Consider the multiple testing problem of testing null hypotheses $H_1,...,H_s$. A classical approach to dealing with the multiplicity problem is to restrict attention to procedures that control the familywise error rate ($\mathit{FWER}$), the probability of even one false rejection. But if $s$ is large, control of the $\mathit{FWER}$ is so stringent that the ability of a procedure that controls the $\mathit{FWER}$ to detect false null hypotheses is limited. It is therefore desirable to consider other measures of error control. This article considers two generalizations of the $\mathit{FWER}$. The first is the $k-\mathit{FWER}$, in which one is willing to tolerate $k$ or more false rejections for some fixed $k\geq 1$. The second is based on the false discovery proportion ($\mathit{FDP}$), defined to be the number of false rejections divided by the total number of rejections (and defined to be 0 if there are no rejections). Benjamini and Hochberg [J. Roy. Statist. Soc. Ser. B 57 (1995) 289--300] proposed control of the false discovery rate ($\mathit{FDR}$), by which they meant that, for fixed $α$, $E(\mathit{FDP})\leqα$. Here, we consider control of the $\mathit{FDP}$ in the sense that, for fixed $γ$ and $α$, $P\{\mathit{FDP}>γ\}\leq α$. Beginning with any nondecreasing sequence of constants and $p$-values for the individual tests, we derive stepup procedures that control each of these two measures of error control without imposing any assumptions on the dependence structure of the $p$-values. We use our results to point out a few interesting connections with some closely related stepdown procedures. We then compare and contrast two $\mathit{FDP}$-controlling procedures obtained using our results with the stepup procedure for control of the $\mathit{FDR}$ of Benjamini and Yekutieli [Ann. Statist. 29 (2001) 1165--1188].
Consider the multiple testing problem of testing k null hypotheses, where the unknown family of distributions is assumed to satisfy a certain monotonicity assumption. Attention is restricted to procedures that control the familywise error rate in the strong sense and which satisfy a monotonicity condition. Under these assumptions, we prove certain maximin optimality results for some well-known stepdown and stepup procedures.
A classical approach for dealing with the multiple testing problem is to restrict attention to procedures that control the familywise error rate (FWER), the probability of at least one false rejection. In many applications, one might be willing to tolerate more than one false rejection provided the number of such cases is controlled, thereby increasing the ability of the procedure to detect false null hypotheses. This suggests replacing control of the FWER by controlling the probability of $k$ or more false rejections, which is called the $k$-FWER. In this article, a unified approach is presen…
In many applications of multiple hypothesis testing where more than one false rejection can be tolerated, procedures controlling error rates measuring at least $k$ false rejections, instead of at least one, for some fixed $k\ge 1$ can potentially increase the ability of a procedure to detect false null hypotheses. The $k$-FWER, a generalized version of the usual familywise error rate (FWER), is such an error rate that has recently been introduced in the literature and procedures controlling it have been proposed. A further generalization of a result on the $k$-FWER is provided in this article.…
In a multiple testing problem where one is willing to tolerate a few false rejections, procedure controlling the familywise error rate (FWER) can potentially be improved in terms of its ability to detect false null hypotheses by generalizing it to control the $k$-FWER, the probability of falsely rejecting at least $k$ null hypotheses, for some fixed $k>1$. Simes' test for testing the intersection null hypothesis is generalized to control the $k$-FWER weakly, that is, under the intersection null hypothesis, and Hochberg's stepup procedure for simultaneous testing of the individual null hypothes…
Closed testing and partitioning are recognized as fundamental principles of familywise error control. In this paper, we argue that sequential rejection can be considered equally fundamental as a general principle of multiple testing. We present a general sequentially rejective multiple testing procedure and show that many well-known familywise error controlling methods can be constructed as special cases of this procedure, among which are the procedures of Holm, Shaffer and Hochberg, parallel and serial gatekeeping procedures, modern procedures for multiple testing in graphs, resampling-based …
The $γ$-FDP and $k$-FWER multiple testing error metrics, which are tail probabilities of the respective error statistics, have become popular recently as less-stringent alternatives to the FDR and FWER. We propose general and flexible stepup and stepdown procedures for testing multiple hypotheses about sequential (or streaming) data that simultaneously control both the type I and II versions of $γ$-FDP, or $k$-FWER. The error control holds regardless of the dependence between data streams, which may be of arbitrary size and shape. All that is needed is a test statistic for each data stream tha…
