Self-Consistency Estimation of Distributions Based on Truncated and Doubly Censored Survival Data with Applications to AIDS Cohort Studies

Gomez and Lagakos (1994) propose a nonparametric method for estimating the distribution of a survival time when the origin and end points defining the survival time suffer interval-censoring and right-censoring, respectively. In some situations, the end point also suffers interval-censoring as well as truncation. In this paper, we consider this general situation and propose a two-step estimation procedure for the estimation of the distribution of a survival time based on doubly interval-censored and truncated data. The proposed method generalizes the methods proposed by DeGruttola and Lagakos (1989) and Sun (1995) and is more efficient than that given in Gomez and Lagakos (1994). The approach is based on self-consistency equations. The method is illustrated by an analysis of an AIDS cohort study.     

Nonparametric estimation of current status data with dependent censoring

This paper discusses nonparametric estimation of a survival function when one observes only current status data (McKeown and Jewell, Lifetime Data Anal 16:215-230, 2010; Sun, The statistical analysis of interval-censored failure time data, 2006; Sun and Sun, Can J Stat 33:85-96, 2005). In this case, each subject is observed only once and the failure time of interest is observed to be either smaller or larger than the observation or censoring time. If the failure time and the observation time can be assumed to be independent, several methods have been developed for the problem. Here we will focus on the situation where the independent assumption does not hold and propose two simple estimation procedures under the copula model framework. The proposed estimates allow one to perform sensitivity analysis or identify the shape of a survival function among other uses. A simulation study performed indicates that the two methods work well and they are applied to a motivating example from a tumorigenicity study.     

A Nonparametric Test for Interval-Censored Failure Time Data with Unequal Censoring

This article considers nonparametric comparison of survival functions, one of the most commonly required task in survival studies. For this, several test procedures have been proposed for interval-censored failure time data in which distributions of censoring intervals are identical among different treatment groups. Sometimes the distributions may depend on treatments and thus not be the same. A class of test statistics is proposed for situations where the distributions may be different for subjects in different treatment groups. The asymptotic normality of the test statistics is established and the test procedure is evaluated by simulations, which suggest that it works well for practical situations. An illustrative example is provided.     

A semiparametric regression cure model for doubly censored data

This paper discusses regression analysis of doubly censored failure time data when there may exist a cured subgroup. By doubly censored data, we mean that the failure time of interest denotes the elapsed time between two related events and the observations on both event times can suffer censoring (Sun in The statistical analysis of interval-censored failure time data. Springer, New York, 2006). One typical example of such data is given by an acquired immune deficiency syndrome cohort study. Although many methods have been developed for their analysis (De Gruttola and Lagakos in Biometrics 45:1–12, 1989; Sun et al. in Biometrics 55:909–914, 1999; 60:637–643, 2004; Pan in Biometrics 57:1245–1250, 2001), it does not seem to exist an established method for the situation with a cured subgroup. This paper discusses this later problem and presents a sieve approximation maximum likelihood approach. In addition, the asymptotic properties of the resulting estimators are established and an extensive simulation study indicates that the method seems to work well for practical situations. An application is also provided.     

Testing the proportional odds model for interval-censored data

This paper discusses the goodness-of-fit test for the proportional odds model for K-sample interval-censored failure time data, which frequently occur in, for example, periodic follow-up survival studies. The proportional odds model has a feature that allows the ratio of two hazard functions to be monotonic and converge to one and provides an important tool for the modeling of survival data. To test the model, a procedure is proposed, which is a generalization of the method given in Dauxois and Kirmani [Dauxois JY, Kirmani SNUA (2003) Biometrika 90:913–922]. The asymptotic distribution of the procedure is established and its properties are evaluated by simulation studies     

A transformation approach for the analysis of interval-censored failure time data

This paper discusses the analysis of interval-censored failure time data, which has recently attracted a great amount of attention (Li and Pu, Lifetime Data Anal 9:57–70, 2003; Sun, The statistical analysis of interval-censored data, 2006; Tian and Cai, Biometrika 93(2):329–342, 2006; Zhang et al., Can J Stat 33:61–70, 2005). Interval-censored data mean that the survival time of interest is observed only to belong to an interval and they occur in many fields including clinical trials, demographical studies, medical follow-up studies, public health studies and tumorgenicity experiments. A major difficulty with the analysis of interval-censored data is that one has to deal with a censoring mechanism that involves two related variables. For the inference, we present a transformation approach that transforms general interval-censored data into current status data, for which one only needs to deal with one censoring variable and the inference is thus much easy. We apply this general idea to regression analysis of interval-censored data using the additive hazards model and numerical studies indicate that the method performs well for practical situations. An illustrative example is provided.     

