Proportional hazards regression with interval-censored and left-truncated data

This paper considers the estimation of the regression coefficients in the Cox proportional hazards model with left-truncated and interval-censored data. Using the approaches of Pan [A multiple imputation approach to Cox regression with interval-censored data, Biometrics 56 (2000), pp. 199–203] and Heller [Proportional hazards regression with interval censored data using an inverse probability weight, Lifetime Data Anal. 17 (2011), pp. 373–385], we propose two estimates of the regression coefficients. The first estimate is based on a multiple imputation methodology. The second estimate uses an inverse probability weight to select event time pairs where the ordering is unambiguous. A simulation study is conducted to investigate the performance of the proposed estimators. The proposed methods are illustrated using the Centers for Disease Control and Prevention (CDC) acquired immunodeficiency syndrome (AIDS) Blood Transfusion Data.     

Multiple imputation for competing risks regression with interval-censored data

ABSTRACT

We present here an extension of Pan's multiple imputation approach to Cox regression in the setting of interval-censored competing risks data. The idea is to convert interval-censored data into multiple sets of complete or right-censored data and to use partial likelihood methods to analyse them. The process is iterated, and at each step, the coefficient of interest, its variance–covariance matrix, and the baseline cumulative incidence function are updated from multiple posterior estimates derived from the Fine and Gray sub-distribution hazards regression given augmented data. Through simulation of patients at risks of failure from two causes, and following a prescheduled programme allowing for informative interval-censoring mechanisms, we show that the proposed method results in more accurate coefficient estimates as compared to the simple imputation approach. We have implemented the method in the MIICD R package, available on the CRAN website.     

Shared frailty model for recurrent event data with multiple causes

The topic of heterogeneity in the analysis of recurrent event data has received considerable attention recent times. Frailty models are widely employed in such situations as they allow us to model the heterogeneity through common random effect. In this paper, we introduce a shared frailty model for gap time distributions of recurrent events with multiple causes. The parameters of the model are estimated using EM algorithm. An extensive simulation study is used to assess the performance of the method. Finally, we apply the proposed model to a real-life data.     

Estimation of the additive hazards model with interval-censored data and missing covariates

The additive hazards model is one of the most commonly used regression models in the analysis of failure time data and many methods have been developed for its inference in various situations. However, no established estimation procedure exists when there are covariates with missing values and the observed responses are interval-censored; both types of complications arise in various settings including demographic, epidemiological, financial, medical and sociological studies. To address this deficiency, we propose several inverse probability weight-based and reweighting-based estimation procedures for the situation where covariate values are missing at random. The resulting estimators of regression model parameters are shown to be consistent and asymptotically normal. The numerical results that we report from a simulation study suggest that the proposed methods work well in practical situations. An application to a childhood cancer survival study is provided. The Canadian Journal of Statistics 48: 499–517; 2020 © 2020 Statistical Society of Canada     

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.     

Using Frailties in the Accelerated Failure Time Model

The accelerated failuretime (AFT) model is an important alternative to the Cox proportionalhazards model (PHM) in survival analysis. For multivariate failuretime data we propose to use frailties to explicitly account forpossible correlations (and heterogeneity) among failure times.An EM-like algorithm analogous to that in the frailty model forthe Cox model is adapted. Through simulation it is shown thatits performance compares favorably with that of the marginalindependence approach. For illustration we reanalyze a real dataset.     

Additive risks regression model for middle censored exponentiated-exponential lifetime data

Jammalamadaka and Mangalam introduced middle censoring which refers to data arising in situations, where the exact lifetime becomes unobservable if it falls within a random censoring interval. In the present article, we propose an additive risks regression model for a lifetime data subject to middle censoring, where the lifetimes are assumed to follow exponentiated exponential distribution. The regression parameters are estimated using the Expectation-Maximization algorithm. Asymptotic normality of the estimator is proposed. We report a simulation study to assess the finite sample properties of the estimator. We then analyze a real-life data on survival times of larynx cancer patients studied by Karduan.     

Estimation in the Cox proportional hazards model with doubly censored and truncated data

In longitudinal studies, the proportional hazard model is often used to analyse covariate effects on the duration time, defined as the elapsed time between the first and 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 proportional model. A simulation study is conducted to investigate the performance of the proposed estimator.     

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.     

Mixture cure model with an application to interval mapping of quantitative trait loci

When censored time-to-event data are used to map quantitative trait loci (QTL), the existence of nonsusceptible subjects entails extra challenges. If the heterogeneous susceptibility is ignored or inappropriately handled, we may either fail to detect the responsible genetic factors or find spuriously significant locations. In this article, an interval mapping method based on parametric mixture cure models is proposed, which takes into consideration of nonsusceptible subjects. The proposed model can be used to detect the QTL that are responsible for differential susceptibility and/or time-to-event trait distribution. In particular, we propose a likelihood-based testing procedure with genome-wide significance levels calculated using a resampling method. The performance of the proposed method and the importance of considering the heterogeneous susceptibility are demonstrated by simulation studies and an application to survival data from an experiment on mice infected with Listeria monocytogenes.     

