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Randomized controlled trials are considered the gold standard to evaluate the treatment effect (estimand) for efficacy and safety. According to the recent International Council on Harmonisation (ICH)-E9 addendum (R1), intercurrent events…

Methodology · Statistics 2021-11-24 Junxiang Luo , Stephen J. Ruberg , Yongming Qu

Observational studies can play a useful role in assessing the comparative effectiveness of competing treatments. In a clinical trial the randomization of participants to treatment and control groups generally results in well-balanced groups…

In time-to-event settings, the presence of competing events complicates the definition of causal effects. Here we propose the new separable effects to study the causal effect of a treatment on an event of interest. The separable direct…

The synthetic control (SC) method is a popular approach for estimating treatment effects from observational panel data. It rests on a crucial assumption that we can write the treated unit as a linear combination of the untreated units. This…

Methodology · Statistics 2023-02-27 Achille Nazaret , Claudia Shi , David M. Blei

Semi-competing risks refer to the phenomenon that the terminal event (such as death) can censor the non-terminal event (such as disease progression) but not vice versa. The treatment effect on the terminal event can be delivered either…

Methodology · Statistics 2024-10-10 Yuhao Deng , Yi Wang , Xiao-Hua Zhou

Estimating heterogeneous treatment effects with machine learning has attracted substantial attention in both academic research and industrial practice. However, the two communities often evaluate models under markedly different conditions.…

Machine Learning · Computer Science 2026-05-26 George Panagopoulos

In the first stage of a two-stage study, the researcher uses a statistical model to impute the unobserved exposures. In the second stage, imputed exposures serve as covariates in epidemiological models. Imputation error in the first stage…

Applications · Statistics 2021-07-19 Ron Sarafian , Itai Kloog , Jonathan D. Rosenblatt

Recent work has focused on nonparametric estimation of conditional treatment effects, but inference has remained relatively unexplored. We propose a class of nonparametric tests for both quantitative and qualitative treatment effect…

Methodology · Statistics 2026-04-07 Oliver Dukes , Mats J. Stensrud , Riccardo Brioschi , Aaron Hudson

Adaptive sample size re-estimation, early stopping, and trial re-design at interim analyses can reduce expected sample sizes in randomised trials. Cluster randomised trials, in which groups of participants are randomly allocated to…

Methodology · Statistics 2026-03-09 Samuel I. Watson , James Martin

The recently published ICH E9 addendum on estimands in clinical trials provides a framework for precisely defining the treatment effect that is to be estimated, but says little about estimation methods. Here we report analyses of a clinical…

Applications · Statistics 2023-09-25 Camila Olarte Parra , Rhian M. Daniel , David Wright , Jonathan W. Bartlett

Survival time is the primary endpoint of many randomized controlled trials, and a treatment effect is typically quantified by the hazard ratio under the assumption of proportional hazards. Awareness is increasing that in many settings this…

Methodology · Statistics 2023-10-04 Robin Ristl , Heiko Götte , Armin Schüler , Martin Posch , Franz König

Recently, there has been a surge in methodological development for the difference-in-differences (DiD) approach to evaluate causal effects. Standard methods in the literature rely on the parallel trends assumption to identify the average…

Methodology · Statistics 2023-10-17 Pan Zhao , Yifan Cui

Two problems that arise in making causal inferences for non-mortality outcomes such as bronchopulmonary dysplasia (BPD) are unmeasured confounding and censoring by death, i.e., the outcome is only observed when subjects survive. In…

Methodology · Statistics 2018-02-20 Kwonsang Lee , Scott A. Lorch , Dylan S. Small

Differences-in-differences (DiD) is a causal inference method for observational longitudinal data that assumes parallel expected potential outcome trajectories between treatment groups under the counterfactual scenario where all units…

Methodology · Statistics 2026-05-12 Michael Jetsupphasuk , Didong Li , Michael G. Hudgens

In this paper we present two strategies to enable "parallelization across the method" for spectral deferred corrections (SDC). Using standard low-order time-stepping methods in an iterative fashion, SDC can be seen as preconditioned Picard…

Numerical Analysis · Mathematics 2017-03-24 Robert Speck

The difference-in-differences (DID) design is one of the most popular methods used in empirical economics research. However, there is almost no work examining what the DID method identifies in the presence of a misclassified treatment…

Econometrics · Economics 2026-05-01 Augustine Denteh , Désiré Kédagni

The triple-differences (TD) design is a popular identification strategy for causal effects in settings where researchers do not believe the parallel trends assumption of conventional difference-in-differences (DiD) is satisfied. TD designs…

Methodology · Statistics 2023-07-11 Anton Strezhnev

Beyond conditional average treatment effects, treatments may impact the entire outcome distribution in covariate-dependent ways, for example, by altering the variance or tail risks for specific subpopulations. We propose a novel estimand to…

Machine Learning · Statistics 2026-03-18 Saksham Jain , Alex Luedtke

The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…

Methodology · Statistics 2025-09-03 Wei Zhang , Zhiwei Zhang , Aiyi Liu

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
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