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.     

Estimation of the mean quality-adjusted survival using a multistate model for the sojourn times

In clinical trials, it may be of interest taking into account physical and emotional well-being in addition to survival when comparing treatments. Quality-adjusted survival time has the advantage of incorporating information about both survival time and quality-of-life. In this paper, we discuss the estimation of the expected value of the quality-adjusted survival, based on multistate models for the sojourn times in health states. Semiparametric and parametric (with exponential distribution) approaches are considered. A simulation study is presented to evaluate the performance of the proposed estimator and the jackknife resampling method is used to compute bias and variance of the estimator.     

Multiple imputation methods for recurrent event data with missing event category

Frequently in clinical and epidemiologic studies, the event of interest is recurrent (i.e., can occur more than once per subject). When the events are not of the same type, an analysis which accounts for the fact that events fall into different categories will often be more informative. Often, however, although event times may always be known, information through which events are categorized may potentially be missing. Complete‐case methods (whose application may require, for example, that events be censored when their category cannot be determined) are valid only when event categories are missing completely at random. This assumption is rather restrictive. The authors propose two multiple imputation methods for analyzing multiple‐category recurrent event data under the proportional means/rates model. The use of a proper or improper imputation technique distinguishes the two approaches. Both methods lead to consistent estimation of regression parameters even when the missingness of event categories depends on covariates. The authors derive the asymptotic properties of the estimators and examine their behaviour in finite samples through simulation. They illustrate their approach using data from an international study on dialysis.     

Comparison of goodness of fit tests for the cox proportional hazards model

The proportional hazards regression model of Cox(1972) is widely used in analyzing survival data. We examine several goodness of fit tests for checking the proportionality of hazards in the Cox model with two-sample censored data, and compare the performance of these tests by a simulation study. The strengths and weaknesses of the tests are pointed out. The effects of the extent of random censoring on the size and power are also examined. Results of a simulation study demonstrate that Gill and Schumacher's test is most powerful against a broad range of monotone departures from the proportional hazards assumption, but it may not perform as well fail for alternatives of nonmonotone hazard ratio. For the latter kind of alternatives, Andersen's test may detect patterns of irregular changes in hazards.     

A semi-Markov multistate model for estimation of the mean quality-adjusted survival for non-progressive processes

We discuss the estimation of the expected value of the quality-adjusted survival, based on multistate models. We generalize an earlier work, considering the sojourn times in health states are not identically distributed, for a given vector of covariates. Approaches based on semiparametric and parametric (exponential and Weibull distributions) methodologies are considered. A simulation study is conducted to evaluate the performance of the proposed estimator and the jackknife resampling method is used to estimate the variance of such estimator. An application to a real data set is also included.     

Weighted log‐rank test for time‐to‐event data in immunotherapy trials with random delayed treatment effect and cure rate

A cancer clinical trial with an immunotherapy often has 2 special features, which are patients being potentially cured from the cancer and the immunotherapy starting to take clinical effect after a certain delay time. Existing testing methods may be inadequate for immunotherapy clinical trials, because they do not appropriately take the 2 features into consideration at the same time, hence have low power to detect the true treatment effect. In this paper, we proposed a piece‐wise proportional hazards cure rate model with a random delay time to fit data, and a new weighted log‐rank test to detect the treatment effect of an immunotherapy over a chemotherapy control. We showed that the proposed weight was nearly optimal under mild conditions. Our simulation study showed a substantial gain of power in the proposed test over the existing tests and robustness of the test with misspecified weight. We also introduced a sample size calculation formula to design the immunotherapy clinical trials using the proposed weighted log‐rank test.     

Maximum likelihood methods for complex sample data: logistic regression and discrete proportional hazards models

To estimate model parameters from complex sample data. we apply maximum likelihood techniques to the complex sample data from the finite population, which is treated as a sample from an i nfinite superpopulation. General asymptotic distribution theory is developed and then applied to both logistic regression and discrete proportional hazards models. Data from the Lipid Research Clinics Program areused to illustrate each model, demonstrating the effects on inference of neglecting the sampling design during parameter estimation. These empirical results also shed light on the issue of model-based vs. design-based inferences.     

A Survey of Microcomputer Survival Analysis Software: The Need for an Integrated Framework

This paper surveys commercially available MS-DOS and Microsoft Windows based microcomputer software for survival analysis, especially for Cox proportional hazards regression and parametric survival models. Emphasis is given to functionality, documentation, generality, and flexibility of software. A discussion of the need for software integration is given, which leads to the conclusion that survival analysis software not closely tied to a well-designed package will not meet an analyst's general needs. Some standalone programs are good tools for teaching the theory of some survival analysis procedures, but they may not teach the student good data analysis techniques such as critically examining regression assumptions. We contrast typical software with a general, integrated, modeling framework that is available with S-PLUS.     

Some recent developments for regression analysis of multivariate failure time data

Cox's seminal 1972 paper on regression methods for possibly censored failure time data popularized the use of time to an event as a primary response in prospective studies. But one key assumption of this and other regression methods is that observations are independent of one another. In many problems, failure times are clustered into small groups where outcomes within a group are correlated. Examples include failure times for two eyes from one person or for members of the same family.This paper presents a survey of models for multivariate failure time data. Two distinct classes of models are considered: frailty and marginal models. In a frailty model, the correlation is assumed to derive from latent variables (frailties) common to observations from the same cluster. Regression models are formulated for the conditional failure time distribution given the frailties. Alternatively, marginal models describe the marginal failure time distribution of each response while separately modelling the association among responses from the same cluster.We focus on recent extensions of the proportional hazards model for multivariate failure time data. Model formulation, parameter interpretation and estimation procedures are considered.     

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.     

