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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

External controls from historical trials or observational data can augment randomized controlled trials when large-scale randomization is impractical or unethical, such as in drug evaluation for rare diseases. However, non-randomized…

Methodology · Statistics 2025-05-08 Ke Zhu , Shu Yang , Xiaofei Wang

In recent years, real-world external controls have grown in popularity as a tool to empower randomized placebo-controlled trials, particularly in rare diseases or cases where balanced randomization is unethical or impractical. However, as…

Methodology · Statistics 2024-11-14 Chenyin Gao , Shu Yang , Mingyang Shan , Wenyu Ye , Ilya Lipkovich , Douglas Faries

This paper is concerned with false discovery rate (FDR) control in large-scale multiple testing problems. We first propose a new data-driven testing procedure for controlling the FDR in large-scale t-tests for one-sample mean problem. The…

Statistics Theory · Mathematics 2020-03-02 Changliang Zou , Haojie Ren , Xu Guo , Runze Li

In current clinical trial development, historical information is receiving more attention as it provides utility beyond sample size calculation. Meta-analytic-predictive (MAP) priors and robust MAP priors have been proposed for…

Methodology · Statistics 2022-08-03 Tianyu Zhan , Yiwang Zhou , Ziqian Geng , Yihua Gu , Jian Kang , Li Wang , Xiaohong Huang , Elizabeth H. Slate

High dimensional case control studies are ubiquitous in the biological sciences, particularly genomics. To maximise power while constraining cost and to minimise type-1 error rates, researchers typically seek to replicate findings in a…

Methodology · Statistics 2017-07-11 James Liley

Randomized experiments are the gold standard for causal inference but face significant challenges in business applications, including limited traffic allocation, the need for heterogeneous treatment effect estimation, and the complexity of…

Methodology · Statistics 2025-08-18 Zhenkang Peng , Chengzhang Li , Ying Rong , Renyu Zhang

Shared controls in platform trials comprise concurrent and non-concurrent controls. For a given experimental arm, non-concurrent controls refer to data from patients allocated to the control arm before the arm enters the trial. The use of…

A/B tests, also known as randomized controlled experiments (RCTs), are the gold standard for evaluating the impact of new policies, products, or decisions. However, these tests can be costly in terms of time and resources, potentially…

Machine Learning · Statistics 2025-01-03 Shima Nassiri , Mohsen Bayati , Joe Cooprider

In pharmaceutical and toxicological research, historical control data are increasingly used to validate concurrent control groups, typically via the construction of historical control limits. While methods have been described for continuous…

Methodology · Statistics 2026-03-24 Sören Budig , Frank Schaarschmidt , Max Menssen

Hybrid randomized controlled trials (hybrid RCTs) integrate external control data, such as historical or concurrent data, with data from randomized trials. While numerous frequentist and Bayesian methods, such as the test-then-pool and…

Methodology · Statistics 2025-10-07 Han Chang Chiam , Franz König , Martin Posch

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

Multiple heterogeneous data sources are becoming increasingly available for statistical analyses in the era of big data. As an important example in finite-population inference, we develop a unified framework of the test-and-pool approach to…

Methodology · Statistics 2023-05-30 Chenyin Gao , Shu Yang

Randomized controlled trials (RCTs) are the gold standard for assessing drug safety and efficacy. However, RCTs have some drawbacks which have led to the use of single-arm studies to make certain internal drug development and regulatory…

Recently, several Test Case Prioritization (TCP) techniques have been proposed to order test cases for achieving a goal during test execution, particularly, revealing faults sooner. In the Model-Based Testing (MBT) context, such techniques…

Software Engineering · Computer Science 2017-08-11 João Felipe Silva Ouriques , Emanuela Gadelha Cartaxo , Patrícia Duarte Lima Machado

Randomized controlled trials (RCTs) often exhibit limited inferential efficiency in estimating treatment effects due to small sample sizes. In recent years, the combination of external controls has gained increasing attention as a means of…

Methodology · Statistics 2025-10-06 Qinwei Yang , Jingyi Li , Peng Wu

Observational studies provide the only evidence on the effectiveness of interventions when randomized controlled trials (RCTs) are impractical due to cost, ethical concerns, or time constraints. While many methodologies aim to draw causal…

Platform trials allow treatment arms to enter and exit over time while maintaining a shared control arm, yielding concurrent and non-concurrent controls (NCC). Pooling NCC is often motivated as a strategy to improve statistical efficiency,…

Methodology · Statistics 2026-03-12 Antonio D'Alessandro , Samrachana Adhikari , Michele Santacatterina

While randomized controlled trials (RCTs) are critical for establishing the efficacy of new therapies, there are limitations regarding what comparisons can be made directly from trial data. RCTs are limited to a small number of comparator…

The integration of real-world data (RWD) and randomized controlled trials (RCT) is increasingly important for advancing causal inference in scientific research. This combination holds great promise for enhancing the efficiency of causal…

Methodology · Statistics 2024-07-02 Xi Lin , Jens Magelund Tarp , Robin J. Evans
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