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.     

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.     

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.     

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.     

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.     

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].     

Reducing bias in parameter estimates from stepwise regression in proportional hazards regression with right-censored data

When variable selection with stepwise regression and model fitting are conducted on the same data set, competition for inclusion in the model induces a selection bias in coefficient estimators away from zero. In proportional hazards regression with right-censored data, selection bias inflates the absolute value of parameter estimate of selected parameters, while the omission of other variables may shrink coefficients toward zero. This paper explores the extent of the bias in parameter estimates from stepwise proportional hazards regression and proposes a bootstrap method, similar to those proposed by Miller (Subset Selection in Regression, 2nd edn. Chapman & Hall/CRC, 2002) for linear regression, to correct for selection bias. We also use bootstrap methods to estimate the standard error of the adjusted estimators. Simulation results show that substantial biases could be present in uncorrected stepwise estimators and, for binary covariates, could exceed 250% of the true parameter value. The simulations also show that the conditional mean of the proposed bootstrap bias-corrected parameter estimator, given that a variable is selected, is moved closer to the unconditional mean of the standard partial likelihood estimator in the chosen model, and to the population value of the parameter. We also explore the effect of the adjustment on estimates of log relative risk, given the values of the covariates in a selected model. The proposed method is illustrated with data sets in primary biliary cirrhosis and in multiple myeloma from the Eastern Cooperative Oncology Group.     

Maximum likelihood estimation in the proportional hazards model of random censorship

The maximum likelihood estimator (MLE) for the survival function S_Tunder the proportional hazards model of censorship is derived and shown to differ from the Abdushukurov-Cheng-Lin estimator when the class of allowable distributions includes all continuous and discrete distributions. The estimators are compared via an example. The MLE is calculated using a Newton-Raphson iterative procedure and implemented via a FORTRAN algorithm.     

A formal test for the stationarity of the incidence rate using data from a prevalent cohort study with follow-up

In a prevalent cohort study with follow-up, the incidence process is not directly observed since only the onset times of prevalent cases can be ascertained. Assessing the “stationarity” of the underlying incidence process can be important for at least three reasons, including an improvement in efficiency when estimating the survivor function. We propose, for the first time, a formal test for stationarity using data from a prevalent cohort study with follow-up. The test makes use of a characterization of stationarity, an extension of this characterization developed in this paper, and of a test for matched pairs of right censored data. We report the results from a power study assuming varying degrees of departure from the null hypothesis of stationarity. The test is also applied to data obtained as part of the Canadian Study of Health and Aging (CSHA) to verify whether the incidence rate of dementia amongst the elderly in Canada has remained constant.     

Uniqueness of permuted treatment estimator distributions in the proportional hazards model

We discuss findings regarding the permutation distributions of treatment effect estimators in the proportional hazards model. For fixed sample size n, we will prove that all uncensored and untied event times yield the same permutation distribution of treatment effect estimators in the proportional hazards model. In other words this distribution is irrelevant with respect to the actual event times. We will show several uniqueness properties under different conditions. These properties are useful for small sample permutation tests and also helpful to large sample cases.     

Proportional hazards model for discrete data: Some new developments

ABSTRACT

Many times, a product lifetime can be described through a non negative integer valued random variable. In this article, we propose a proportional hazards model for discrete data analogous to the version for continuous data. Some ageing properties of the model are discussed. Stochastic comparison of pair of random variables that follow the model are also made. A new test based on U-statistics is developed for testing that the proportionality parameter in the proposed model is 1. The asymptotic properties of the proposed test are studied. We present some numerical results to asses the performance of the test procedure.     

Small sample confidence intervals for survival functions under the proportional hazards model

We develop a saddlepoint-based method for generating small sample confidence bands for the population surviival function from the Kaplan-Meier (KM), the product limit (PL), and Abdushukurov-Cheng-Lin (ACL) survival function estimators, under the proportional hazards model. In the process we derive the exact distribution of these estimators and developed mid-ppopulation tolerance bands for said estimators. Our saddlepoint method depends upon the Mellin transform of the zero-truncated survival estimator which we derive for the KM, PL, and ACL estimators. These transforms are inverted via saddlepoint approximations to yield highly accurate approximations to the cumulative distribution functions of the respective cumulative hazard function estimators and these distribution functions are then inverted to produce our saddlepoint confidence bands. For the KM, PL and ACL estimators we compare our saddlepoint confidence bands with those obtained from competing large sample methods as well as those obtained from the exact distribution. In our simulation studies we found that the saddlepoint confidence bands are very close to the confidence bands derived from the exact distribution, while being much easier to compute, and outperform the competing large sample methods in terms of coverage probability.     

