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When incorporating historical control data into the analysis of current randomized controlled trial data, it is critical to account for differences between the datasets. When the cause of the difference is an unmeasured factor and…

Methodology · Statistics 2025-09-10 Tomohiro Ohigashi , Kazushi Maruo , Takashi Sozu , Masahiko Gosho

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

The primary analysis in two-arm clinical trials usually involves inference on a scalar treatment effect parameter; e.g., depending on the outcome, the difference of treatment-specific means, risk difference, risk ratio, or odds ratio. Most…

Methodology · Statistics 2022-04-25 Anastasios A. Tsiatis , Marie Davidian

Platform trials have become increasingly popular for drug development programs, attracting interest from statisticians, clinicians and regulatory agencies. Many statistical questions related to designing platform trials - such as the impact…

In pharmaceutical and toxicological research, historical control data are increasingly used to validate concurrent control groups, typically via the construction of historical control limits. While methods have been described for continuous…

Methodology · Statistics 2026-03-24 Sören Budig , Frank Schaarschmidt , Max Menssen

Under what circumstances is it a threat to the parallel trends assumption required for Difference in Differences (DiD) studies if treatment decisions are based on past values of the outcome? We explore via simulation studies whether…

Methodology · Statistics 2022-08-02 Zach Shahn

Multi-Arm Multi-Stage (MAMS) platform trials are an efficient tool for the comparison of several treatments. Suppose we wish to add a treatment to a trial already in progress, to access the benefits of a MAMS design. How should this be…

Applications · Statistics 2021-05-25 Thomas Burnett , Franz König , Thomas Jaki

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

When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…

Methodology · Statistics 2020-08-03 Johannes Krisam , Dorothea Weber , Richard F. Schlenk , Meinhard Kieser

Background: trials to identify the minimal effective treatment duration are needed in different therapeutic areas, including bacterial infections, TB and Hepatitis--C. However, standard non-inferiority designs have several limitations,…

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

Difference-in-differences is based on a parallel trends assumption, which states that changes over time in average potential outcomes are independent of treatment assignment, possibly conditional on covariates. With time-varying treatments,…

Methodology · Statistics 2024-06-25 Nicholas Illenberger , Iván Díaz , Audrey Renson

This paper considers identifying and estimating causal effect parameters in a staggered treatment adoption setting -- that is, where a researcher has access to panel data and treatment timing varies across units. We consider the case where…

Econometrics · Economics 2023-08-08 Brantly Callaway , Emmanuel Selorm Tsyawo

Randomized trials and observational studies, more often than not, run over a certain period of time. The treatment effect evolves during this period which provides crucial insights into the treatment response and the long-term effects. Many…

Methodology · Statistics 2020-04-13 Shu Li , Peter Bühlmann

This paper considers the identification of dynamic treatment effects with panel data, in complex designs where the treatment may not be binary and may not be absorbing. We first show that under no-anticipation and parallel-trends…

Econometrics · Economics 2025-12-23 Clément de Chaisemartin , Xavier D'Haultfœuille

Difference-in-differences (DID) is popular because it can allow for unmeasured confounding when the key assumption of parallel trends holds. However, there exists little guidance on how to decide a priori whether this assumption is…

Methodology · Statistics 2025-05-07 Audrey Renson , Oliver Dukes , Zach Shahn

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…

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

Randomized trials are considered the gold standard for making informed decisions in medicine, yet they often lack generalizability to the patient populations in clinical practice. Observational studies, on the other hand, cover a broader…

Methodology · Statistics 2026-04-14 Piersilvio De Bartolomeis , Javier Abad , Konstantin Donhauser , Fanny Yang

Externally controlled trials (ECTs) are increasingly used when randomized controls are infeasible, unethical, or insufficient, including applications in rare diseases, oncology, pediatrics, and post-approval effectiveness research. Although…