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Consider a situation with two treatments, the first of which is randomized but the second is not, and the multifactor version of this. Interest is in treatment effects, defined using standard factorial notation. We define estimators for the…

The interpretation of randomised clinical trial results is often complicated by intercurrent events. For instance, rescue medication is sometimes given to patients in response to worsening of their disease, either in addition to the…

Methodology · Statistics 2021-02-12 Hege Michiels , Cristina Sotto , An Vandebosch , Stijn Vansteelandt

In cluster-randomized trials (CRTs), entire clusters of individuals are randomized to treatment, and outcomes within a cluster are typically correlated. While frequentist approaches are standard practice for CRT analysis, Bayesian methods…

Methodology · Statistics 2025-11-27 Ruyi Liu , Joshua L. Warren , Yuki Ohnishi , Donna Spiegelman , Liangyuan Hu , Fan Li

Case-control designs are an important tool in contrasting the effects of well-defined treatments. In this paper, we reconsider classical concepts, assumptions and principles and explore when the results of case-control studies can be…

Methodology · Statistics 2021-05-06 Bas B. L. Penning de Vries , Rolf H. H. Groenwold

In cluster randomized trials, the average treatment effect among individuals (i-ATE) can be different from the cluster average treatment effect (c-ATE) when informative cluster size is present, i.e., when treatment effects or participant…

Methodology · Statistics 2025-10-02 Bryan S. Blette , Zhe Chen , Brennan C. Kahan , Andrew Forbes , Michael O. Harhay , Fan Li

Treatment effect estimation is a fundamental problem in causal inference. We focus on designing efficient randomized controlled trials, to accurately estimate the effect of some treatment on a population of $n$ individuals. In particular,…

Machine Learning · Computer Science 2022-10-14 Raghavendra Addanki , David Arbour , Tung Mai , Cameron Musco , Anup Rao

When studying treatment effects in multilevel studies, investigators commonly use (semi-)parametric estimators, which make strong parametric assumptions about the outcome, the treatment, and/or the correlation structure between study units…

Methodology · Statistics 2022-05-12 Chan Park , Hyunseung Kang

We consider a potential outcomes model in which interference may be present between any two units but the extent of interference diminishes with spatial distance. The causal estimand is the global average treatment effect, which compares…

Methodology · Statistics 2022-09-16 Michael P. Leung

In studies of discrimination, researchers often seek to estimate a causal effect of race or gender on outcomes. For example, in the criminal justice context, one might ask whether arrested individuals would have been subsequently charged or…

Methodology · Statistics 2022-04-06 Johann Gaebler , William Cai , Guillaume Basse , Ravi Shroff , Sharad Goel , Jennifer Hill

In a completely randomized experiment, the variances of treatment effect estimators in the finite population are usually not identifiable and hence not estimable. Although some estimable bounds of the variances have been established in the…

Statistics Theory · Mathematics 2022-09-20 Ruoyu Wang , Qihua Wang , Wang Miao , Xiaohua Zhou

In experiments that study social phenomena, such as peer influence or herd immunity, the treatment of one unit may influence the outcomes of others. Such "interference between units" violates traditional approaches for causal inference, so…

Methodology · Statistics 2023-08-30 David Choi

Composite endpoints are increasingly used in clinical trials to capture treatment effects across multiple or hierarchically ordered outcomes. Although inference procedures based on win statistics, such as the win ratio, win odds, and net…

Methodology · Statistics 2025-10-28 Xi Fang , Zhiqiang Cao , Fan Li

Causal identification of treatment effects for infectious disease outcomes in interconnected populations is challenging because infection outcomes may be transmissible to others, and treatment given to one individual may affect others'…

Methodology · Statistics 2021-05-11 Xiaoxuan Cai , Eben Kenah , Forrest W. Crawford

Estimating the causal effect of a treatment or health policy with observational data can be challenging due to an imbalance of and a lack of overlap between treated and control covariate distributions. In the presence of limited overlap,…

Methodology · Statistics 2025-03-24 Martha Barnard , Jared D. Huling , Julian Wolfson

RCTs sometimes test interventions that aim to improve existing services targeted to a subset of individuals identified after randomization. Accordingly, the treatment could affect the composition of service recipients and the offered…

Methodology · Statistics 2022-05-18 Peter Z. Schochet

The estimand framework included in the addendum to the ICH E9 guideline facilitates discussions to ensure alignment between the key question of interest, the analysis, and interpretation. Therapeutic knowledge and drug mechanism play a…

Other Quantitative Biology · Quantitative Biology 2023-04-17 Steven Sun , Hans-Jochen Weber , Emily Butler , Kaspar Rufibach , Satrajit Roychoudhury

We establish the inferential properties of the mean-difference estimator for the average treatment effect in randomized experiments where each unit in a population is randomized to one of two treatments and then units within treatment…

Statistics Theory · Mathematics 2019-02-19 Zach Branson , Tirthankar Dasgupta

The parallel cluster randomized trial with baseline (PB-CRT) is a common variant of the standard parallel cluster randomized trial (P-CRT). We define two natural estimands in the context of PB-CRTs with informative cluster sizes, the…

Methodology · Statistics 2025-05-01 Kenneth Menglin Lee , Fan Li

Causal mediation analysis in cluster-randomized trials (CRTs) is complicated by the presence of multiple mediators, intracluster correlation, and within-cluster interference. Existing mediation methods often fall short in accommodating…

Methodology · Statistics 2026-04-14 Jiaqi Tong , Chao Cheng , Fan Li

We investigate large-sample properties of treatment effect estimators under unknown interference in randomized experiments. The inferential target is a generalization of the average treatment effect estimand that marginalizes over potential…

Statistics Theory · Mathematics 2019-10-25 Fredrik Sävje , Peter M. Aronow , Michael G. Hudgens