The proportional hazards assumption in the commonly used Cox model for censored failure time data is often violated in scientific studies. Yang and Prentice (2005) proposed a novel semiparametric two-sample model that includes the proportional hazards model and the proportional odds model as sub-models, and accommodates crossing survival curves. The model leaves the baseline hazard unspecified and the two model parameters can be interpreted as the short-term and long-term hazard ratios. Inference procedures were developed based on a pseudo score approach. Although extension to accommodate covariates was mentioned, no formal procedures have been provided or proved. Furthermore, the pseudo score approach may not be asymptotically efficient. We study the extension of the short-term and long-term hazard ratio model of Yang and Prentice (2005) to accommodate potentially time-dependent covariates. We develop efficient likelihood-based estimation and inference procedures. The nonparametric maximum likelihood estimators are shown to be consistent, asymptotically normal, and asymptotically efficient. Extensive simulation studies demonstrate that the proposed methods perform well in practical settings. The proposed method captured the phenomenon of crossing hazards in a cancer clinical trial and identified a genetic marker with significant long-term effect missed by using the proportional hazards model on age-at-onset of alcoholism in a genetic study.
When facing multivariate covariates, general semiparametric regression techniques come at hand to propose flexible models that are unexposed to the curse of dimensionality. In this work a semiparametric copula-based estimator for conditional quantiles is investigated for complete or right-censored data. In spirit, the methodology is extending the recent work of Noh et al. (2013) and Noh et al. (2015), as the main idea consists in appropriately defining the quantile regression in terms of a multivariate copula and marginal distributions. Prior estimation of the latter and simple plug-in lead to…
Interval-censored competing risks data arise when each study subject may experience an event or failure from one of several causes and the failure time is not observed exactly but rather known to lie in an interval between two successive examinations. We formulate the effects of possibly time-varying covariates on the cumulative incidence or sub-distribution function (i.e., the marginal probability of failure from a particular cause) of competing risks through a broad class of semiparametric regression models that captures both proportional and non-proportional hazards structures for the sub-d…
This work was motivated by observational studies in pregnancy with spontaneous abortion (SAB) as outcome. Clearly some women experience the SAB event but the rest do not. In addition, the data are left truncated due to the way pregnant women are recruited into these studies. For those women who do experience SAB, their exact event times are sometimes unknown. Finally, a small percentage of the women are lost to follow-up during their pregnancy. All these give rise to data that are left truncated, partly interval and right-censored, and with a clearly defined cured portion. We consider the non-…
Interval-censored multi-state data arise in many studies of chronic diseases, where the health status of a subject can be characterized by a finite number of disease states and the transition between any two states is only known to occur over a broad time interval. We formulate the effects of potentially time-dependent covariates on multi-state processes through semiparametric proportional intensity models with random effects. We adopt nonparametric maximum likelihood estimation (NPMLE) under general interval censoring and develop a stable expectation-maximization (EM) algorithm. We show that …
We express the joint Rényi entropy of progressively censored order statistics in terms of an incomplete integral of the hazard function, and provide a simple estimate of the joint Rényi entropy of progressively Type-II censored data. Then we establish a goodness of fit test statistic based on the Rényi Kullback-Leibler information with the progressively Type-II censored data, and compare its performance with the leading test statistic. A Monte Carlo simulation study shows that the proposed test statistic shows better powers than the leading test statistic against the alternatives with monotone…
In this article, the weighted empirical likelihood is applied to a general setting of two-sample semiparametric models, which includes biased sampling models and case-control logistic regression models as special cases. For various types of censored data, such as right censored data, doubly censored data, interval censored data and partly interval-censored data, the weighted empirical likelihood-based semiparametric maximum likelihood estimator $(\tildeθ_n,\tilde{F}_n)$ for the underlying parameter $θ_0$ and distribution $F_0$ is derived, and the strong consistency of $(\tildeθ_n,\tilde{F}_n)$…
The SiZer method is extended to nonparametric hazard estimation and also to censored density and hazard estimation. The new method allows quick, visual statistical inference about the important issue of statistically significant increases and decreases in the smooth curve estimate. This extension has required the opening of a new avenue of research on the interface between statistical inference and scale space.