A flexible Bayesian non-parametric approach for fitting the odds to case II interval-censored data

Interval-censored survival data arise often in medical applications and clinical trials [Wang L, Sun J, Tong X. Regression analyis of case II interval-censored failure time data with the additive hazards model. Statistica Sinica. 2010;20:1709–1723]. However, most of existing interval-censored survival analysis techniques suffer from challenges such as heavy computational cost or non-proportionality of hazard rates due to complicated data structure [Wang L, Lin X. A Bayesian approach for analyzing case 2 interval-censored data under the semiparametric proportional odds model. Statistics & Probability Letters. 2011;81:876–883; Banerjee T, Chen M-H, Dey DK, et al. Bayesian analysis of generalized odds-rate hazards models for survival data. Lifetime Data Analysis. 2007;13:241–260]. To address these challenges, in this paper, we introduce a flexible Bayesian non-parametric procedure for the estimation of the odds under interval censoring, case II. We use Bernstein polynomials to introduce a prior for modeling the odds and propose a novel and easy-to-implement sampling manner based on the Markov chain Monte Carlo algorithms to study the posterior distributions. We also give general results on asymptotic properties of the posterior distributions. The simulated examples show that the proposed approach is quite satisfactory in the cases considered. The use of the proposed method is further illustrated by analyzing the hemophilia study data [McMahan CS, Wang L. A package for semiparametric regression analysis of interval-censored data; 2015. http://CRAN.R-project.org/package=ICsurv.     

Non-parametric estimation with doubly censored data

Data from longitudinal studies in which an initiating event and a subsequent event occur in sequence are called 'doubly censored' data if the time of both events is interval-censored. This paper is concerned with using doubly censored data to estimate the distribution function of the so-called 'duration time', i.e. the elapsed time between the originating event and the subsequent event. The paper proposes a generalization of the Gomez and Lagakos two-step method for the case where both the time to the initiating event and the duration time are continuous. This approach is applied to estimate the AIDS-latency time from a haemophiliacs cohort.     

Maximum likelihood estimation for the proportional odds model with mixed interval-censored failure time data

This article discusses regression analysis of mixed interval-censored failure time data. Such data frequently occur across a variety of settings, including clinical trials, epidemiologic investigations, and many other biomedical studies with a follow-up component. For example, mixed failure times are commonly found in the two largest studies of long-term survivorship after childhood cancer, the datasets that motivated this work. However, most existing methods for failure time data consider only right-censored or only interval-censored failure times, not the more general case where times may be mixed. Additionally, among regression models developed for mixed interval-censored failure times, the proportional hazards formulation is generally assumed. It is well-known that the proportional hazards model may be inappropriate in certain situations, and alternatives are needed to analyze mixed failure time data in such cases. To fill this need, we develop a maximum likelihood estimation procedure for the proportional odds regression model with mixed interval-censored data. We show that the resulting estimators are consistent and asymptotically Gaussian. An extensive simulation study is performed to assess the finite-sample properties of the method, and this investigation indicates that the proposed method works well for many practical situations. We then apply our approach to examine the impact of age at cranial radiation therapy on risk of growth hormone deficiency in long-term survivors of childhood cancer.     

