Piecewise proportional hazards models with interval-censored data

We consider the piecewise proportional hazards (PWPH) model with interval-censored (IC) relapse times under the distribution-free set-up. The partial likelihood approach is not applicable for IC data, and the generalized likelihood approach has not been studied in the literature. It turns out that under the PWPH model with IC data, the semi-parametric MLE (SMLE) of the covariate effect under the standard generalized likelihood may not be unique and may not be consistent. In fact, the parameter under the PWPH model with IC data is not identifiable unless the identifiability assumption is imposed. We propose a modification to the likelihood function so that its SMLE is unique. Under the identifiability assumption, our simulation study suggests that the SMLE is consistent. We apply the method to our cancer relapse time data and conclude that the bone marrow micrometastasis does not have a significant prognostic factor.     

Maximum likelihood estimation for the proportional hazards model with partly interval-censored data

Summary. The maximum likelihood estimator (MLE) for the proportional hazards model with partly interval-censored data is studied. Under appropriate regularity conditions, the MLEs of the regression parameter and the cumulative hazard function are shown to be consistent and asymptotically normal. Two methods to estimate the variance–covariance matrix of the MLE of the regression parameter are considered, based on a generalized missing information principle and on a generalized profile information procedure. Simulation studies show that both methods work well in terms of the bias and variance for samples of moderate size. An example illustrates the methods.     

Testing the proportional odds model for interval-censored data

This paper discusses the goodness-of-fit test for the proportional odds model for K-sample interval-censored failure time data, which frequently occur in, for example, periodic follow-up survival studies. The proportional odds model has a feature that allows the ratio of two hazard functions to be monotonic and converge to one and provides an important tool for the modeling of survival data. To test the model, a procedure is proposed, which is a generalization of the method given in Dauxois and Kirmani [Dauxois JY, Kirmani SNUA (2003) Biometrika 90:913–922]. The asymptotic distribution of the procedure is established and its properties are evaluated by simulation studies     

Consistency of The MMGLE under the piecewise proportional hazards models with interval-censored data

Wong et al. [(2018), ‘Piece-wise Proportional Hazards Models with Interval-censored Data’, Journal of Statistical Computation and Simulation, 88, 140–155] studied the piecewise proportional hazards (PWPH) model with interval-censored (IC) data under the distribution-free set-up. It is well known that the partial likelihood approach is not applicable for IC data, and Wong et al. (2018) showed that the standard generalised likelihood approach does not work either. They proposed the maximum modified generalised likelihood estimator (MMGLE) and the simulation results suggest that the MMGLE is consistent. We establish the consistency and asymptotically normality of the MMGLE.     

A corrected likelihood method for the proportional hazards model with covariates subject to measurement error

There has been extensive interest in discussing inference methods for survival data when some covariates are subject to measurement error. It is known that standard inferential procedures produce biased estimation if measurement error is not taken into account. With the Cox proportional hazards model a number of methods have been proposed to correct bias induced by measurement error, where the attention centers on utilizing the partial likelihood function. It is also of interest to understand the impact on estimation of the baseline hazard function in settings with mismeasured covariates. In this paper we employ a weakly parametric form for the baseline hazard function and propose simple unbiased estimating functions for estimation of parameters. The proposed method is easy to implement and it reveals the connection between the naive method ignoring measurement error and the corrected method with measurement error accounted for. Simulation studies are carried out to evaluate the performance of the estimators as well as the impact of ignoring measurement error in covariates. As an illustration we apply the proposed methods to analyze a data set arising from the Busselton Health Study [Knuiman, M.W., Cullent, K.J., Bulsara, M.K., Welborn, T.A., Hobbs, M.S.T., 1994. Mortality trends, 1965 to 1989, in Busselton, the site of repeated health surveys and interventions. Austral. J. Public Health 18, 129–135].     

Model diagnostics for the proportional hazards model with length-biased data

Length-biased data are frequently encountered in prevalent cohort studies. Many statistical methods have been developed to estimate the covariate effects on the survival outcomes arising from such data while properly adjusting for length-biased sampling. Among them, regression methods based on the proportional hazards model have been widely adopted. However, little work has focused on checking the proportional hazards model assumptions with length-biased data, which is essential to ensure the validity of inference. In this article, we propose a statistical tool for testing the assumed functional form of covariates and the proportional hazards assumption graphically and analytically under the setting of length-biased sampling, through a general class of multiparameter stochastic processes. The finite sample performance is examined through simulation studies, and the proposed methods are illustrated with the data from a cohort study of dementia in Canada.

     

Oracle inequalities for the Lasso in the additive hazards model with interval-censored data

This article studies the absolute penalized convex function estimator in sparse and high-dimensional additive hazards model. Under such model, we assume that the failure time data are interval-censored and the number of time-dependent covariates can be larger than the sample size. We establish oracle inequalities based on some natural extensions of the compatibility and cone invertibility factors of the Hessian matrix at the true parameters in the model. Some similar inequalities based on an extension of the restricted eigenvalue are also established. Under mild conditions, we prove that the compatibility and cone invertibility factors and the restricted eigenvalues are bounded from below by positive constants for time-dependent covariates.     

