PERMUTATION TESTS AND OTHER TEST STATISTICS FOR ILL-BEHAVED DATA: EXPERIENCE OF THE NINDS t-PA STROKE TRIAL

Permutation tests are often used to analyze data since they may not require one to make assumptions regarding the form of the distribution to have a random and independent sample selection. We initially considered a permutation test to assess the treatment effect on computed tomography lesion volume in the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Trial, which has highly skewed data. However, we encountered difficulties in summarizing the permutation test results on the lesion volume. In this paper, we discuss some aspects of permutation tests and illustrate our findings. This experience with the NINDS t-PA Stroke Trial data emphasizes that permutation tests are useful for clinical trials and can be used to validate assumptions of an observed test statistic. The permutation test places fewer restrictions on the underlying distribution but is not always distribution-free or an exact test, especially for ill-behaved data. Quasi-likelihood estimation using the generalized estimating equation (GEE) approach on transformed data seems to be a good choice for analyzing CT lesion data, based on both its corresponding permutation test and its clinical interpretation.     

Exact Poly-K Test

For animal carcinogenicity study with multiple dose groups, positive trend test and pairwise comparisons of treated groups with control are generally performed using the Cochran-Armitage, Peto test, or Poly-K test. These tests are asymptotically normal. The exact version of Cochran-Armitage and Peto tests are available based on the permutation test assuming fixed column and row totals. For Poly-K test column totals depend on the mortality pattern of the animals and can not be kept fixed over the permutations of the animals. In this work a modification of the permutation test is suggested that can be applied on exact Poly-K test.     

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.     

The split sample permutation t-tests

Without the exchangeability assumption, permutation tests for comparing two population means do not provide exact control of the probability of making a Type I error. Another drawback of permutation tests is that it cannot be used to test hypothesis about one population. In this paper, we propose a new type of permutation tests for testing the difference between two population means: the split sample permutation t-tests. We show that the split sample permutation t-tests do not require the exchangeability assumption, are asymptotically exact and can be easily extended to testing hypothesis about one population. Extensive simulations were carried out to evaluate the performance of two specific split sample permutation t-tests: the split in the middle permutation t-test and the split in the end permutation t-test. The simulation results show that the split in the middle permutation t-test has comparable performance to the permutation test if the population distributions are symmetric and satisfy the exchangeability assumption. Otherwise, the split in the end permutation t-test has significantly more accurate control of level of significance than the split in the middle permutation t-test and other existing permutation tests.     

Multivariate tests comparing binomial probabilities, with application to safety studies for drugs

Summary.  In magazine advertisements for new drugs, it is common to see summary tables that compare the relative frequency of several side-effects for the drug and for a placebo, based on results from placebo-controlled clinical trials. The paper summarizes ways to conduct a global test of equality of the population proportions for the drug and the vector of population proportions for the placebo. For multivariate normal responses, the Hotelling T ²-test is a well-known method for testing equality of a vector of means for two independent samples. The tests in the paper are analogues of this test for vectors of binary responses. The likelihood ratio tests can be computationally intensive or have poor asymptotic performance. Simple quadratic forms comparing the two vectors provide alternative tests. Much better performance results from using a score-type version with a null-estimated covariance matrix than from the sample covariance matrix that applies with an ordinary Wald test. For either type of statistic, asymptotic inference is often inadequate, so we also present alternative, exact permutation tests. Follow-up inferences are also discussed, and our methods are applied to safety data from a phase II clinical trial.     

Permutation tests of scale using deviances

Robust tests for comparing scale parameters, based on deviances—absolute deviations from the median—are examined. Higgins (2004) proposed a permutation test for comparing two treatments based on the ratio of deviances, but the performance of this procedure has not been investigated. A simulation study examines the performance of Higgins’ test relative to other tests of scale utilizing deviances that have been shown in the literature to have good properties. An extension of Higgins’ procedure to three or more treatments is proposed, and a second simulation study compares its performance to other omnibus tests for comparing scale. While no procedure emerged as a preferred choice in every scenario, Higgins’ tests are found to perform well overall with respect to Type I error rate and power.     

Significance levels and confidence intervals for permutation tests

A computational algorithm is given which calculates exact significance levels of a wide class of permutation tests in the one and two sample problems. This class includes the permutation test based on the means, locally most powerful permutation tests and linear rank tests. When a shift model is assumed confidence intervals can also be obtained. Approximate methods, based on asymptotic expansions, are also presented.     