Multistate models can be used to describe transitions over time across states. In the presence of interval-censored times for transitions, the likelihood is constructed using transition probabilities. Models are specified using proportional hazards model for the transitions. Time-dependency is usually defined by parametric models, which can be too restrictive. Nonparametric hazards specification with splines allow for flexible modelling of time-dependency without making strong model assumptions. Penalised maximum likelihood is used to estimate the models. Selecting the optimal amount of smooth…
In this paper, we mainly discuss the cure model with survival data. Different from the usual survival data with right-censoring, we incorporate the features of left-truncation and measurement error in covariates. Generally speaking, left-truncation causes a biased sample in survival analysis; measurement error in covariates may incur a tremendous bias if we do not deal with it properly. To deal with these challenges, we propose a flexible way to analyze left-truncated survival data and correct measurement error in covariates. The theoretical results are also established in this paper.
In many semiparametric models that are parameterized by two types of parameters---a Euclidean parameter of interest and an infinite-dimensional nuisance parameter---the two parameters are bundled together, that is, the nuisance parameter is an unknown function that contains the parameter of interest as part of its argument. For example, in a linear regression model for censored survival data, the unspecified error distribution function involves the regression coefficients. Motivated by developing an efficient estimating method for the regression parameters, we propose a general sieve M-theorem…
In this paper, we study a novel approach for the estimation of quantiles when facing potential right censoring of the responses. Contrary to the existing literature on the subject, the adopted strategy of this paper is to tackle censoring at the very level of the loss function usually employed for the computation of quantiles, the so-called "check" function. For interpretation purposes, a simple comparison with the latter reveals how censoring is accounted for in the newly proposed loss function. Subsequently, when considering the inclusion of covariates for conditional quantile estimation, by…
In reliability and life testing studies, the topic of estimating hazard rate has received great attention in recent years since an estimate of hazard rate is a quite useful tool for making decisions. Some works have included nonparametric approaches while some have considered parametric structural models for complete as well as censored data sets; see Meeker et al. (1992), Antoniadis and Grégoire (1999), Rai and Singh (2003), Bezandry et al. (2005), Brunel and Comte (2008), and Mahapatra et al. (2012). Depending on the shapes of the hazard rate, efficiencies differ markedly across proposed est…
We propose a class of dimension reduction methods for right censored survival data using a counting process representation of the failure process. Semiparametric estimating equations are constructed to estimate the dimension reduction subspace for the failure time model. The proposed method addresses two fundamental limitations of existing approaches. First, using the counting process formulation, it does not require any estimation of the censoring distribution to compensate the bias in estimating the dimension reduction subspace. Second, the nonparametric part in the estimating equations is a…
We consider linear regression model estimation where the covariate of interest is randomly censored. Under a non-informative censoring mechanism, one may obtain valid estimates by deleting censored observations. However, this comes at a cost of lost information and decreased efficiency, especially under heavy censoring. Other methods for dealing with censored covariates, such as ignoring censoring or replacing censored observations with a fixed number, often lead to severely biased results and are of limited practicality. Parametric methods based on maximum likelihood estimation as well as sem…
As a specific proportional hazard rates model, sequential order statistics can be used to describe the lifetimes of load-sharing systems. Inference for these systems needs to account for small sample sizes, which are prevalent in reliability applications. By exploiting the probabilistic structure of sequential order statistics, we derive exact finite sample inference procedures to test for the load-sharing parameters and for the nonparametrically specified baseline distribution, treating the respective other part as a nuisance quantity. This improves upon previous approaches for the model, whi…
This research is motivated by discovering and underpinning genetic causes for the progression of a bilateral eye disease, Age-related Macular Degeneration (AMD), of which the primary outcomes, progression times to late-AMD, are bivariate and interval-censored due to intermittent assessment times. We propose a novel class of copula-based semiparametric transformation models for bivariate data under general interval censoring, which includes the case 1 interval censoring (current status data) and case 2 interval censoring. Specifically, the joint likelihood is modeled through a two-parameter Arc…
