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Background. Designing trials to reduce treatment duration is important in several therapeutic areas, including TB and antibiotics. We recently proposed a new randomised trial design to overcome some of the limitations of standard two-arm…

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

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

Randomized controlled trials (RCTs) are the gold standard for evaluating causal effects but are often costly and difficult to scale; consequently, they are frequently augmented with auxiliary external controls in many applications. Prior…

Methodology · Statistics 2026-05-28 Jiawei Shan , Yiteng Tu , Guanbo Wang , Chao Ying , Jiwei Zhao

In conventional randomized controlled trials, adjustment for baseline values of covariates known to be at least moderately associated with the outcome increases the power of the trial. Recent work has shown particular benefit for more…

Methodology · Statistics 2023-11-27 James Willard , Shirin Golchi , Erica EM Moodie

The primary goal of randomized trials is to compare the effects of different interventions on some outcome of interest. In addition to the treatment assignment and outcome, data on baseline covariates, such as demographic characteristics or…

Applications · Statistics 2014-01-09 Alisa J. Stephens , Eric J. Tchetgen Tchetgen , Victor De Gruttola

The sample size of a clinical trial relies on information about nuisance parameters such as the outcome variance. When no or only limited information is available, it has been proposed to include an internal pilot study in the design of the…

Applications · Statistics 2017-07-18 Tobias Mütze , Tim Friede

In a recent simulation study, Goodman et al. (2019) compare several methods with regard to their type I and type II error rates in case of a thick null hypothesis that includes all values that are practically equivalent to the point null…

Methodology · Statistics 2022-06-07 Robin Tim Dreher , Leona Hoffmann , Arne Kramer-Sunderbrink , Peter Pütz , Robin Werner

Statistical significance of both the original and the replication study is a commonly used criterion to assess replication attempts, also known as the two-trials rule in drug development. However, replication studies are sometimes conducted…

Applications · Statistics 2024-05-31 Leonhard Held , Samuel Pawel , Charlotte Micheloud

Real-time hybrid testing is a method in which a substructure of the system is realised experimentally and the rest numerically. The two parts interact in real time to emulate the dynamics of the full system. Such experiments however are…

Dynamical Systems · Mathematics 2024-06-04 Sandor Beregi , David A. W. Barton , Djamel Rezgui , Simon A. Neild

When testing multiple hypotheses, a suitable error rate should be controlled even in exploratory trials. Conventional methods to control the False Discovery Rate (FDR) assume that all p-values are available at the time point of test…

Methodology · Statistics 2021-12-21 Sonja Zehetmayer , Martin Posch , Franz Koenig

Background: We aimed to design a Bayesian adaption trial through extensive simulations to determine values for key design parameters, demonstrate error rates, and establish the expected sample size. The complexity of the proposed outcome…

Loss of power and clear description of treatment differences are key issues in designing and analyzing a clinical trial where non-proportional hazard is a possibility. A log-rank test may be very inefficient and interpretation of the hazard…

Applications · Statistics 2021-01-13 Satrajit Roychoudhury , Keaven M Anderson , Jiabu Ye , Pralay Mukhopadhyay

Response-adaptive randomization (RAR) can increase participant benefit in clinical trials, but also complicates statistical analysis. The burn-in period (a non-adaptive initial stage) is commonly used to mitigate this disadvantage, yet…

Methodology · Statistics 2025-10-14 Edwin Y. N. Tang , Stef Baas , Daniel Kaddaj , Lukas Pin , David S. Robertson , Sofía S. Villar

Identifying signals that replicate across multiple studies is essential for establishing robust scientific evidence, yet existing methods for high-dimensional replicability analysis either rely on restrictive modeling assumptions, are…

Methodology · Statistics 2026-03-05 Haochen Lei , Yan Li , Hongyuan Cao

Estimands using the treatment policy strategy for addressing intercurrent events are common in Phase III clinical trials. One estimation approach for this strategy is retrieved dropout whereby observed data following an intercurrent event…

The learned policy of model-free offline reinforcement learning (RL) methods is often constrained to stay within the support of datasets to avoid possible dangerous out-of-distribution actions or states, making it challenging to handle…

Machine Learning · Computer Science 2022-10-11 Jiafei Lyu , Xiu Li , Zongqing Lu

Randomized controlled trials (RCTs) are the gold standard for causal inference, yet practical constraints often limit the size of the concurrent control arm. Borrowing control data from previous trials offers a potential efficiency gain,…

Methodology · Statistics 2026-03-17 Linying Yang , Xing Liu , Robin J. Evans

The incorporation of "real-world data" to supplement the analysis of trials and improve decision-making has spurred the development of statistical techniques to account for introduced confounding. Recently, "hybrid" methods have been…

We study a statistical framework for replicability based on a recently proposed quantitative measure of replication success, the sceptical $p$-value. A recalibration is proposed to obtain exact overall Type-I error control if the effect is…

Methodology · Statistics 2023-11-10 Charlotte Micheloud , Fadoua Balabdaoui , Leonhard Held