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  1. Abstract

    E-values have gained attention as potential alternatives to p-values as measures of uncertainty, significance and evidence. In brief, e-values are realized by random variables with expectation at most one under the null; examples include betting scores, (point null) Bayes factors, likelihood ratios and stopped supermartingales. We design a natural analogue of the Benjamini-Hochberg (BH) procedure for false discovery rate (FDR) control that utilizes e-values, called the e-BH procedure, and compare it with the standard procedure for p-values. One of our central results is that, unlike the usual BH procedure, the e-BH procedure controls the FDR at the desired level—with no correction—for any dependence structure between the e-values. We illustrate that the new procedure is convenient in various settings of complicated dependence, structured and post-selection hypotheses, and multi-armed bandit problems. Moreover, the BH procedure is a special case of the e-BH procedure through calibration between p-values and e-values. Overall, the e-BH procedure is a novel, powerful and general tool for multiple testing under dependence, that is complementary to the BH procedure, each being an appropriate choice in different applications.

     
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  2. Modern data analysis frequently involves large-scale hypothesis testing, which naturally gives rise to the problem of maintaining control of a suitable type I error rate, such as the false discovery rate (FDR). In many biomedical and technological applications, an additional complexity is that hypotheses are tested in an online manner, one-by-one over time. However, traditional procedures that control the FDR, such as the Benjamini-Hochberg procedure, assume that all p-values are available to be tested at a single time point. To address these challenges, a new field of methodology has developed over the past 15 years showing how to control error rates for online multiple hypothesis testing. In this framework, hypotheses arrive in a stream, and at each time point the analyst decides whether to reject the current hypothesis based both on the evidence against it, and on the previous rejection decisions. In this paper, we present a comprehensive exposition of the literature on online error rate control, with a review of key theory as well as a focus on applied examples.We also provide simulation results comparing different online testing algorithms and an up-to-date overview of the many methodological extensions that have been proposed. 
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  3. Scholkopf, Bernhard ; Uhler, Caroline ; Zhang, Kun (Ed.)
    In order to test if a treatment is perceptibly different from a placebo in a randomized experiment with covariates, classical nonparametric tests based on ranks of observations/residuals have been employed (eg: by Rosenbaum), with finite-sample valid inference enabled via permutations. This paper proposes a different principle on which to base inference: if — with access to all covariates and outcomes, but without access to any treatment assignments — one can form a ranking of the subjects that is sufficiently nonrandom (eg: mostly treated followed by mostly control), then we can confidently conclude that there must be a treatment effect. Based on a more nuanced, quantifiable, version of this principle, we design an interactive test called i-bet: the analyst forms a single permutation of the subjects one element at a time, and at each step the analyst bets toy money on whether that subject was actually treated or not, and learns the truth immediately after. The wealth process forms a real-valued measure of evidence against the global causal null, and we may reject the null at level if the wealth ever crosses 1= . Apart from providing a fresh “game-theoretic” principle on which to base the causal conclusion, the i-bet has other statistical and computational benefits, for example (A) allowing a human to adaptively design the test statistic based on increasing amounts of data being revealed (along with any working causal models and prior knowledge), and (B) not requiring permutation resampling, instead noting that under the null, the wealth forms a nonnegative martingale, and the type-1 error control of the aforementioned decision rule follows from a tight inequality by Ville. Further, if the null is not rejected, new subjects can later be added and the test can be simply continued, without any corrections (unlike with permutation p-values). Numerical experiments demonstrate good power under various heterogeneous treatment effects. We first describe i-bet test for two-sample comparisons with unpaired data, and then adapt it to paired data, multi-sample comparison, and sequential settings; these may be viewed as interactive martingale variants of the Wilcoxon, Kruskal-Wallis, and Friedman tests. 
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  4. Bruna, Joan ; Hesthaven, Jan ; Zdeborova, Lenka (Ed.)
