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.     

Semiparametric Methods for Clustered Recurrent Event Data

In biomedical studies, the event of interest is often recurrent and within-subject events cannot usually be assumed independent. In addition, individuals within a cluster might not be independent; for example, in multi-center or familial studies, subjects from the same center or family might be correlated. We propose methods of estimating parameters in two semi-parametric proportional rates/means models for clustered recurrent event data. The first model contains a baseline rate function which is common across clusters, while the second model features cluster-specific baseline rates. Dependence structures for patients-within-cluster and events-within-patient are both unspecified. Estimating equations are derived for the regression parameters. For the common baseline model, an estimator of the baseline mean function is proposed. The asymptotic distributions of the model parameters are derived, while finite-sample properties are assessed through a simulation study. Using data from a national organ failure registry, the proposed methods are applied to the analysis of technique failures among Canadian dialysis patients.     

Confidence intervals for the first crossing point of two hazard functions

The phenomenon of crossing hazard rates is common in clinical trials with time to event endpoints. Many methods have been proposed for testing equality of hazard functions against a crossing hazards alternative. However, there has been relatively few approaches available in the literature for point or interval estimation of the crossing time point. The problem of constructing confidence intervals for the first crossing time point of two hazard functions is considered in this paper. After reviewing a recent procedure based on Cox proportional hazard modeling with Box-Cox transformation of the time to event, a nonparametric procedure using the kernel smoothing estimate of the hazard ratio is proposed. The proposed procedure and the one based on Cox proportional hazard modeling with Box-Cox transformation of the time to event are both evaluated by Monte–Carlo simulations and applied to two clinical trial datasets.     

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.     

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.     

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.     

Comparison of preliminary test estimators based on generalized order statistics from proportional hazard family using Pitman measure of closeness

In this article, based on generalized order statistics from a family of proportional hazard rate model, we use a statistical test to generate a class of preliminary test estimators and shrinkage preliminary test estimators for the proportionality parameter. These estimators are compared under Pitman measure of closeness (PMC) as well as MSE criteria. Although the PMC suffers from non transitivity, in the first class of estimators, it has the transitivity property and we obtain the Pitman-closest estimator. Analytical and graphical methods are used to show the range of parameter in which preliminary test and shrinkage preliminary test estimators perform better than their competitor estimators. Results reveal that when the prior information is not too far from its real value, the proposed estimators are superior based on both mentioned criteria.     

A semiparametric Bayesian approach for joint modeling of longitudinal trait and event time

Inference on the whole biological system is the recent focus in bioscience. Different biomarkers, although seem to function separately, can actually control some event(s) of interest simultaneously. This fundamental biological principle has motivated the researchers for developing joint models which can explain the biological system efficiently. Because of the advanced biotechnology, huge amount of biological information can be easily obtained in current years. Hence dimension reduction is one of the major issues in current biological research. In this article, we propose a Bayesian semiparametric approach of jointly modeling observed longitudinal trait and event-time data. A sure independence screening procedure based on the distance correlation and a modified version of Bayesian Lasso are used for dimension reduction. Traditional Cox proportional hazards model is used for modeling the event-time. Our proposed model is used for detecting marker genes controlling the biomass and first flowering time of soybean plants. Simulation studies are performed for assessing the practical usefulness of the proposed model. Proposed model can be used for the joint analysis of traits and diseases for humans, animals and plants.     

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.     

Fitting Cox Models with Doubly Censored Data Using Spline‐Based Sieve Marginal Likelihood

In some applications, the failure time of interest is the time from an originating event to a failure event while both event times are interval censored. We propose fitting Cox proportional hazards models to this type of data using a spline‐based sieve maximum marginal likelihood, where the time to the originating event is integrated out in the empirical likelihood function of the failure time of interest. This greatly reduces the complexity of the objective function compared with the fully semiparametric likelihood. The dependence of the time of interest on time to the originating event is induced by including the latter as a covariate in the proportional hazards model for the failure time of interest. The use of splines results in a higher rate of convergence of the estimator of the baseline hazard function compared with the usual non‐parametric estimator. The computation of the estimator is facilitated by a multiple imputation approach. Asymptotic theory is established and a simulation study is conducted to assess its finite sample performance. It is also applied to analyzing a real data set on AIDS incubation time.     

A basis approach to goodness-of-fit testing in recurrent event models

A class of tests for the hypothesis that the baseline hazard function in Cox's proportional hazards model and for a general recurrent event model belongs to a parametric family C identical with {lambda(0)(.; xi): xi in Xi} is proposed. Finite properties of the tests are examined via simulations, while asymptotic properties of the tests under a contiguous sequence of local alternatives are studied theoretically. An application of the tests to the general recurrent event model, which is an extended minimal repair model admitting covariates, is demonstrated. In addition, two real data sets are used to illustrate the applicability of the proposed tests.     