Bayesian regression analysis of data with censored initiating and terminating times: applications to aids

Data with censored initiating and terminating times arises quite frequently in acquired immunodeficiency syndrome (AIDS) epidemiologic studies. Analysis of such data involves a complicated bivariate likelihood, which is difficult to deal with computationally. Bayesian analysis, op the other hand, presents added complexities that have yet to be resolved. By exploiting the simple form of a complete data likelihood and utilizing the power of a Markov Chain Monte Carlo (MCMC) algorithm, this paper presents a methodology for fitting Bayesian regression models to such data. The proposed methods extend the work of Sinha (1997), who considered non-parametric Bayesian analysis of this type of data. The methodology is illustiated with an application to a cohort of HIV infected hemophiliac patients.     

The Cox-Aalen model for left-truncated and mixed interval-censored data

Scheike and Zhang [An additive-multiplicative Cox-Aalen regression model. Scand J Stat. 2002;29:75–88] proposed a flexible additive-multiplicative hazard model, called the Cox-Aalen model, by replacing the baseline hazard function in the well-known Cox model with a covariate-dependent Aalen model, which allows for both fixed and dynamic covariate effects. In this paper, based on left-truncated and mixed interval-censored (LT-MIC) data, we consider maximum likelihood estimation for the Cox-Aalen model with fixed covariates. We propose expectation-maximization (EM) algorithms for obtaining the conditional maximum likelihood estimators (cMLE) of the regression coefficients for the Cox-Aalen model. We establish the consistency of the cMLE. Numerical studies show that estimation via the EM algorithms performs well.     

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.     

A Comparison of Methods for Analysing a Nested Frailty Model to Child Survival in Malawi

Demographic and Health Surveys collect child survival times that are clustered at the family and community levels. It is assumed that each cluster has a specific, unobservable, random frailty that induces an association in the survival times within the cluster. The Cox proportional hazards model, with family and community random frailties acting multiplicatively on the hazard rate, is presented. The estimation of the fixed effect and the association parameters of the modified model is then examined using the Gibbs sampler and the expectation–maximization (EM) algorithm. The methods are compared using child survival data collected in the 1992 Demographic and Health Survey of Malawi. The two methods lead to very similar estimates of fixed effect parameters. However, the estimates of random effect variances from the EM algorithm are smaller than those of the Gibbs sampler. Both estimation methods reveal considerable family variation in the survival of children, and very little variability over the communities.     

Inference on semiparametric transformation model with general interval-censored failure time data

Failure time data occur in many areas and in various censoring forms and many models have been proposed for their regression analysis such as the proportional hazards model and the proportional odds model. Another choice that has been discussed in the literature is a general class of semiparmetric transformation models, which include the two models above and many others as special cases. In this paper, we consider this class of models when one faces a general type of censored data, case K informatively interval-censored data, for which there does not seem to exist an established inference procedure. For the problem, we present a two-step estimation procedure that is quite flexible and can be easily implemented, and the consistency and asymptotic normality of the proposed estimators of regression parameters are established. In addition, an extensive simulation study is conducted and suggests that the proposed procedure works well for practical situations. An application is also provided.     

Aalen's linear model for doubly censored data

Double censoring often occurs in registry studies when left censoring is present in addition to right censoring. In this work, we examine estimation of Aalen's nonparametric regression coefficients based on doubly censored data. We propose two estimation techniques. The first type of estimators, including ordinary least squared (OLS) estimator and weighted least squared (WLS) estimators, are obtained using martingale arguments. The second type of estimator, the maximum likelihood estimator (MLE), is obtained via expectation-maximization (EM) algorithms that treat the survival times of left censored observations as missing. Asymptotic properties, including the uniform consistency and weak convergence, are established for the MLE. Simulation results demonstrate that the MLE is more efficient than the OLS and WLS estimators.     

Cox regression for current status data with mismeasured covariates

Covariate measurement error problems have been extensively studied in the context of right‐censored data but less so for current status data. Motivated by the zebrafish basal cell carcinoma (BCC) study, where the occurrence time of BCC was only known to lie before or after a sacrifice time and where the covariate (Sonic hedgehog expression) was measured with error, the authors describe a semiparametric maximum likelihood method for analyzing current status data with mismeasured covariates under the proportional hazards model. They show that the estimator of the regression coefficient is asymptotically normal and efficient and that the profile likelihood ratio test is asymptotically Chi‐squared. They also provide an easily implemented algorithm for computing the estimators. They evaluate their method through simulation studies, and illustrate it with a real data example. The Canadian Journal of Statistics 39: 73–88; 2011 © 2011 Statistical Society of Canada     

Nonparametric test for stratum effects in the cox model with interval-censored data

The testing of the stratum effects in the Cox model is an important and commonly asked question in medical research as well as in many other fields. In this paper, we will discuss the problem where one observes interval-censored failure time data and generalize the procedure given in Sun and Yang (2000 Sun, J., and I. Yang. 2000. Nonparametric test for stratum effects in the cox model. Lifetime Data Analysis 6:321–30.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) for right-censored data. The asymptotic distribution of the new test statistic is established and the simulation study conducted for the evaluation of the finite sample properties of the method suggests that the generalized procedure seems to work well for practical situations. An application is provided.     

Regression analysis of interval-censored failure time data with cured subgroup and mismeasured covariates

Abstract

Failure time data occur in many areas and also in various forms and in particular, many authors have discussed regression analysis of failure time data in the presence of interval censoring, a cured subgroup or mismeasured covariates. However, it does not seem to exist an established procedure that can deal with all three issues together. Corresponding to this, we propose a sieve maximum likelihood estimation procedure that takes into account all three issues with the use of the SIMEX algorithm. The asymptotic properties of the proposed estimators are established, and an extensive simulation study is also conducted and suggests that the proposed method works well for practical situations.