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

In incident cohort studies, it is common to include subjects who have experienced a certain event within a calendar time window. For all the included individuals, the time of the previous events is retrospectively confirmed and the occurrence of subsequent events is observed during the follow-up periods. During the follow-up periods, subjects may undergo three successive events. Since the second/third duration process becomes observable only if the first/second event has occurred, the data is subject to double truncation and right censoring. We consider two cases: the case when the first event time is subject to double truncation and the case when the second event time is subject to double truncation. Using the inverse-probability-weighted approach, we propose nonparametric and semiparametric estimators for the estimation of the joint survival function of three successive duration times. We establish the asymptotic properties of the proposed estimators and conduct a simulation study 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.     

Hazard-based nonparametric survivor function estimation

Summary.  A representation is developed that expresses the bivariate survivor function as a function of the hazard function for truncated failure time variables. This leads to a class of nonparametric survivor function estimators that avoid negative mass. The transformation from hazard function to survivor function is weakly continuous and compact differentiable, so that such properties as strong consistency, weak convergence to a Gaussian process and bootstrap applicability for a hazard function estimator are inherited by the corresponding survivor function estimator. The set of point mass assignments for a survivor function estimator is readily obtained by using a simple matrix calculation on the set of hazard rate estimators. Special cases arise from a simple empirical hazard rate estimator, and from an empirical hazard rate estimator following the redistribution of singly censored observations within strips. The latter is shown to equal van der Laan's repaired nonparametric maximum likelihood estimator, for which a Greenwood-like variance estimator is given. Simulation studies are presented to compare the moderate sample performance of various nonparametric survivor function estimators.     

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.     

Gamma failure‐time mixture models: yet another way to establish efficacy

Using a Yamaguchi‐type generalized gamma failure‐time mixture model, we analyse the data from a study of autologous and allogeneic bone marrow transplantation in the treatment of high‐risk refractory acute lymphoblastic leukaemia, focusing on the time to recurrence of disease. We develop maximum likelihood techniques for the joint estimation of the surviving fractions and the survivor functions. This includes an approximation to the derivative of the survivor function with respect to the shape parameter. We obtain the maximum likelihood estimates of the model parameters. We also compute the variance‐covariance matrix of the parameter estimators. The extended family of generalized gamma failure‐time mixture models is flexible enough to include many commonly used failure‐time distributions as special cases. Yet these models are not used in practice because of computational difficulties. We claim that we have overcome this problem. The proposed approximation to the derivative of the survivor function with respect to the shape parameter can be used in any statistical package. We also address the issue of lack of identifiability. We point out that there can be a substantial advantage to using the gamma failure‐time mixture models over nonparametric methods. Copyright © 2003 John Wiley & Sons, Ltd.     

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.     

Nonparametric Bayes estimation of gap-time distribution with recurrent event data

Nonparametric Bayes (NPB) estimation of the gap-time survivor function governing the time to occurrence of a recurrent event in the presence of censoring is considered. In our Bayesian approach, the gap-time distribution, denoted by F, has a Dirichlet process prior with parameter α. We derive NPB and nonparametric empirical Bayes (NPEB) estimators of the survivor function F?=1?F and construct point-wise credible intervals. The resulting Bayes estimator of F? extends that based on single-event right-censored data, and the PL-type estimator is a limiting case of this Bayes estimator. Through simulation studies, we demonstrate that the PL-type estimator has smaller biases but higher root-mean-squared errors (RMSEs) than those of the NPB and the NPEB estimators. Even in the case of a mis-specified prior measure parameter α, the NPB and the NPEB estimators have smaller RMSEs than the PL-type estimator, indicating robustness of the NPB and NPEB estimators. In addition, the NPB and NPEB estimators are smoother (in some sense) than the PL-type estimator.     

Nonparametric estimation of the conditional mean residual life function with censored data

The conditional mean residual life (MRL) function is the expected remaining lifetime of a system given survival past a particular time point and the values of a set of predictor variables. This function is a valuable tool in reliability and actuarial studies when the right tail of the distribution is of interest, and can be more informative than the survivor function. In this paper, we identify theoretical limitations of some semi-parametric conditional MRL models, and propose two nonparametric methods of estimating the conditional MRL function. Asymptotic properties such as consistency and normality of our proposed estimators are established. We investigate via simulation study the empirical properties of the proposed estimators, including bootstrap pointwise confidence intervals. Using Monte Carlo simulations we compare the proposed nonparametric estimators to two popular semi-parametric methods of analysis, for varying types of data. The proposed estimators are demonstrated on the Veteran’s Administration lung cancer trial.     

