Tests for homogeneity of extreme value scale parameters

It is often assumed in situations in which life data from Weibull or extreme-value distributions are involved that data in different samples come from extreme-value distributions with the same scale parameter (equivalently, Weibull distributions with the same shape parameter). This paper proposes a number of tests for homogeneity for extreme-value scale parameters, based on a number of commonly used estimators for these scale parameters. Previous theoretical work and some simulation results provided here indicate that the null distributions of the test statistics proposed are well approximated by the x2 distribution under a wide range of conditions     

Weighted Mean Survival Test Statistics: a Class of Distance Tests for Censored Survival Data

A class of test statistics is introduced which is sensitive against the alternative of stochastic ordering in the two-sample censored data problem. The test statistics for evaluating a cumulative weighted difference in survival distributions are developed while taking into account the imbalances in base-line covariates between two groups. This procedure can be used to test the null hypothesis of no treatment effect, especially when base-line hazards cross and prognostic covariates need to be adjusted. The statistics are semiparametric, not rank based, and can be written as integrated weighted differences in estimated survival functions, where these survival estimates are adjusted for covariate imbalances. The asymptotic distribution theory of the tests is developed, yielding test procedures that are shown to be consistent under a fixed alternative. The choice of weight function is discussed and relies on stability and interpretability considerations. An example taken from a clinical trial for acquired immune deficiency syndrome is presented.     

Adaptive Test for Testing the Difference in Survival Distributions

An adaptive test is proposed for the problem of testing the difference in survival distributions when the shape of the hazard ratio is unknown, hence the efficient test is unknown. The proposed adaptive test selects a test statistic from a finite set of the weighted logrank statistics T on the basis of the estimates of the efficiencies of the tests in T for given data. The efficiency estimator uses the length of the test based nonparametric confidence interval for the shift in a time transformed shift model. The suggested adaptive test is shown to be asymptotically efficient among the tests in T under the time transformed shift model and conditions commonly used in survival analysis. Simulations demonstrate that the adaptive test enjoys good small sample properties and in most situations is more powerful than the test using the maximum of the tests in T.     

A nonparametric test for current status data with unequal censoring

Nonparametric tests for the comparison of different treatments based on current status data are proposed. For this problem, most methods proposed in the literature require that observation times on all subjects follow the same distribution. In other words, censoring distributions are identical between the treatment groups. In this paper, we focus on the situation where the censoring distributions may be different for subjects in different treatment groups and the test that can take this unequal censoring into account is given. The asymptotic distribution of the test proposed is derived. The method proposed is applied to data arising from a tumorigenicity experiment.     

Nonparametric two-sample tests for dispersion differences based on placements

Two different two-sample tests for dispersion differences based on placement statistics are proposed. The means and variances of the test statistics are derived, and asymptotic normality is established for both. Variants of the proposed tests based on reversing the X and Y labels in the test statistic calculations are shown to have different small-sample properties; for both pairs of tests, one member of the pair will be resolving, the other nonresolving. The proposed tests are similar in spirit to the dispersion tests of both Mood and Hollander; comparative simulation results for these four tests are given. For small sample sizes, the powers of the proposed tests are approximately equal to the powers of the tests of both Mood and Hollander for samples from the normal, Cauchy and exponential distributions. The one-sample limiting distributions are also provided, yielding useful approximations to the exact tests when one sample is much larger than the other. A bootstrap test may alternatively be performed. The proposed test statistics may be used with lightly censored data by substituting Kaplan-Meier estimates for the empirical distribution functions.     

