arXiv subjects

Marc Ditzhaus

Publications and source records attributed to Marc Ditzhaus.

30 records · Page 2Linked to original sources

arXiv2021

Studentized Permutation Method for Comparing Restricted Mean Survival Times with Small Sample from Randomized Trials

Recent observations, especially in cancer immunotherapy clinical trials with time-to-event outcomes, show that the commonly used proportial hazard assumption is often not justifiable, hampering an appropriate analyse of the data by hazard ratios. An attractive alternative advocated is given by the restricted mean survival time (RMST), which does not rely on any model assumption and can always be interpreted intuitively. As pointed out recently by Horiguchi and Uno (2020), methods for the RMST based on asymptotic theory suffer from inflated type-I error under small sample sizes. To overcome this problem, they suggested a permutation strategy leading to more convincing results in simulations. However, their proposal requires an exchangeable data set-up between comparison groups which may be limiting in practice. In addition, it is not possible to invert their testing procedure to obtain valid confidence intervals, which can provide more in-depth information. In this paper, we address these limitations by proposing a studentized permutation test as well as the corresponding permutation-based confidence intervals. In our extensive simulation study, we demonstrate the advantage of our new method, especially in situations with relative small sample sizes and unbalanced groups. Finally we illustrate the application of the proposed method by re-analysing data from a recent lung cancer clinical trial.

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arXiv2020

A kernel test for quasi-independence

We consider settings in which the data of interest correspond to pairs of ordered times, e.g, the birth times of the first and second child, the times at which a new user creates an account and makes the first purchase on a website, and the entry and survival times of patients in a clinical trial. In these settings, the two times are not independent (the second occurs after the first), yet it is still of interest to determine whether there exists significant dependence {\em beyond} their ordering in time. We refer to this notion as "quasi-(in)dependence". For instance, in a clinical trial, to avoid biased selection, we might wish to verify that recruitment times are quasi-independent of survival times, where dependencies might arise due to seasonal effects. In this paper, we propose a nonparametric statistical test of quasi-independence. Our test considers a potentially infinite space of alternatives, making it suitable for complex data where the nature of the possible quasi-dependence is not known in advance. Standard parametric approaches are recovered as special cases, such as the classical conditional Kendall's tau, and log-rank tests. The tests apply in the right-censored setting: an essential feature in clinical trials, where patients can withdraw from the study. We provide an asymptotic analysis of our test-statistic, and demonstrate in experiments that our test obtains better power than existing approaches, while being more computationally efficient.

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arXiv2020

Inferring median survival differences in general factorial designs via permutation tests

Factorial survival designs with right-censored observations are commonly inferred by Cox regression and explained by means of hazard ratios. However, in case of non-proportional hazards, their interpretation can become cumbersome; especially for clinicians. We therefore offer an alternative: median survival times are used to estimate treatment and interaction effects and null hypotheses are formulated in contrasts of their population versions. Permutation-based tests and confidence regions are proposed and shown to be asymptotically valid. Their type-1 error control and power behavior are investigated in extensive simulations, showing the new methods' wide applicability. The latter is complemented by an illustrative data analysis.

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arXiv2020

Permutation inference in factorial survival designs with the CASANOVA

We propose inference procedures for general nonparametric factorial survival designs with possibly right-censored data. Similar to additive Aalen models, null hypotheses are formulated in terms of cumulative hazards. Thereby, deviations are measured in terms of quadratic forms in Nelson-Aalen-type integrals. Different to existing approaches this allows to work without restrictive model assumptions as proportional hazards. In particular, crossing survival or hazard curves can be detected without a significant loss of power. For a distribution-free application of the method, a permutation strategy is suggested. The resulting procedures' asymptotic validity as well as their consistency are proven and their small sample performances are analyzed in extensive simulations. Their applicability is finally illustrated by analyzing an oncology data set.

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arXiv2020

Permutation test for the multivariate coefficient of variation in factorial designs

New inference methods for the multivariate coefficient of variation and its reciprocal, the standardized mean, are presented. While there are various testing procedures for both parameters in the univariate case, it is less known how to do inference in the multivariate setting appropriately. There are some existing procedures but they rely on restrictive assumptions on the underlying distributions. We tackle this problem by applying Wald-type statistics in the context of general, potentially heteroscedastic factorial designs. In addition to the $k$-sample case, higher-way layouts can be incorporated into this framework allowing the discussion of main and interaction effects. The resulting procedures are shown to be asymptotically valid under the null hypothesis and consistent under general alternatives. To improve the finite sample performance, we suggest permutation versions of the tests and shown that the tests' asymptotic properties can be transferred to them. An exhaustive simulation study compares the new tests, their permutation counterparts and existing methods. To further analyse the differences between the tests, we conduct two illustrative real data examples.

