A generalized Fleming and Harrington's class of tests for interval‐censored data

The class $G^{\rho,\lambda }$ of weighted log‐rank tests proposed by Fleming & Harrington [Fleming & Harrington (1991) Counting Processes and Survival Analysis, Wiley, New York] has been widely used in survival analysis and is nowadays, unquestionably, the established method to compare, nonparametrically, k different survival functions based on right‐censored survival data. This paper extends the $G^{\rho,\lambda }$ class to interval‐censored data. First we introduce a new general class of rank based tests, then we show the analogy to the above proposal of Fleming & Harrington. The asymptotic behaviour of the proposed tests is derived using an observed Fisher information approach and a permutation approach. Aiming to make this family of tests interpretable and useful for practitioners, we explain how to interpret different choices of weights and we apply it to data from a cohort of intravenous drug users at risk for HIV infection. The Canadian Journal of Statistics 40: 501–516; 2012 © 2012 Statistical Society of Canada     

Saddlepoint p-values for a class of tests for comparing competing risks with censored data

One of the general problems in clinical trials and mortality rates is the comparison of competing risks. Most of the test statistics used for independent and dependent risks with censored data belong to the class of weighted linear rank tests in its multivariate version. In this paper, we introduce the saddlepoint approximations as accurate and fast approximations for the exact p-values of this class of tests instead of the asymptotic and permutation simulated calculations. Real data examples and extensive simulation studies showed the accuracy and stability performance of the saddlepoint approximations over different scenarios of lifetime distributions, sample sizes and censoring.     

The weighted log-rank class under truncated binomial design: saddlepoint p-values and confidence intervals

The randomization design used to collect the data provides basis for the exact distributions of the permutation tests. The truncated binomial design is one of the commonly used designs for forcing balance in clinical trials to eliminate experimental bias. In this article, we consider the exact distribution of the weighted log-rank class of tests for censored data under the truncated binomial design. A double saddlepoint approximation for p-values of this class is derived under the truncated binomial design. The speed and accuracy of the saddlepoint approximation over the normal asymptotic facilitate the inversion of the weighted log-rank tests to determine nominal 95% confidence intervals for treatment effect with right censored data.     

Saddlepoint <Emphasis Type="Italic">p</Emphasis>-values and confidence intervals for a class of two sample permutation tests for current status and panel count data

The current status and panel count data frequently arise from cancer and tumorigenicity studies when events currently occur. A common and widely used class of two sample tests, for current status and panel count data, is the permutation class. We manipulate the double saddlepoint method to calculate the exact mid-p-values of the underlying permutation distributions of this class of tests. Permutation simulations are replaced by analytical saddlepoint computations which provide extremely accurate mid-p-values that are exact for most practical purposes and almost always more accurate than normal approximations. The method is illustrated using two real tumorigenicity panel count data. To compare the saddlepoint approximation with the normal asymptotic approximation, a simulation study is conducted. The speed and accuracy of the saddlepoint method facilitate the calculation of the confidence interval for the treatment effect. The inversion of the mid-p-values to calculate the confidence interval for the mean rate of development of the recurrent event is discussed.     

A Family of Goodness‐of‐Fit Tests for Copulas Based on Characteristic Functions

A general class of rank statistics based on the characteristic function is introduced for testing goodness‐of‐fit hypotheses about the copula of a continuous random vector. These statistics are defined as L ₂ weighted functional distances between a nonparametric estimator and a semi‐parametric estimator of the characteristic function associated with a copula. It is shown that these statistics behave asymptotically as degenerate V ‐statistics of order four and that the limit distributions have representations in terms of weighted sums of independent chi‐square variables. The consistency of the tests against general alternatives is established and an asymptotically valid parametric bootstrap is suggested for the computation of the critical values of the tests. The behaviour of the new tests in small and moderate sample sizes is investigated with the help of simulations and compared with a competing test based on the empirical copula. Finally, the methodology is illustrated on a five‐dimensional data set.     

