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PURPOSE Providing rapid answers and early acces to patients to innovative treatments without randomized clinical trial (RCT) is growing, with benefit estimated from single-arm trials. This has become common in oncology, impacting the…

As clinical decision-making increasingly moves toward individualized and context-specific treatment recommendations, reliance on any single evidence source, randomized or observational, may be insufficient. Principled integration of…

The standard paradigm for confirmatory clinical trials is to compare experimental treatments with a control, for example the standard of care or a placebo. However, it is not always the case that a suitable control exists. Efficient…

Methodology · Statistics 2024-10-29 Thomas Burnett , Thomas Jaki

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 are an important study design for evaluating drug efficacy and safety without enrolling patients into a control arm. Although they do not provide the gold-standard evidence of randomized controlled trials, they are…

Applications · Statistics 2026-05-14 Daniele Bertolini , Franklin Fuller , Aaron M. Smith , Jonathan R. Walsh , Run Zhuang

One approach for increasing the efficiency of randomized trials is the use of "external controls" -- individuals who received the control treatment studied in the trial during routine practice or in prior experimental studies. Existing…

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

We argue that randomized controlled trials (RCTs) are special even among settings where average treatment effects are identified by a nonparametric unconfoundedness assumption. This claim follows from two results of Robins and Ritov (1997):…

Methodology · Statistics 2021-09-28 P. M. Aronow , James M. Robins , Theo Saarinen , Fredrik Sävje , Jasjeet Sekhon

The randomized controlled trial (RCT) is the gold standard for estimating the average treatment effect (ATE) of a medical intervention but requires 100s-1000s of subjects, making it expensive and difficult to implement. While a cross-over…

Signal Processing · Electrical Eng. & Systems 2023-05-10 Sayeri Lala , Niraj K. Jha

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

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

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…

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

Randomized controlled trials (RCTs) have been the cornerstone of clinical evidence; however, their cost, duration, and restrictive eligibility criteria limit power and external validity. Studies using real-world data (RWD), historically…

Methodology · Statistics 2025-11-26 Shu Yang , Margaret Gamalo , Haoda Fu

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

The use of historical controls offers a valuable alternative when traditional randomized controlled trials are not feasible. However, such approaches may introduce bias due to temporal changes in patient populations, diagnostic criteria,…

Methodology · Statistics 2025-12-24 Marco Ratta , Pavel Mozgunov , Sandrine Boulet , Moreno Ursino

Randomized control trials (RCTs) have been the gold standard to evaluate the effectiveness of a program, policy, or treatment on an outcome of interest. However, many RCTs assume that study participants are willing to share their…

Applications · Statistics 2021-12-07 Manjusha Kancharla , Hyunseung Kang

Randomized Controlled Trials (RCT) are the current gold standards to empirically measure the effect of a new drug. However, they may be of limited size and resorting to complementary non-randomized data, referred to as observational, is…

Methodology · Statistics 2025-06-11 Ahmed Boughdiri , Julie Josse , Erwan Scornet

Randomized clinical trials are the gold standard when estimating the average treatment effect. However, they are usually not a random sample from the real-world population because of the inclusion/exclusion rules. Meanwhile, observational…

Methodology · Statistics 2024-12-11 Kuan Jiang , Wenjie Hu , Shu Yang , Xinxing Lai , Xiaohua Zhou

With more and better clinical data being captured outside of clinical studies and greater data sharing of clinical studies, external controls may become a more attractive alternative to randomized clinical trials. Both industry and…