also consider the estimation of Kendall’s tau for two gap times by expressing it as an integral functional of the bivariate survival function. The asymptotic properties of the proposed estimators are established. Simulation studies are conducted to investigate their finite sample performance.     

Nonparametric maximum likelihood estimation for artificially truncated absence data

In manpower planning it is cornmoniy tue case tnat employees withuraw from active service for a period of time before returning to take up post at a later date. Such periods of absence are frequently of major concern to employers who are anxious to ensure that employees return as soon as possible. The distribution of duration of such periods of absence are therefore of considerable interest as is the probability that such employees will ever return to active service. In this paper we derive a nonparametric estimator for such a lifetime distribution based on renewal data which are subject to various forms of incompleteness, namely right censoring, left and right truncation, and forward recurrence. Artificial truncation is used to ensure that the data are time homogeneous. A nonparametric maximum likelihood estimator for the lifetime.     

Estimation of the bivariate cause-specific distribution function with doubly censored competing risks data

In this article, we consider estimating the bivariate cause-specific distribution function when both components are subject to double censoring. We propose two types of estimators as generalizations of the Dabrowska and Campbell and Földes estimators. The asymptotical properties of the proposed estimators are established. A simulation study is conducted to investigate the performance of the proposed estimators.