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When making treatment selection decisions, it is essential to include a causal effect estimation analysis to compare potential outcomes under different treatments or controls, assisting in optimal selection. However, merely estimating…

Machine Learning · Statistics 2024-10-08 Sherly Alfonso-Sánchez , Kristina P. Sendova , Cristián Bravo

Cluster-randomized trials (CRTs) are widely used to evaluate group-level interventions and increasingly collect multiple outcomes capturing complementary dimensions of benefit and risk. Investigators often seek a single global summary of…

Methodology · Statistics 2026-01-22 Xinyuan Chen , Fan Li

Estimating treatment effects conditional on observed covariates can improve the ability to tailor treatments to particular individuals. Doing so effectively requires dealing with potential confounding, and also enough data to adequately…

Although randomized controlled trials have long been regarded as the ``gold standard'' for evaluating treatment effects, there is no natural prevention from post-treatment events. For example, non-compliance makes the actual treatment…

Methodology · Statistics 2025-04-25 Qinqing Liu , Xiang Peng , Tao Zhang , Yuhao Deng

Recent research in causal inference has made important progress in addressing challenges to the external validity of trial findings. Such methods weight trial participant data to more closely resemble the distribution of effect-modifying…

Methodology · Statistics 2024-07-18 Justin M. Clark , Kollin W. Rott , James S. Hodges , Jared D. Huling

There has been a growing interest in covariate adjustment in the analysis of randomized controlled trials in past years. For instance, the U.S. Food and Drug Administration recently issued guidance that emphasizes the importance of…

Methodology · Statistics 2023-06-12 Kelly Van Lancker , Frank Bretz , Oliver Dukes

The proximal causal inference framework enables the identification and estimation of causal effects in the presence of unmeasured confounding by leveraging two disjoint sets of observed strong proxies: negative control treatments and…

Methodology · Statistics 2025-12-16 Antonio Olivas-Martinez , Peter B. Gilbert , Andrea Rotnitzky

Intercurrent (post-treatment) events occur frequently in randomized trials, and investigators often express interest in treatment effects that suitably take account of these events. A naive conditioning on intercurrent events does not have…

Methodology · Statistics 2021-11-17 Mats J. Stensrud , Oliver Dukes

Pragmatic clinical trials evaluate the effectiveness of health interventions in real-world settings. Negative spillover can arise in a pragmatic trial if the study intervention affects how scarce resources are allocated between patients in…

Methodology · Statistics 2024-12-20 Sean Mann

The call for patient-focused drug development is loud and clear, as expressed in the 21st Century Cures Act and in recent guidelines and initiatives of regulatory agencies. Among the factors contributing to modernized drug development and…

Experimentation is widely utilized for causal inference and data-driven decision-making across disciplines. In an A/B experiment, for example, an online business randomizes two different treatments (e.g., website designs) to their customers…

Methodology · Statistics 2025-01-15 Wenxuan Guo , JungHo Lee , Panos Toulis

Uncertainty quantification of causal effects is crucial for safety-critical applications such as personalized medicine. A powerful approach for this is conformal prediction, which has several practical benefits due to model-agnostic…

Machine Learning · Computer Science 2026-02-04 Maresa Schröder , Dennis Frauen , Jonas Schweisthal , Konstantin Heß , Valentyn Melnychuk , Stefan Feuerriegel

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…

Applied researchers in biomedicine and related fields are often interested in estimating the causal effect of a treatment or intervention. Although randomized clinical trials are considered the gold standard for establishing causal effects,…

Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical…

Applications · Statistics 2016-06-22 Elias Chaibub Neto

Randomized trials are often conducted with separate randomizations across multiple sites such as schools, voting districts, or hospitals. These sites can differ in important ways, including the site's implementation, local conditions, and…

Methodology · Statistics 2018-03-19 Lo-Hua Yuan , Avi Feller , Luke W. Miratrix

A platform trial is an innovative clinical trial design that uses a master protocol to evaluate multiple treatments, where patients are often assigned to different subsets of treatment arms based on individual characteristics, enrollment…

Randomized trials balance all covariates on average and provide the gold standard for estimating treatment effects. Chance imbalances nevertheless exist more or less in realized treatment allocations and intrigue an important question: what…

Methodology · Statistics 2023-07-18 Anqi Zhao , Peng Ding

When considering the effect a treatment will cause in a population of interest, we often look to evidence from randomized controlled trials. In settings where multiple trials on a treatment are available, we may wish to synthesize the…

Methodology · Statistics 2023-09-08 Nicole Schnitzler , Eloise Kaizar

In many clinical trials, individuals in different subgroups have experience differential treatment effects. This leads to individualized differences in treatment benefit. In this article, we introduce the general concept of predictive…

Methodology · Statistics 2018-07-11 Debashis Ghosh , Youngjoo Cho