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In learning-phase clinical trials in drug development, adaptive designs can be efficient and highly informative when used appropriately. In this article, we extend the multiple comparison procedures with modeling techniques (MCP-Mod)…

Methodology · Statistics 2021-08-02 Shiyang Ma , Michael P. McDermott

Reducing the number of experimental units is one of the three pillars of the 3R principles (Replace, Reduce, Refine) in animal research. At the same time, statistical error rates need to be controlled to enable reliable inferences and…

Methodology · Statistics 2026-05-08 Leonhard Held , Fadoua Balabdaoui , Saverio Fontana , Samuel Pawel

This paper introduces a new Phase I design aimed at enhancing the performance of existing methods, including algorithm-based, model-based, and model-assisted designs. The design, developed by integrating the concept of Fisher information,…

Applications · Statistics 2024-12-11 Xiaojun Zhu

Adaptive designs are commonly used in clinical and drug development studies for optimum utilization of available resources. In this article, we consider the problem of estimating the effect of the selected (better) treatment using a…

Statistics Theory · Mathematics 2023-01-24 Masihuddin , Neeraj Misra

Computerized adaptive testing is becoming increasingly popular due to advancement of modern computer technology. It differs from the conventional standardized testing in that the selection of test items is tailored to individual examinee's…

Statistics Theory · Mathematics 2009-06-11 Hua-Hua Chang , Zhiliang Ying

For many machine learning problems, data is abundant and it may be prohibitive to make multiple passes through the full training set. In this context, we investigate strategies for dynamically increasing the effective sample size, when…

Machine Learning · Computer Science 2016-10-10 Hadi Daneshmand , Aurelien Lucchi , Thomas Hofmann

Adaptive experiments are becoming increasingly popular in real-world applications for effectively maximizing in-sample welfare and efficiency by data-driven sampling. Despite their growing prevalence, however, the statistical foundations…

Statistics Theory · Mathematics 2026-04-15 Ziang Niu , Zhimei Ren

The analysis of screening experiments is often done in two stages, starting with factor selection via an analysis under a main effects model. The success of this first stage is influenced by three components: (1) main effect estimators'…

Methodology · Statistics 2024-03-19 Jonathan W. Stallrich , Michael McKibben

This paper studies a two-stage model of experimentation, where the researcher first samples representative units from an eligible pool, then assigns each sampled unit to treatment or control. To implement balanced sampling and assignment,…

Econometrics · Economics 2023-08-22 Max Cytrynbaum

We consider the problem of efficient inference of the Average Treatment Effect in a sequential experiment where the policy governing the assignment of subjects to treatment or control can change over time. We first provide a central limit…

Machine Learning · Statistics 2024-03-05 Thomas Cook , Alan Mishler , Aaditya Ramdas

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

Over time, clinical trials have increasingly incorporated complex design and analysis elements such as interim analyses, adaptations, multiple endpoints, and sophisticated multiplicity schemes for multiple endpoints and/or treatment arms…

Design of experiments has traditionally relied on the frequentist hypothesis testing framework where the optimal size of the experiment is specified as the minimum sample size that guarantees a required level of power. Sample size…

Methodology · Statistics 2025-08-07 Shirin Golchi , Luke Hagar

Clinical trials with time-to-event endpoints, such as overall survival (OS) or progression-free survival (PFS), are fundamental for evaluating new treatments, particularly in immuno-oncology. However, modern therapies, such as…

Methodology · Statistics 2025-09-10 James Salsbury , Jeremy Oakley , Steven Julious , Lisa Hampson

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

Adaptive Phase 2/3 designs hold great promise in contemporary oncology drug development, especially when limited data from Phase 1 dose-finding is insufficient for identifying an optimal dose. However, there is a general concern about…

Applications · Statistics 2025-02-25 Cong Chen , Mo Huang

After a brief review of recent advances in sequential analysis involving sequential generalized likelihood ratio tests, we discuss their use in psychometric testing and extend the asymptotic optimality theory of these sequential tests to…

Methodology · Statistics 2025-01-08 Jay Bartroff , Matthew Finkelman , Tze Leung Lai

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

Group sequential designs enable interim analyses and potential early stopping for efficacy or futility. While these adaptations improve trial efficiency and ethical considerations, they also introduce bias into the adapted analyses. We…

Methodology · Statistics 2025-10-07 G. Caruso , W. F. Rosenberger , P. Mozgunov , N. Flournoy

Recent FDA guidance on adaptive clinical trial designs defines bias as "a systematic tendency for the estimate of treatment effect to deviate from its true value", and states that it is desirable to obtain and report estimates of treatment…