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arXiv2020

QANOVA: Quantile-based Permutation Methods For General Factorial Designs

Population means and standard deviations are the most common estimands to quantify effects in factorial layouts. In fact, most statistical procedures in such designs are built towards inferring means or contrasts thereof. For more robust analyses, we consider the population median, the interquartile range (IQR) and more general quantile combinations as estimands in which we formulate null hypotheses and calculate compatible confidence regions. Based upon simultaneous multivariate central limit theorems and corresponding resampling results, we derive asymptotically correct procedures in general, potentially heteroscedastic, factorial designs with univariate endpoints. Special cases cover robust tests for the population median or the IQR in arbitrary crossed one-, two- and higher-way layouts with potentially heteroscedastic error distributions. In extensive simulations we analyze their small sample properties and also conduct an illustrating data analysis comparing children's height and weight from different countries.

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arXiv2019

Dependence correction of multiple tests with applications to sparsity

The present paper establishes new multiple procedures for simultaneous testing of a large number of hypotheses under dependence. Special attention is devoted to experiments with rare false hypotheses. This sparsity assumption is typically for various genome studies when a portion of remarkable genes should be detected. The aim is to derive tests which control the false discovery rate (FDR) always at finite sample size. The procedures are compared for the set up of dependent and independent $p$-values. It turns out that the FDR bounds differ by a dependency factor which can be used as a correction quantity. We offer sparsity modifications and improved dependence tests which generalize the Benjamini-Yekutieli test and adaptive tests in the sense of Storey. As a byproduct, an early stopped test is presented in order to bound the number of rejections. The new procedures perform well for real genome data examples.

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arXiv2018

Wild bootstrap logrank tests with broader power functions for testing superiority

We introduce novel wild bootstrap procedures for testing superiority in unpaired two-sample survival data. By combining different classical weighted logrank test we obtain tests with broader power behavior. Right censoring within the data is allowed and may differ between the groups. The tests are shown to be asymptotically exact under the null, consistent for fixed alternatives and admissible for a larger set of local alternatives. Beside these asymptotic properties we also illustrate the procedures' strength in simulations for finite sample sizes. The tests are implemented in the novel R-package mdir.logrank and its application is demonstrated in an exemplary data analysis.

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arXiv2018

Detectability of nonparametric signals: higher criticism versus likelihood ratio

We study the signal detection problem in high dimensional noise data (possibly) containing rare and weak signals. Log-likelihood ratio (LLR) tests depend on unknown parameters, but they are needed to judge the quality of detection tests since they determine the detection regions. The popular Tukey's higher criticism (HC) test was shown to achieve the same completely detectable region as the LLR test does for different (mainly) parametric models. We present a novel technique to prove this result for very general signal models, including even nonparametric $p$-value models. Moreover, we address the following questions which are still pending since the initial paper of Donoho and Jin: What happens on the border of the completely detectable region, the so-called detection boundary? Does HC keep its optimality there? In particular, we give a complete answer for the heteroscedastic normal mixture model. As a byproduct, we give some new insights about the LLR test's behavior on the detection boundary by discussing, among others, Pitmans's asymptotic efficiency as an application of Le Cam's theory.

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arXiv2018

More powerful logrank permutation tests for two-sample survival data

Weighted logrank tests are a popular tool for analyzing right censored survival data from two independent samples. Each of these tests is optimal against a certain hazard alternative, for example the classical logrank test for proportional hazards. But which weight function should be used in practical applications? We address this question by a flexible combination idea leading to a testing procedure with broader power. Beside the test's asymptotic exactness and consistency its power behaviour under local alternatives is derived. All theoretical properties can be transferred to a permutation version of the test, which is even finitely exact under exchangeability and showed a better finite sample performance in our simulation study. The procedure is illustrated in a real data example.

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arXiv2018

Signal detection via Phi-divergences for general mixtures

In this paper we are interested in testing whether there are any signals hidden in high dimensional noise data. Therefore we study the family of goodness-of-fit tests based on $Φ$-divergences including the test of Berk and Jones as well as Tukey's higher criticism test. The optimality of this family is already known for the heterogeneous normal mixture model. We now present a technique to transfer this optimality to more general models. For illustration we apply our results to dense signal and sparse signal models including the exponential-$χ^2$ mixture model and general exponential families as the normal, exponential and Gumbel distribution. Beside the optimality of the whole family we discuss the power behavior on the detection boundary and show that the whole family has no power there, whereas the likelihood ratio test does.

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arXiv2018

On the consistency of adaptive multiple tests

Much effort has been done to control the "false discovery rate" (FDR) when $m$ hypotheses are tested simultaneously. The FDR is the expectation of the "false discovery proportion" $\text{FDP}=V/R$ given by the ratio of the number of false rejections $V$ and all rejections $R$. In this paper, we have a closer look at the FDP for adaptive linear step-up multiple tests. These tests extend the well known Benjamini and Hochberg test by estimating the unknown amount $m_0$ of the true null hypotheses. We give exact finite sample formulas for higher moments of the FDP and, in particular, for its variance. Using these allows us a precise discussion about the consistency of adaptive step-up tests. We present sufficient and necessary conditions for consistency on the estimators $\widehat m_0$ and the underlying probability regime. We apply our results to convex combinations of generalized Storey type estimators with various tuning parameters and (possibly) data-driven weights. The corresponding step-up tests allow a flexible adaptation. Moreover, these tests control the FDR at finite sample size. We compare these tests to the classical Benjamini and Hochberg test and discuss the advantages of it.

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