Bivariate symmetry tests for complete and competing risks data: a saddlepoint approach

A class of bivariate symmetry tests for complete data and competing risks data is considered. Saddlepoint approximation for the exact p-values of the underlying permutation distribution of these tests is derived. Several simulation studies are conducted to evaluate the performance of the saddlepoint approximation and the asymptotic approximation. The saddlepoint approximation was found to be highly accurate and superior to the asymptotic approximations in replicating the exact permutation significance.     

On a new goodness‐of‐fit process for families of copulas

A goodness‐of‐fit procedure is proposed for parametric families of copulas. The new test statistics are functionals of an empirical process based on the theoretical and sample versions of Spearman's dependence function. Conditions under which this empirical process converges weakly are seen to hold for many families including the Gaussian, Frank, and generalized Farlie–Gumbel–Morgenstern systems of distributions, as well as the models with singular components described by Durante [Durante ( 2007 ) Comptes Rendus Mathématique. Académie des Sciences. Paris, 344, 195–198]. Thanks to a parametric bootstrap method that allows to compute valid P‐values, it is shown empirically that tests based on Cramér–von Mises distances keep their size under the null hypothesis. Simulations attesting the power of the newly proposed tests, comparisons with competing procedures and complete analyses of real hydrological and financial data sets are presented. The Canadian Journal of Statistics 37: 80‐101; 2009 © 2009 Statistical Society of Canada     

Large‐sample tests of extreme‐value dependence for multivariate copulas

Starting from the characterization of extreme‐value copulas based on max‐stability, large‐sample tests of extreme‐value dependence for multivariate copulas are studied. The two key ingredients of the proposed tests are the empirical copula of the data and a multiplier technique for obtaining approximate p‐values for the derived statistics. The asymptotic validity of the multiplier approach is established, and the finite‐sample performance of a large number of candidate test statistics is studied through extensive Monte Carlo experiments for data sets of dimension two to five. In the bivariate case, the rejection rates of the best versions of the tests are compared with those of the test of Ghoudi et al. (1998) recently revisited by Ben Ghorbal et al. (2009). The proposed procedures are illustrated on bivariate financial data and trivariate geological data. The Canadian Journal of Statistics 39: 703–720; 2011. © 2011 Statistical Society of Canada     

Bounded influence nonlinear signed‐rank regression

In this paper we consider weighted generalized‐signed‐rank estimators of nonlinear regression coefficients. The generalization allows us to include popular estimators such as the least squares and least absolute deviations estimators but by itself does not give bounded influence estimators. Adding weights results in estimators with bounded influence function. We establish conditions needed for the consistency and asymptotic normality of the proposed estimator and discuss how weight functions can be chosen to achieve bounded influence function of the estimator. Real life examples and Monte Carlo simulation experiments demonstrate the robustness and efficiency of the proposed estimator. An example shows that the weighted signed‐rank estimator can be useful to detect outliers in nonlinear regression. The Canadian Journal of Statistics 40: 172–189; 2012 © 2012 Statistical Society of Canada     

Goodness‐of‐fit testing based on a weighted bootstrap: A fast large‐sample alternative to the parametric bootstrap

The process comparing the empirical cumulative distribution function of the sample with a parametric estimate of the cumulative distribution function is known as the empirical process with estimated parameters and has been extensively employed in the literature for goodness‐of‐fit testing. The simplest way to carry out such goodness‐of‐fit tests, especially in a multivariate setting, is to use a parametric bootstrap. Although very easy to implement, the parametric bootstrap can become very computationally expensive as the sample size, the number of parameters, or the dimension of the data increase. An alternative resampling technique based on a fast weighted bootstrap is proposed in this paper, and is studied both theoretically and empirically. The outcome of this work is a generic and computationally efficient multiplier goodness‐of‐fit procedure that can be used as a large‐sample alternative to the parametric bootstrap. In order to approximately determine how large the sample size needs to be for the parametric and weighted bootstraps to have roughly equivalent powers, extensive Monte Carlo experiments are carried out in dimension one, two and three, and for models containing up to nine parameters. The computational gains resulting from the use of the proposed multiplier goodness‐of‐fit procedure are illustrated on trivariate financial data. A by‐product of this work is a fast large‐sample goodness‐of‐fit procedure for the bivariate and trivariate t distribution whose degrees of freedom are fixed. The Canadian Journal of Statistics 40: 480–500; 2012 © 2012 Statistical Society of Canada     

