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Dose groups are compared with a control assuming an order restriction usually by the Williams trend test. Here, as an alternative, two variants of the closed testing procedure are considered, one where global Williams tests are used in the…

Applications · Statistics 2021-01-01 Ludwig A. Hothorn

Several treatments are usually compared with a control using the Dunnett test. As an alternative, three variants of the closed testing approach are considered, one with ANOVA-F-tests, one with MCT-GrandMean and one with global Dunnett-tests…

Applications · Statistics 2020-12-09 Ludwig A. Hothorn

Clinical trials often involve the assessment of multiple endpoints to comprehensively evaluate the efficacy and safety of interventions. In the work, we consider a global nonparametric testing procedure based on multivariate rank for the…

Methodology · Statistics 2023-06-29 Kexuan Li , Lingli Yang , Shaofei Zhao , Susie Sinks , Luan Lin , Peng Sun

The standard paradigm for confirmatory clinical trials is to compare experimental treatments with a control, for example the standard of care or a placebo. However, it is not always the case that a suitable control exists. Efficient…

Methodology · Statistics 2024-10-29 Thomas Burnett , Thomas Jaki

In a randomised clinical trial, when the result of the primary endpoint shows a significant benefit, the secondary endpoints are scrutinised to identify additional effects of the treatment. However, this approach entails a risk of…

We describe a general framework for weighted parametric multiple test procedures based on the closure principle. We utilize general weighting strategies that can reflect complex study objectives and include many procedures in the literature…

Methodology · Statistics 2019-08-14 Dong Xi , Ekkehard Glimm , Willi Maurer , Frank Bretz

Pragmatic trials evaluating health care interventions often adopt cluster randomization due to scientific or logistical considerations. Previous reviews have shown that co-primary endpoints are common in pragmatic trials but infrequently…

Methodology · Statistics 2022-05-03 Siyun Yang , Mirjam Moerbeek , Monica Taljaard , Fan Li

A central goal in designing clinical trials is to find the test that maximizes power (or equivalently minimizes required sample size) for finding a false null hypothesis subject to the constraint of type I error. When there is more than one…

Methodology · Statistics 2022-09-21 Ruth Heller , Abba Krieger , Saharon Rosset

Data with multiple functional recordings at each observational unit are increasingly common in various fields including medical imaging and environmental sciences. To conduct inference for such observations, we develop a paired two-sample…

Methodology · Statistics 2025-06-16 Colin Decker , Dehan Kong , Stanislav Volgushev

The problem of multiple hypothesis testing with observation control is considered in both fixed sample size and sequential settings. In the fixed sample size setting, for binary hypothesis testing, the optimal exponent for the maximal error…

Information Theory · Computer Science 2013-09-05 Sirin Nitinawarat , George Atia , Venugopal V. Veeravalli

Randomized experiments play a major role in data-driven decision making across many different fields and disciplines. In medicine, for example, randomized controlled trials (RCTs) are the backbone of clinical trial methodology for testing…

Applications · Statistics 2016-08-30 Andrew W. Correia

To identify statistically significant conclusions, it is proposed to simultaneously test hypotheses and alternatives. It is shown that, under the condition of free combination of hypotheses and alternatives, the closure method leads to…

Methodology · Statistics 2025-09-15 P. A. Koldanov , A. P. Koldanov

Statistical discoveries are often obtained through multiple hypothesis testing. A variety of procedures exists to evaluate multiple hypotheses, for instance the ones of Benjamini-Hochberg, Bonferroni, Holm or Sidak. We are particularly…

Statistics Theory · Mathematics 2018-10-17 Georg Hahn

There has been an increasing use of master protocols in oncology clinical trials because of its efficiency and flexibility to accelerate cancer drug development. Depending on the study objective and design, a master protocol trial can be a…

Applications · Statistics 2023-11-13 Jie Chen , Xiaoyun , Li , Chengxing , Lu , Sammy Yuan , Godwin Yung , Jingjing Ye , Hong Tian , Jianchang Lin

Randomized clinical trials (RCTs) are widely considered the gold standard for evaluating the effectiveness of new treatments or interventions in drug development. Still, they may not be feasible in certain cases, such as with rare diseases…

Methodology · Statistics 2025-08-05 Di Ran , Fanni Zhang , Sima Shahsavari , Kristine Broglio , Alasdair Henderson , Binbing Yu

Multiple hypothesis testing problems arise naturally in science. In this paper, we introduce the new Fast Closed Testing (FACT) method for multiple testing, controlling the family-wise error rate. This error rate is state of the art in many…

Methodology · Statistics 2020-01-22 Edgar Dobriban

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…

Methodology · Statistics 2018-02-22 Robin Ristl , Dong Xi , Ekkehard Glimm , Martin Posch

The Dunnett procedure compares several treatment or dose groups with a control group, while controlling the familywise error rate. When deviations from the normal distribution and heterogeneous variances occur, the nominal $\alpha$ level…

Applications · Statistics 2019-05-07 Ludwig A. Hothorn , Felix M. Kluxen

The closure principle is fundamental in multiple testing and has been used to derive many efficient procedures with familywise error rate control. However, it is often unsuitable for modern research, which involves flexible multiple testing…

Methodology · Statistics 2024-05-27 Lasse Fischer , Marta Bofill Roig , Werner Brannath

The choice of sample size in the context of co-primary endpoints for a randomised trial is discussed. Current guidance can leave endpoints with unequal marginal power. A method is provided to achieve equal marginal power by using the…

Methodology · Statistics 2026-02-23 Simon Bond
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