One‐sample and two‐sample analysis of heterogeneous person–time data in clinical trials

In this paper, we investigate the performance of different parametric and nonparametric approaches for analyzing overdispersed person–time–event rates in the clinical trial setting. We show that the likelihood‐based parametric approach may not maintain the right size for the tested overdispersed person–time–event data. The nonparametric approaches may use an estimator as either the mean of the ratio of number of events over follow‐up time within each subjects or the ratio of the mean of the number of events over the mean follow‐up time in all the subjects. Among these, the ratio of the means is a consistent estimator and can be studied analytically. Asymptotic properties of all estimators were studied through numerical simulations. This research shows that the nonparametric ratio of the mean estimator is to be recommended in analyzing overdispersed person–time data. When sample size is small, some resampling‐based approaches can yield satisfactory results. Copyright © 2012 John Wiley & Sons, Ltd.     

Nonparametric estimation in the illness-death model using prevalent data

We study nonparametric estimation of the illness-death model using left-truncated and right-censored data. The general aim is to estimate the multivariate distribution of a progressive multi-state process. Maximum likelihood estimation under censoring suffers from problems of uniqueness and consistency, so instead we review and extend methods that are based on inverse probability weighting. For univariate left-truncated and right-censored data, nonparametric maximum likelihood estimation can be considerably improved when exploiting knowledge on the truncation distribution. We aim to examine the gain in using such knowledge for inverse probability weighting estimators in the illness-death framework. Additionally, we compare the weights that use truncation variables with the weights that integrate them out, showing, by simulation, that the latter performs more stably and efficiently. We apply the methods to intensive care units data collected in a cross-sectional design, and discuss how the estimators can be easily modified to more general multi-state models.     

Nonparametric bayes estimation of the survival function from a record of failures and follow-ups

In some observational studies, we have random censoring model. However, the data available may be partially observable censored data consisting of the observed failure times and only those nonfailure times which are subject to follow-up. Suzuki (1985) discussed the problem of nonparametric estimation of the survival function from such partially observable censored data. In this article, we derive a nonparametric Bayes estimator of the survival function for such data of failures and follow-ups under a Dirichlet process prior and squared error loss. The limiting properties such as the mean square consistency, weak convergence and strong consistency of the Bayes estimator are studied. Finally, the procedures developed are illustrated by means of an example.     

Cross-validated mixed-datatype bandwidth selection for nonparametric cumulative distribution/survivor functions

ABSTRACT

We propose a computationally efficient data-driven least square cross-validation method to optimally select smoothing parameters for the nonparametric estimation of cumulative distribution/survivor functions. We allow for general multivariate covariates that can be continuous, discrete/ordered categorical or a mix of either. We provide asymptotic analysis, examine finite-sample properties through Monte Carlo simulation, and consider an illustration involving nonparametric copula modeling. We also demonstrate how the approach can also be used to construct a smooth Kolmogorov–Smirnov test that has a slightly better power profile than its nonsmooth counterpart.     

IMPROVING THE NUMERICAL TECHNIQUE FOR COMPUTING THE ACCUMULATED DISTRIBUTION OF A QUADRATIC FORM IN NORMAL VARIABLES

This paper is concerned with the technique of numerically evaluating the cumulative distribution function of a quadratic form in normal variables. The efficiency of two new truncation bounds and all existing truncation bounds are investigated. We also find that the suggestion in the literature for further splitting truncation errors might reduce computational efficiency, and the optimum splitting rate could be different in different situations. A practical solution is provided. The paper also discusses a modified secant algorithm for finding the critical value of the distribution at any given significance level.     

Multiple event times in the presence of informative censoring: modeling and analysis by copulas

Motivated by a breast cancer research program, this paper is concerned with the joint survivor function of multiple event times when their observations are subject to informative censoring caused by a terminating event. We formulate the correlation of the multiple event times together with the time to the terminating event by an Archimedean copula to account for the informative censoring. Adapting the widely used two-stage procedure under a copula model, we propose an easy-to-implement pseudo-likelihood based procedure for estimating the model parameters. The approach yields a new estimator for the marginal distribution of a single event time with semicompeting-risks data. We conduct both asymptotics and simulation studies to examine the proposed approach in consistency, efficiency, and robustness. Data from the breast cancer program are employed to illustrate this research.