A uniform saddlepoint expansion for the null‐distribution of the wilcoxon‐mann‐whitney statistic

The authors give the exact coefficient of 1/N in a saddlepoint approximation to the Wilcoxon‐Mann‐Whitney null‐distribution. This saddlepoint approximation is obtained from an Edgeworth approximation to the exponentially tilted distribution. Moreover, the rate of convergence of the relative error is uniformly of order O (1/N) in a large deviation interval as defined in Feller (1971). The proposed method for computing the coefficient of 1/N can be used to obtain the exact coefficients of 1/Nⁱ, for any i. The exact formulas for the cumulant generating function and the cumulants, needed for these results, are those of van Dantzig (1947‐1950).     

Designing cancer immunotherapy trials with delayed treatment effect using maximin efficiency robust statistics

The indirect mechanism of action of immunotherapy causes a delayed treatment effect, producing delayed separation of survival curves between the treatment groups, and violates the proportional hazards assumption. Therefore using the log‐rank test in immunotherapy trial design could result in a severe loss efficiency. Although few statistical methods are available for immunotherapy trial design that incorporates a delayed treatment effect, recently, Ye and Yu proposed the use of a maximin efficiency robust test (MERT) for the trial design. The MERT is a weighted log‐rank test that puts less weight on early events and full weight after the delayed period. However, the weight function of the MERT involves an unknown function that has to be estimated from historical data. Here, for simplicity, we propose the use of an approximated maximin test, the V₀ test, which is the sum of the log‐rank test for the full data set and the log‐rank test for the data beyond the lag time point. The V₀ test fully uses the trial data and is more efficient than the log‐rank test when lag exits with relatively little efficiency loss when no lag exists. The sample size formula for the V₀ test is derived. Simulations are conducted to compare the performance of the V₀ test to the existing tests. A real trial is used to illustrate cancer immunotherapy trial design with delayed treatment effect.     

Multivariate two‐sample permutation tests for trials with multiple time‐to‐event outcomes

Clinical trials involving multiple time‐to‐event outcomes are increasingly common. In this paper, permutation tests for testing for group differences in multivariate time‐to‐event data are proposed. Unlike other two‐sample tests for multivariate survival data, the proposed tests attain the nominal type I error rate. A simulation study shows that the proposed tests outperform their competitors when the degree of censored observations is sufficiently high. When the degree of censoring is low, it is seen that naive tests such as Hotelling's T² outperform tests tailored to survival data. Computational and practical aspects of the proposed tests are discussed, and their use is illustrated by analyses of three publicly available datasets. Implementations of the proposed tests are available in an accompanying R package.     

Robust Lagrange multiplier test for detecting ARCH/GARCH effect using permutation and bootstrap

The Lagrange Multiplier (LM) test is one of the principal tools to detect ARCH and GARCH effects in financial data analysis. However, when the underlying data are non‐normal, which is often the case in practice, the asymptotic LM test, based on the χ²‐approximation of critical values, is known to perform poorly, particularly for small and moderate sample sizes. In this paper we propose to employ two re‐sampling techniques to find critical values of the LM test, namely permutation and bootstrap. We derive the properties of exactness and asymptotically correctness for the permutation and bootstrap LM tests, respectively. Our numerical studies indicate that the proposed re‐sampled algorithms significantly improve size and power of the LM test in both skewed and heavy‐tailed processes. We also illustrate our new approaches with an application to the analysis of the Euro/USD currency exchange rates and the German stock index. The Canadian Journal of Statistics 40: 405–426; 2012 © 2012 Statistical Society of Canada     

Saddlepoint approximations for some models of circular data

In this article we provide saddlepoint approximations for some important models of circular data. The particularity of these saddlepoint approximations is that they do not require solving the saddlepoint equation iteratively, so their evaluation is immediate. We first give very accurate approximations to P-values, critical values and power functions for some optimal tests regarding the concentration parameter under wrapped symmetric α-stable and circular normal models. Then, we consider an approximation to the distribution of a projection of the two-dimensional Pearson random walk with exponential step sizes.     

