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Surrogate endpoints are very important in regulatory decision-making in healthcare, in particular if they can be measured early compared to the long-term final clinical outcome and act as good predictors of clinical benefit. Bivariate…

Surrogate endpoints play an important role in drug development when they can be used to measure treatment effect early compared to the final clinical outcome and to predict clinical benefit or harm. Such endpoints are assessed for their…

The use of valid surrogate endpoints is an important stake in clinical research to help reduce both the duration and cost of a clinical trial and speed up the evaluation of interesting treatments. Several methods have been proposed in the…

Methodology · Statistics 2025-02-13 Quentin Le Coent , Virginie Rondeau , Catherine Legrand

A surrogate endpoint S in a clinical trial is an outcome that may be measured earlier or more easily than the true outcome of interest T. In this work, we extend causal inference approaches to validate such a surrogate using potential…

Methodology · Statistics 2022-02-04 Emily Roberts , Michael Elliott , Jeremy M. G. Taylor

In meta-analytic modeling, the functional relationship between a primary and surrogate endpoint is estimated using summary data from a set of completed clinical trials. Parameters in the meta-analytic model are used to assess the quality of…

Methodology · Statistics 2025-08-07 James P. Long , Abhishikta Roy , Ehsan Irajizad , Kim-Anh Do , Yu Shen

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

Copula mixed models for trivariate (or bivariate) meta-analysis of diagnostic test accuracy studies accounting (or not) for disease prevalence have been proposed in the biostatistics literature to synthesize information. However, many…

Methodology · Statistics 2018-07-12 Aristidis K. Nikoloulopoulos

When direct measurement of a clinically relevant primary endpoint in a clinical trial is infeasible, a surrogate endpoint may be used instead to infer treatment effects. Trial-level surrogates predict the average treatment effect on the…

Methodology · Statistics 2026-05-06 Arthur Hughes , Rodolphe Thiébaut , Layla Parast , Boris P. Hejblum

A common practice in clinical trials is to evaluate a treatment effect on an intermediate endpoint when the true outcome of interest would be difficult or costly to measure. We consider how to validate intermediate endpoints in a…

Methodology · Statistics 2022-11-30 Emily K. Roberts , Michael R. Elliott , Jeremy M. G. Taylor

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…

Motivated by challenges in the analysis of biomedical data and observational studies, we develop statistical boosting for the general class of bivariate distributional copula regression with arbitrary marginal distributions, which is suited…

Methodology · Statistics 2024-03-05 Guillermo Briseño Sanchez , Nadja Klein , Hannah Klinkhammer , Andreas Mayr

We introduce in this paper an extension of the meta-analytic (MA) framework for evaluating surrogate endpoints. While the MA framework is regarded as the gold standard for surrogate endpoint evaluation, it is limited in its ability to…

Methodology · Statistics 2025-09-03 Florian Stijven , Peter B. Gilbert

The current statistical procedures implemented in statistical software packages for pooling of diagnostic test accuracy data include hSROC regression and the bivariate random-effects meta-analysis model (BRMA). However, these models do not…

Methodology · Statistics 2016-04-08 Victoria N Nyaga , Marc Arbyn , Marc Aerts

A time-varying bivariate copula joint model, which models the repeatedly measured longitudinal outcome at each time point and the survival data jointly by both the random effects and time-varying bivariate copulas, is proposed in this…

Methodology · Statistics 2024-12-03 Zili Zhang , Christiana Charalambous , Peter Foster

Mediation analysis is a useful tool to evaluate surrogate endpoints in clinical trials. We propose a novel method, the M-survival learner, for estimating heterogeneous indirect treatment effects in the presence of censored outcomes. The…

Methodology · Statistics 2026-04-16 Xingyu Li , Qing Liu , Xun Jiang , Hong Amy Xia , Brian P. Hobbs , Peng Wei

Diagnostic test accuracy studies typically report the number of true positives, false positives, true negatives and false negatives. There usually exists a negative association between the number of true positives and true negatives,…

Methodology · Statistics 2015-11-06 Aristidis K. Nikoloulopoulos

Surrogate endpoints are used in place of long-term outcomes in randomized experiments when observing the real outcome for a large enough cohort is prohibitively expensive or impractical. A short-term surrogate is good if the result of an…

Time-to-event semi-competing risk endpoints may be correlated when both events are occurring on the same individual. These events and the association between them may also be influenced by individual characteristics. In this paper, we…

Methodology · Statistics 2023-04-07 Yinghui Wei , Malgorzata Wojtys , Lexy Sorrell , Peter Rowe

Inferring causal effects on long-term outcomes using short-term surrogates is crucial to rapid innovation. However, even when treatments are randomized and surrogates fully mediate their effect on outcomes, it's possible that we get the…

Methodology · Statistics 2023-11-09 Aurélien Bibaut , Nathan Kallus , Simon Ejdemyr , Michael Zhao

Copulas are mathematical objects that fully capture the dependence structure among random variables and hence, offer a great flexibility in building multivariate stochastic models. In statistics, a copula is used as a general way of…

Methodology · Statistics 2013-10-01 Abhik Ghosh , Aritra Chakravorty
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