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Clinical trials with longitudinal outcomes typically include missing data due to missed assessments or structural missingness of outcomes after intercurrent events handled with a hypothetical strategy. Approaches based on Bayesian random…

Multiple imputation is a well-established general technique for analyzing data with missing values. A convenient way to implement multiple imputation is sequential regression multiple imputation (SRMI), also called chained equations…

The use of flexible machine-learning (ML) models to generate imputations of missing data within the framework of Multiple Imputation (MI) has recently gained traction, particularly in observational settings. For randomised controlled trials…

Methodology · Statistics 2025-10-07 Mia S. Tackney , Jonathan W. Bartlett , Elizabeth Williamson , Kim May Lee

Background: Existing guidelines for handling missing data are generally not consistent with the goals of prediction modelling, where missing data can occur at any stage of the model pipeline. Multiple imputation (MI), often heralded as the…

Methodology · Statistics 2022-06-27 Rose Sisk , Matthew Sperrin , Niels Peek , Maarten van Smeden , Glen P. Martin

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

Missing data on response variables are common in clinical studies. Corresponding to the uncertainty of missing mechanism, theoretical frameworks on controlled imputation have been developed. In practice, it is recommended to conduct a…

Methodology · Statistics 2022-03-08 Tony Wang , Ying Liu

A standard assumption for causal inference about the joint effects of time-varying treatment is that one has measured sufficient covariates to ensure that within covariate strata, subjects are exchangeable across observed treatment values,…

Methodology · Statistics 2022-08-04 Andrew Ying , Wang Miao , Xu Shi , Eric J. Tchetgen Tchetgen

When studying the association between treatment and a clinical outcome, a parametric multivariable model of the conditional outcome expectation is often used to adjust for covariates. The treatment coefficient of the outcome model targets a…

Methodology · Statistics 2026-05-07 Antonio Remiro-Azócar , Anna Heath , Gianluca Baio

Simulation-Based Inference (SBI) is an approach to statistical inference where simulations from an assumed model are used to construct estimators and confidence sets. SBI is often used when the likelihood is intractable and to construct…

Methodology · Statistics 2025-08-05 Lorenzo Tomaselli , Valérie Ventura , Larry Wasserman

Multiple imputation (MI) is a method for repairing and analyzing data with missing values. MI replaces missing values with a sample of random values drawn from an imputation model. The most popular form of MI, which we call posterior draw…

Methodology · Statistics 2019-11-18 Paul T. von Hippel , Jonathan Bartlett

Longitudinal studies are frequently used in medical research and involve collecting repeated measures on individuals over time. Observations from the same individual are invariably correlated and thus an analytic approach that accounts for…

In many clinical trials, outcomes of interest include binary-valued endpoints. It is not uncommon that a binary-valued outcome is dichotomized from a continuous outcome at a threshold of clinical interest. To reach the objective, common…

Applications · Statistics 2021-08-05 Chenchen Ma , Xin Shen , Yongming Qu , Yu Du

Negative controls are increasingly used to evaluate the presence of potential unmeasured confounding in observational studies. Beyond the use of negative controls to detect the presence of residual confounding, proximal causal inference…

Methodology · Statistics 2024-06-06 Jiewen Liu , Chan Park , Kendrick Li , Eric J. Tchetgen Tchetgen

Use of prediction models is widely recommended by clinical guidelines, but usually requires complete information on all predictors that is not always available in daily practice. We describe two methods for real-time handling of missing…

Missing covariate data commonly occur in epidemiological and clinical research, and are often dealt with using multiple imputation (MI). Imputation of partially observed covariates is complicated if the substantive model is non-linear (e.g.…

Methodology · Statistics 2014-02-17 Jonathan W. Bartlett , Shaun R. Seaman , Ian R. White , James R. Carpenter

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

Missing data is unavoidable in longitudinal clinical trials, and outcomes are not always normally distributed. In the presence of outliers or heavy-tailed distributions, the conventional multiple imputation with the mixed model with…

Methodology · Statistics 2022-03-22 Siyi Liu , Yilong Zhang , Gregory T Golm , Guanghan , Liu , Shu Yang

Multiple imputation (MI) is an established technique to handle missing data in observational studies. Joint modeling (JM) and fully conditional specification (FCS) are commonly used methods for imputing multilevel clustered data. However,…

Methodology · Statistics 2022-09-28 Mei Dong , Aya Mitani

Selective inference aims at providing valid inference after a data-driven selection of models or hypotheses. It is essential to avoid overconfident results and replicability issues. While significant advances have been made in this area for…

Methodology · Statistics 2025-03-14 Matteo D'Alessandro , Magne Thoresen

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
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