Group sequential monitoring based on the weighted log‐rank test statistic with the Fleming–Harrington class of weights in cancer vaccine studies

In recent years, immunological science has evolved, and cancer vaccines are now approved and available for treating existing cancers. Because cancer vaccines require time to elicit an immune response, a delayed treatment effect is expected and is actually observed in drug approval studies. Accordingly, we propose the evaluation of survival endpoints by weighted log‐rank tests with the Fleming–Harrington class of weights. We consider group sequential monitoring, which allows early efficacy stopping, and determine a semiparametric information fraction for the Fleming–Harrington family of weights, which is necessary for the error spending function. Moreover, we give a flexible survival model in cancer vaccine studies that considers not only the delayed treatment effect but also the long‐term survivors. In a Monte Carlo simulation study, we illustrate that when the primary analysis is a weighted log‐rank test emphasizing the late differences, the proposed information fraction can be a useful alternative to the surrogate information fraction, which is proportional to the number of events. Copyright © 2016 John Wiley & Sons, Ltd.     

On the incidence–prevalence relation and length‐biased sampling

For many diseases, logistic constraints render large incidence studies difficult to carry out. This becomes a drawback, particularly when a new study is needed each time the incidence rate is investigated in a new population. By carrying out a prevalent cohort study with follow‐up it is possible to estimate the incidence rate if it is constant. The authors derive the maximum likelihood estimator (MLE) of the overall incidence rate, λ, as well as age‐specific incidence rates, by exploiting the epidemiologic relationship, (prevalence odds) = (incidence rate) × (mean duration) (P/[1 ? P] = λ × µ). The authors establish the asymptotic distributions of the MLEs and provide approximate confidence intervals for the parameters. Moreover, the MLE of λ is asymptotically most efficient and is the natural estimator obtained by substituting the marginal maximum likelihood estimators for P and µ into P/[1 ? P] = λ × µ. Following‐up the subjects allows the authors to develop these widely applicable procedures. The authors apply their methods to data collected as part of the Canadian Study of Health and Ageing to estimate the incidence rate of dementia amongst elderly Canadians. The Canadian Journal of Statistics © 2009 Statistical Society of Canada     

Implications of random cut‐points theory for the Mann‐Whitney and binomial tests

Through random cut‐points theory, the author extends inference for ordered categorical data to the unspecified continuum underlying the ordered categories. He shows that a random cut‐point Mann‐Whitney test yields slightly smaller p‐values than the conventional test for most data. However, when at least P% of the data lie in one of the k categories (with P = 80 for k = 2, P = 67 for k = 3,…, P = 18 for k = 30), he also shows that the conventional test can yield much smaller p‐values, and hence misleadingly liberal inference for the underlying continuum. The author derives formulas for exact tests; for k = 2, the Mann‐Whitney test is but a binomial test.     

Wilcoxon's signed‐rank statistic: what null hypothesis and why it matters

In statistical literature, the term ‘signed‐rank test’ (or ‘Wilcoxon signed‐rank test’) has been used to refer to two distinct tests: a test for symmetry of distribution and a test for the median of a symmetric distribution, sharing a common test statistic. To avoid potential ambiguity, we propose to refer to those two tests by different names, as ‘test for symmetry based on signed‐rank statistic’ and ‘test for median based on signed‐rank statistic’, respectively. The utility of such terminological differentiation should become evident through our discussion of how those tests connect and contrast with sign test and one‐sample t‐test. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.     

Estimating probabilities from invariant permutation distributions

Summary We introduce variance reduction techniques as general tools for estimating probabilities from invariant permutation distributions. The paper discusses importance sampling, antithetic sampling and control variates sampling as alternatives to uniform Monte Carlo sampling for estimating exact critical values orP-values in a broad class of permutation tests. Results may be extended to permutation confidence intervals and linear rank tests. An asymptotic theory is provided for each proposed variance reduction method. Invited paper at the Conference held in Bologna, Italy, 27–28 May 1993, on ?Statistical Tests: Methodology and Econometric Applications?.