English
Related papers

Related papers: Tutorial for Surrogate Endpoint Validation Using J…

200 papers

In many real-world causal inference applications, the primary outcomes (labels) are often partially missing, especially if they are expensive or difficult to collect. If the missingness depends on covariates (i.e., missingness is not…

Machine Learning · Statistics 2024-05-24 Zhenghao Zeng , David Arbour , Avi Feller , Raghavendra Addanki , Ryan Rossi , Ritwik Sinha , Edward H. Kennedy

Surrogate models provide compact relations between user-defined input parameters and output quantities of interest, enabling the efficient evaluation of complex parametric systems in many-query settings. Such capabilities are essential in a…

Numerical Analysis · Mathematics 2026-03-16 Matteo Giacomini , Pedro Díez

When evaluating the effectiveness of a treatment, policy, or intervention, the desired measure of effectiveness may be expensive to collect, not routinely available, or may take a long time to occur. In these cases, it is sometimes possible…

Methodology · Statistics 2022-11-10 Denis Agniel , Layla Parast , Boris Hejblum

The development of statistical methods to evaluate surrogate markers is an active area of research. In many clinical settings, the surrogate marker is not simply a single measurement but is instead a longitudinal trajectory of measurements…

Methodology · Statistics 2024-02-28 Denis Agniel , Layla Parast

Clinical trials or studies oftentimes require long-term and/or costly follow-up of participants to evaluate a novel treatment/drug/vaccine. There has been increasing interest in the past few decades in using short-term surrogate outcomes as…

Methodology · Statistics 2024-12-19 Xuan Wang , Tianxi Cai , Lu Tian , Layla Parast

Surrogate markers are most commonly studied within the context of randomized clinical trials. However, the need for alternative outcomes extends beyond these settings and may be more pronounced in real-world public health and social science…

Methodology · Statistics 2025-04-23 Rebecca Knowlton , Layla Parast

The optimization of large-scale multibody systems is a numerically challenging task, in particular when considering multiple conflicting criteria at the same time. In this situation, we need to approximate the Pareto set of optimal…

Optimization and Control · Mathematics 2024-12-20 Augustina C. Amakor , Manuel B. Berkemeier , Meike Wohlleben , Walter Sextro , Sebastian Peitz

Trial level surrogates are useful tools for improving the speed and cost effectiveness of trials, but surrogates that have not been properly evaluated can cause misleading results. The evaluation procedure is often contextual and depends on…

Methodology · Statistics 2022-08-23 Michael C Sachs , Erin E Gabriel , Alessio Crippa , Michael J Daniels

In many randomized trials, outcomes such as essays or open-ended responses must be manually scored as a preliminary step to impact analysis, a process that is costly and limiting. Model-assisted estimation offers a way to combine surrogate…

Methodology · Statistics 2026-02-16 Reagan Mozer , Nicole E. Pashley , Luke Miratrix

Surrogate endpoints are often used in place of expensive, delayed, or rare true endpoints in clinical trials. However, regulatory authorities require thorough evaluation to accept these surrogate endpoints as reliable substitutes. One…

Mediation analysis for survival outcomes is challenging. Most existing methods quantify the treatment effect using the hazard ratio (HR) and attempt to decompose the HR into the direct effect of treatment plus an indirect, or mediated,…

Adaptive subgroup enrichment design is an efficient design framework that allows accelerated development for investigational treatments while also having flexibility in population selection within the course of the trial. The adaptive…

Methodology · Statistics 2022-10-21 Liwen Wu , Qing Li , Mengya Liu , Jianchang Lin

Surrogate markers are often used in clinical trials to evaluate treatment effects when primary outcomes are costly, invasive, or take a long time to observe. However, reliance on surrogates can lead to the surrogate paradox, where a…

Methodology · Statistics 2025-06-17 Emily Hsiao , Lu Tian , Layla Parast

An intermediate response measure that accurately predicts efficacy in a new setting can reduce trial cost and time to product licensure. In this paper, we define a trial level general surrogate as a trial level intermediate response that…

Methodology · Statistics 2015-07-08 Erin E. Gabriel , Michael J. Daniels , M. Elizabeth Halloran

Objective: Traditionally validation of surrogate endpoints has been carried out using RCT data. However, RCT data may be too limited to validate surrogate endpoints. In this paper, we sought to improve validation of surrogate endpoints with…

Applications · Statistics 2021-12-17 Lorna Wheaton , Anastasios Papanikos , Anne Thomas , Sylwia Bujkiewicz

Surrogate models are often used as computationally efficient approximations to complex simulation models, enabling tasks such as solving inverse problems, sensitivity analysis, and probabilistic forward predictions, which would otherwise be…

Machine Learning · Statistics 2026-05-13 Philipp Reiser , Paul-Christian Bürkner , Anneli Guthke

Mediation analysis seeks to identify and quantify the paths by which an exposure affects an outcome. Intermediate variables which are effected by the exposure and which effect the outcome are known as mediators. There exists extensive work…

Methodology · Statistics 2020-11-13 James P. Long , Ehsan Irajizad , James D. Doecke , Kim-Anh Do , Min Jin Ha

The identification of surrogate markers is motivated by their potential to make decisions sooner about a treatment effect. However, few methods have been developed to actually use a surrogate marker to test for a treatment effect in a…

Methodology · Statistics 2024-09-17 Layla Parast , Jay Bartroff

Often in Phase 3 clinical trials measuring a long-term time-to-event endpoint, such as overall survival or progression-free survival, investigators also collect repeated measures on biomarkers which may be predictive of the primary…

Methodology · Statistics 2022-11-30 Abigail J. Burdon , Lisa V. Hampson , Christopher Jennison

In many decision-making problems, the primary outcome is expensive, time-consuming, or difficult to observe, so individualized treatment rules (ITRs) may be instead learned from surrogate endpoints. However, a surrogate that is highly…

Methodology · Statistics 2026-04-13 Zeyu Xu , Xiaojie Mao , Hao Mei , Yue Liu