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In randomized clinical trials (RCTs), the accurate estimation of marginal treatment effects is crucial for determining the efficacy of interventions. Enhancing the statistical power of these analyses is a key objective for statisticians.…

Methodology · Statistics 2026-01-30 Emilie Højbjerre-Frandsen , Mark J. van der Laan , Alejandro Schuler

Randomized controlled trials (RCT's) allow researchers to estimate causal effects in an experimental sample with minimal identifying assumptions. However, to generalize or transport a causal effect from an RCT to a target population,…

Methodology · Statistics 2022-02-08 Melody Huang

Objective: Randomised controlled trials (RCTs) are widely considered as gold standard for assessing the effectiveness of new health interventions. When treatment non-compliance is present in RCTs, the treatment effect in the subgroup of…

Applications · Statistics 2025-03-25 Theodosios Papazoglou , Ed Waddingham , Alastair Young

Population-adjusted indirect comparisons estimate treatment effects when access to individual patient data is limited and there are cross-trial differences in effect modifiers. Popular methods include matching-adjusted indirect comparison…

Applications · Statistics 2021-11-05 Antonio Remiro-Azócar , Anna Heath , Gianluca Baio

The ability to generalize experimental results from randomized control trials (RCTs) across locations is crucial for informing policy decisions in targeted regions. Such generalization is often hindered by the lack of identifiability due to…

Econometrics · Economics 2021-12-10 Xinkun Nie , Guido Imbens , Stefan Wager

In clinical and epidemiological studies, hazard ratios are often applied to compare treatment effects between two groups for survival data. For competing risks data, the corresponding quantities of interest are cause-specific hazard ratios…

Applications · Statistics 2021-12-21 Hongji Wu , Hao Yuan , Zijing Yang , Yawen Hou , Zheng Chen

Meta-analyses of clinical trials targeting rare events face particular challenges when the data lack adequate numbers of events for all treatment arms. Especially when the number of studies is low, standard meta-analysis methods can lead to…

Applications · Statistics 2020-01-20 Burak Kürsad Günhan , Christian Röver , Tim Friede

While randomised controlled trials (RCTs) are the gold standard for estimating causal treatment effects, their limited sample sizes and restrictive criteria make it difficult to extrapolate to a broader population. Observational data, while…

Methodology · Statistics 2025-09-09 Stephanie Riley , Ricardo Silva , Matthew Sperrin

For toxicology studies, the validation of the concurrent control group by historical control data (HCD) has become requirements. This validation is usually done by historical control limits (HCL), which should cover the observations of the…

Applications · Statistics 2025-07-18 Max Menssen , Jonathan Rathjens

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

In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment…

Methodology · Statistics 2022-10-05 Dasom Lee , Shu Yang , Xiaofei Wang

External control arms can inform early clinical development of experimental drugs and provide efficacy evidence for regulatory approval. However, accessing sufficient real-world or historical clinical trials data is challenging. Indeed,…

Evidence syntheses and meta-analyses are used to inform clinical practice guidelines and health economic evaluations. However, heterogeneity of treatment effects poses a significant challenge. Conventional meta-analysis addresses…

The recent 21st Century Cures Act propagates innovations to accelerate the discovery, development, and delivery of 21st century cures. It includes the broader application of Bayesian statistics and the use of evidence from clinical…

Applications · Statistics 2020-02-10 Satrajit Roychoudhury , Beat Neuenschwander

BACKGROUND: Random-effects meta-analysis within a hierarchical normal modeling framework is commonly implemented in a wide range of evidence synthesis applications. More general problems may even be tackled when considering meta-regression…

Computation · Statistics 2022-12-27 Christian Röver , Tim Friede

Context: Indirect treatment comparisons (ITC) are essential when direct head-to-head evidence is unavailable. Their reliability depends on rigorous methodological choices and careful assessment of underlying assumptions. Appropriate…

Methodology · Statistics 2026-05-12 Louise Baschet , Ana Jarne , Matthias Monnereau , Clémence Fradet , Axel Benoist

Subgroup analyses within randomized controlled trials are often underpowered due to limited sample sizes. We address this challenge by leveraging trial participants outside the subgroup of interest to augment estimation within the subgroup.…

Methodology · Statistics 2026-05-18 Sky Qiu , Nerissa Nance , Rachael Phillips , Jens Tarp , Maya Petersen , Mark van der Laan

Estimating causal effects on time-to-event outcomes from observational data is particularly challenging due to censoring, limited sample sizes, and non-random treatment assignment. The need for answering such "when-if" questions--how the…

Machine Learning · Computer Science 2025-11-19 Jessy Xinyi Han , Devavrat Shah

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

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…

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