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With the evolution of single-cell RNA sequencing techniques into a standard approach in genomics, it has become possible to conduct cohort-level causal inferences based on single-cell-level measurements. However, the individual gene…

Methodology · Statistics 2025-04-23 Jin-Hong Du , Zhenghao Zeng , Edward H. Kennedy , Larry Wasserman , Kathryn Roeder

Identifying prognostic factors for disease progression is a cornerstone of medical research. Repeated assessments of a marker outcome are often used to evaluate disease progression, and the primary research question is to identify factors…

Computation · Statistics 2022-10-24 Brian Kwan , Lin Liu , David Strong , H. Irene Su , Loki Natarajan

Inverse probability of treatment weighting (IPTW) is a popular propensity score (PS)-based approach to estimate causal effects in observational studies at risk of confounding bias. A major issue when estimating the PS is the presence of…

Evaluating heterogeneity of treatment effects (HTE) across subgroups is common in both randomized trials and observational studies. Although several statistical challenges of HTE analyses including low statistical power and multiple…

Methodology · Statistics 2024-07-10 Noorie Hyun , Abisola E. Idu , Andrea J. Cook , Jennifer F. Bobb

This paper presents a simulation study comparing the performance of generalized joint regression models (GJRM) with generalized linear mixed models (GLMM) and generalized estimating equations (GEE) for regression of longitudinal data with…

Methodology · Statistics 2025-11-07 Aydin Sareff-Hibbert , Gillian Z. Heller

General Effect Modelling (GEM) is an umbrella over different methods that utilise effects in the analyses of data with multiple design variables and multivariate responses. To demonstrate the methodology, we here use GEM in gene expression…

Binary endpoints are common in clinical trials and conditional odds ratios have traditionally been used to assess treatment effects. However, the interpretation of odds ratios is difficult, they are non-collapsible and rely on strong…

Methodology · Statistics 2026-05-20 Martin Schnuerch , Alex Ocampo , Klaus Kähler Holst , Christian Stock

In clinical trials, mixed effects models for repeated measures (MMRM) and pattern mixture models (PMM) are often used to analyze longitudinal continuous outcomes. We describe a simple missing data imputation algorithm for the MMRM that can…

Methodology · Statistics 2016-10-13 Yongqiang Tang

Cluster randomization trials commonly employ multiple endpoints. When a single summary of treatment effects across endpoints is of primary interest, global hypothesis testing/effect estimation methods represent a common analysis strategy.…

Methodology · Statistics 2025-05-19 E. Davies Smith , V. Jairath , G. Zou

Generalized linear models, such as logistic regression, are widely used to model the association between a treatment and a binary outcome as a function of baseline covariates. However, the coefficients of a logistic regression model…

Methodology · Statistics 2022-01-04 Jiaqi Yin , Sonia Markes , Thomas S. Richardson , Linbo Wang

In the era of big data, secondary outcomes have become increasingly important alongside primary outcomes. These secondary outcomes, which can be derived from traditional endpoints in clinical trials, compound measures, or risk prediction…

Methodology · Statistics 2025-12-16 Daxuan Deng , Peisong Han , Shuo Chen , Ming Wang , Chixiang Chen

Comparative binary outcome data are of fundamental interest in statistics and are often pooled in meta-analyses. Here we examine the simplest case where for each study there are two patient groups and a binary event of interest, giving rise…

Methodology · Statistics 2018-06-12 Rose Baker , Dan Jackson

Large-scale hypothesis testing has become a ubiquitous problem in high-dimensional statistical inference, with broad applications in various scienfitic disciplines. One relevant application is constituted by imaging mass spectrometry (IMS)…

Methodology · Statistics 2021-08-19 Vladimir Vutov , Thorsten Dickhaus

Model-X approaches to testing conditional independence between a predictor and an outcome variable given a vector of covariates usually assume exact knowledge of the conditional distribution of the predictor given the covariates.…

Methodology · Statistics 2023-02-10 Ziang Niu , Abhinav Chakraborty , Oliver Dukes , Eugene Katsevich

Causal inference on multiple non-independent outcomes raises serious challenges, because multivariate techniques that properly account for the outcome's dependence structure need to be considered. We focus on the case of binary outcomes…

Methodology · Statistics 2018-05-11 Monia Lupparelli , Alessandra Mattei

Composite endpoints that combine multiple outcomes on different scales are common in clinical trials, particularly in chronic conditions. In many of these cases, patients will have to cross a predefined responder threshold in each of the…

Methodology · Statistics 2019-02-20 Martina McMenamin , Jessica K. Barrett , Anna Berglind , James M. S. Wason

Generalized Linear Mixed Models (GLMMs) are widely used for analysing clustered data. One well-established method of overcoming the integral in the marginal likelihood function for GLMMs is penalized quasi-likelihood (PQL) estimation,…

Statistics Theory · Mathematics 2024-05-03 Xu Ning , Francis Hui , Alan Welsh

Linear mixed models (LMMs) are a popular class of methods for analyzing longitudinal and clustered data. However, such models can be sensitive to outliers, and this can lead to biased inference on model parameters and inaccurate prediction…

Methodology · Statistics 2025-03-28 Shonosuke Sugasawa , Francis K. C. Hui , Alan H. Welsh

In precision medicine, Dynamic Treatment Regimes (DTRs) are treatment protocols that adapt over time in response to a patient's observed characteristics. A DTR is a set of decision functions that takes an individual patient's information as…

Methodology · Statistics 2022-03-17 Cong Jiang , Michael Wallace , Mary Thompson

Sequential Multiple-Assignment Randomized Trials (SMARTs) play an increasingly important role in psychological and behavioral health research. This experimental approach enables researchers to answer scientific questions about how to…

Methodology · Statistics 2023-06-21 John J. Dziak , Daniel Almirall , Walter Dempsey , Catherine Stanger , Inbal Nahum-Shani
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