Patient-specific meta-analysis for risk assessment using multivariate proportional hazards regression

We propose a method for assessing an individual patient's risk of a future clinical event using clinical trial or cohort data and Cox proportional hazards regression, combining the information from several studies using meta-analysis techniques. The method combines patient-specific estimates of the log cumulative hazard across studies, weighting by the relative precision of the estimates, using either fixed- or random-effects meta-analysis calculations. Risk assessment can be done for any future patient using a few key summary statistics determined once and for all from each study. Generalizations of the method to logistic regression and linear models are immediate. We evaluate the methods using simulation studies and illustrate their application using real data.     

A scale-location adjustment for proportional hazards deviance residuals

We show that deviance residuals derived using the proportional hazards assumption (including Cox regression) are not asymptotically standard normal, but that a scale-location adjustment makes them nearly standard normal, even for moderate sample sizes. This adjustment should aid in outlier detection, as it allows a more exact assessment of when a deviance residual is unusually large.     

Bayesian analysis of generalized odds-rate hazards models for survival data

In the analysis of censored survival data Cox proportional hazards model (1972) is extremely popular among the practitioners. However, in many real-life situations the proportionality of the hazard ratios does not seem to be an appropriate assumption. To overcome such a problem, we consider a class of nonproportional hazards models known as generalized odds-rate class of regression models. The class is general enough to include several commonly used models, such as proportional hazards model, proportional odds model, and accelerated life time model. The theoretical and computational properties of these models have been re-examined. The propriety of the posterior has been established under some mild conditions. A simulation study is conducted and a detailed analysis of the data from a prostate cancer study is presented to further illustrate the proposed methodology.     

Nonparametric tests for stratified additive hazards model based on current status data

Stratified regression models are commonly employed when study subjects may come from possibly different strata such as different medical centers, and for the situation, one common question of interest is to test the existence of the stratum effect. To address this, there exists some literature on the testing of the stratum effects under the framework of the proportional hazards model when one observes right-censored data or interval-censored data. In this paper, we consider the situation under the additive hazards model when one faces current status data, for which there does not seem to exist an established test procedure. The asymptotic distributions of the proposed test procedure are provided. Also a simulation study is performed to evaluate the performance of the proposed method and indicates that it works well for practical situations. The approach is applied to a set of real current status data from a tumorigenicity study.     

Statistical inference for generalized case-cohort design under the proportional hazards model with parameter constraints

ABSTRACT

The generalized case-cohort design is widely used in large cohort studies to reduce the cost and improve the efficiency. Taking prior information of parameters into consideration in modeling process can further raise the inference efficiency. In this paper, we consider fitting proportional hazards model with constraints for generalized case-cohort studies. We establish a working likelihood function for the estimation of model parameters. The asymptotic properties of the proposed estimator are derived via the Karush-Kuhn-Tucker conditions, and their finite properties are assessed by simulation studies. A modified minorization-maximization algorithm is developed for the numerical calculation of the constrained estimator. An application to a Wilms tumor study demonstrates the utility of the proposed method in practice.     

A class of tests of proportional hazards assumption for left-truncated and right-censored data

In this paper, we proposed a class of tests of proportional hazards assumption for left-truncated and right-censored data based on a pair of estimators of the hazard ratio constant. Using counting process and martingale theory, the asymptotically normal distribution of the test statistic is derived and a family of consistent estimators of variance are also provided. Extensive simulation studies were conducted to evaluate the performance of the proposed test statistics under finite sample situations. Two real data sets are analyzed to illustrate our method.     

Progressively Type-I interval censored competing risks data for the proportional hazards family

In this article, we consider some problems of estimation and prediction when progressive Type-I interval censored competing risks data are from the proportional hazards family. The maximum likelihood estimators of the unknown parameters are obtained. Based on gamma priors, the Lindely's approximation and importance sampling methods are applied to obtain Bayesian estimators under squared error and linear–exponential loss functions. Several classical and Bayesian point predictors of censored units are provided. Also, based on given producer's and consumer's risks accepting sampling plans are considered. Finally, the simulation study is given by Monte Carlo simulations to evaluate the performances of the different methods.     

The random-effects proportional hazards model with grouped survival data: a comparison between the grouped continuous and continuation ratio versions

Summary.  When analysing grouped time survival data having a hierarchical structure it is often appropriate to assume a random-effects proportional hazards model for the latent continuous time and then to derive the corresponding grouped time model. There are two formally equivalent grouped time versions of the proportional hazards model obtained from different perspec-tives, known as the continuation ratio and the grouped continuous models. However, the two models require distinct estimation procedures and, more importantly, they differ substantially when extended to time-dependent covariates and/or non-proportional effects. The paper discusses these issues in the context of random-effects models, illustrating the main points with an application to a complex data set on job opportunities for a cohort of graduates.