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The estimands framework outlined in ICH E9 (R1) describes the components needed to precisely define the effects to be estimated in clinical trials, which includes how post-baseline "intercurrent" events (IEs) are to be handled. In…

Methodology · Statistics 2023-08-28 Thomas Drury , Juan J Abellan , Nicky Best , Ian R. White

We develop a functional proportional hazards mixture cure (FPHMC) model with scalar and functional covariates measured at the baseline. The mixture cure model, useful in studying populations with a cure fraction of a particular event of…

Methodology · Statistics 2023-03-31 Rahul Ghosal , Marcos Matabuena , Jiajia Zhang

In many clinical trials, outcomes of interest include binary-valued endpoints. It is not uncommon that a binary-valued outcome is dichotomized from a continuous outcome at a threshold of clinical interest. To reach the objective, common…

Applications · Statistics 2021-08-05 Chenchen Ma , Xin Shen , Yongming Qu , Yu Du

Modeling symptom progression to identify informative subjects for a new Huntington's disease clinical trial is problematic since time to diagnosis, a key covariate, can be heavily censored. Imputation is an appealing strategy where censored…

Methodology · Statistics 2025-02-11 Sarah C. Lotspeich , Tanya P. Garcia

Missing values in tabular data restrict the use and performance of machine learning, requiring the imputation of missing values. The most popular imputation algorithm is arguably multiple imputations using chains of equations (MICE), which…

Machine Learning · Computer Science 2022-03-01 Manar D Samad , Sakib Abrar , Norou Diawara

Population adjustment methods such as matching-adjusted indirect comparison (MAIC) are increasingly used to compare marginal treatment effects when there are cross-trial differences in effect modifiers and limited patient-level data. MAIC…

Methodology · Statistics 2022-05-12 Antonio Remiro-Azócar , Anna Heath , Gianluca Baio

Causal analysis based on non-uniform embedding schemes is an important way to detect the underlying interactions between dynamic systems. However, there are still some obstacles to estimate high-dimensional conditional mutual information…

Methodology · Statistics 2020-02-19 Ziyu Jia , Youfang Lin , Zehui Jiao , Yan Ma , Jing Wang

Over the past decade, the use of machine learning (ML) models in healthcare applications has rapidly increased. Despite high performance, modern ML models do not always capture patterns the end user requires. For example, a model may…

The recently published ICH E9 addendum on estimands in clinical trials provides a framework for precisely defining the treatment effect that is to be estimated, but says little about estimation methods. Here we report analyses of a clinical…

Applications · Statistics 2023-09-25 Camila Olarte Parra , Rhian M. Daniel , David Wright , Jonathan W. Bartlett

Hybrid controlled trials (HCTs), which augment randomized controlled trials (RCTs) with external controls (ECs), are increasingly receiving attention as a way to address limited power, slow accrual, and ethical concerns in clinical…

Methodology · Statistics 2025-05-02 Jiajun Liu , Ke Zhu , Shu Yang , Xiaofei Wang

The Binary Emax model is widely employed in dose-response analysis during drug development, where missing data often pose significant challenges. Addressing nonignorable missing binary responses, where the likelihood of missing data is…

Methodology · Statistics 2026-01-01 Jiangshan Zhang , Vivek Pradhan , Yuxi Zhao

Clinical prediction models (CPMs) are used to predict clinically relevant outcomes or events. Typically, prognostic CPMs are derived to predict the risk of a single future outcome. However, with rising emphasis on the prediction of…

Methodology · Statistics 2020-10-29 Glen P. Martin , Matthew Sperrin , Kym I. E. Snell , Iain Buchan , Richard D. Riley

Causal discovery algorithms estimate causal graphs from observational data. This can provide a valuable complement to analyses focussing on the causal relation between individual treatment-outcome pairs. Constraint-based causal discovery…

Methodology · Statistics 2021-08-31 Janine Witte , Ronja Foraita , Vanessa Didelez

Clustered observations are ubiquitous in controlled and observational studies and arise naturally in multi-centre trials or longitudinal surveys. We present a novel model for the analysis of clustered observations where the marginal…

Methodology · Statistics 2022-11-03 Luisa Barbanti , Torsten Hothorn

Three-level data structures arising from repeated measures on individuals clustered within larger units are common in health research studies. Missing data are prominent in such studies and are often handled via multiple imputation (MI).…

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

Imputing missing values is common practice in label-free quantitative proteomics. Imputation aims at replacing a missing value with a user-defined one. However, the imputation itself may not be optimally considered downstream of the…

Methodology · Statistics 2022-09-08 Marie Chion , Christine Carapito , Frédéric Bertrand

Mixture cure models are widely used in survival analysis when a portion of patients is considered cured and is no longer at risk for the event of interest. In clinical settings, dynamic survival prediction is particularly important to…

Methodology · Statistics 2025-09-24 Marta Cipriani , Marco Alfò , Mirko Signorelli

The clinical trial is a pivotal and costly process, often spanning multiple years and requiring substantial financial resources. Therefore, the development of clinical trial outcome prediction models aims to exclude drugs likely to fail and…

Machine Learning · Computer Science 2025-01-29 Wenhao Zheng , Liaoyaqi Wang , Dongshen Peng , Hongxia Xu , Yun Li , Hongtu Zhu , Tianfan Fu , Huaxiu Yao

Multiple imputation (MI) is a popular approach for dealing with missing data arising from non-response in sample surveys. Multiple imputation by chained equations (MICE) is one of the most widely used MI algorithms for multivariate data,…

Machine Learning · Computer Science 2022-03-22 Zhenhua Wang , Olanrewaju Akande , Jason Poulos , Fan Li
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