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We consider the problem of estimating the average treatment effect (ATE) when both randomized control trial (RCT) data and external real-world data (RWD) are available. We decompose the ATE estimand as the difference between a pooled-ATE…

Methodology · Statistics 2025-01-22 Mark van der Laan , Sky Qiu , Jens Magelund Tarp , Lars van der Laan

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

While randomized controlled trials (RCTs) are the gold-standard for establishing the efficacy and safety of a medical treatment, real-world evidence (RWE) generated from real-world data (RWD) has been vital in post-approval monitoring and…

Randomized controlled trials (RCTs) often suffer from limited inferential efficiency in estimating treatment effects due to their small sample sizes. In recent years, incorporating external controls (ECs) has gained increasing attention as…

Methodology · Statistics 2026-04-16 Qinwei Yang , Jingyi Li , Peng Wu , Shu Yang

Randomized controlled trials (RCTs) are the gold standard for evaluating the causal effect of a treatment; however, they often have limited sample sizes and sometimes poor generalizability. On the other hand, non-randomized, observational…

Methodology · Statistics 2021-09-23 Shuxiao Chen , Bo Zhang , Ting Ye

Screening patients for clinical trial eligibility remains a manual, time-consuming, and resource-intensive process. We present a secure, scalable proof-of-concept system for Artificial Intelligence (AI)-augmented patient-trial matching that…

We describe how the target trial framework can be used to plan and report analyses that attempt to answer causal questions by combining information from multiple, diverse sources. Such analyses may involve comparisons of treatments…

Methodology · Statistics 2026-05-26 Lawson Ung , Miguel A. Hernán , Issa J. Dahabreh

Adaptive enrichment allows for pre-defined patient subgroups of interest to be investigated throughout the course of a clinical trial. Many trials which measure a long-term time-to-event endpoint often also routinely collect repeated…

Methodology · Statistics 2024-02-26 Abigail J. Burdon , Richard D. Baird , Thomas Jaki

It is highly desirable to borrow information from external data to augment a control arm in a randomized clinical trial, especially in settings where the sample size for the control arm is limited. However, a main challenge in borrowing…

Methodology · Statistics 2023-11-01 Dehua Bi , Tianjian Zhou , Wei Zhong , Yuan Ji

Bridging the gap between internal and external validity is crucial for heterogeneous treatment effect estimation. Randomised controlled trials (RCTs), favoured for their internal validity due to randomisation, often encounter challenges in…

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,…

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

Combination drug therapies hold significant promise for enhancing treatment efficacy, particularly in fields such as oncology, immunotherapy, and infectious diseases. However, designing clinical trials for these regimens poses unique…

Methodology · Statistics 2025-06-04 Nan Miles Xi , Man Mandy Jin , Lin Wang , Xin Huang

Complementary features of randomized controlled trials (RCTs) and observational studies (OSs) can be used jointly to estimate the average treatment effect of a target population. We propose a calibration weighting estimator that enforces…

Methodology · Statistics 2022-02-16 Dasom Lee , Shu Yang , Lin Dong , Xiaofei Wang , Donglin Zeng , Jianwen Cai

A/B testing is a widely-used paradigm within marketing optimization because it promises identification of causal effects and because it is implemented out of the box in most messaging delivery software platforms. Modern businesses, however,…

Machine Learning · Computer Science 2023-05-03 Schaun Wheeler

Randomized controlled trials are the gold standard for causal inference and play a pivotal role in modern evidence-based medicine. However, the sample sizes they use are often too limited to draw significant causal conclusions for subgroups…

Methodology · Statistics 2024-04-26 Xi Lin , Jens Magelund Tarp , Robin J. Evans

Existing statistical methods for the analysis of micro-randomized trials (MRTs) are designed to estimate causal excursion effects using data from a single MRT. In practice, however, researchers can often find previous MRTs that employ…

Methodology · Statistics 2025-05-13 Easton Huch , Inbal Nahum-Shani , Lindsey Potter , Cho Lam , David W. Wetter , Walter Dempsey

Multi-arm trials are gaining interest in practice given the statistical and logistical advantages they can offer. The standard approach uses a fixed allocation ratio, but there is a call for making it adaptive and skewing the allocation of…

Methodology · Statistics 2026-01-16 Gianmarco Caruso , Pavel Mozgunov

Causal inference is vital for informed decision-making across fields such as biomedical research and social sciences. Randomized controlled trials (RCTs) are considered the gold standard for internal validity of inferences, whereas…

Methodology · Statistics 2025-12-02 Ruoqi Yu , Bikram Karmakar , Jessica Vandeleest , Eleanor Bimla Schwarz

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
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