Comparing waiting times in a multi-stage model: A log-rank approach

A proper log-rank test for comparing two waiting (i.e. sojourn, gap) times under right censored data has been absent in the survival literature. The classical log-rank test provides a biased comparison even under independent right censoring since the censoring induced on the time since state entry depends on the entry time unless the hazards are semi-Markov. We develop test statistics for comparing K waiting time distributions from a multi-stage model in which censoring and waiting times may be dependent upon the transition history in the multi-stage model. To account for such dependent censoring, the proposed test statistics utilize an inverse probability of censoring weighted (IPCW) approach previously employed to define estimators for the cumulative hazard and survival function for waiting times in multi-stage models. We develop the test statistics as analogues to K-sample log-rank statistics for failure time data, and weak convergence to a Gaussian limit is demonstrated. A simulation study demonstrates the appropriateness of the test statistics in designs that violate typical independence assumptions for multi-stage models, under which naive test statistics for failure time data perform poorly, and illustrates the superiority of the test under proportional hazards alternatives to a Mann–Whitney type test. We apply the test statistics to an existing data set of burn patients.     

The Gini concentration test for survival data

We apply the well known Gini index to the measurement of concentration in survival times within groups of patients, and as a way to compare the distribution of survival times across groups of patients in clinical studies. In particular, we propose an estimator of a restricted version of the index from right censored data. We derive the asymptotic distribution of the resulting Gini statistic, and construct an estimator for its asymptotic variance. We use these results to propose a novel test for differences in the heterogeneity of survival distributions, which may suggest the presence of a differential treatment effect for some groups of patients. We focus in particular on traditional and generalized cure rate models, i.e., mixture models with a distribution of the lifetimes of the cured patients that is either degenerate at infinity or has a density. Results from a simulation study suggest that the Gini index is useful in some situations, and that it should be considered together with existing tests (in particular, the Log-rank, Wilcoxon, and Gray–Tsiatis tests). Use of the test is illustrated on the classic data arising from the Eastern Cooperative Oncology Group melanoma clinical trial E1690.     

Survival analysis using inverse probability of treatment weighted methods based on the generalized propensity score

In survival analysis, treatment effects are commonly evaluated based on survival curves and hazard ratios as causal treatment effects. In observational studies, these estimates may be biased due to confounding factors. The inverse probability of treatment weighted (IPTW) method based on the propensity score is one of the approaches utilized to adjust for confounding factors between binary treatment groups. As a generalization of this methodology, we developed an exact formula for an IPTW log‐rank test based on the generalized propensity score for survival data. This makes it possible to compare the group differences of IPTW Kaplan–Meier estimators of survival curves using an IPTW log‐rank test for multi‐valued treatments. As causal treatment effects, the hazard ratio can be estimated using the IPTW approach. If the treatments correspond to ordered levels of a treatment, the proposed method can be easily extended to the analysis of treatment effect patterns with contrast statistics. In this paper, the proposed method is illustrated with data from the Kyushu Lipid Intervention Study (KLIS), which investigated the primary preventive effects of pravastatin on coronary heart disease (CHD). The results of the proposed method suggested that pravastatin treatment reduces the risk of CHD and that compliance to pravastatin treatment is important for the prevention of CHD. Copyright © 2009 John Wiley & Sons, Ltd.     

A log rank type test in observational survival studies with stratified sampling

In randomized clinical trials, the log rank test is often used to test the null hypothesis of the equality of treatment-specific survival distributions. In observational studies, however, the ordinary log rank test is no longer guaranteed to be valid. In such studies we must be cautious about potential confounders; that is, the covariates that affect both the treatment assignment and the survival distribution. In this paper, two cases were considered: the first is when it is believed that all the potential confounders are captured in the primary database, and the second case where a substudy is conducted to capture additional confounding covariates. We generalize the augmented inverse probability weighted complete case estimators for treatment-specific survival distribution proposed in Bai et al. (Biometrics 69:830–839, 2013) and develop the log rank type test in both cases. The consistency and double robustness of the proposed test statistics are shown in simulation studies. These statistics are then applied to the data from the observational study that motivated this research.     

Goodness of fit tests for the multiple logistic regression model

Several test statistics are proposed for the purpose of assessing the goodness of fit of the multiple logistic regression model. The test statistics are obtained by applying a chi-square test for a contingency table in which the expected frequencies are determined using two different grouping strategies and two different sets of distributional assumptions. The null distributions of these statistics are examined by applying the theory for chi-square tests of Moore Spruill (1975) and through computer simulations. All statistics are shown to have a chi-square distribution or a distribution which can be well approximated by a chi-square. The degrees of freedom are shown to depend on the particular statistic and the distributional assumptions.

