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.     

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.     

Efficient Estimation of an Additive Quantile Regression Model

Abstract. In this paper, two non‐parametric estimators are proposed for estimating the components of an additive quantile regression model. The first estimator is a computationally convenient approach which can be viewed as a more viable alternative to existing kernel‐based approaches. The second estimator involves sequential fitting by univariate local polynomial quantile regressions for each additive component with the other additive components replaced by the corresponding estimates from the first estimator. The purpose of the extra local averaging is to reduce the variance of the first estimator. We show that the second estimator achieves oracle efficiency in the sense that each estimated additive component has the same variance as in the case when all other additive components were known. Asymptotic properties are derived for both estimators under dependent processes that are strictly stationary and absolutely regular. We also provide a demonstrative empirical application of additive quantile models to ambulance travel times.     

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.     

An additive marginal regression model for clustered recurrent event in the presence of a terminal event

In this article, an additive rate model is proposed for clustered recurrent event with a terminal event. The subjects are clustered by some property. For the clustered subjects, the recurrent event is precluded by the death. An estimating equation is developed for the model parameter and the baseline rate function. The asymptotic properties of the resulting estimators are established. In addition, a goodness-of-fit test is presented to assess the adequacy of the model. The finite-sample behavior of the proposed estimators is evaluated through simulation studies, and an application to a bladder cancer data is illustrated.     

A Marginal Additive Rates Model for Recurrent Event Data with a Terminal Event

Recurrent events data with a terminal event often arise in many longitudinal studies. Most of existing models assume multiplicative covariate effects and model the conditional recurrent event rate given survival. In this article, we propose a marginal additive rates model for recurrent events with a terminal event, and develop two procedures for estimating the model parameters. The asymptotic properties of the resulting estimators are established. In addition, some numerical procedures are presented for model checking. The finite-sample behavior of the proposed methods is examined through simulation studies, and an application to a bladder cancer study is also illustrated.     

Additive–multiplicative rates model for recurrent events

Recurrent events are frequently encountered in biomedical studies. Evaluating the covariates effects on the marginal recurrent event rate is of practical interest. There are mainly two types of rate models for the recurrent event data: the multiplicative rates model and the additive rates model. We consider a more flexible additive–multiplicative rates model for analysis of recurrent event data, wherein some covariate effects are additive while others are multiplicative. We formulate estimating equations for estimating the regression parameters. The estimators for these regression parameters are shown to be consistent and asymptotically normally distributed under appropriate regularity conditions. Moreover, the estimator of the baseline mean function is proposed and its large sample properties are investigated. We also conduct simulation studies to evaluate the finite sample behavior of the proposed estimators. A medical study of patients with cystic fibrosis suffered from recurrent pulmonary exacerbations is provided for illustration of the proposed method.     

Additive Transformation Models for Recurrent Events

In this article, we propose a class of additive transformation models for recurrent event data, which includes the additive rates model as a special case. The new models offer great flexibility in formulating the effects of covariates on the mean function of recurrent events. Estimating equation approaches are developed for the model parameters, and asymptotic properties of the resulting estimators are established. In addition, a model checking procedure is presented to assess the adequacy of the model. The finite sample performance of the proposed estimators is examined through simulation studies, and an application to a bladder cancer study is presented.     

SEMIPARAMETRIC ADDITIVE RISKS REGRESSION FOR TWO-STAGE DESIGN SURVIVAL STUDIES

In this article we study a semiparametric additive risks model (McKeague and Sasieni (1994)) for two-stage design survival data where accurate information is available only on second stage subjects, a subset of the first stage study. We derive two-stage estimators by combining data from both stages. Large sample inferences are developed. As a by-product, we also obtain asymptotic properties of the single stage estimators of McKeague and Sasieni (1994) when the semiparametric additive risks model is misspecified. The proposed two-stage estimators are shown to be asymptotically more efficient than the second stage estimators. They also demonstrate smaller bias and variance for finite samples. The developed methods are illustrated using small intestine cancer data from the SEER (Surveillance, Epidemiology, and End Results) Program.     

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.     

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.     

