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Randomized controlled trials (RCTs) are the accepted standard for treatment effect estimation but they can be infeasible due to ethical reasons and prohibitive costs. Single-arm trials, where all patients belong to the treatment group, can…

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…

The use of information from real world to assess the effectiveness of medical products is becoming increasingly popular and more acceptable by regulatory agencies. According to a strategic real-world evidence framework published by U.S.…

Methodology · Statistics 2022-03-22 Jianghao Li , Yu Du , Huayu Liu , Yanyao Yi

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

While randomized controlled trials (RCTs) are the gold standard for estimating treatment effects in medical research, there is increasing use of and interest in using real-world data for drug development. One such use case is the…

Methodology · Statistics 2021-10-11 Devin Incerti , Michael T Bretscher , Ray Lin , Chris Harbron

Randomized controlled trials (RCTs) are widely regarded as the gold standard for causal inference in biomedical research. For instance, when estimating the average treatment effect on the treated (ATT), a doubly robust estimation procedure…

Methodology · Statistics 2025-09-26 Chi-Shian Dai , Chao Ying , Yang Ning , Jiwei Zhao

External controls (ECs) from historical trials or real-world data have gained increasing attention as a way to augment hybrid and single-arm trials, especially when balanced randomization is infeasible. While most existing work has focused…

Methodology · Statistics 2025-12-15 Yujing Gao , Xiang Zhang , Shu Yang

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

The availability of electronic health records (EHR) has opened opportunities to supplement increasingly expensive and difficult to carry out randomized controlled trials (RCT) with evidence from readily available real world data. In this…

Methodology · Statistics 2023-05-09 Noirrit Kiran Chandra , Abhra Sarkar , John F. de Groot , Ying Yuan , Peter Müller

Randomized controlled trials (RCTs) face inherent limitations, such as ethical or resource constraints, which lead to a limited number of study participants. To address these limitations, recent research endeavors have sought to incorporate…

Methodology · Statistics 2025-02-20 Peijin Wang , Hwanhee Hong , Kyungeun Jeon , Laine Elliott Thomas

While randomized trials may be the gold standard for evaluating the effectiveness of the treatment intervention, in some special circumstances, single-arm clinical trials utilizing external control may be considered. The causal treatment…

Methodology · Statistics 2025-05-26 Huan Wang , Fei Wu , Yeh-Fong Chen

Externally controlled trials (ECTs) are increasingly used when randomized controls are infeasible, unethical, or insufficient, including applications in rare diseases, oncology, pediatrics, and post-approval effectiveness research. Although…

Randomized experiments play a major role in data-driven decision making across many different fields and disciplines. In medicine, for example, randomized controlled trials (RCTs) are the backbone of clinical trial methodology for testing…

Applications · Statistics 2016-08-30 Andrew W. Correia

Randomized controlled trials (RCTs) in oncology often allow control group participants to crossover to experimental treatments, a practice that, while often ethically necessary, complicates the accurate estimation of long-term treatment…

Methodology · Statistics 2025-02-12 Harlan Campbell , Nicholas Latimer , Jeroen P Jansen , Shannon Cope

Subgroup analyses of randomized controlled trials (RCTs) constitute an important component of the drug development process in precision medicine. In particular, subgroup analyses of early-stage trials often influence the design and…

Methodology · Statistics 2025-02-12 Daniel Schwartz , Riddhiman Saha , Steffen Ventz , Lorenzo Trippa

Single-arm trials (SATs) may be used to support regulatory submissions in settings where there is a high unmet medical need and highly promising early efficacy data undermine the equipoise needed for randomization. In this context,…

Platform trials are multi-arm designs that simultaneously evaluate multiple treatments for a single disease within the same overall trial structure. Unlike traditional randomized controlled trials, they allow treatment arms to enter and…

Methodology · Statistics 2024-12-16 Michele Santacatterina , Federico Macchiavelli Giron , Xinyi Zhang , Ivan Diaz

There has been an increasing use of master protocols in oncology clinical trials because of its efficiency and flexibility to accelerate cancer drug development. Depending on the study objective and design, a master protocol trial can be a…

Applications · Statistics 2023-11-13 Jie Chen , Xiaoyun , Li , Chengxing , Lu , Sammy Yuan , Godwin Yung , Jingjing Ye , Hong Tian , Jianchang Lin

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

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
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