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In epidemiological cohort studies, the relative risk (also known as risk ratio) is a major measure of association to summarize the results of two treatments or exposures. Generally, it measures the relative change in disease risk as a…

Methodology · Statistics 2022-07-05 Gopal Nath , Krishna K. Saha , Suojin Wang

Stepped wedge cluster-randomized trial (CRTs) designs randomize clusters of individuals to intervention sequences, ensuring that every cluster eventually transitions from a control period to receive the intervention under study by the end…

Stepped wedge cluster randomized trials (SW-CRTs) have become increasingly popular and are used for a variety of interventions and outcomes, often chosen for their feasibility advantages. SW-CRTs must account for time trends in the outcome…

Methodology · Statistics 2024-07-16 Lee Kennedy-Shaffer , Victor De Gruttola , Marc Lipsitch

Covariate adjustment can enhance precision and power in clinical trials, yet its application to the win odds remains unclear. The win odds is an extension of the win ratio that counts ties as half a win for the treatment and the control…

Methodology · Statistics 2026-04-08 Cyrill Scheidegger , Simon Wandel , Tobias Mütze

The primary analysis for longitudinal randomized controlled trials (RCTs) often compares treatment groups at the last timepoint, referred to as the landmark time. Assuming data are normally distributed and missing at random, the mixed model…

Methodology · Statistics 2026-03-18 Guangyong Zou , Shi-Fang Qui , Joshua Zou , Emma Davies Smith , Yun-Hee Choi , Yuhan Bi

Randomized clinical trials (RCTs) are widely considered the gold standard for evaluating the effectiveness of new treatments or interventions in drug development. Still, they may not be feasible in certain cases, such as with rare diseases…

Methodology · Statistics 2025-08-05 Di Ran , Fanni Zhang , Sima Shahsavari , Kristine Broglio , Alasdair Henderson , Binbing Yu

Cluster-randomized trials (CRTs) involve randomizing entire groups of participants -- called clusters -- to treatment arms but are often comprised of a limited or fixed number of available clusters. While covariate adjustment can account…

Methodology · Statistics 2022-11-29 Angela Y. Zhu , Nandita Mitra , Karla Hemming , Michael O. Harhay , Fan Li

Cluster randomized trails (CRT) have been widely employed in medical and public health research. Many clinical count outcomes, such as the number of falls in nursing homes, exhibit excessive zero values. In the presence of zero inflation,…

Applications · Statistics 2020-09-23 Zhengyang Zhou , Dateng Li , Song Zhang

This paper studies inference in cluster randomized trials where treatment status is determined according to a "matched pairs" design. Here, by a cluster randomized experiment, we mean one in which treatment is assigned at the level of the…

Econometrics · Economics 2025-08-14 Yuehao Bai , Jizhou Liu , Azeem M. Shaikh , Max Tabord-Meehan

Background: In settings where proof-of-principle trials have succeeded but the effectiveness of different forms of implementation remains uncertain, trials that not only generate information about intervention effects but also provide…

Quantitative Methods · Quantitative Biology 2017-05-16 Guy Harling , Rui Wang , Jukka-Pekka Onnela , Victor De Gruttola

Stepped wedge cluster randomized trials (SW-CRTs) with binary outcomes are increasingly used in prevention and implementation studies. Marginal models represent a flexible tool for analyzing SW-CRTs with population-averaged interpretations,…

Methodology · Statistics 2021-01-05 Fan Li , Hengshi Yu , Paul J. Rathouz , Elizabeth L. Turner , John S. Preisser

Most cluster randomized trials (CRTs) randomize fewer than 30-40 clusters in total. When performing inference for such ``small'' CRTs, it is important to use methods that appropriately account for the small sample size. When the generalized…

Methodology · Statistics 2025-12-01 Shifeng Sun , Xueqi Wang , Zhuoran Hou , Elizabeth L. Turner

In observational studies, adjusting for confounders is required if a treatment comparison is planned. A crude comparison of the primary endpoint without covariate adjustment will suffer from biases, and the addition of regression models…

Methodology · Statistics 2026-02-11 Shiyu Shu , Toshimitsu Hamasaki , Scott Evans , Lauren Komarow , David van Duin , Guoqing Diao

Sample size calculations can be challenging with skewed continuous outcomes in randomized controlled trials (RCTs). Standard t-test-based calculations may require data transformation, which may be difficult before data collection.…

There are multiple cluster randomised trial designs that vary in when the clusters cross between control and intervention states, when observations are made within clusters, and how many observations are made at that time point. Identifying…

Methodology · Statistics 2023-07-20 Samuel I. Watson , Alan Girling , Karla Hemming

Cluster-randomized trials (CRTs) are widely used to evaluate interventions delivered at the clinic, practice, or community level. Although standard analyses typically target average treatment effects, such summaries mask potentially…

Methodology · Statistics 2026-04-16 Changjun Li , Xi Fang , Michael O. Harhay , Andrew B. Forbes , F. Perry Wilson , Guangyu Tong , Fan Li

Quantifying causal effects in the presence of complex and multivariate outcomes remains a key challenge in treatment evaluation. For hierarchical multivariate outcomes, the FDA recommends the Win Ratio and Generalized Pairwise Comparisons…

Methodology · Statistics 2026-03-24 Mathieu Even , Julie Josse

A practical limitation of cluster randomized controlled trials (cRCTs) is that the number of available clusters may be small, resulting in an increased risk of baseline imbalance under simple randomization. Constrained randomization…

Methodology · Statistics 2022-01-19 Yunji Zhou , Elizabeth L. Turner , Ryan A. Simmons , Fan Li

Cluster-level dynamic treatment regimens can be used to guide sequential, intervention or treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level DTR, the…

Methodology · Statistics 2016-07-15 Timothy NeCamp , Amy Kilbourne , Daniel Almirall

The win ratio is a general method of comparing locations of distributions of two independent, ordinal random variables, and it can be estimated without distributional assumptions. In this paper we provide a unified theory of win ratio…