The power of each of the proposed statistics is examined for the normal, linear, and exponential alternative models using computer simulations.     

Ordered Tests for Right–Censored Survival Data

In comparative clinical trials or animal carcinogenesis studies, the effect of increasing dose levels of an agent or an increasing number of additional modalities are frequently evaluated on the prolonged survival time of patients with a particular disease. It is of particular interest to test the ordered alternative that a treatment level increase leads to better survival. This paper considers an ordered test based on the two–sample weighted Kaplan–Meier statistics (Pepe & Fleming, 1989, 1991). It evaluates asymptotic relative efficiencies of the proposed ordered weighted Kaplan–Meier test, the competing ordered weighted logrank test (Liu et al., 1993) and modified ordered logrank test (Liu & Tsai, 1999) under Lehmann alternatives, for various piecewise exponential survival distributions. Finally, it demonstrates the proposed test on an appropriate dataset.     

Identification of the minimum effective dose based on weighted Kaplan–Meier statistics

Testing procedures are considered for identifying the minimum effective dose (MED) in a dose–response study with randomly right-censored survival data, where the MED is defined to be the smallest dose level under study that has survival advantage over the zero dose control. The proposed testing procedures are implemented in a step-down manner together with three different types of weighted Kaplan–Meier statistics. Comparative results of a Monte Carlo error rate and power/bias study for a variety of survival and censoring distributions are then presented and discussed. The application of the proposed procedures is finally illustrated for identifying the MED of the diethylstilbestrol in the treatment of prostate cancer.     

Approximate tests for the equality of two cumulative incidence functions of a competing risk

In the context of a competing risks set-up, we discuss different inference procedures for testing equality of two cumulative incidence functions, where the data may be subject to independent right-censoring or left-truncation. To this end, we compare two-sample Kolmogorov–Smirnov- and Cramér–von Mises-type test statistics. Since, in general, their corresponding asymptotic limit distributions depend on unknown quantities, we utilize wild bootstrap resampling as well as approximation techniques to construct adequate test decisions. Here, the latter procedures are motivated from tests for heteroscedastic factorial designs but have not yet been proposed in the survival context. A simulation study shows the performance of all considered tests under various settings and finally a real data example about bloodstream infection during neutropenia is used to illustrate their application.     

Nonparametric tests for right-censored data with biased sampling

Testing the equality of two survival distributions can be difficult in a prevalent cohort study when non random sampling of subjects is involved. Due to the biased sampling scheme, independent censoring assumption is often violated. Although the issues about biased inference caused by length-biased sampling have been widely recognized in statistical, epidemiological and economical literature, there is no satisfactory solution for efficient two-sample testing. We propose an asymptotic most efficient nonparametric test by properly adjusting for length-biased sampling. The test statistic is derived from a full likelihood function, and can be generalized from the two-sample test to a k-sample test. The asymptotic properties of the test statistic under the null hypothesis are derived using its asymptotic independent and identically distributed representation. We conduct extensive Monte Carlo simulations to evaluate the performance of the proposed test statistics and compare them with the conditional test and the standard logrank test for different biased sampling schemes and right-censoring mechanisms. For length-biased data, empirical studies demonstrated that the proposed test is substantially more powerful than the existing methods. For general left-truncated data, the proposed test is robust, still maintains accurate control of type I error rate, and is also more powerful than the existing methods, if the truncation patterns and right-censoring patterns are the same between the groups. We illustrate the methods using two real data examples.     