     

IMPROVING THE NUMERICAL TECHNIQUE FOR COMPUTING THE ACCUMULATED DISTRIBUTION OF A QUADRATIC FORM IN NORMAL VARIABLES

ABSTRACT

This paper is concerned with the technique of numerically evaluating the cumulative distribution function of a quadratic form in normal variables. The efficiency of two new truncation bounds and all existing truncation bounds are investigated. We also find that the suggestion in the literature for further splitting truncation errors might reduce computational efficiency, and the optimum splitting rate could be different in different situations. A practical solution is provided. The paper also discusses a modified secant algorithm for finding the critical value of the distribution at any given significance level.     

Parametric Proportional Odds Frailty Models

We define a parametric proportional odds frailty model to describe lifetime data incorporating heterogeneity between individuals. An unobserved individual random effect, called frailty, acts multiplicatively on the odds of failure by time t. We investigate fitting by maximum likelihood and by least squares. For the latter, the parametric survivor function is fitted to the nonparametric Kaplan–Meier estimate at the observed failure times. Bootstrap standard errors and confidence intervals are obtained for the least squares estimates. The models are applied successfully to simulated data and to two real data sets. Least squares estimates appear to have smaller bias than maximum likelihood.     

Smooth Plug‐in Inverse Estimators in the Current Status Continuous Mark Model

Abstract. We consider the problem of estimating the joint distribution function of the event time and a continuous mark variable when the event time is subject to interval censoring case 1 and the continuous mark variable is only observed in case the event occurred before the time of inspection. The non‐parametric maximum likelihood estimator in this model is known to be inconsistent. We study two alternative smooth estimators, based on the explicit (inverse) expression of the distribution function of interest in terms of the density of the observable vector. We derive the pointwise asymptotic distribution of both estimators.     

Computationally simple estimation and improved efficiency for special cases of double truncation

Doubly truncated survival data arise when event times are observed only if they occur within subject specific intervals of times. Existing iterative estimation procedures for doubly truncated data are computationally intensive (Turnbull 38:290–295, 1976; Efron and Petrosian 94:824–825, 1999; Shen 62:835–853, 2010a). These procedures assume that the event time is independent of the truncation times, in the sample space that conforms to their requisite ordering. This type of independence is referred to as quasi-independence. In this paper we identify and consider two special cases of quasi-independence: complete quasi-independence and complete truncation dependence. For the case of complete quasi-independence, we derive the nonparametric maximum likelihood estimator in closed-form. For the case of complete truncation dependence, we derive a closed-form nonparametric estimator that requires some external information, and a semi-parametric maximum likelihood estimator that achieves improved efficiency relative to the standard nonparametric maximum likelihood estimator, in the absence of external information. We demonstrate the consistency and potentially improved efficiency of the estimators in simulation studies, and illustrate their use in application to studies of AIDS incubation and Parkinson’s disease age of onset.     

A simple,doubly robust,efficient estimator for survival functions using pseudo observations

Survival functions are often estimated by nonparametric estimators such as the Kaplan‐Meier estimator. For valid estimation, proper adjustment for confounding factors is needed when treatment assignment may depend on confounding factors. Inverse probability weighting is a commonly used approach, especially when there is a large number of potential confounders to adjust for. Direct adjustment may also be used if the relationship between the time‐to‐event and all confounders can be modeled. However, either approach requires a correctly specified model for the relationship between confounders and treatment allocation or between confounders and the time‐to‐event. We propose a pseudo‐observation–based doubly robust estimator, which is valid when either the treatment allocation model or the time‐to‐event model is correctly specified and is generally more efficient than the inverse probability weighting approach. The approach can be easily implemented using standard software. A simulation study was conducted to evaluate this approach under a number of scenarios, and the results are presented and discussed. The results confirm robustness and efficiency of the proposed approach. A real data example is also provided for illustration.     

Improving estimation efficiency for semi-competing risks data with partially observed terminal event

Semi-competing risks data arise when two types of events, non-terminal and terminal, may be observed. When the terminal event occurs first, it censors the non-terminal event. Otherwise the terminal event is observable after the occurrence of the non-terminal event. In practice, it can be hard to ascertain all terminal event information after the non-terminal event. Yu and Yiannoutsos [(2015), ‘Marginal and Conditional Distribution Estimation from Double-Sampled Semi-Competing Risks Data’, Scandinavian Journal of Statistics, 42, 87–103] considered a setting when the terminal event is ascertained via double sampling from only a subset of patients who experienced the non-terminal event. They discussed estimation for marginal and conditional distributions under this double sampled semi-competing risk data framework. We propose a more efficient estimation method in the same setting by fully utilising the non-terminal event information. The efficiency gain can be substantial as observed in our simulation study.