Bayesian statistical inference of the loglogistic model with interval-censored lifetime data

Interval-censored data arise when a failure time say, T cannot be observed directly but can only be determined to lie in an interval obtained from a series of inspection times. The frequentist approach for analysing interval-censored data has been developed for some time now. It is very common due to unavailability of software in the field of biological, medical and reliability studies to simplify the interval censoring structure of the data into that of a more standard right censoring situation by imputing the midpoints of the censoring intervals. In this research paper, we apply the Bayesian approach by employing Lindley's 1980, and Tierney and Kadane 1986 numerical approximation procedures when the survival data under consideration are interval-censored. The Bayesian approach to interval-censored data has barely been discussed in literature. The essence of this study is to explore and promote the Bayesian methods when the survival data been analysed are is interval-censored. We have considered only a parametric approach by assuming that the survival data follow a loglogistic distribution model. We illustrate the proposed methods with two real data sets. A simulation study is also carried out to compare the performances of the methods.     

Generalized Log-Rank Tests for Interval-Censored Failure Time Data

Abstract.  Several non-parametric test procedures have been proposed for incomplete survival data: interval-censored failure time data. However, most of them have unknown asymptotic properties with heuristically derived and/or complicated variance estimation. This article presents a class of generalized log-rank tests for this type of survival data and establishes their asymptotics. The methods are evaluated using simulation studies and illustrated by a set of real data from a cancer study.     

Joint analysis of interval-censored failure time data and panel count data

Interval-censored failure time data and panel count data are two types of incomplete data that commonly occur in event history studies and many methods have been developed for their analysis separately (Sun in The statistical analysis of interval-censored failure time data. Springer, New York, 2006; Sun and Zhao in The statistical analysis of panel count data. Springer, New York, 2013). Sometimes one may be interested in or need to conduct their joint analysis such as in the clinical trials with composite endpoints, for which it does not seem to exist an established approach in the literature. In this paper, a sieve maximum likelihood approach is developed for the joint analysis and in the proposed method, Bernstein polynomials are used to approximate unknown functions. The asymptotic properties of the resulting estimators are established and in particular, the proposed estimators of regression parameters are shown to be semiparametrically efficient. In addition, an extensive simulation study was conducted and the proposed method is applied to a set of real data arising from a skin cancer study.     

On estimation and diagnostics analysis in log-generalized gamma regression model for interval-censored data

The interval-censored survival data appear very frequently, where the event of interest is not observed exactly but it is only known to occur within some time interval. In this paper, we propose a location-scale regression model based on the log-generalized gamma distribution for modelling interval-censored data. We shall be concerned only with parametric forms. The proposed model for interval-censored data represents a parametric family of models that has, as special submodels, other regression models which are broadly used in lifetime data analysis. Assuming interval-censored data, we consider a frequentist analysis, a Jackknife estimator and a non-parametric bootstrap for the model parameters. We derive the appropriate matrices for assessing local influence on the parameter estimates under different perturbation schemes and present some techniques to perform global influence.     

Median regression model with left truncated and interval-censored data

We consider the problem of fitting a heteroscedastic median regression model from left-truncated and interval-censored data. It is demonstrated that the adapted Efron’s self-consistency equation of McKeague, Subramanian, and Sun (2001) can be extended to analyze left-truncated and interval-censored data. The asymptotic property of the proposed estimator is established. We evaluate the finite sample performance of the proposed estimators through simulation studies.     

Estimation of the Association for Bivariate Interval-censored Failure Time Data

Abstract.  Multivariate failure time data frequently occur in medical studies and the dependence or association among survival variables is often of interest ( Biometrics , 51 , 1995, 1384; Stat. Med. , 18 , 1999, 3101; Biometrika , 87 , 2000, 879; J. Roy. Statist. Soc. Ser. B , 65 , 2003, 257). We study the problem of estimating the association between two related survival variables when they follow a copula model and only bivariate interval-censored failure time data are available. For the problem, a two-stage estimation procedure is proposed and the asymptotic properties of the proposed estimator are established. Simulation studies are conducted to assess the finite sample properties of the presented estimate and the results suggest that the method works well for practical situations. An example from an acquired immunodeficiency syndrome clinical trial is discussed.     