A spatial scan statistic for survival data based on generalized life distribution

ABSTRACT

For many years, detection of clusters has been of great public health interest and widely studied. Several methods have been developed to detect clusters and their performance has been evaluated in various contexts. Spatial scan statistics are widely used for geographical cluster detection and inference. Different types of discrete or continuous data can be analyzed using spatial scan statistics for Bernoulli, Poisson, ordinal, exponential, and normal models. In this paper, we propose a scan statistic for survival data which is based on generalized life distribution model that provides three important life distributions, viz. Weibull, exponential, and Rayleigh. The proposed method is applied to the survival data of tuberculosis patients in Nainital district of Uttarakhand, India, for the year 2004–05. The Monte Carlo simulation studies reveal that the proposed method performs well for different survival distributions.     

Multivariate hypothesis testing using generalized and {2}-inverses – with applications

The use of generalized inverses in Wald's-type quadratic forms of test statistics having singular normal limiting distributions does not guarantee to obtain chi-square limiting distributions. In this article, the use of {2} -inverses for that problem is investigated. Alternatively, Imhof-based test statistics can also be defined, which converge in distribution to weighted sum of chi-square variables. The asymptotic distributions of these test statistics under the null and alternative hypotheses are discussed. Under fixed and local alternatives, the asymptotic powers are compared theoretically. Simulation studies are also performed to compare the exact powers of the test statistics in finite samples. A data analysis on the temperature and precipitation variability in the European Alps illustrates the proposed methods.     

Testing for ordered failure rates under general progressive censoring

For exponentially distributed failure times under general progressive censoring schemes, testing procedures for ordered failure rates are proposed using the likelihood ratio principle. Constrained maximum likelihood estimators of the failure rates are found. The asymptotic distributions of the test statistics are shown to be mixtures of chi-square distributions. When testing the equality of the failure rates, a simulation study shows that the proposed test with restricted alternative has improved power over the usual chi-square statistic with an unrestricted alternative. The proposed methods are illustrated using data of survival times of patients with squamous carcinoma of the oropharynx.     

Robust inference from multiple test statistics via permutations: a better alternative to the single test statistic approach for randomized trials

Formal inference in randomized clinical trials is based on controlling the type I error rate associated with a single pre‐specified statistic. The deficiency of using just one method of analysis is that it depends on assumptions that may not be met. For robust inference, we propose pre‐specifying multiple test statistics and relying on the minimum p‐value for testing the null hypothesis of no treatment effect. The null hypothesis associated with the various test statistics is that the treatment groups are indistinguishable. The critical value for hypothesis testing comes from permutation distributions. Rejection of the null hypothesis when the smallest p‐value is less than the critical value controls the type I error rate at its designated value. Even if one of the candidate test statistics has low power, the adverse effect on the power of the minimum p‐value statistic is not much. Its use is illustrated with examples. We conclude that it is better to rely on the minimum p‐value rather than a single statistic particularly when that single statistic is the logrank test, because of the cost and complexity of many survival trials. Copyright © 2013 John Wiley & Sons, Ltd.     

Tests for comparing a sequence of bernoulli random variables to a sequence of known probabilities

The problem of determining whether a sequence of observed Bernoulli variates is consistent with a hypothesized underlying sequence of known probabilities is considered. A family of asymptotically normal test statistics is proposed, members of which are shown to be asymptotically locally optimal against specific types of alternatives. For small samples, a skewness correction is shown to improve greatly the adequacy of the asymptotic approximations to the null distributions of the proposed test statistics. The application of testing for increased cancer risk in families is considered, and modifications to the test statistics which adjust for the method of family ascertainment are indicated     

Rank Tests for Clustered Survival Data

In a clinical trial, we may randomize subjects (called clusters) to different treatments (called groups), and make observations from multiple sites (called units) of each subject. In this case, the observations within each subject could be dependent, whereas those from different subjects are independent. If the outcome of interest is the time to an event, we may use the standard rank tests proposed for independent survival data, such as the logrank and Wilcoxon tests, to test the equality of marginal survival distributions, but their standard error should be modified to accommodate the possible intracluster correlation. In this paper we propose a method of calculating the standard error of the rank tests for two-sample clustered survival data. The method is naturally extended to that for K-sample tests under dependence.