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This paper shows how to use a randomized saturation experimental design to identify and estimate causal effects in the presence of spillovers--one person's treatment may affect another's outcome--and one-sided non-compliance--subjects can…

The estimand framework proposes different strategies to address intercurrent events. The treatment policy strategy seems to be the most favoured as it is closely aligned with the pre-addendum intention-to-treat principle. All data for all…

Methodology · Statistics 2025-07-21 Sunita Rehal , Nicky Best , Sarah Watts , Thomas Drury

In a randomised clinical trial, when the result of the primary endpoint shows a significant benefit, the secondary endpoints are scrutinised to identify additional effects of the treatment. However, this approach entails a risk of…

Randomized experiments can provide unbiased estimates of sample average treatment effects. However, estimates of population treatment effects can be biased when the experimental sample and the target population differ. In this case, the…

Methodology · Statistics 2022-11-10 Wenqi Shi , Xi Lin

Interference arises when an individual's potential outcome depends on the individual treatment level, but also on the treatment level of others. A common assumption in the causal inference literature in the presence of interference is…

Methodology · Statistics 2018-05-15 Georgia Papadogeorgou , Fabrizia Mealli , Corwin M. Zigler

As the COVID-19 pandemic progresses, researchers are reporting findings of randomized trials comparing standard care with care augmented by experimental drugs. The trials have small sample sizes, so estimates of treatment effects are…

Econometrics · Economics 2020-06-02 Charles F. Manski , Aleksey Tetenov

Post-treatment confounding is a common problem in causal inference, including special cases of noncompliance, truncation by death, surrogate endpoint, etc. Principal stratification (Frangakis and Rubin 2002) is a general framework for…

Computation · Statistics 2023-04-07 Bo Liu , Fan Li

The ICH E9 (R1) addendum on estimands, coupled with recent advancements in causal inference, has prompted a shift towards using model-free treatment effect estimands that are more closely aligned with the underlying scientific question.…

Methodology · Statistics 2024-10-11 Stijn Vansteelandt , Kelly Van Lancker

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

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

The primary analysis in two-arm clinical trials usually involves inference on a scalar treatment effect parameter; e.g., depending on the outcome, the difference of treatment-specific means, risk difference, risk ratio, or odds ratio. Most…

Methodology · Statistics 2022-04-25 Anastasios A. Tsiatis , Marie Davidian

In placebo-controlled randomized trials, the post-randomization use of concomitant medications may be higher in the placebo arm than in the treatment arm. This may dilute the full benefits of the randomized drug as estimated by the…

A growing number of researchers are conducting randomized experiments to analyze causal relationships in network settings where units influence one another. A dominant methodology for analyzing these experiments is design-based, leveraging…

Methodology · Statistics 2024-07-30 Ambarish Chattopadhyay , Kosuke Imai , Jose R. Zubizarreta

Understanding treatment effect heterogeneity has become increasingly important in many fields. In this paper we study distributions and quantiles of individual treatment effects to provide a more comprehensive and robust understanding of…

Methodology · Statistics 2026-03-31 Zhe Chen , Xinran Li

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

Clinical trials usually target average treatment effects, but treatment decisions are made for individuals. This tension motivates a common criticism of evidence-based medicine: a treatment that is beneficial on average may be inappropriate…

Applications · Statistics 2026-05-29 Zach Shahn , Mats Stensrud

The creation of the ICH E9 (R1) estimands framework has led to more precise specification of the treatment effects of interest in the design and statistical analysis of clinical trials. However, it is unclear how the new framework relates…

Methodology · Statistics 2024-12-20 Thomas Drury , Jonathan W. Bartlett , David Wright , Oliver N. Keene

A draft addendum to ICH E9 has been released for public consultation in August 2017. The addendum focuses on two topics particularly relevant for randomized confirmatory clinical trials: estimands and sensitivity analyses. The need to amend…

Methodology · Statistics 2023-04-17 Kaspar Rufibach

Trial engagement effects are effects of trial participation on the outcome that are not mediated by treatment assignment. Most work on extending (generalizing or transporting) causal inferences from a randomized trial to a target population…

Methodology · Statistics 2024-07-23 Lawson Ung , Tyler J. VanderWeele , Issa J. Dahabreh

We systematically investigate issues due to mis-specification that arise in estimating causal effects when (treatment) interference is informed by a network available pre-intervention, i.e., in situations where the outcome of a unit may…

Methodology · Statistics 2018-10-22 Vishesh Karwa , Edoardo M. Airoldi
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