Cox's proportional hazards model is one of the most popular statistical models to evaluate associations of exposure with a censored failure time outcome. When confounding factors are not fully observed, the exposure hazard ratio estimated using a Cox model is subject to unmeasured confounding bias. To address this, we propose a novel approach for the identification and estimation of the causal hazard ratio in the presence of unmeasured confounding factors. Our approach is based on a binary instrumental variable, and an additional no-interaction assumption in a first stage regression of the tre…
We discuss semiparametric regression when only the ranks of responses are observed. The model is $Y_i = F (\mathbf{x}_i'{\boldsymbolβ}_0 + \varepsilon_i)$, where $Y_i$ is the unobserved response, $F$ is a monotone increasing function, $\mathbf{x}_i$ is a known $p-$vector of covariates, ${\boldsymbolβ}_0$ is an unknown $p$-vector of interest, and $\varepsilon_i$ is an error term independent of $\mathbf{x}_i$. We observe $\{(\mathbf{x}_i,R_n(Y_i)) : i = 1,\ldots ,n\}$, where $R_n$ is the ordinal rank function. We explore a novel estimator under Gaussian assumptions. We discuss the literature, ap…
We propose a new class of semiparametric regression models of mean residual life for censored outcome data. The models, which enable us to estimate the expected remaining survival time and generalize commonly used mean residual life models, also conduct covariate dimension reduction. Using the geometric approaches in semiparametrics literature and the martingale properties with survival data, we propose a flexible inference procedure that relaxes the parametric assumptions on the dependence of mean residual life on covariates and how long a patient has lived. We show that the estimators for th…
Case-cohort design, an outcome-dependent sampling design for censored survival data, is increasingly used in biomedical research. The development of asymptotic theory for a case-cohort design in the current literature primarily relies on counting process stochastic integrals. Such an approach, however, is rather limited and lacks theoretical justification for outcome-dependent weighted methods due to non-predictability. Instead of stochastic integrals, we derive asymptotic properties for case-cohort studies based on a general Z-estimation theory for semiparametric models with bundled parameter…
Interval censoring arises frequently in clinical, epidemiological, financial, and sociological studies, where the event or failure of interest is known only to occur within an interval induced by periodic monitoring. We formulate the effects of potentially time-dependent covariates on the interval-censored failure time through a broad class of semiparametric transformation models that encompasses proportional hazards and proportional odds models. We consider nonparametric maximum likelihood estimation for this class of models with an arbitrary number of monitoring times for each subject. We de…
Maximum approximate Bernstein likelihood estimates of the baseline density function and the regression coefficients in the proportional hazard regression models based on interval-censored event time data are proposed. This results in not only a smooth estimate of the survival function which enjoys faster convergence rate but also improved estimates of the regression coefficients. Simulation shows that the finite sample performance of the proposed method is better than the existing ones. The proposed method is illustrated by real data applications.
We consider parameter estimation in a regression model corresponding to an iid sequence of censored observations of a finite state modulated renewal process. The model assumes a similar form as in Cox regression except that the baseline intensities are functions of the backwards recurrence time of the process and a time dependent covariate. As a result of this it falls outside the class of multiplicative intensity models. We use kernel estimation to construct estimates of the regression coefficints and the baseline cumulative hazards. We give conditions for consistency and asymptotic normality…
Under a single-index regression assumption, we introduce a new semiparametric procedure to estimate a conditional density of a censored response. The regression model can be seen as a generalization of Cox regression model and also as a profitable tool to perform dimension reduction under censoring. This technique extends the results of Delecroix et al. (2003). We derive consistency and asymptotic normality of our estimator of the index parameter by proving its asymptotic equivalence with the (uncomputable) maximum likelihood estimator, using martingales results for counting processes and argu…
This work presents novel and powerful tests for comparing non-proportional hazard functions, based on sample-space partitions. Right censoring introduces two major difficulties which make the existing sample-space partition tests for uncensored data non-applicable: (i) the actual event times of censored observations are unknown; and (ii) the standard permutation procedure is invalid in case the censoring distributions of the groups are unequal. We overcome these two obstacles, introduce invariant tests, and prove their consistency. Extensive simulations reveal that under non-proportional alter…
Many insurance premium principles are defined and various estimation procedures introduced in the literature. In this paper, we focus on the estimation of the excess-of-loss reinsurance premium when the risks are randomly right-censored. The asymptotic normality of the proposed estimator is established under suitable conditions and its performance evaluated through sets of simulated data.
