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The estimands framework outlined in ICH E9 (R1) describes the components needed to precisely define the effects to be estimated in clinical trials, which includes how post-baseline "intercurrent" events (IEs) are to be handled. In…

Methodology · Statistics 2023-08-28 Thomas Drury , Juan J Abellan , Nicky Best , Ian R. White

Methods to handle missing data have been extensively explored in the context of estimation and descriptive studies, with multiple imputation being the most widely used method in clinical research. However, in the context of clinical risk…

Methodology · Statistics 2024-11-25 Junhui Mi , Rahul D. Tendulkar , Sarah M. C. Sittenfeld , Sujata Patil , Emily C. Zabor

Population adjustment methods such as matching-adjusted indirect comparison (MAIC) are increasingly used to compare marginal treatment effects when there are cross-trial differences in effect modifiers and limited patient-level data. MAIC…

Methodology · Statistics 2022-05-12 Antonio Remiro-Azócar , Anna Heath , Gianluca Baio

Multiple imputation has become one of the standard methods in drawing inferences in many incomplete data applications. Applications of multiple imputation in relatively more complex settings, such as high-dimensional clustered data, require…

Methodology · Statistics 2025-04-08 Qiushuang Li , Recai Yucel

Estimating causal effects in a target population with unmeasured confounders is challenging, especially when instrumental variables (IVs) are unavailable. However, IVs from auxiliary populations with similar problems can help infer causal…

Methodology · Statistics 2025-08-06 Wei Li , Jiapeng Liu , Peng Ding , Zhi Geng

Interventional effects have been proposed as a solution to the unidentifiability of natural (in)direct effects under mediator-outcome confounders affected by the exposure. Such confounders are an intrinsic characteristic of studies with…

Methodology · Statistics 2022-03-30 Iván Díaz , Nicholas Williams , Kara E. Rudolph

Missing data is a significant problem impacting all domains. State-of-the-art framework for minimizing missing data bias is multiple imputation, for which the choice of an imputation model remains nontrivial. We propose a multiple…

Machine Learning · Computer Science 2018-02-20 Lovedeep Gondara , Ke Wang

Understanding the pathways whereby an intervention has an effect on an outcome is a common scientific goal. A rich body of literature provides various decompositions of the total intervention effect into pathway specific effects.…

Methodology · Statistics 2020-01-20 David Benkeser

Mediation analysis is an important analytic tool commonly used in a broad range of scientific applications. In this article, we study the problem of mediation analysis when there are multivariate and conditionally dependent mediators, and…

Methodology · Statistics 2025-01-28 Lan Luo , Chengchun Shi , Jitao Wang , Zhenke Wu , Lexin Li

The task of inferring high-level causal variables from low-level observations, commonly referred to as causal representation learning, is fundamentally underconstrained. As such, recent works to address this problem focus on various…

Machine Learning · Statistics 2024-03-26 Simon Bing , Urmi Ninad , Jonas Wahl , Jakob Runge

Missing values in electronic health record (EHR) data pose a significant challenge for epidemiologic research. Traditional methods for handling missing data, like mean imputation, may introduce bias. Multiple imputation (MI) offers a…

Analyses of causal mediation often involve exposure-induced confounders or, relatedly, multiple mediators. In such applications, researchers aim to estimate a variety of different quantities, including interventional direct and indirect…

Methodology · Statistics 2025-06-18 Jesse Zhou , Geoffrey T. Wodtke

Intensive longitudinal data, characterized by frequent measurements across numerous time points, are increasingly common due to advances in wearable devices and mobile health technologies. We consider evaluating causal mediation pathways…

Methodology · Statistics 2025-06-26 Tianchen Qian

Missing data are ubiquitous in empirical databases, yet statistical analyses typically require complete data matrices. Multiple imputation offers a principled solution for filling these gaps. This study evaluates the performance of several…

Computation · Statistics 2026-02-05 Enzo Porto Brasil

Attrition is a common occurrence in cluster randomised trials (CRTs) which leads to missing outcome data. Two approaches for analysing such trials are cluster-level analysis and individual-level analysis. This paper compares the performance…

Methodology · Statistics 2016-03-15 Anower Hossain , Karla Diaz-Ordaz , Jonathan W. Bartlett

This paper combines causal mediation analysis with double machine learning to control for observed confounders in a data-driven way under a selection-on-observables assumption in a high-dimensional setting. We consider the average indirect…

Econometrics · Economics 2021-02-17 Helmut Farbmacher , Martin Huber , Lukáš Lafférs , Henrika Langen , Martin Spindler

Causal effect estimation from observational data is one of the essential problems in causal inference. However, most estimation methods rely on the strong assumption that all confounders are observed, which is impractical and untestable in…

Methodology · Statistics 2023-02-14 Yubai Yuan , Annie Qu

Introduction In analysis of time-to-event outcomes, a mixture cure (MC) model is preferred over a standard survival model when the sample includes individuals who will never experience the event of interest. Motivated by a cohort study of…

Applications · Statistics 2026-04-02 Changchang Xu , Laurent Briollais , Irene L Andrulis , Shelley B Bull

Multiple imputation (MI) has become one of the main procedures used to treat missing data, but the guidelines from the methodological literature are not easily transferred to multilevel research. For models including random slopes, proper…

Methodology · Statistics 2016-06-30 Simon Grund , Oliver Lüdtke , Alexander Robitzsch

We consider assessing causal mediation in the presence of a post-treatment event (examples include noncompliance, a clinical event, or death). We identify natural mediation effects for the entire study population and for each principal…

Methodology · Statistics 2024-09-13 Chao Cheng , Fan Li