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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

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

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

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

Sequential parallel comparison design (SPCD) clinical trials aim to adjust active treatment effect estimates for placebo response to minimize the impact of placebo responders on the estimates. This is potentially accomplished using a two…

Adaptive seamless designs combine confirmatory testing, a domain of phase III trials, with features such as treatment or subgroup selection, typically associated with phase II trials. They promise to increase the efficiency of development…

Methodology · Statistics 2019-01-25 Tim Friede , Nigel Stallard , Nicholas Parsons

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

The Stepped Wedge Design (SWD) is a form of cluster randomized trial, usually comparing two treatments, which is divided into time periods and sequences, with clusters allocated to sequences. Typically all sequences start with the standard…

Methodology · Statistics 2020-11-06 John N. S. Matthews

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

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

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 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

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

Glaucoma is one of the leading causes of irreversible blindness worldwide. Glaucoma prognosis is essential for identifying at-risk patients and enabling timely intervention to prevent blindness. Many existing approaches rely on historical…

Computer Vision and Pattern Recognition · Computer Science 2025-09-17 Yiran Song , Yikai Zhang , Silvia Orengo-Nania , Nian Wang , Fenglong Ma , Rui Zhang , Yifan Peng , Mingquan Lin

Cohort-based enrollment can slow down dose-finding trials since the outcomes of the previous cohort must be fully evaluated before the next cohort can be enrolled. This results in frequent suspension of patient enrollment. The issue is…

Applications · Statistics 2020-01-01 Tianjian Zhou , Wentian Guo , Yuan Ji

Although a variety of methods have been proposed for sequential recommendation, it is still far from being well solved partly due to two challenges. First, the existing methods often lack the simultaneous consideration of the global…

Information Retrieval · Computer Science 2022-08-10 Lihua Chen , Ning Yang , Philip S Yu

Due to ethical and economical reasons, sequential single-arm trial designs are used for assessing the therapeutic efficacy of new treatments in phase II trials. Simon's 2-stage design and Lan-DeMets' $\alpha$-spending function method with…

Methodology · Statistics 2023-03-31 Tasuku Inao , Isao Yokota

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 identification of surrogate markers is motivated by their potential to make decisions sooner about a treatment effect. However, few methods have been developed to actually use a surrogate marker to test for a treatment effect in a…

Methodology · Statistics 2024-09-17 Layla Parast , Jay Bartroff

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
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