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A simple device for balancing for a continuous covariate in clinical trials is to stratify by whether the covariate is above or below some target value, typically the predicted median. This raises an issue as to which model should be used…

Methodology · Statistics 2025-10-24 Stephen Senn , Franz König , Martin Posch

Identifying covariates that modify treatment effects is a central problem in causal inference. Yet existing data-adaptive procedures do not provide finite-sample control over the expected number of false discoveries, risking spurious…

Methodology · Statistics 2026-05-12 Falco J. Bargagli-Stoffi , Omar Melikechi

Estimation of treatment effect for principal strata has been studied for more than two decades. Existing research exclusively focuses on the estimation, but there is little research on forming and testing hypotheses for principal…

Methodology · Statistics 2021-12-20 Yongming Qu , Stephen J. Ruberg , Junxiang Luo , Ilya Lipkovich

Estimating treatment effects for subgroups defined by post-treatment behavior (i.e., estimating causal effects in a principal stratification framework) can be technically challenging and heavily reliant on strong assumptions. We investigate…

Methodology · Statistics 2017-08-17 Luke Miratrix , Jane Furey , Avi Feller , Todd Grindal , Lindsay C. Page

A surrogate endpoint S in a clinical trial is an outcome that may be measured earlier or more easily than the true outcome of interest T. In this work, we extend causal inference approaches to validate such a surrogate using potential…

Methodology · Statistics 2022-02-04 Emily Roberts , Michael Elliott , Jeremy M. G. Taylor

Clinical trials often allow patients in the control arm to switch to the treatment arm if their physical conditions are worse than certain tolerance levels. For instance, treatment switching arises in the Concorde clinical trial, which aims…

Applications · Statistics 2023-09-06 Alessandra Mattei , Peng Ding , Veronica Ballerini , Fabrizia Mealli

Regression discontinuity designs are widely used when treatment assignment is determined by whether a running variable exceeds a predefined threshold. However, most research focuses on estimating local causal effects at the threshold,…

Methodology · Statistics 2025-01-06 Xinqin Feng , Wenjie Hu , Pu Yang , Tingyu Li , Xiao-Hua Zhou

This paper studies inference in randomized controlled trials with covariate-adaptive randomization when there are multiple treatments. More specifically, we study inference about the average effect of one or more treatments relative to…

Econometrics · Economics 2019-01-21 Federico A. Bugni , Ivan A. Canay , Azeem M. Shaikh

Randomized clinical trials typically aim to estimate a marginal treatment effect. While covariate adjustment can improve precision, it may change the estimand in nonlinear models due to noncollapsibility, leading to conditional rather than…

Methodology · Statistics 2026-05-25 Leticia Wuethrich , Torsten Hothorn

The analysis of natural direct and principal stratum direct effects has a controversial history in statistics and causal inference as these effects are commonly identified with either untestable cross world independence or graphical…

Statistics Theory · Mathematics 2020-05-13 Jaffer M. Zaidi , Tyler J. VanderWeele

We consider continuous-time survival or more general event-history settings, where the aim is to infer the causal effect of a time-dependent treatment process. This is formalised as the effect on the outcome event of a (possibly…

Methodology · Statistics 2024-04-23 Kjetil Røysland , Pål Ryalen , Mari Nygård , Vanessa Didelez

The participants in randomized trials and other studies used for causal inference are often not representative of the populations seen by clinical decision-makers. To account for differences between populations, researchers may consider…

Methodology · Statistics 2022-07-12 Anders Huitfeldt , Sonja A. Swanson , Mats Julius Stensrud , Etsuji Suzuki

In multicenter randomized trials, when effect modifiers have a different distribution across centers, comparisons between treatment groups that average over centers may not apply to any of the populations underlying the individual centers.…

We investigate the bounding problem of causal effects in experimental studies in which the outcome is truncated by death, meaning that the subject dies before the outcome can be measured. Causal effects cannot be point identified without…

Methodology · Statistics 2024-04-29 Aixian Chen , Xia Cui , Guangren Yang

This research was motivated by studying anti-drug antibody (ADA) formation and its potential impact on long-term benefit of a biologic treatment in a randomized controlled trial, in which ADA status was not only unobserved in the control…

Methodology · Statistics 2021-01-13 Shengchun Kong , Dominik Heinzmann , Sabine Lauer , Tian Lu

Estimating the long-term effects of treatments is of interest in many fields. A common challenge in estimating such treatment effects is that long-term outcomes are unobserved in the time frame needed to make policy decisions. One approach…

Methodology · Statistics 2024-08-23 Susan Athey , Raj Chetty , Guido Imbens , Hyunseung Kang

The International Council for Harmonization (ICH) E9 (R1) addendum provides the estimand framework to formulate treatment effects in a clinical trial. One of the attributes of an estimand the framework describes is intercurrent events.…

This paper provides a new approach for identifying and estimating the Average Treatment Effect on the Treated under a linear factor model that allows for multiple time-varying unobservables. Unlike the majority of the literature on…

Econometrics · Economics 2025-03-28 Koki Fusejima , Takuya Ishihara

The hypothesis of homogeneous treatment effects is central to the instrumental variables literature. This assumption signifies that treatment effects are constant across all subjects. It allows to interpret instrumental variable estimates…

Econometrics · Economics 2023-04-17 Jad Beyhum , Jean-Pierre Florens , Elia Lapenta , Ingrid Van Keilegom

The sufficient cause framework has been used for decades to improve our understanding of both basic and more complex causal concepts in epidemiology, such as mediation and interaction. Here, we make use of this framework to provide a…

Methodology · Statistics 2026-04-08 Bronner P. Gonçalves , Eiji Yamamoto , Etsuji Suzuki