Choice of Parametric Accelerated Life and Proportional Hazards Models for Survival Data: Asymptotic Results

We discuss the impact of misspecifying fully parametric proportional hazards and accelerated life models. For the uncensored case, misspecified accelerated life models give asymptotically unbiased estimates of covariate effect, but the shape and scale parameters depend on the misspecification. The covariate, shape and scale parameters differ in the censored case. Parametric proportional hazards models do not have a sound justification for general use: estimates from misspecified models can be very biased, and misleading results for the shape of the hazard function can arise. Misspecified survival functions are more biased at the extremes than the centre. Asymptotic and first order results are compared. If a model is misspecified, the size of Wald tests will be underestimated. Use of the sandwich estimator of standard error gives tests of the correct size, but misspecification leads to a loss of power. Accelerated life models are more robust to misspecification because of their log-linear form. In preliminary data analysis, practitioners should investigate proportional hazards and accelerated life models; software is readily available for several such models.     

Diagnostic tests for bias of estimating equations in weighted regression with missing covariates

The authors propose two tests, one parametric and the other semiparametric, for testing bias of estimating equations in weighted regression with partially missing covariates when the primary regression model is correctly specified. More generally, the proposed tests may be thought of as a diagnostic tool for the combined package of the primary regression model and the missingness assumptions. The asymptotic null distributions of the two test statistics are derived under the assumption of missingness at random for the partially missing covariates. A small scale simulation study completes the work.     

Goodness of fit tests with interval censored data

Cramér–von Mises type goodness of fit tests for interval censored data case 2 are proposed based on a resampling method called the leveraged bootstrap, and their asymptotic consistency is shown. The proposed tests are computationally efficient, and in fact can be applied to other types of censored data, including right censored data, doubly censored data and (mixture of) case k interval censored data. Some simulation results and an example from AIDS research are presented.     

Likelihood-based inference for the transmuted log-logistic model in the presence of right-censored data

Although new transmuted distributions have been widely proposed in the last few years, it is rarely to find those class of models applied in survival analysis in the presence of censored lifetimes. In this context, we are concerned in applying the transmuted log-logistic model in the study of discharge times of patients treated with the Linezolid drug. For model fitting, we use and compare different profile likelihood methods. Analysis of residuals and influence are also presented. All results are validated in a simulation study by considering the bootstrap techniques.     

Theoretical properties of tests for spatial clustering of count data

Testing for spatial clustering of count data is an important problem in spatial data analysis. Several procedures have been proposed to this end but despite their extensive use, studies of their fundamental theoretical properties are almost non‐existent. The authors suggest two conditions that any reasonable test for spatial clustering should satisfy. The latter are based on the notion that the null hypothesis should be rejected almost surely as the amount of spatial clustering tends to infinity. The authors show that the chisquared test and the Potthoff—Whittinghill V have both properties but that other classical tests do not.     

A 3-parameter Gompertz distribution for survival data with competing risks,with an application to breast cancer data

The cumulative incidence function is of great importance in the analysis of survival data when competing risks are present. Parametric modeling of such functions, which are by nature improper, suggests the use of improper distributions. One frequently used improper distribution is that of Gompertz, which captures only monotone hazard shapes. In some applications, however, subdistribution hazard estimates have been observed with unimodal shapes. An extension to the Gompertz distribution is presented which can capture unimodal as well as monotone hazard shapes. Important properties of the proposed distribution are discussed, and the proposed distribution is used to analyze survival data from a breast cancer clinical trial.     

Monte carlo results for conditional survival tests under randomly censored data

Within a Monte Carlo study finite sample results are obtained for different generalized rank tests based on randomly censored life time data. It is pointed out that conditional tests should be applied in practice whenever drastic differences between the censoring distributions for the underlying groups do not appear. The tests are slight modifications of known permutation tests for censored data.     

Semiparametric Efficient Estimation in the Generalized Odds-Rate Class of Regression Models for Right-Censored Time-to-Event Data

The generalized odds-rate class of regression models for time to event data is indexed by a non-negative constant and assumes thatg(S(t|Z)) = (t) + Zwhere g(s) = log(^-1(s-) for > 0, g₀(s) = log(- log s), S(t|Z) is the survival function of the time to event for an individual with qx1 covariate vector Z, is a qx1 vector of unknown regression parameters, and (t) is some arbitrary increasing function of t. When =0, this model is equivalent to the proportional hazards model and when =1, this model reduces to the proportional odds model. In the presence of right censoring, we construct estimators for and exp((t)) and show that they are consistent and asymptotically normal. In addition, we show that the estimator for is semiparametric efficient in the sense that it attains the semiparametric variance bound.     

Testing the effect of treatment on survival time with an immediate intermediate event

In this paper, we consider testing the effects of treatment on survival time when a subject experiences an immediate intermediate event (IE) prior to death or predetermined endpoint. A two-stage model incorporating both (i) the effects of the covariates on the immediate IE and (ii) survival regression with the immediate IE and other covariates is presented. We study the likelihood ratio test (LRT) for testing the treatment effect based on the proposed two stage model. We propose two procedures: an asymptotic-based procedure and a resampling-based procedure, to approximate the null distribution of the LRT. We numerically show the advantages of the two stage modeling over the existing single stage survival model with interactions between the covariates and the immediate IE. In addition, an illustrative empirical example is provided.     

Effect of censoring on adjusting for covariates in comparison of survival times

The increase in the variance of the estimate of treatment effect which results from omitting a dichotomous or continuous covariate is quantified as a function of censoring. The efficiency of not adjusting for a covariate is measured by the ratio of the variance obtained with and without adjustment for the covariate. The variance is derived using the Weibull proportional hazards model. Under random censoring, the efficiency of not adjusting for a continuous covariate is an increasing function of the percentage of censored observations.