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Benkeser et al. demonstrate how adjustment for baseline covariates in randomized trials can meaningfully improve precision for a variety of outcome types. Their findings build on a long history, starting in 1932 with R.A. Fisher and…

Methodology · Statistics 2026-03-03 Laura B. Balzer , Erica Cai , Lucas Godoy Garraza , Pracheta Amaranath

In multiple testing several criteria to control for type I errors exist. The false discovery rate, which evaluates the expected proportion of false discoveries among the rejected null hypotheses, has become the standard approach in this…

Methodology · Statistics 2023-11-03 Jacobo de Uña-Álvarez

In large scale genetic association studies, a primary aim is to test for association between genetic variants and a disease outcome. The variants of interest are often rare, and appear with low frequency among subjects. In this situation,…

Methodology · Statistics 2017-12-20 Arjun Sondhi , Kenneth Martin Rice

Multiple imputation (MI) has become popular for analyses with missing data in medical research. The standard implementation of MI is based on the assumption of data being missing at random (MAR). However, for missing data generated by…

Methodology · Statistics 2019-01-03 Tra My Pham , James R Carpenter , Tim P Morris , Angela M Wood , Irene Petersen

This paper proposes a novel criterion for the allocation of patients in Phase~I dose-escalation clinical trials aiming to find the maximum tolerated dose (MTD). Conventionally, using a model-based approach the next patient is allocated to…

Methodology · Statistics 2018-07-17 Pavel Mozgunov , Thomas Jaki

Historical data about disease outcomes can be integrated into the analysis of clinical trials in many ways. We build on existing literature that uses prognostic scores from a predictive model to increase the efficiency of treatment effect…

Methodology · Statistics 2020-12-25 David Walsh , Alejandro Schuler , Diana Hall , Jon Walsh , Charles Fisher

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…

Identifying subgroups of patients with an enhanced response to a new treatment has become an area of increased interest in the last few years. When there is knowledge about possible subpopulations with an enhanced treatment effect before…

Methodology · Statistics 2018-11-27 Marius Thomas , Björn Bornkamp , Martin Posch , Franz König

There is growing interest in platform trials that allow for adding of new treatment arms as the trial progresses as well as being able to stop treatments part way through the trial for either lack of benefit/futility or for superiority. In…

Methodology · Statistics 2021-12-14 Peter Greenstreet , Thomas Jaki , Alun Bedding , Chris Harbron , Pavel Mozgunov

Simultaneous statistical inference has been a cornerstone in the statistics methodology literature because of its fundamental theory and paramount applications. The mainstream multiple testing literature has traditionally considered two…

Statistics Theory · Mathematics 2025-03-21 Monitirtha Dey , Subir Kumar Bhandari

We address the problem of correcting group discriminations within a score function, while minimizing the individual error. Each group is described by a probability density function on the set of profiles. We first solve the problem…

Artificial Intelligence · Computer Science 2018-06-11 El Mahdi El Mhamdi , Rachid Guerraoui , Lê Nguyên Hoang , Alexandre Maurer

Nonlinear longitudinal proportional effect models have been proposed to improve power and provide direct estimates of the proportional treatment effect in randomized clinical trials. These models assume a fixed proportional treatment effect…

Methodology · Statistics 2026-01-23 Michael C. Donohue , Philip S. Insel , Oliver Langford

Generalized linear mixed models (GLMM) are commonly used to analyze clustered data, but when the number of clusters is small to moderate, standard statistical tests may produce elevated type I error rates. Small-sample corrections have been…

Methodology · Statistics 2023-11-07 Hongxiang Qiu , Andrea J. Cook , Jennifer F. Bobb

This paper presents a survey on some recent advances for the type I error rate control in multiple testing methodology. We consider the problem of controlling the $k$-family-wise error rate (kFWER, probability to make $k$ false discoveries…

Methodology · Statistics 2011-03-15 Etienne Roquain

There is tremendous interest in precision medicine as a means to improve patient outcomes by tailoring treatment to individual characteristics. An individualized treatment rule formalizes precision medicine as a map from patient information…

Machine Learning · Statistics 2020-05-28 Daniel J. Luckett , Eric B. Laber , Michael R. Kosorok

Group sequential designs in clinical trials allow for interim efficacy and futility monitoring. Adjustment for baseline covariates can increase power and precision of estimated effects. However, inconsistently applying covariate adjustment…

Methodology · Statistics 2023-08-11 Marlena S. Bannick , Sonya L. Heltshe , Noah Simon

When the distribution of treatment effect modifiers differs between the trial sample and target population, inverse probability weighting (IPSW) can be applied to achieve an unbiased estimate of the population average treatment effect in…

Applications · Statistics 2022-03-04 Albee Y. Ling , Maria E. Montez-Rath , Kris Kapphahn , Manisha Desai

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

An important objective in the development of targeted therapies is to identify the populations where the treatment under consideration has positive benefit risk balance. We consider pivotal clinical trials, where the efficacy of a treatment…

I introduce a simple permutation procedure to test conventional (non-sharp) hypotheses about the effect of a binary treatment in the presence of a finite number of large, heterogeneous clusters when the treatment effect is identified by…

Econometrics · Economics 2023-02-08 Andreas Hagemann