When the observations are not quantified and are known to be less than a threshold value, the concept of left censoring needs to be included in the analysis of such datasets. In many real multi component lifetime systems left censored data is very common. The usual assumption that components which are part of a system, work independently seems not appropriate in a number of applications. For instance it is more realistic to acknowledge that the working status of a component affects the remaining components. When you have left-censored data, it is more meaningful to use the reversed hazard rate…
This paper considers inference in a linear regression model with random right censoring and outliers. The number of outliers can grow with the sample size while their proportion goes to zero. The model is semiparametric and we make only very mild assumptions on the distribution of the error term, contrary to most other existing approaches in the literature. We propose to penalize the estimator proposed by Stute for censored linear regression by the l1-norm. We derive rates of convergence and establish asymptotic normality of the estimator of the regression coefficients. Our estimator has the s…
This paper proposes a decorrelation-based approach to test hypotheses and construct confidence intervals for the low dimensional component of high dimensional proportional hazards models. Motivated by the geometric projection principle, we propose new decorrelated score, Wald and partial likelihood ratio statistics. Without assuming model selection consistency, we prove the asymptotic normality of these test statistics, establish their semiparametric optimality. We also develop new procedures for constructing pointwise confidence intervals for the baseline hazard function and baseline survival…
This paper considers the nonparametric maximum likelihood estimator (MLE) for the joint distribution function of an interval censored survival time and a continuous mark variable. We provide a new explicit formula for the MLE in this problem. We use this formula and the mark specific cumulative hazard function of Huang and Louis (1998) to obtain the almost sure limit of the MLE. This result leads to necessary and sufficient conditions for consistency of the MLE which imply that the MLE is inconsistent in general. We show that the inconsistency can be repaired by discretizing the marks. Our the…
A comprehensive, unified approach to modeling arbitrarily censored spatial survival data is presented for the three most commonly-used semiparametric models: proportional hazards, proportional odds, and accelerated failure time. Unlike many other approaches, all manner of censored survival times are simultaneously accommodated including uncensored, interval censored, current-status, left and right censored, and mixtures of these. Left-truncated data are also accommodated leading to models for time-dependent covariates. Both georeferenced (location exactly observed) and areally observed (locati…
Continuous-time multi-state survival models can be used to describe health-related processes over time. In the presence of interval-censored times for transitions between the living states, the likelihood is constructed using transition probabilities. Models can be specified using parametric or semi-parametric shapes for the hazards. Semi-parametric hazards can be fitted using $P$-splines and penalised maximum likelihood estimation. This paper presents a method to estimate flexible multi-state models which allows for parametric and semi-parametric hazard specifications. The estimation is based…
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, among many others. In many such studies, the event time of interest is not directly observed but is known relative to periodic examination times; i.e., practitioners observe either current status or interval-censored data. The analysis of data of this structure is often fraught with many difficulties. Further exacerbating this issue, in some such studies the observed data also consists of instantaneous failures; i.e., the event…
We consider a class of doubly weighted rank-based estimating methods for the transformation (or accelerated failure time) model with missing data as arise, for example, in case-cohort studies. The weights considered may not be predictable as required in a martingale stochastic process formulation. We treat the general problem as a semiparametric estimating equation problem and provide proofs of asymptotic properties for the weighted estimators, with either true weights or estimated weights, by using empirical process theory where martingale theory may fail. Simulations show that the outcome-de…
A new method for the analysis of time to ankylosis complication on a dataset of replanted teeth is proposed. In this context of left-censored, interval-censored and right-censored data, a Cox model with piecewise constant baseline hazard is introduced. Estimation is carried out with the EM algorithm by treating the true event times as unobserved variables. This estimation procedure is shown to produce a block diagonal Hessian matrix of the baseline parameters. Taking advantage of this interesting feature of the estimation method a L0 penalised likelihood method is implemented in order to autom…