Gaussian models for degradation processes-part I: Methods for the analysis of biomarker data

We present two stochastic models that describe the relationship between biomarker process values at random time points, event times, and a vector of covariates. In both models the biomarker processes are degradation processes that represent the decay of systems over time. In the first model the biomarker process is a Wiener process whose drift is a function of the covariate vector. In the second model the biomarker process is taken to be the difference between a stationary Gaussian process and a time drift whose drift parameter is a function of the covariates. For both models we present statistical methods for estimation of the regression coefficients. The first model is useful for predicting the residual time from study entry to the time a critical boundary is reached while the second model is useful for predicting the latency time from the infection until the time the presence of the infection is detected. We present our methods principally in the context of conducting inference in a population of HIV infected individuals.     

A new test for single against competing risks models in duration analysis

This paper shows that the single-risk duration model with two event types is a limiting case of bivariate dependent competing risks model, where the joint distribution of event times are degenerate. Then a new test is proposed for the null hypothesis of single risk against dependent competing risks model under the proportional hazard model assumption.     

Semiparametric proportional means model for marker data contingent on recurrent event

In many biomedical studies with recurrent events, some markers can only be measured when events happen. For example, medical cost attributed to hospitalization can only incur when patients are hospitalized. Such marker data are contingent on recurrent events. In this paper, we present a proportional means model for modelling the markers using the observed covariates contingent on the recurrent event. We also model the recurrent event via a marginal rate model. Estimating equations are constructed to derive the point estimators for the parameters in the proposed models. The estimators are shown to be asymptotically normal. Simulation studies are conducted to examine the finite-sample properties of the proposed estimators and the proposed method is applied to a data set from the Vitamin A Community Trial.     

Weighting methods for ties between event times and covariate change times

Recent work has shown that the presence of ties between an outcome event and the time that a binary covariate changes or jumps can lead to biased estimates of regression coefficients in the Cox proportional hazards model. One proposed solution is the Equally Weighted method. The coefficient estimate of the Equally Weighted method is defined to be the average of the coefficient estimates of the Jump Before Event method and the Jump After Event method, where these two methods assume that the jump always occurs before or after the event time, respectively. In previous work, the bootstrap method was used to estimate the standard error of the Equally Weighted coefficient estimate. However, the bootstrap approach was computationally intensive and resulted in overestimation. In this article, two new methods for the estimation of the Equally Weighted standard error are proposed. Three alternative methods for estimating both the regression coefficient and the corresponding standard error are also proposed. All the proposed methods are easy to implement. The five methods are investigated using a simulation study and are illustrated using two real datasets.     

A class of accelerated means regression models for recurrent event data

In this article, we propose a general class of accelerated means regression models for recurrent event data. The class includes the proportional means model, the accelerated failure time model and the accelerated rates model as special cases. The new model offers great flexibility in formulating the effects of covariates on the mean functions of counting processes while leaving the stochastic structure completely unspecified. For the inference on the model parameters, estimating equation approaches are developed and both large and final sample properties of the proposed estimators are established. In addition, some graphical and numerical procedures are presented for model checking. An illustration with multiple-infection data from a clinic study on chronic granulomatous disease is also provided.     

An extended proportional hazards model for interval-censored data subject to instantaneous failures

Lifetime Data Analysis - The proportional hazards (PH) model is arguably one of the most popular models used to analyze time to event data arising from clinical trials and longitudinal studies. In...     

Jointly modeling longitudinal proportional data and survival times with an application to the quality of life data in a breast cancer trial

Motivated by the joint analysis of longitudinal quality of life data and recurrence free survival times from a cancer clinical trial, we present in this paper two approaches to jointly model the longitudinal proportional measurements, which are confined in a finite interval, and survival data. Both approaches assume a proportional hazards model for the survival times. For the longitudinal component, the first approach applies the classical linear mixed model to logit transformed responses, while the second approach directly models the responses using a simplex distribution. A semiparametric method based on a penalized joint likelihood generated by the Laplace approximation is derived to fit the joint model defined by the second approach. The proposed procedures are evaluated in a simulation study and applied to the analysis of breast cancer data motivated this research.     

Interval-censored data with misclassification: a Bayesian approach

Survival data involving silent events are often subject to interval censoring (the event is known to occur within a time interval) and classification errors if a test with no perfect sensitivity and specificity is applied. Considering the nature of this data plays an important role in estimating the time distribution until the occurrence of the event. In this context, we incorporate validation subsets into the parametric proportional hazard model, and show that this additional data, combined with Bayesian inference, compensate the lack of knowledge about test sensitivity and specificity improving the parameter estimates. The proposed model is evaluated through simulation studies, and Bayesian analysis is conducted within a Gibbs sampling procedure. The posterior estimates obtained under validation subset models present lower bias and standard deviation compared to the scenario with no validation subset or the model that assumes perfect sensitivity and specificity. Finally, we illustrate the usefulness of the new methodology with an analysis of real data about HIV acquisition in female sex workers that have been discussed in the literature.