Invariance of linearity of regression and related characterizations of some classical discrete distributions

Rao (1963) introduced what we call an additive damage model. In this model, original observation is subjected to damage according to a specified probability law by the survival distribution. In this paper, we consider a bivariate observation with second component subjected to damage. Using the invariance of linearity of regression of the first component on the second under the transition of the second component from the original to the damaged state, we obtain the characterizations of the Poisson, binomial and negative binomial distributions within the framework of the additive damage model.     

Adjusting regression attenuation in the Cox proportional hazards model

In the measurement error Cox proportional hazards model, the naive maximum partial likelihood estimator (MPLE) is asymptotically biased. In this paper, we give the formula of the asymptotic bias for the additive measurement error Cox model. By adjusting for this error, we derive an adjusted MPLE that is less biased. The bias can be further reduced by adjusting for the estimator second and even third time. This estimator has the advantage of being easy to apply. The performance of the proposed estimator is evaluated through a simulation study.     

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.     

Analysis of Panel Count Data with Dependent Observation Times

In this article, a semiparametric approach is proposed for the regression analysis of panel count data. Panel count data commonly arise in clinical trials and demographical studies where the response variable is the number of multiple recurrences of the event of interest and observation times are not fixed, varying from subject to subject. It is assumed that two processes exist in this data: the first is for a recurrent event and the second is for observation time. Many studies have been done to estimate mean function and regression parameters under the independency between recurrent event process and observation time process. In this article, the same statistical inference is studied, but the situation where these two processes may be related is also considered. The mixed Poisson process is applied for the recurrent event processes, and a frailty intensity function for the observation time is also used, respectively. Simulation studies are conducted to study the performance of the suggested methods. The bladder tumor data are applied to compare previous studie' results.     

Estimating Marginal Effects in Accelerated Failure Time Models for Serial Sojourn Times Among Repeated Events

Recurrent event data are commonly encountered in longitudinal studies when events occur repeatedly over time for each study subject. An accelerated failure time (AFT) model on the sojourn time between recurrent events is considered in this article. This model assumes that the covariate effect and the subject-specific frailty are additive on the logarithm of sojourn time, and the covariate effect maintains the same over distinct episodes, while the distributions of the frailty and the random error in the model are unspecified. With the ordinal nature of recurrent events, two scale transformations of the sojourn times are derived to construct semiparametric methods of log-rank type for estimating the marginal covariate effects in the model. The proposed estimation approaches/inference procedures also can be extended to the bivariate events, which alternate themselves over time. Examples and comparisons are presented to illustrate the performance of the proposed methods.     

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 additive marginal regression models for multiple type recurrent events

Recurrent event data are often encountered in biomedical research, for example, recurrent infections or recurrent hospitalizations for patients after renal transplant. In many studies, there are more than one type of events of interest. Cai and Schaube (Lifetime Data Anal 10:121-138, 2004) advocated a proportional marginal rate model for multiple type recurrent event data. In this paper, we propose a general additive marginal rate regression model. Estimating equations approach is used to obtain the estimators of regression coefficients and baseline rate function. We prove the consistency and asymptotic normality of the proposed estimators. The finite sample properties of our estimators are demonstrated by simulations. The proposed methods are applied to the India renal transplant study to examine risk factors for bacterial, fungal and viral infections.     

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.     

Quantile regression estimation of partially linear additive models

In this paper, we consider the estimation of partially linear additive quantile regression models where the conditional quantile function comprises a linear parametric component and a nonparametric additive component. We propose a two-step estimation approach: in the first step, we approximate the conditional quantile function using a series estimation method. In the second step, the nonparametric additive component is recovered using either a local polynomial estimator or a weighted Nadaraya–Watson estimator. Both consistency and asymptotic normality of the proposed estimators are established. Particularly, we show that the first-stage estimator for the finite-dimensional parameters attains the semiparametric efficiency bound under homoskedasticity, and that the second-stage estimators for the nonparametric additive component have an oracle efficiency property. Monte Carlo experiments are conducted to assess the finite sample performance of the proposed estimators. An application to a real data set is also illustrated.