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Using administrative patient-care data such as Electronic Health Records (EHR) and medical/ pharmaceutical claims for population-based scientific research has become increasingly common. With vast sample sizes leading to very small standard…

Methodology · Statistics 2023-08-21 Ritoban Kundu , Xu Shi , Jean Morrison , Jessica Barrett , Bhramar Mukherjee

Pragmatic trials increasingly define outcomes using real-world data such as electronic health records, where assessments are collected during routine care rather than at fixed timepoints. Consequently, these uncontrolled assessments may be…

When randomized controlled trials are impractical or unethical to simultaneously compare multiple treatments, indirect treatment comparisons using single-arm trials offer valuable evidence for health technology assessments, especially for…

Methodology · Statistics 2025-09-30 Yuru Zhu , Huiyuan Wang , Haitao Chu , Yumou Qiu , Yong Chen

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

It is increasingly common to augment randomized controlled trial with external controls from observational data, to evaluate the treatment effect of an intervention. Traditional approaches to treatment effect estimation involve ambiguous…

Methodology · Statistics 2025-03-28 Bo Liu , Laine Thomas , Rury R. Holman , Fan Li

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

Covariate adjustment is an important tool in the analysis of randomized clinical trials and observational studies. It can be used to increase efficiency and thus power, and to reduce possible bias. While most statistical tests in randomized…

Methodology · Statistics 2011-08-03 Xiaoru Wu , Zhiliang Ying

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…

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

Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision-making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls…

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

In situations where it is difficult to enroll patients in randomized controlled trials, external data can improve efficiency and feasibility. In such cases, adaptive trial designs could be used to decrease enrollment in the control arm of…

Methodology · Statistics 2020-10-02 Brian D. Segal , W. Katherine Tan

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

There has been a growing interest in covariate adjustment in the analysis of randomized controlled trials in past years. For instance, the U.S. Food and Drug Administration recently issued guidance that emphasizes the importance of…

Methodology · Statistics 2023-06-12 Kelly Van Lancker , Frank Bretz , Oliver Dukes

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…

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

Platform trials are a more efficient way of testing multiple treatments compared to running separate trials. In this paper we consider platform trials where, if a treatment is found to be superior to the control, it will become the new…

Methodology · Statistics 2023-11-30 Peter Greenstreet , Thomas Jaki , Alun Bedding , Pavel Mozgunov

Individualized treatment decisions can improve health outcomes, but using data to make these decisions in a reliable, precise, and generalizable way is challenging with a single dataset. Leveraging multiple randomized controlled trials…

The use of patient-level information from previous studies, registries, and other external datasets can support the analysis of single-arm and randomized controlled trials to evaluate and test experimental treatments. However, the…

Methodology · Statistics 2025-10-23 Gopal Kotecha , Daniel E. Schwartz , Steffen Ventz , Lorenzo Trippa

The question of how individual patient data from cohort studies or historical clinical trials can be leveraged for designing more powerful, or smaller yet equally powerful, clinical trials becomes increasingly important in the era of…

Methodology · Statistics 2022-09-01 Sandra Siegfried , Stephen Senn , Torsten Hothorn