The random partition masking model for interval-censored and masked competing risks data

We study the nonparametric maximum likelihood estimate (NPMLE) of the cdf or sub-distribution functions of the failure time for the failure causes in a series system. The study is motivated by a cancer research data (from the Memorial Sloan-Kettering Cancer Center) with interval-censored time and masked failure cause. The NPMLE based on this data set suggests that the existing masking models are not appropriate. We propose a new model called the random partition masking model, which does not rely on the commonly used symmetry assumption (namely, given the failure cause, the probability of observing the masked failure causes is independent of the failure time; see Flehinger et al. Inference about defects in the presence of masking, Technometrics 38 (1996), pp. 247–255). The RPM model is easier to implement in simulation studies than the existing models. We discuss the algorithms for computing the NPMLE and study its asymptotic properties. Our simulation and data analysis indicate that the NPMLE is feasible for a moderate sample size.     

Buckley–James-type estimation of quantile regression with recurrent gap time data

In longitudinal studies, an individual may potentially undergo a series of repeated recurrence events. The gap times, which are referred to as the times between successive recurrent events, are typically the outcome variables of interest. Various regression models have been developed in order to evaluate covariate effects on gap times based on recurrence event data. The proportional hazards model, additive hazards model, and the accelerated failure time model are all notable examples. Quantile regression is a useful alternative to the aforementioned models for survival analysis since it can provide great flexibility to assess covariate effects on the entire distribution of the gap time. In order to analyze recurrence gap time data, we must overcome the problem of the last gap time subjected to induced dependent censoring, when numbers of recurrent events exceed one time. In this paper, we adopt the Buckley–James-type estimation method in order to construct a weighted estimation equation for regression coefficients under the quantile model, and develop an iterative procedure to obtain the estimates. We use extensive simulation studies to evaluate the finite-sample performance of the proposed estimator. Finally, analysis of bladder cancer data is presented as an illustration of our proposed methodology.     

Semiparametric inference for a two-stage outcome-dependent sampling design with interval-censored failure time data

Lifetime Data Analysis - We propose a two-stage outcome-dependent sampling design and inference procedure for studies that concern interval-censored failure time outcomes. This design enhances the...     

Estimation and goodness-of-fit for the Cox model with various types of censored data

The currently existing estimation methods and goodness-of-fit tests for the Cox model mainly deal with right censored data, but they do not have direct extension to other complicated types of censored data, such as doubly censored data, interval censored data, partly interval-censored data, bivariate right censored data, etc. In this article, we apply the empirical likelihood approach to the Cox model with complete sample, derive the semiparametric maximum likelihood estimators (SPMLE) for the Cox regression parameter and the baseline distribution function, and establish the asymptotic consistency of the SPMLE. Via the functional plug-in method, these results are extended in a unified approach to doubly censored data, partly interval-censored data, and bivariate data under univariate or bivariate right censoring. For these types of censored data mentioned, the estimation procedures developed here naturally lead to Kolmogorov-Smirnov goodness-of-fit tests for the Cox model. Some simulation results are presented.     

Singly and Doubly Censored Current Status Data: Estimation, Asymptotics and Regression

In biostatistical applications interest often focuses on the estimation of the distribution of time between two consecutive events. If the initial event time is observed and the subsequent event time is only known to be larger or smaller than an observed point in time, then the data is described by the well-understood singly censored current status model, also known as interval censored data, case I. Jewell et al. (1994) extended this current status model by allowing the initial time to be unobserved, with its distribution over an observed interval [A, B] known; the data is referred to as doubly censored current status data. This model has applications in AIDS partner studies. If the initial time is known to be uniformly distribute d, the model reduces to a submodel of the current status model with the same asymptotic information bounds as in the current status model, but the distribution of interest is essentially the derivative of the distribution of interest in the current status model. As a consequence the non-parametric maximum likelihood estimator is inconsistent. Moreover, this submodel contains only smooth heavy tailed distributions for which no moments exist. In this paper, we discuss the connection between the singly censored current status model and the doubly censored current status model (for the uniform initial time) in detail and explain the difficulties in estimation which arise in the doubly censored case. We propose a regularized MLE corresponding with the current status model. We prove rate results, efficiency of smooth functionals of the regularized MLE, and present a generally applicable efficient method for estimation of regression parameters, which does not rely on the existence of moments. We also discuss extending these ideas to a non-uniform distribution for the initial time.