A Nonparametric Test Procedure Based on a Group of Quantile Tests

In this article, we consider nonparametric test procedures based on a group of quantile test statistics. We consider the quadratic form for the two-sided test and the maximal and summing types of statistics for the one-sided alternatives. Then we derive the null limiting distributions of the proposed test statistics using the large sample approximation theory. Also, we consider applying the permutation principle to obtain the null distribution. In this vein, we may consider the supremum type, which should use the permutation principle for obtaining the null distribution. Then we illustrate our procedure with an example and compare the proposed tests with other existing tests including the individual quantile tests by obtaining empirical powers through simulation study. Also, we comment on the related discussions to this testing procedure as concluding remarks. Finally we prove the lemmas and theorems in the appendices.     

A non-parametric maximum test for the Behrens–Fisher problem

Non-normality and heteroscedasticity are common in applications. For the comparison of two samples in the non-parametric Behrens–Fisher problem, different tests have been proposed, but no single test can be recommended for all situations. Here, we propose combining two tests, the Welch t test based on ranks and the Brunner–Munzel test, within a maximum test. Simulation studies indicate that this maximum test, performed as a permutation test, controls the type I error rate and stabilizes the power. That is, it has good power characteristics for a variety of distributions, and also for unbalanced sample sizes. Compared to the single tests, the maximum test shows acceptable type I error control.     

On the theory of modified randomization tests for nonparametric hypotheses

A general randomization test for nonparametric hypotheses which is a modification of permutation tests in proposed. The exact level of the test is derived and under mild gegularity conditions, a general result on the consistency of the power function is obtained. Applications to several testing problems are considered. Asymptotic expansions of the power of this test are derived with respect to contiguous alternatives thus test are derived with respect to contiguous alternatives thus enabling us to make deficiency comparisons with permutation tests. The paper concludes with some Monte Carlo simulations verifying the theoretical results derived.     

Pairwise comparison of scale using deviances

Permutation tests based on medians are examined for pairwise comparison of scale. Tests that have been found in the literature to be effective for comparing scale for two groups are extended to the case of all pairwise comparisons, using the Tukey-type adjustment of Richter and McCann [Multiple comparison of medians using permutation tests. J Mod Appl Stat Methods. 2007;6(2):399–412] to guarantee strong Type I error rate control. Power and Type I error rate estimates are computed using simulated data. A method based on the ratio of deviances performed best and appears to be the best overall test.     

An exact two-sample test based on the baumgartner-weiss-schindler statistic and a modification of lepage's test

It is shown that the nonparametric two-saniDle test recently proposed by Baumgartner, WeiB, Schindler (1998, Biometrics, 54, 1129-1135) does not control the type I error rate in case of small sample sizes. We investigate the exact permutation test based on their statistic and demonstrate that this test is almost not conservative. Comparing exact tests, the procedure based on the new statistic has a less conservative size and is, according to simulation results, more powerful than the often employed Wilcoxon test. Furthermore, the new test is also powerful with regard to less restrictive settings than the location-shift model. For example, the test can detect location-scale alternatives. Therefore, we use the test to create a powerful modification of the nonparametric location-scale test according to Lepage (1971, Biometrika, 58, 213-217). Selected critical values for the proposed tests are given.     

Simultaneous tests for homogeneity of two zero-inflated (beta) populations

ABSTRACT

Motivated by an example in marine science, we use Fisher’s method to combine independent likelihood ratio tests (LRTs) and asymptotic independent score tests to assess the equivalence of two zero-inflated Beta populations (mixture distributions with three parameters). For each test, test statistics for the three individual parameters are combined into a single statistic to address the overall difference between the two populations. We also develop non parametric and semiparametric permutation-based tests for simultaneously comparing two or three features of unknown populations. Simulations show that the likelihood-based tests perform well for large sample sizes and that the statistics based on combining LRT statistics outperforms the ones based on combining score test statistics. The permutation-based tests have overall better performance in terms of both power and type I error rate. Our methods are easy to implement and computationally efficient, and can be expanded to more than two populations and to other multiple parameter families. The permutation tests are entirely generic and can be useful in various applications dealing with zero (or other) inflation.     

BAHADUR SLOPES FOR COMPARISONS OF TESTS BASED ON RESAMPLING

Let X₁,…, X_n be random variables symmetric about θ from a common unknown distribution F_θ(x) =F(x–θ). To test the null hypothesis H₀:θ= 0 against the alternative H₁:θ > 0, permutation tests can be used at the cost of computational difficulties. This paper investigates alternative tests that are computationally simpler, notably some bootstrap tests which are compared with permutation tests. Of these the symmetrical bootstrap-f test competes very favourably with the permutation test in terms of Bahadur asymptotic efficiency, so it is a very attractive alternative.     