Maximum likelihood estimation for the proportional odds model with mixed interval-censored failure time data

This article discusses regression analysis of mixed interval-censored failure time data. Such data frequently occur across a variety of settings, including clinical trials, epidemiologic investigations, and many other biomedical studies with a follow-up component. For example, mixed failure times are commonly found in the two largest studies of long-term survivorship after childhood cancer, the datasets that motivated this work. However, most existing methods for failure time data consider only right-censored or only interval-censored failure times, not the more general case where times may be mixed. Additionally, among regression models developed for mixed interval-censored failure times, the proportional hazards formulation is generally assumed. It is well-known that the proportional hazards model may be inappropriate in certain situations, and alternatives are needed to analyze mixed failure time data in such cases. To fill this need, we develop a maximum likelihood estimation procedure for the proportional odds regression model with mixed interval-censored data. We show that the resulting estimators are consistent and asymptotically Gaussian. An extensive simulation study is performed to assess the finite-sample properties of the method, and this investigation indicates that the proposed method works well for many practical situations. We then apply our approach to examine the impact of age at cranial radiation therapy on risk of growth hormone deficiency in long-term survivors of childhood cancer.     

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 goodness-of-fit test for the stratified proportional hazards model for survival data

Abstract

Goodness-of-fit testing is addressed in the stratified proportional hazards model for survival data. A test statistic based on within-strata cumulative sums of martingale residuals over covariates is proposed and its asymptotic distribution is derived under the null hypothesis of model adequacy. A Monte Carlo procedure is proposed to approximate the critical value of the test. Simulation studies are conducted to examine finite-sample performance of the proposed statistic.     

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.     

Efficient estimation for the proportional hazards model with bivariate current status data

We consider efficient estimation of regression and association parameters jointly for bivariate current status data with the marginal proportional hazards model. Current status data occur in many fields including demographical studies and tumorigenicity experiments and several approaches have been proposed for regression analysis of univariate current status data. We discuss bivariate current status data and propose an efficient score estimation approach for the problem. In the approach, the copula model is used for joint survival function with the survival times assumed to follow the proportional hazards model marginally. Simulation studies are performed to evaluate the proposed estimates and suggest that the approach works well in practical situations. A real life data application is provided for illustration.     

Optimal partitioning for the proportional hazards model

This paper discusses methods for clustering a continuous covariate in a survival analysis model. The advantages of using a categorical covariate defined from discretizing a continuous covariate (via clustering) is (i) enhanced interpretability of the covariate''s impact on survival and (ii) relaxing model assumptions that are usually required for survival models, such as the proportional hazards model. Simulations and an example are provided to illustrate the methods.     

The two-way proportional hazards model

Summary. Survival analysis problems often involve dual timescales, most commonly calendar date and lifetime, the latter being the elapsed time since an initiating event such as a heart transplant. In our main example attention is focused on the hazard rate of 'death' as a function of calendar date. Three different estimates are discussed, one each from proportional hazards analyses on the lifetime and the calendar date scales, and one from a symmetric approach called here the 'two-way proportional hazards model', a multiplicative hazards model going back to Lexis in the 1870s. The three are connected through a Poisson generalized linear model for the Lexis diagram. The two-way model is shown to combine the information from the two 'one-way' proportional hazards analyses efficiently, at the cost of more extensive parametric modelling.     

Time-discrete beta-process model for interval-censored survival data

Grouped survival data with possible interval censoring arise in a variety of settings. This paper presents nonparametric Bayes methods for the analysis of such data. The random cumulative hazard, common to every subject, is assumed to be a realization of a Lévy process. A time-discrete beta process, introduced by Hjort, is considered for modeling the prior process. A sampling-based Monte Carlo algorithm is used to find posterior estimates of several quantities of interest. The methodology presented here is used to check further modeling assumptions. Also, the methodology developed in this paper is illustrated with data for the times to cosmetic deterioration of breast-cancer patients. An extension of the methodology is presented to deal with two interval-censored times in tandem data (as with some AIDS incubation data).     

Variable selection in proportional hazards cure model with time-varying covariates,application to US bank failures*

From a survival analysis perspective, bank failure data are often characterized by small default rates and heavy censoring. This empirical evidence can be explained by the existence of a subpopulation of banks likely immune from bankruptcy. In this regard, we use a mixture cure model to separate the factors with an influence on the susceptibility to default from the ones affecting the survival time of susceptible banks. In this paper, we extend a semi-parametric proportional hazards cure model to time-varying covariates and we propose a variable selection technique based on its penalized likelihood. By means of a simulation study, we show how this technique performs reasonably well. Finally, we illustrate an application to commercial bank failures in the United States over the period 2006–2016.     

A proportional hazards model for the analysis of doubly censored competing risks data

ABSTRACT

Competing risks data are common in medical research in which lifetime of individuals can be classified in terms of causes of failure. In survival or reliability studies, it is common that the patients (objects) are subjected to both left censoring and right censoring, which is refereed as double censoring. The analysis of doubly censored competing risks data in presence of covariates is the objective of this study. We propose a proportional hazards model for the analysis of doubly censored competing risks data, using the hazard rate functions of Gray (1988 Gray, R.J. (1988). A class of k-sample tests for comparing the cumulative incidence of a competing risk. Ann. Statist. 16:1141–1154.[Crossref], [Web of Science ®] , [Google Scholar]), while focusing upon one major cause of failure. We derive estimators for regression parameter vector and cumulative baseline cause specific hazard rate function. Asymptotic properties of the estimators are discussed. A simulation study is conducted to assess the finite sample behavior of the proposed estimators. We illustrate the method using a real life doubly censored competing risks data.     

Survival analysis based on the proportional hazards model and survey data

The authors propose methods based on the stratified Cox proportional hazards model that account for the fact that the data have been collected according to a complex survey design. The methods they propose are based on the theory of estimating equations in conjunction with empirical process theory. The authors also discuss issues concerning ignorable sampling design, and the use of weighted and unweighted procedures. They illustrate their methodology by an analysis of jobless spells in Statistics Canada's Survey of Labour and Income Dynamics. They discuss briefly problems concerning weighting, model checking, and missing or mismeasured data. They also identify areas for further research.