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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

Group sequential designs in clinical trials allow for interim efficacy and futility monitoring. Adjustment for baseline covariates can increase power and precision of estimated effects. However, inconsistently applying covariate adjustment…

Methodology · Statistics 2023-08-11 Marlena S. Bannick , Sonya L. Heltshe , Noah Simon

Count data and recurrent events in clinical trials, such as the number of lesions in magnetic resonance imaging in multiple sclerosis, the number of relapses in multiple sclerosis, the number of hospitalizations in heart failure, and the…

Applications · Statistics 2019-03-07 Tobias Mütze , Ekkehard Glimm , Heinz Schmidli , Tim Friede

We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly…

Methodology · Statistics 2013-07-25 Daniel Zelterman

Recently there has been much work on early phase cancer designs that incorporate both toxicity and efficacy data, called Phase I-II designs because they combine elements of both phases. However, they do not explicitly address the Phase II…

Methodology · Statistics 2014-02-12 Jay Bartroff , Tze Leung Lai , Balasubramanian Narasimhan

The primary analysis in two-arm clinical trials usually involves inference on a scalar treatment effect parameter; e.g., depending on the outcome, the difference of treatment-specific means, risk difference, risk ratio, or odds ratio. Most…

Methodology · Statistics 2022-04-25 Anastasios A. Tsiatis , Marie Davidian

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

The Bayes factor, the data-based updating factor from prior to posterior odds, is a principled measure of relative evidence for two competing hypotheses. It is naturally suited to sequential data analysis in settings such as clinical trials…

Methodology · Statistics 2026-01-07 Samuel Pawel , Leonhard Held

When the infection prevalence of a disease is low, Dorfman showed 80 years ago that testing groups of people can prove more efficient than testing people individually. Our goal in this paper is to propose new group testing algorithms that…

Methodology · Statistics 2020-07-23 Marco Cuturi , Olivier Teboul , Quentin Berthet , Arnaud Doucet , Jean-Philippe Vert

The use of drug combinations in clinical trials is increasingly common during the last years since a more favorable therapeutic response may be obtained by combining drugs. In phase I clinical trials, most of the existing methodology…

Methodology · Statistics 2020-02-17 José L. Jiménez , Sungjin Kim , Mourad Tighiouart

Sequential decision making significantly speeds up research and is more cost-effective compared to fixed-n methods. We present a method for sequential decision making for stratified count data that retains Type-I error guarantee or false…

Methodology · Statistics 2023-02-23 Rosanne J. Turner , Peter D. Grünwald

Clinical trials usually involve sequential patient entry. When designing a clinical trial, it is often desirable to include a provision for interim analyses of accumulating data with the potential for stopping the trial early. We review…

Methodology · Statistics 2023-03-13 Tianjian Zhou , Yuan Ji

In single-arm phase II oncology trials, the most popular choice of design is Simon's two-stage design, which allows early stopping at one interim analysis. However, the expected trial sample size can be reduced further by allowing…

Methodology · Statistics 2019-09-09 Martin Law , Michael J. Grayling , Adrian P. Mander

Group sequential designs (GSDs) are widely used in confirmatory trials to allow interim monitoring while preserving control of the type I error rate. In the frequentist framework, O'Brien-Fleming-type stopping boundaries dominate practice…

Methodology · Statistics 2026-01-16 Zhangyi He , Feng Yu , Suzie Cro , Laurent Billot

It is crucial to design Phase II cancer clinical trials that balance the efficiency of treatment selection with clinical practicality. Sargent and Goldberg proposed a frequentist design that allow decision-making even when the primary…

Methodology · Statistics 2025-05-15 Moka Komaki , Satoru Shinoda , Haiyan Zheng , Kouji Yamamoto

Sequential trial design is an important statistical approach to increase the efficiency of clinical trials. Bayesian sequential trial design relies primarily on conducting a Monte Carlo simulation under the hypotheses of interest and…

Methodology · Statistics 2025-12-01 Riko Kelter , Samuel Pawel

Sequential likelihood ratio testing is found to be most powerful in sequential studies with early stopping rules when grouped data come from the one-parameter exponential family. First, to obtain this elusive result, the probability measure…

Methodology · Statistics 2021-01-28 Sergey Tarima , Nancy Flournoy

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 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

Background: When planning a cluster randomized trial, evaluators often have access to an enumerated cohort representing the target population of clusters. Practicalities of conducting the trial, such as the need to oversample clusters with…

Methodology · Statistics 2024-09-19 Sarah E. Robertson , Jon A. Steingrimsson , Issa J. Dahabreh