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In this paper, we propose a computer-oriented method of construction of optimal group sequential hypothesis tests with variable group sizes. In particular, for independent and identically distributed observations we obtain the form of…

Methodology · Statistics 2023-03-30 Andrey Novikov

In a group sequential clinical trial, accumulated data are analysed at numerous time-points in order to allow early decisions about a hypothesis of interest. These designs have historically been recommended for their ethical, administrative…

Computation · Statistics 2017-11-29 Michael Grayling , James Wason , Adrian Mander

Group sequential designs drive innovation in clinical, industrial, and corporate settings. Early stopping for failure in sequential designs conserves experimental resources, whereas early stopping for success accelerates access to improved…

Methodology · Statistics 2025-11-27 Luke Hagar , Shirin Golchi , Marina B. Klein

In group sequential designs, where several data looks are conducted for early stopping, we generally assume the vector of test statistics from the sequential analyses follows (at least approximately or asymptotially) a multivariate normal…

Statistics Theory · Mathematics 2024-04-22 Long-Hao Xu , Tobias Mütze , Frank Konietschke , Tim Friede

Group sequential design (GSD) is widely used in clinical trials in which correlated tests of multiple hypotheses are used. Multiple primary objectives resulting in tests with known correlations include evaluating 1) multiple experimental…

Methodology · Statistics 2021-03-22 Keaven M. Anderson , Zifang Guo , Jing Zhao , Linda Z. Sun

We describe group sequential tests which efficiently incorporate information from multiple endpoints allowing for early stopping at pre-planned interim analyses. We formulate a testing procedure where several outcomes are examined, and…

Methodology · Statistics 2024-05-09 Abigail J. Burdon , Thomas Jaki

In this paper, we study randomized methods for feedback design of uncertain systems. The first contribution is to derive the sample complexity of various constrained control problems. In particular, we show the key role played by the…

Systems and Control · Computer Science 2014-07-22 T. Alamo , R. Tempo , A. Luque , D. R. Ramirez

Non-proportional hazards (NPH) are often observed in clinical trials with time-to-event endpoints. A common example is a long-term clinical trial with a delayed treatment effect in immunotherapy for cancer. When designing clinical trials…

Methodology · Statistics 2025-09-18 Yujie Zhao , Yilong Zhang , Larry Leon , Keaven M. Anderson

The win ratio is increasingly used in randomized trials due to its intuitive clinical interpretation, ability to incorporate the relative importance of composite endpoints, and its capacity for combining different types of outcomes (e.g.…

Methodology · Statistics 2026-02-02 Tracy Bergemann , Tim Hanson

A group sequential clinical trial design can be an attractive option when planning a pivotal trial as this approach has the ability to stop the trial early for success, whilst also being well accepted from a regulatory review perspective.…

Applications · Statistics 2023-03-03 Fraser I Lewis

Crossover designs are an extremely useful tool to investigators, whilst group sequential methods have proven highly proficient at improving the efficiency of parallel group trials. Yet, group sequential methods and crossover designs have…

Methodology · Statistics 2017-10-11 Michael Grayling , James Wason , Adrian Mander

Due to the high cost and high failure rate of Phase III trials, seamless Phase II/III designs are more and more popular to trial efficiency. A potential attraction of Phase II/III design is to allow a randomized proof-of-concept stage prior…

Applications · Statistics 2022-06-28 Guanhong Miao , Jason J. Z. Liao , Jing Yang , Keaven Anderson

Adaptive approaches, allowing for more flexible trial design, have been proposed for individually randomized trials to save time or reduce sample size. However, adaptive designs for cluster-randomized trials in which groups of participants…

Methodology · Statistics 2022-01-10 Junwei Shen , Shirin Golchi , Erica E. M. Moodie , David Benrimoh

Group sequential designs (GSDs) are well established and the most commonly used adaptive design in confirmatory clinical trials with interim analyses. However, they remain underutilised, and their implementation involves unique theoretical…

Methodology · Statistics 2025-09-09 Zhangyi He , Suzie Cro , Laurent Billot

To generalize inferences from a randomized trial to the target population of all trial-eligible individuals, investigators can use nested trial designs, where the randomized individuals are nested within a cohort of trial-eligible…

Likelihood methods for measuring statistical evidence obey the likelihood principle while maintaining bounded and well-controlled frequency properties. These methods lend themselves to sequential study designs because they measure the…

Methodology · Statistics 2017-11-07 Jeffrey D Blume , Leena Choi

We propose a general, modular method for significance testing of groups (or clusters) of variables in a high-dimensional linear model. In presence of high correlations among the covariables, due to serious problems of identifiability, it is…

Statistics Theory · Mathematics 2015-02-12 Jacopo Mandozzi , Peter Bühlmann

The Win Ratio has gained significant traction in cardiovascular trials as a novel method for analyzing composite endpoints (Pocock and others, 2012). Compared with conventional approaches based on time to the first event, the Win Ratio…

Methodology · Statistics 2024-10-10 Baoshan Zhang , Yuan Wu

Recently, methodology was presented to facilitate the incorporation of interim analyses in stepped-wedge (SW) cluster randomised trials (CRTs). Here, we extend this previous discussion. We detail how the stopping boundaries, allocation…

Methodology · Statistics 2018-03-28 Michael Grayling , David Robertson , James Wason , Adrian Mander

We propose a sequential design method aiming at the estimation of an extreme quantile based on a sample of dichotomic data corresponding to peaks over a given threshold. This study is motivated by an industrial challenge in material…

Methodology · Statistics 2020-04-06 Michel Broniatowski , Emilie Miranda
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