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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…

Machine learning is increasingly used to select which individuals receive limited-resource interventions in domains such as human services, education, development, and more. However, it is often not apparent what the right quantity is for…

Machine Learning · Computer Science 2025-03-20 Vibhhu Sharma , Bryan Wilder

Identifying patient subgroups with different treatment responses is an important task to inform medical recommendations, guidelines, and the design of future clinical trials. Existing approaches for treatment effect estimation primarily…

Methodology · Statistics 2025-12-10 Vincent Jeanselme , Chang Ho Yoon , Fabian Falck , Brian Tom , Jessica Barrett

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,…

Clinical trials with a hybrid control arm (a control arm constructed from a combination of randomized patients and real-world data on patients receiving usual care in standard clinical practice) have the potential to decrease the cost of…

Methodology · Statistics 2021-08-20 Joanna Harton , Brian Segal , Ronac Mamtani , Nandita Mitra , Rebecca Hubbard

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

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

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

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

Randomized Controlled Trials (RCTs) represent a gold standard when developing policy guidelines. However, RCTs are often narrow, and lack data on broader populations of interest. Causal effects in these populations are often estimated using…

Machine Learning · Computer Science 2023-03-07 Zeshan Hussain , Michael Oberst , Ming-Chieh Shih , David Sontag

Augmenting the control arm in clinical trials with external data can improve statistical power for demonstrating treatment effects. In many time-to-event outcome trials, participants are subject to truncation by death. Direct application of…

Methodology · Statistics 2025-06-24 Zehao Su , Helene C. W. Rytgaard , Henrik Ravn , Frank Eriksson

Although randomized controlled trials (RCTs) are a cornerstone of comparative effectiveness, they typically have much smaller sample size than observational studies because of financial and ethical considerations. Therefore there is…

Methodology · Statistics 2023-11-16 Lauren D. Liao , Emilie Højbjerre-Frandsen , Alan E. Hubbard , Alejandro Schuler

Randomized Controlled Trials (RCTs) are the gold standard for evaluating the effect of new medical treatments. Treatments must pass stringent regulatory conditions in order to be approved for widespread use, yet even after the regulatory…

Machine Learning · Statistics 2025-03-13 Omer Noy Klein , Alihan Hüyük , Ron Shamir , Uri Shalit , Mihaela van der Schaar

Randomized controlled trials (RCTs) often include subgroup analyses to assess whether treatment effects vary across pre-specified patient populations. However, these analyses frequently suffer from small sample sizes which limit the power…

Leveraging external or historical data to improve the efficiency of randomized clinical trials without introducing bias or inflating the Type I error rate remains challenging. Recent work on externally trained prognostic scores, such as…

Methodology · Statistics 2026-05-28 Junyi Zhou , Qing Liu , May Mo , Amy Xia

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

Random effects meta-analysis is widely used for synthesizing studies under the assumption that underlying effects come from a normal distribution. However, under certain conditions the use of alternative distributions might be more…

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

We develop a method for hybrid analyses that uses external controls to augment internal control arms in randomized controlled trials (RCT) where the degree of borrowing is determined based on similarity between RCT and external control…

Methodology · Statistics 2023-05-11 Evan Kwiatkowski , Jiawen Zhu , Xiao Li , Herbert Pang , Grazyna Lieberman , Matthew A. Psioda

Comparative binary outcome data are of fundamental interest in statistics and are often pooled in meta-analyses. Here we examine the simplest case where for each study there are two patient groups and a binary event of interest, giving rise…

Methodology · Statistics 2018-06-12 Rose Baker , Dan Jackson