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Multi-regional clinical trials (MRCTs) enable efficient global drug development by assessing treatment effects across regions within a single protocol. While powered for overall efficacy, MRCTs are typically not designed to provide…

In most medical research, the average treatment effect is used to evaluate a treatment's performance. However, precision medicine requires knowledge of individual treatment effects: What is the difference between a unit's measurement under…

Computation · Statistics 2022-08-30 Mingyang Cai , Stef van Buuren , Gerko Vink

Many epidemiological questions concern potential interventions to alter the pathways presumed to mediate an association. For example, we consider a study that investigates the benefit of interventions in young adulthood for ameliorating the…

Methodology · Statistics 2020-07-14 Margarita Moreno-Betancur , Paul Moran , Denise Becker , George C Patton , John B Carlin

Cluster-randomized trials (CRTs) are experimental designs where groups or clusters of participants, rather than the individual participants themselves, are randomized to intervention groups. Analyzing CRT requires distinguishing between…

Methodology · Statistics 2025-10-10 Xi Fang , Bingkai Wang , Liangyuan Hu , Fan Li

Understanding treatment heterogeneity is essential to the development of precision medicine, which seeks to tailor medical treatments to subgroups of patients with similar characteristics. One of the challenges to achieve this goal is that…

Methodology · Statistics 2019-08-21 Shujie Ma , Jian Huang , Zhiwei Zhang , Mingming Liu

In settings with few treated units, Difference-in-Differences (DID) estimators are not consistent, and are not generally asymptotically normal. This poses relevant challenges for inference. While there are inference methods that are valid…

Econometrics · Economics 2023-02-08 Luis Alvarez , Bruno Ferman

The aim of clinical effectiveness research using repositories of electronic health records is to identify what health interventions 'work best' in real-world settings. Since there are several reasons why the net benefit of intervention may…

Methodology · Statistics 2020-06-19 Jie Zhu , Blanca Gallego

Recent methodological developments have introduced new black-box approaches to better estimate heterogeneous treatment effects; however, these methods fall short of providing interpretable characterizations of the underlying individuals who…

Methodology · Statistics 2025-08-19 Melody Huang , Tiffany M. Tang , Ana M. Kenney

Non-adherence to assigned treatment is common in randomised controlled trials (RCTs). Recently, there has been an increased interest in estimating causal effects of treatment received, for example the so-called local average treatment…

Methodology · Statistics 2018-12-05 Karla DiazOrdaz , James Carpenter

Often both Aggregate Data (AD) studies and Individual Patient Data (IPD) studies are available for specific treatments. Combining these two sources of data could improve the overall meta-analytic estimates of treatment effects. Moreover,…

Methodology · Statistics 2021-11-15 Neha Agarwala , Junyong Park , Anindya Roy

Evaluating blocked randomized experiments from a potential outcomes perspective has two primary branches of work. The first focuses on larger blocks, with multiple treatment and control units in each block. The second focuses on matched…

Methodology · Statistics 2024-05-31 Nicole E. Pashley , Luke W. Miratrix

Indirect treatment comparisons (ITCs) are essential in Health Technology Assessment (HTA) when head-to-head clinical trials are absent. A common challenge arises when attempting to compare a treatment with available individual patient data…

Computation · Statistics 2026-01-16 Nathan Green

There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed…

Methodology · Statistics 2023-08-25 Peter Greenstreet , Thomas Jaki , Alun Bedding , Pavel Mozgunov

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

Suppose one is interested in estimating causal effects in the presence of potentially unmeasured confounding with the aid of a valid instrumental variable. This paper investigates the problem of making inferences about the average treatment…

Methodology · Statistics 2020-12-15 BaoLuo Sun , Wang Miao

This study investigates the identification power gained by combining experimental data, in which treatment is randomized, with observational data, in which treatment is self-selected, for distributional treatment effect (DTE) parameters.…

Econometrics · Economics 2026-04-24 Shosei Sakaguchi

Multi-regional clinical trials (MRCTs) play an increasingly crucial role in global pharmaceutical development by expediting data gathering and regulatory approval across diverse patient populations. However, differences in recruitment…

Methodology · Statistics 2024-04-15 Kaiyuan Hua , Hwanhee Hong , Xiaofei Wang

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 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

In paired randomized experiments individuals in a given matched pair may differ on prognostically important covariates despite the best efforts of practitioners. We examine the use of regression adjustment as a way to correct for persistent…

Methodology · Statistics 2017-11-27 Colin B. Fogarty