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Simultaneous tests of superiority and non-inferiority hypotheses on multiple endpoints are often performed in clinical trials to demonstrate that a new treatment is superior over a control on at least one endpoint and non-inferior on the…

Methodology · Statistics 2023-10-02 Wenfeng Chen , Naiqing Zhao , Guoyou Qin , Jie Chen

In a randomized controlled trial, treatment switching (also called contamination or crossover) occurs when a patient initially assigned to one treatment arm changes to another arm during the course of follow-up. Overlooking treatment…

Methodology · Statistics 2022-09-27 Andrew Ying

Leveraging external controls -- relevant individual patient data under control from external trials or real-world data -- has the potential to reduce the cost of randomized controlled trials (RCTs) while increasing the proportion of trial…

Methodology · Statistics 2022-07-13 Yanyao Yi , Ying Zhang , Yu Du , Ting Ye

Bridging the gap between internal and external validity is crucial for heterogeneous treatment effect estimation. Randomised controlled trials (RCTs), favoured for their internal validity due to randomisation, often encounter challenges in…

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

Recently, the scientific community has questioned the statistical reproducibility of many empirical results, especially in the field of machine learning. To contribute to the resolution of this reproducibility crisis, we propose a…

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

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 gold standard for estimating causal effects is randomized controlled trial (RCT) or A/B testing where a random group of individuals from a population of interest are given treatment and the outcome is compared to a random group of…

Machine Learning · Computer Science 2025-05-09 Ahmed Sayeed Faruk , Jason Sulskis , Elena Zheleva

A platform trial with a master protocol provides an infrastructure to ethically and efficiently evaluate multiple treatment options in multiple diseases. Given that certain study drugs can enter or exit a platform trial, the randomization…

Methodology · Statistics 2025-07-15 Tianyu Zhan , Jane Zhang , Lei Shu , Yihua Gu

Time-to-event data with long-term survivors (L-TS), subjects who never experience the event, have been reported in multiple areas of oncology as therapies have improved. Conventional two-sample tests ignore L-TS, but alternatives have been…

Methodology · Statistics 2026-05-06 Yu Bi , Durbadal Ghosh , Subodh Selukar

When an experimenter has the option of running an adaptive trial, is it admissible to ignore this option and run a non-adaptive trial instead? We provide a negative answer to this question in the best-arm identification problem, where the…

Machine Learning · Statistics 2025-06-06 Guido Imbens , Chao Qin , Stefan Wager

We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding…

Applications · Statistics 2011-08-09 Ying Yuan , Guosheng Yin

This paper presents the link between stochastic approximation and clinical trials based on randomized urn models investigated in Bai and Hu (1999,2005) and Bai, Hu and Shen (2002). We reformulate the dynamics of both the urn composition and…

Probability · Mathematics 2017-01-19 Sophie Laruelle , Gilles Pagès

Randomized clinical trials are often designed to assess whether a test treatment prolongs survival relative to a control treatment. Increased patient heterogeneity, while desirable for generalizability of results, can weaken the ability of…

Methodology · Statistics 2020-04-30 Devan V. Mehrotra , Rachel Marceau West

Nonparametric tests for equality of multivariate distributions are frequently desired in research. It is commonly required that test-procedures based on relatively small samples of vectors accurately control the corresponding Type I Error…

Methodology · Statistics 2021-01-14 Ablert Vexler , Gregory Gurevich , Li Zou

Meta-analysis is a statistical method used in evidence synthesis for combining, analyzing and summarizing studies that have the same target endpoint and aims to derive a pooled quantitative estimate using fixed and random effects models or…

Methodology · Statistics 2022-04-25 Ivette Raices Cruz , Matthias C. M. Troffaes , Johan Lindström , Ullrika Sahlin

Existing sequential generalized estimating equation methodology for longitudinal and group-correlated data focuses on narrow hypotheses concerning treatment efficacy and often makes modeling assumptions that impede the desirable robustness…

Methodology · Statistics 2026-03-16 Nathan T. Provost , Abdus S. Wahed

Early-phase clinical trials face the challenge of selecting optimal drug doses that balance safety and efficacy due to uncertain dose-response relationships and varied participant characteristics. Traditional randomized dose allocation…

Methodology · Statistics 2026-02-13 Rohit Kanrar , Chunlin Li , Zara Ghodsi , Margaret Gamalo

Online experiments are widely used for improving online services. While doing online experiments, The student t-test is the most widely used hypothesis testing technique. In practice, however, the normality assumption on which the t-test…

Methodology · Statistics 2023-12-25 Zheng Cai , Bo Hu , Zhihua Zhu