This paper addresses the following general scenario: A scientist wishes to perform a battery of experiments, each generating a sequential stream of data, to investigate some phenomenon. The scientist would like to control the overall error rate in order to draw statistically-valid conclusions from each experiment, while being as efficient as possible. The between-stream data may differ in distribution and dimension but also may be highly correlated, even duplicated exactly in some cases. Treating each experiment as a hypothesis test and adopting the familywise error rate (FWER) metric, we give…
The probability of false discovery proportion (FDP) exceeding $γ\in[0,1)$, defined as $γ$-FDP, has received much attention as a measure of false discoveries in multiple testing. Although this measure has received acceptance due to its relevance under dependency, not much progress has been made yet advancing its theory under such dependency in a nonasymptotic setting, which motivates our research in this article. We provide a larger class of procedures containing the stepup analog of, and hence more powerful than, the stepdown procedure in Lehmann and Romano [Ann. Statist. 33 (2005) 1138-1154] …
We present a unifying approach to multiple testing procedures for sequential (or streaming) data by giving sufficient conditions for a sequential multiple testing procedure to control the familywise error rate (FWER), extending to the sequential domain the work of Goeman and Solari (2010) who accomplished this for fixed sample size procedures. Together we call these conditions the "rejection principle for sequential tests," which we then apply to some existing sequential multiple testing procedures to give simplified understanding of their FWER control. Next the principle is applied to derive …
Biological research often involves testing a growing number of null hypotheses as new data is accumulated over time. We study the problem of online control of the familywise error rate (FWER), that is testing an apriori unbounded sequence of hypotheses (p-values) one by one over time without knowing the future, such that with high probability there are no false discoveries in the entire sequence. This paper unifies algorithmic concepts developed for offline (single batch) FWER control and online false discovery rate control to develop novel online FWER control methods. Though many offline FWER…
We present a novel method for controlling the $k$-familywise error rate ($k$-FWER) in the linear regression setting using the knockoffs framework first introduced by Barber and Candès. Our procedure, which we also refer to as knockoffs, can be applied with any design matrix with at least as many observations as variables, and does not require knowing the noise variance. Unlike other multiple testing procedures which act directly on $p$-values, knockoffs is specifically tailored to linear regression and implicitly accounts for the statistical relationships between hypothesis tests of different …
In this paper, the problem of error control of stepwise multiple testing procedures is considered. For two-sided hypotheses, control of both type 1 and type 3 (or directional) errors is required, and thus mixed directional familywise error rate control and mixed directional false discovery rate control are each considered by incorporating both types of errors in the error rate. Mixed directional familywise error rate control of stepwise methods in multiple testing has proven to be a challenging problem, as demonstrated in Shaffer (1980). By an appropriate formulation of the problem, some new s…
We consider the class of all multiple testing methods controlling tail probabilities of the false discovery proportion, either for one random set or simultaneously for many such sets. This class encompasses methods controlling familywise error rate, generalized familywise error rate, false discovery exceedance, joint error rate, simultaneous control of all false discovery proportions, and others, as well as seemingly unrelated methods such as gene set testing in genomics and cluster inference methods in neuroimaging. We show that all such methods are either equivalent to a closed testing metho…
In applications such as clinical safety analysis, the data of the experiments usually consists of frequency counts. In the analysis of such data, researchers often face the problem of multiple testing based on discrete test statistics, aimed at controlling family-wise error rate (FWER). Most existing FWER controlling procedures are developed for continuous data, which are often conservative when analyzing discrete data. By using minimal attainable $p$-values, several FWER controlling procedures have been specifically developed for discrete data in the literature. In this paper, by utilizing kn…
In this paper, we consider the problem of simultaneously testing many two-sided hypotheses when rejections of null hypotheses are accompanied by claims of the direction of the alternative. The fundamental goal is to construct methods that control the mixed directional familywise error rate, which is the probability of making any type 1 or type 3 (directional) error. In particular, attention is focused on cases where the hypotheses are ordered as $H_1 , \ldots, H_n$, so that $H_{i+1}$ is tested only if $H_1 , \ldots, H_i$ have all been previously rejected. In this situation, one can control the…
