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Augmenting randomized controlled trials (RCTs) with external real-world data (RWD) has the potential to improve the finite sample efficiency of treatment effect estimators. We describe using adaptive targeted maximum likelihood estimation…

Methodology · Statistics 2025-01-30 Sky Qiu , Jens Tarp , Andrew Mertens , Mark van der Laan

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…

We consider the problem of estimating personalized treatment policies that are "externally valid" or "generalizable": they perform well in target populations that differ from the experimental (or training) population from which the data are…

Econometrics · Economics 2025-11-10 Christopher Adjaho , Timothy Christensen

We propose a test-based elastic integrative analysis of the randomized trial and real-world data to estimate treatment effect heterogeneity with a vector of known effect modifiers. When the real-world data are not subject to bias, our…

Methodology · Statistics 2022-11-30 Shu Yang , Chenyin Gao , Donglin Zeng , Xiaofei Wang

Externally controlled trials are crucial in clinical development when randomized controlled trials are unethical or impractical. These trials consist of a full treatment arm with the experimental treatment and a full external control arm.…

Methodology · Statistics 2025-03-11 Chenyin Gao , Xiang Zhang , Shu Yang

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 a randomized control trial, the precision of an average treatment effect estimator can be improved either by collecting data on additional individuals, or by collecting additional covariates that predict the outcome variable. We propose…

Methodology · Statistics 2017-09-27 Pedro Carneiro , Sokbae Lee , Daniel Wilhelm

We present a general framework for using existing data to estimate the efficiency gain from using a covariate-adjusted estimator of a marginal treatment effect in a future randomized trial. We describe conditions under which it is possible…

Methodology · Statistics 2021-05-03 Xiudi Li , Sijia Li , Alex Luedtke

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

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

Although there is now a large literature on policy evaluation and learning, much of the prior work assumes that the treatment assignment of one unit does not affect the outcome of another unit. Unfortunately, ignoring interference can lead…

Methodology · Statistics 2025-04-02 Yi Zhang , Kosuke Imai

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…

Longitudinal studies are often subject to missing data. The ICH E9(R1) addendum addresses the importance of defining a treatment effect estimand with the consideration of intercurrent events. Jump-to-reference (J2R) is one classically…

Methodology · Statistics 2023-12-06 Siyi Liu , Shu Yang , Yilong Zhang , Guanghan , Liu

We consider the challenges associated with causal inference in settings where data from a randomized trial is augmented with control data from an external source to improve efficiency in estimating the average treatment effect (ATE).…

Censored survival data are common in clinical trials, but small control groups can pose challenges, particularly in rare diseases or where balanced randomization is impractical. Recent approaches leverage external controls from historical…

Methodology · Statistics 2025-05-16 Chenyin Gao , Shu Yang , Mingyang Shan , Wenyu Wendy Ye , Ilya Lipkovich , Douglas Faries

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

Augmenting a randomized controlled trial (RCT) with external data may increase power at the risk of introducing bias. To select and analyze the experiment (RCT alone or combined with external data) with the optimal bias-variance tradeoff,…

Maintaining the quality of manufactured products at a desired level is known to increase customer satisfaction and profitability. Shewhart control chart is the most widely used in statistical process control (SPC) technique to monitor the…

Other Statistics · Statistics 2018-12-31 Burak Alakent , Ece C. Mutlu

Suppose we have individual data from an internal study and various summary statistics from relevant external studies. External summary statistics have the potential to improve statistical inference for the internal population; however, it…

Methodology · Statistics 2026-02-06 Wenjie Hu , Ruoyu Wang , Wei Li , Wang Miao

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