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Randomized clinical trials (RCTs) are widely considered the gold standard for evaluating the effectiveness of new treatments or interventions in drug development. Still, they may not be feasible in certain cases, such as with rare diseases…

Methodology · Statistics 2025-08-05 Di Ran , Fanni Zhang , Sima Shahsavari , Kristine Broglio , Alasdair Henderson , Binbing Yu

Nonlinear longitudinal proportional effect models have been proposed to improve power and provide direct estimates of the proportional treatment effect in randomized clinical trials. These models assume a fixed proportional treatment effect…

Methodology · Statistics 2026-01-23 Michael C. Donohue , Philip S. Insel , Oliver Langford

In situations where it is difficult to enroll patients in randomized controlled trials, external data can improve efficiency and feasibility. In such cases, adaptive trial designs could be used to decrease enrollment in the control arm of…

Methodology · Statistics 2020-10-02 Brian D. Segal , W. Katherine Tan

Hybrid controlled trials (HCTs), which augment randomized controlled trials (RCTs) with external controls (ECs), are increasingly receiving attention as a way to address limited power, slow accrual, and ethical concerns in clinical…

Methodology · Statistics 2025-05-02 Jiajun Liu , Ke Zhu , Shu Yang , Xiaofei Wang

There is growing interest in a hybrid control design in which a randomized controlled trial is augmented with an external control arm from a previous trial or real world data. Existing methods for analyzing hybrid control studies include…

Methodology · Statistics 2025-01-30 Zhiwei Zhang , Jialuo Liu , Wei Liu

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

In this study, variable acceptance sampling plans under Type I hybrid censoring is designed for a lot of independent and identical units with exponential lifetimes using Bayesian estimate of the parameter $\vartheta$. This approach is new…

Statistics Theory · Mathematics 2023-11-29 Ashlyn Maria Mathai , Mahesh Kumar

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

In many real-world applications, it is common that a proportion of the data may be missing or only partially observed. We develop a novel two-sample testing method based on the Maximum Mean Discrepancy (MMD) which accounts for missing data…

Methodology · Statistics 2024-05-27 Yijin Zeng , Niall M. Adams , Dean A. Bodenham

Traditional hypothesis tests for differences between binomial proportions are at risk of being too liberal (Wald test) or overly conservative (Fisher's exact test). This problem is exacerbated in small samples. Regulators favour exact…

Methodology · Statistics 2025-07-31 Stef Baas , Yaron Racah , Elad Berkman , Sofia S. Villar

Response-adaptive randomization allows the probabilities of allocating patients to treatments in a clinical trial to change based on the previously observed response data, in order to achieve different experimental goals. One concern over…

Methodology · Statistics 2022-04-13 Ekkehard Glimm , David Robertson

We present a new experimental design procedure that divides a set of experimental units into two groups in order to minimize error in estimating an additive treatment effect. One concern is minimizing error at the experimental design stage…

Methodology · Statistics 2021-02-02 Abba M. Krieger , David Azriel , Adam Kapelner

One class of statistical hypothesis testing procedures is the indisputable equivalence tests, whose main objective is to establish practical equivalence rather than the usual statistical significant difference. These hypothesis tests are…

Methodology · Statistics 2024-01-04 Daniel Ochieng

Use of historical control data to augment a small internal control arm in a randomized control trial (RCT) can lead to significant improvement of the efficiency of the trial. It introduces the risk of potential bias, since the historical…

Methodology · Statistics 2022-10-05 Jixian Wang , Hongtao Zhang , Ram Tiwari

Permutation-based partial-correlation tests guarantee finite-sample Type I error control under any fixed design and exchangeable noise, yet their power can collapse when the permutation-augmented design aligns too closely with the covariate…

Methodology · Statistics 2025-06-04 Tianyi Wang , Guanghui Wang , Zhaojun Wang , Changliang Zou

We study hybrid control trials (HCTs), in which a randomized controlled trial (RCT) is augmented with external control patients. Existing approaches for HCTs typically assume conditional exchangeability of the concurrent and external…

Methodology · Statistics 2025-11-21 Alissa Gordon , Emilie Højbjerre-Frandsen , Alejandro Schuler

Incorporating historical data or real-world evidence has a great potential to improve the efficiency of phase I clinical trials and to accelerate drug development. For model-based designs, such as the continuous reassessment method (CRM),…

Methodology · Statistics 2020-06-11 Yanhong Zhou , J. Jack Lee , Shunguang Wang , Stuart Bailey , Ying Yuan

Accelerated life tests (ALTs) play a crucial role in reliability analyses, providing lifetime estimates of highly reliable products. Among ALTs, step-stress design increases the stress level at predefined times, while maintaining a constant…

Statistics Theory · Mathematics 2024-02-12 Narayanaswamy Balakrishnan , María Jaenada , Leandro Pardo

This paper proposes an adaptive random experiment design (ARED) algorithm that can be applied to optimize the multiple factors and levels experiments. The algorithm takes real-time model error as the adaptive condition, and outputs a model…

Signal Processing · Electrical Eng. & Systems 2020-09-01 Zhou Qiao , Duan Xiaochang , Tang Wei

The win ratio (WR) statistic is increasingly used to evaluate treatment effects based on prioritized composite endpoints, yet existing Bayesian adaptive designs are not directly applicable because the WR is a summary statistic derived from…

Methodology · Statistics 2026-02-20 Di Zhu , Yong Zang