    We derive new algorithms for online multiple testing that provably control false discovery exceedance (FDX) while achieving orders of magnitude more power than previous methods. This statistical advance is enabled by the development of new algorithmic ideas: earlier algorithms are more “static” while our new ones allow for the dynamical adjustment of testing levels based on the amount of wealth the algorithm has accumulated. We demonstrate that our algorithms achieve higher power in a variety of synthetic experiments. We also prove that SupLORD can provide error control for both FDR and FDX, and controls FDR at stopping times. Stopping times are particularly important as they permit the experimenter to end the experiment arbitrarily early while maintaining desired control of the FDR. SupLORD is the first non-trivial algorithm, to our knowledge, that can control FDR at stopping times in the online setting. 
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  5. null (Ed.)
    Biological research often involves testing a growing number of null hypotheses as new data are accumulated over time. We study the problem of online control of the familywise error rate, that is testing an a priori 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) familywise error rate control and online false discovery rate control to develop novel online familywise error rate control methods. Though many offline familywise error rate methods (e.g., Bonferroni, fallback procedures and Sidak’s method) can trivially be extended to the online setting, our main contribution is the design of new, powerful, adaptive online algorithms that control the familywise error rate when the p-values are independent or locally dependent in time. Our numerical experiments demonstrate substantial gains in power, that are also formally proved in an idealized Gaussian sequence model. A promising application to the International Mouse Phenotyping Consortium is described. 
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  6. null (Ed.)
    We consider the problem of asynchronous online testing, aimed at providing control of the false discovery rate (FDR) during a continual stream of data collection and testing, where each test may be a sequential test that can start and stop at arbitrary times. This setting increasingly characterizes real-world applications in science and industry, where teams of researchers across large organizations may conduct tests of hypotheses in a decentralized manner. The overlap in time and space also tends to induce dependencies among test statistics, a challenge for classical methodology, which either assumes (overly optimistically) independence or (overly pessimistically) arbitrary dependence between test statistics. We present a general framework that addresses both of these issues via a unified computational abstraction that we refer to as “conflict sets.” We show how this framework yields algorithms with formal FDR guarantees under a more intermediate, local notion of dependence. We illustrate our algorithms in simulations by comparing to existing algorithms for online FDR control. 
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  7. null (Ed.)
    Summary We propose a general framework based on selectively traversed accumulation rules for interactive multiple testing with generic structural constraints on the rejection set. It combines accumulation tests from ordered multiple testing with data-carving ideas from post-selection inference, allowing highly flexible adaptation to generic structural information. Our procedure defines an interactive protocol for gradually pruning a candidate rejection set, beginning with the set of all hypotheses and shrinking the set with each step. By restricting the information at each step via a technique we call masking, our protocol enables interaction while controlling the false discovery rate in finite samples for any data-adaptive update rule that the analyst may choose. We suggest update rules for a variety of applications with complex structural constraints, demonstrate that selectively traversed accumulation rules perform well in problems ranging from convex region detection to false discovery rate control on directed acyclic graphs, and show how to extend the framework to regression problems where knockoff statistics are available in lieu of $p$-values. 
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  8. null (Ed.)
    The reproducibility debate has caused a renewed interest in changing how one reports uncertainty, from 𝑝-value for testing a null hypothesis to a confidence interval (CI) for the corresponding parameter. When CIs for multiple selected parameters are being reported, the analog of the false discovery rate (FDR) is the false coverage rate (FCR), which is the expected ratio of number of reported CIs failing to cover their respective parameters to the total number of reported CIs. Here, we consider the general problem of FCR control in the online setting, where one encounters an infinite sequence of fixed unknown parameters ordered by time. We propose a novel solution to the problem which only requires the scientist to be able to construct marginal CIs. As special cases, our framework yields algorithms for online FDR control and online sign-classification procedures that control the false sign rate (FSR). All of our methodology applies equally well to prediction intervals, having particular implications for selective conformal inference. 
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