When comparing two distributions, it is often helpful to learn at which quantiles or values there is a statistically significant difference. This provides more information than the binary "reject" or "do not reject" decision of a global goodness-of-fit test. Framing our question as multiple testing across the continuum of quantiles $τ\in(0,1)$ or values $r\in\mathbb{R}$, we show that the Kolmogorov--Smirnov test (interpreted as a multiple testing procedure) achieves strong control of the familywise error rate. However, its well-known flaw of low sensitivity in the tails remains. We provide an …
We study the problem of multiple hypothesis testing for multidimensional data when inter-correlations are present. The problem of multiple comparisons is common in many applications. When the data is multivariate and correlated, existing multiple comparisons procedures based on maximum likelihood estimation could be prohibitively computationally intensive. We propose to construct multiple comparisons procedures based on composite likelihood statistics. We focus on data arising in three ubiquitous cases: multivariate Gaussian, probit, and quadratic exponential models. To help practitioners asse…
Stepwise multiple testing procedures have attracted several statisticians for decades and are also quite popular with statistics users because of their technical simplicity. The Bonferroni procedure has been one of the earliest and most prominent testing rules for controlling the familywise error rate (FWER). A recent article established that the FWER for the Bonferroni method asymptotically (i.e., when the number of hypotheses becomes arbitrarily large) approaches zero under any positively equicorrelated multivariate normal framework. However, similar results for the limiting behaviors of FWE…
Familywise error rate (FWER) has been a cornerstone in simultaneous inference for decades, and the classical Bonferroni method has been one of the most prominent frequentist approaches for controlling FWER. The present article studies the behavior of the FWER for Bonferroni procedure in a multiple testing problem. We establish upper bounds on FWER for Bonferroni method under the equicorrelated and general normal setups in nonasymptotic case.
A resurgence of interest in multiple hypothesis testing has occurred in the last decade. Motivated by studies in genomics, microarrays, DNA sequencing, drug screening, clinical trials, bioassays, education and psychology, statisticians have been devoting considerable research energy in an effort to properly analyze multiple endpoint data. In response to new applications, new criteria and new methodology, many ad hoc procedures have emerged. The classical requirement has been to use procedures which control the strong familywise error rate (FWE) at some predetermined level α. That is, the proba…
Assuming that data are collected sequentially from independent streams, we consider the simultaneous testing of multiple binary hypotheses under two general setups; when the number of signals (correct alternatives) is known in advance, and when we only have a lower and an upper bound for it. In each of these setups, we propose feasible procedures that control, without any distributional assumptions, the familywise error probabilities of both type I and type II below given, user-specified levels. Then, in the case of i.i.d. observations in each stream, we show that the proposed procedures achie…
A sequential multiple testing procedure recently introduced by Heinrich, Bach and Kornmeier allows to "zoom in" on, and thus identify regions with highly significant departures from null-hypotheses. The purpose of this note is to state a cognate of this procedure in general form and to prove that it controls the familywise error. Two possible applications are briefly indicated.
We investigate asymptotically optimal multiple testing procedures for streams of sequential data in the context of prior information on the number of false null hypotheses ("signals"). We show that the "gap" and "gap-intersection" procedures, recently proposed and shown by Song and Fellouris (2017, Electron. J. Statist.) to be asymptotically optimal for controlling type 1 and 2 familywise error rates (FWEs), are also asymptotically optimal for controlling FDR/FNR when their critical values are appropriately adjusted. Generalizing this result, we show that these procedures, again with appropria…
We apply multiple testing procedures to the validation of estimated default probabilities in credit rating systems. The goal is to identify rating classes for which the probability of default is estimated inaccurately, while still maintaining a predefined level of committing type I errors as measured by the familywise error rate (FWER) and the false discovery rate (FDR). For FWER, we also consider procedures that take possible discreteness of the data resp. test statistics into account. The performance of these methods is illustrated in a simulation setting and for empirical default data.
