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Primarily motivated by the drug development process, several publications have now presented methodology for the design of multi-arm multi-stage experiments with normally distributed outcome variables of known variance. Here, we extend…

Methodology · Statistics 2017-12-04 Michael Grayling , James Wason , Adrian Mander

There is growing interest in platform trials that allow for adding of new treatment arms as the trial progresses as well as being able to stop treatments part way through the trial for either lack of benefit/futility or for superiority. In…

Methodology · Statistics 2021-12-14 Peter Greenstreet , Thomas Jaki , Alun Bedding , Chris Harbron , Pavel Mozgunov

Numerous publications have now addressed the principles of designing, analyzing, and reporting the results of, stepped-wedge cluster randomized trials. In contrast, there is little research available pertaining to the design and analysis of…

Methodology · Statistics 2018-06-29 Michael Grayling , Adrian Mander , James Wason

A multi-arm multi-stage trial is a multi-arm trial which includes interim analyses - analysing the data at certain specified points, generally discontinuing treatments which are concluded to not work and proceeding with the remainder. It is…

Methodology · Statistics 2022-11-14 Martin Law

There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed…

Methodology · Statistics 2023-08-25 Peter Greenstreet , Thomas Jaki , Alun Bedding , Pavel Mozgunov

The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…

Methodology · Statistics 2025-09-03 Wei Zhang , Zhiwei Zhang , Aiyi Liu

Multi-arm multi-stage (MAMS) trials have gained popularity to enhance the efficiency of clinical trials, potentially reducing both duration and costs. This paper focuses on designing MAMS trials where no control treatment exists. This can…

Methodology · Statistics 2025-02-12 Peter Greenstreet , Thomas Jaki , Alun Bedding , Pavel Mozgunov

We give a hybrid two stage design which can be useful to estimate the reliability of a parallel-series and/or by duality a series-parallel system, when the component reliabilities are unknown as well as the total numbers of units allowed to…

Applications · Statistics 2012-12-27 Zohra Benkamra , Mekki Terbeche , Mounir Tlemcani

Adaptive designs have been proposed for clinical trials in which the nuisance parameters or alternative of interest are unknown or likely to be misspecified before the trial. Whereas most previous works on adaptive designs and mid-course…

Methodology · Statistics 2011-05-18 Jay Bartroff , Tze Leung Lai

Quantum mechanics for many-body systems may be reduced to the evaluation of integrals in 3N dimensions using Monte-Carlo, providing the Quantum Monte Carlo ab initio methods. Here we limit ourselves to expectation values for trial…

Computational Physics · Physics 2010-11-22 John Robert Trail , Ryo Maezono

Multi-arm multi-stage (MAMS) trials have gained popularity, due to their improved efficiency in evaluating multiple treatments. A traditional MAMS trial often decreases the expected sample size of the trial compared to just running a…

Multi-Arm Multi-Stage (MAMS) platform trials are an efficient tool for the comparison of several treatments. Suppose we wish to add a treatment to a trial already in progress, to access the benefits of a MAMS design. How should this be…

Applications · Statistics 2021-05-25 Thomas Burnett , Franz König , Thomas Jaki

When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…

Methodology · Statistics 2020-08-03 Johannes Krisam , Dorothea Weber , Richard F. Schlenk , Meinhard Kieser

The determination of the sample size required by a crossover trial typically depends on the specification of one or more variance components. Uncertainty about the value of these parameters at the design stage means that there is often a…

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

Multi-arm designs provide an effective means of evaluating several treatments within the same clinical trial. Given the large number of treatments now available for testing in many disease areas, it has been argued that their utilisation…

Computation · Statistics 2019-06-24 Michael J Grayling , James MS Wason

Adaptive sample size re-estimation, early stopping, and trial re-design at interim analyses can reduce expected sample sizes in randomised trials. Cluster randomised trials, in which groups of participants are randomly allocated to…

Methodology · Statistics 2026-03-09 Samuel I. Watson , James Martin

Adaptive experiments are used extensively in online platforms, healthcare and biotechnology, and a variety of other settings. In many of these applications, the main goal is not to precisely estimate a treatment effect, but to demonstrate…

Statistics Theory · Mathematics 2026-03-10 Guido Imbens , Lorenzo Masoero , Alexander Rakhlin , Thomas S. Richardson , Suhas Vijaykumar

We show that deliberately introducing a nested simulation stage can lead to significant variance reductions when comparing two stopping times by Monte Carlo. We derive the optimal number of nested simulations and prove that the algorithm is…

Computational Finance · Quantitative Finance 2014-02-04 Fabian Dickmann , Nikolaus Schweizer

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

The question of selecting the "best" amongst different choices is a common problem in statistics. In drug development, our motivating setting, the question becomes, for example: what is the dose that gives me a pre-specified risk of…

Statistics Theory · Mathematics 2018-03-15 Pavel Mozgunov , Thomas Jaki
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