Multivariate multi-sample tests for location based on data depth

A notion of data depth is used to measure centrality or outlyingness of a data point in a given data cloud. In the context of data depth, the point (or points) having maximum depth is called as deepest point (or points). In the present work, we propose three multi-sample tests for testing equality of location parameters of multivariate populations by using the deepest point (or points). These tests can be considered as extensions of two-sample tests based on the deepest point (or points). The proposed tests are implemented through the idea of Fisher's permutation test. Performance of earlier tests is studied by simulation. Illustration with two real datasets is also provided.     

Some solutions to the multivariate Behrens–Fisher problem for dissimilarity‐based analyses

The essence of the generalised multivariate Behrens–Fisher problem (BFP) is how to test the null hypothesis of equality of mean vectors for two or more populations when their dispersion matrices differ. Solutions to the BFP usually assume variables are multivariate normal and do not handle high‐dimensional data. In ecology, species' count data are often high‐dimensional, non‐normal and heterogeneous. Also, interest lies in analysing compositional dissimilarities among whole communities in non‐Euclidean (semi‐metric or non‐metric) multivariate space. Hence, dissimilarity‐based tests by permutation (e.g., PERMANOVA, ANOSIM) are used to detect differences among groups of multivariate samples. Such tests are not robust, however, to heterogeneity of dispersions in the space of the chosen dissimilarity measure, most conspicuously for unbalanced designs. Here, we propose a modification to the PERMANOVA test statistic, coupled with either permutation or bootstrap resampling methods, as a solution to the BFP for dissimilarity‐based tests. Empirical simulations demonstrate that the type I error remains close to nominal significance levels under classical scenarios known to cause problems for the un‐modified test. Furthermore, the permutation approach is found to be more powerful than the (more conservative) bootstrap for detecting changes in community structure for real ecological datasets. The utility of the approach is shown through analysis of 809 species of benthic soft‐sediment invertebrates from 101 sites in five areas spanning 1960 km along the Norwegian continental shelf, based on the Jaccard dissimilarity measure.     

An extended class of permutation techniques for matched pairs

A class of matched-pairs permutation techniques based on distances between each pair of observed signed values is considered. Although many commonly-used inference techniques for matched pairs are members of this class, some of the more appealing inference techniques among this class have received very little attention. Two new simple rank tests of this class jointly possess both intuitive properties and location-alternative power characteristics which appear more appealing than the corresponding characteristics of either the sign test or the Wllcoxon signed-ranks test. In particular, power comparisons based on slmula-tions indicate that these new rank tests are jointly as good or even vastly superior to the sign test or the Wilcoxon signed-ranks test for location alternatives involving five symmetric distributions. The five distributions selected for these com-parisons include the Laplace, logistic, normal, uniform and a U-shaped distribution     

The Use of Permutation Tests for Variance Components in Linear Mixed Models

Standard asymptotic chi-square distribution of the likelihood ratio and score statistics under the null hypothesis does not hold when the parameter value is on the boundary of the parameter space. In mixed models it is of interest to test for a zero random effect variance component. Some available tests for the variance component are reviewed and a new test within the permutation framework is presented. The power and significance level of the different tests are investigated by means of a Monte Carlo simulation study. The proposed test has a significance level closer to the nominal one and it is more powerful.     

Rotation test with pairwise distance measures of sample vectors in a GLM

One way to cope with high-dimensional data even in small samples is the use of pairwise distance measures—such as the Euclidean distance—between the sample vectors. This is usually done with permutation tests. Here we propose the application of exact parametric rotation tests which are no longer restricted by the finite number of possible permutations of a sample. The method is presented in the framework of the general linear model.     

Conditional Studentized Survival Tests for Randomly Censored Models

It is shown that in the case of heterogenous censoring distributions Studentized survival tests can be carried out as conditional permutation tests given the order statistics and their censoring status. The result is based on a conditional central limit theorem for permutation statistics. It holds for linear test statistics as well as for sup-statistics. The procedure works under one of the following general circumstances for the two-sample problem: the unbalanced sample size case, highly censored data, certain non-convergent weight functions or under alternatives. For instance, the two-sample log rank test can be carried out asymptotically as a conditional test if the relative amount of uncensored observations vanishes asymptotically as long as the number of uncensored observations becomes infinite. Similar results hold whenever the sample sizes and are unbalanced in the sense that and hold.