This article considers the problem of multiple hypothesis testing using $t$-tests. The observed data are assumed to be independently generated conditional on an underlying and unknown two-state hidden model. We propose an asymptotically valid data-driven procedure to find critical values for rejection regions controlling the $k$-familywise error rate ($k$-FWER), false discovery rate (FDR) and the tail probability of false discovery proportion (FDTP) by using one-sample and two-sample $t$-statistics. We only require a finite fourth moment plus some very general conditions on the mean and varian…
In complex clinical trials, multiple research objectives are often grouped into sets of objectives based on their inherent hierarchical relationships. Consequently, the hypotheses formulated to address these objectives are grouped into ordered families of hypotheses and thus to be tested in a pre-defined sequence. In this paper, we introduce a novel Bonferroni based multiple testing procedure for testing hierarchically ordered families of hypotheses. The proposed procedure allows the families to be sequentially tested more than once with updated local critical values. It is proved to control t…
Consider the problem of testing $s$ hypotheses simultaneously. The usual approach restricts attention to procedures that control the probability of even one false rejection, the familywise error rate (FWER). If $s$ is large, one might be willing to tolerate more than one false rejection, thereby increasing the ability of the procedure to correctly reject false null hypotheses. One possibility is to replace control of the FWER by control of the probability of $k$ or more false rejections, which is called the $k$-FWER. We derive both single-step and step-down procedures that control the $k$-FWER…
Bringing Closure to False Discovery Rate Control: A General Principle for Multiple Testing
Carnegie Mellon University（卡内基梅隆大学）；Ca’ Foscari University of Venice（威尼斯福斯卡里宫大学）；University of Bremen（不来梅大学）；University of Twente（特温特大学）；Centrum Wiskunde & Informatica（荷兰数学与计算机科学研究中心）；Leiden University Medical Center（莱顿大学医学中心）
Consider the problem of simultaneously testing null hypotheses H_1,...,H_s. The usual approach to dealing with the multiplicity problem is to restrict attention to procedures that control the familywise error rate (FWER), the probability of even one false rejection. In many applications, particularly if s is large, one might be willing to tolerate more than one false rejection provided the number of such cases is controlled, thereby increasing the ability of the procedure to detect false null hypotheses. This suggests replacing control of the FWER by controlling the probability of k or more fa…
This paper is a review of the popular Benjamini Hochberg Method and other related useful methods of Multiple Hypothesis testing. This is written with the purpose of serving a short but complete easy to understand review of the main article with proper background. The paper titled 'Controlling the False Discovery Rate-a practical and powerful Approach to multiple Testing' by benjamini et. al.[1] proposes a new framework of controlling the False Discovery Rate in a Multiple Hypothesis testing problem. It has been claimed that the procedure proposed in the paper results in a substantial gain in p…
Closed testing procedures are classically used for familywise error rate (FWER) control, but they can also be used to obtain simultaneous confidence bounds for the false discovery proportion (FDP) in all subsets of the hypotheses. In this paper we investigate the special case of closed testing with Simes local tests. We construct a novel fast and exact shortcut which we use to investigate the power of this method when the number of hypotheses goes to infinity. We show that, if a minimal amount of signal is present, the average power to detect false hypotheses at any desired FDP level does not …
The closure and the partitioning principles have been used to build various multiple testing procedures in the past three decades. The essence of these two principles is based on parameter space partitioning. In this article, we propose a novel approach coined the covering principle from the perspective of rejection region coverage in the sample space. The covering principle divides the whole family of null hypotheses into a few overlapped sub-families when there is a priority of making decisions for hypothesis testing. We have proven that the multiple testing procedure constructed by the cove…
We analyze control of the familywise error rate (FWER) in a multiple testing scenario with a great many null hypotheses about the distribution of a high-dimensional random variable among which only a very small fraction are false, or "active". In order to improve power relative to conservative Bonferroni bounds, we explore a coarse-to-fine procedure adapted to a situation in which tests are partitioned into subsets, or "cells", and active hypotheses tend to cluster within cells. We develop procedures for a standard linear model with Gaussian data and a non-parametric case based on generalized …
In confirmatory clinical trials with small sample sizes, hypothesis tests based on asymptotic distributions are often not valid and exact non-parametric procedures are applied instead. However, the latter are based on discrete test statistics and can become very conservative, even more so, if adjustments for multiple testing as the Bonferroni correction are applied. We propose improved exact multiple testing procedures for the setting where two parallel groups are compared in multiple binary endpoints. Based on the joint conditional distribution of test statistics of Fisher's exact tests, opti…
We consider the problem of multiple hypothesis testing when there is a logical nested structure to the hypotheses. When one hypothesis is nested inside another, the outer hypothesis must be false if the inner hypothesis is false. We model the nested structure as a directed acyclic graph, including chain and tree graphs as special cases. Each node in the graph is a hypothesis and rejecting a node requires also rejecting all of its ancestors. We propose a general framework for adjusting node-level test statistics using the known logical constraints. Within this framework, we study a smoothing pr…
Consider the problem of testing multiple null hypotheses. A classical approach to dealing with the multiplicity problem is to restrict attention to procedures that control the familywise error rate ($FWER$), the probability of even one false rejection. However, if $s$ is large, control of the $FWER$ is so stringent that the ability of a procedure which controls the $FWER$ to detect false null hypotheses is limited. Consequently, it is desirable to consider other measures of error control. We will consider methods based on control of the false discovery proportion ($FDP$) defined by the number …
