Comparing Survival Times for Treatments with Those for a Control Under Proportional Hazards

Inferences for survival curves based on right censored data are studied for situations in which it is believed that the treatments have survival times at least as large as the control or at least as small as the control. Testing homogeneity with the appropriate order restricted alternative and testing the order restriction as the null hypothesis are considered. Under a proportional hazards model, the ordering on the survival curves corresponds to an ordering on the regression coefficients. Approximate likelihood methods, which are obtained by applying order restricted procedures to the estimates of the regression coefficients, and ordered analogues to the log rank test, which are based on the score statistics, are considered. Mau's (1988) test, which does not require proportional hazards, is extended to this ordering on the survival curves. Using Monte Carlo techniques, the type I error rates are found to be close to the nominal level and the powers of these tests are compared. Other order restrictions on the survival curves are discussed briefly.     

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.     

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.     

Ordering results on extremes of scaled random variables with dependence and proportional hazards

This study deals with random variables equipped with Archimedean copulas and following scale proportional hazards (SPHs) or revered hazards models. We build the usual stochastic order both between minimums of two SPHs samples with Archimedean survival copulas and between maximums from two scale proportional reversed hazards (PRHs) samples with Archimedean copulas. The hazard rate order between minimums of independent SPHs samples and the reversed hazard rate order between maximums of independent scale PRHs samples are both derived. Also we have a discussion on the dispersive order between minimums from samples with a common Archimedean survival copula. The present results either generalize or improve some related ones in the recent literature.     

Partial orders with respect to continuous covariates and tests for the proportional hazards model

Several omnibus tests of the proportional hazards assumption have been proposed in the literature. In the two-sample case, tests have also been developed against ordered alternatives like monotone hazard ratio and monotone ratio of cumulative hazards. Here we propose a natural extension of these partial orders to the case of continuous and potentially time varying covariates, and develop tests for the proportional hazards assumption against such ordered alternatives. The work is motivated by applications in biomedicine and economics where covariate effects often decay over lifetime. The proposed tests do not make restrictive assumptions on the underlying regression model, and are applicable in the presence of time varying covariates, multiple covariates and frailty. Small sample performance and an application to real data highlight the use of the framework and methodology to identify and model the nature of departures from proportionality.     

Sample size calculation for a proportional hazards mixture cure model with nonbinary covariates

Sample size calculation is a critical issue in clinical trials because a small sample size leads to a biased inference and a large sample size increases the cost. With the development of advanced medical technology, some patients can be cured of certain chronic diseases, and the proportional hazards mixture cure model has been developed to handle survival data with potential cure information. Given the needs of survival trials with potential cure proportions, a corresponding sample size formula based on the log-rank test statistic for binary covariates has been proposed by Wang et al. [25]. However, a sample size formula based on continuous variables has not been developed. Herein, we presented sample size and power calculations for the mixture cure model with continuous variables based on the log-rank method and further modified it by Ewell's method. The proposed approaches were evaluated using simulation studies for synthetic data from exponential and Weibull distributions. A program for calculating necessary sample size for continuous covariates in a mixture cure model was implemented in R.     

Generating data from improper distributions: application to Cox proportional hazards models with cure

Cure rate models are survival models characterized by improper survivor distributions which occur when the cumulative distribution function, say F, of the survival times does not sum up to 1 (i.e. F(+∞)<1). The first objective of this paper is to provide a general approach to generate data from any improper distribution. An application to times to event data randomly drawn from improper distributions with proportional hazards is investigated using the semi-parametric proportional hazards model with cure obtained as a special case of the nonlinear transformation models in [Tsodikov, Semiparametric models: A generalized self-consistency approach, J. R. Stat. Soc. Ser. B 65 (2003), pp. 759–774]. The second objective of this paper is to show by simulations that the bias, the standard error and the mean square error of the maximum partial likelihood (PL) estimator of the hazard ratio as well as the statistical power based on the PL estimator strongly depend on the proportion of subjects in the whole population who will never experience the event of interest.     

Generalizing the standardized hazard ratio to multivariate proportional hazards regression,with an application to clinical~genomic studies

The standardized hazard ratio for univariate proportional hazards regression is generalized as a scalar to multivariate proportional hazards regression. Estimators of the standardized log hazard ratio are developed, with corrections for bias and for regression to the mean in high-dimensional analyses. Tests of point and interval null hypotheses and confidence intervals are constructed. Cohort sampling study designs, commonly used in prospective–retrospective clinical genomic studies, are accommodated.     

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.     

Testing for order among K populations: theory and examples

Testing for stochastic order among K populations is a common and important problem in statistical practice. It arises in the analysis of both planned experiments and observational studies. The authors develop a new nonparametric test for order among K populations that can accommodate any stochastic ordering. The test is based on a maximally selected chi‐bar‐square statistic. The authors find its limiting distribution and use simulations to derive critical values. Three important examples are used to illustrate the applicability of the general method. The authors find that the new tests outperform the existing methods in many practical cases. The Canadian Journal of Statistics 38: 97–115; 2010 © 2009 Statistical Society of Canada     

Stochastic comparisons of order statistics,with applications in relibility

This paper reviews recent developments in the stochastic comparison of order statistics. The results discussed are basically: (l) Stochastic comparisons of linear combinations of order statistics from distributions F and G where G^?1 F is convex or starshaped. (2) Stochastic comparisons of individual order statistics and of vectors of order statistics from underlying heterogeneous distributions by the use of majorization and Schur function theory. (3) Stochastic comparison of random processes. Applications to reliability problems are presented illustrating the use and value of the theoretical results described