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We consider the problem of testing for a dose-related effect based on a candidate set of (typically nonlinear) dose-response models using likelihood-ratio tests. For the considered models this reduces to assessing whether the slope…

Methodology · Statistics 2015-10-22 Georg Gutjahr , Björn Bornkamp

Dose selection is critical in pharmaceutical drug development, as it directly impacts therapeutic efficacy and patient safety of a drug. The Generalized Multiple Comparison Procedures and Modeling (MCP-Mod) approach is commonly used in…

Methodology · Statistics 2025-05-23 Lukas Pin , Oleksandr Sverdlov , Frank Bretz , Björn Bornkamp

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

The Multiple Comparison Procedures with Modeling Techniques (MCP-Mod) framework has been recently approved by the U.S. Food and Administration and European Medicines Agency as fit-per-purpose for phase II studies. Nonetheless, this approach…

Methodology · Statistics 2023-06-16 Márcio A. Diniz , Diego I. Gallardo , Tiago M. Magalhães

In learning-phase clinical trials in drug development, adaptive designs can be efficient and highly informative when used appropriately. In this article, we extend the multiple comparison procedures with modeling techniques (MCP-Mod)…

Methodology · Statistics 2021-08-02 Shiyang Ma , Michael P. McDermott

A common goal in clinical trials is to conduct tests on estimated treatment effects adjusted for covariates such as age or sex. Analysis of Covariance (ANCOVA) is often used in these scenarios to test the global null hypothesis of no…

Methodology · Statistics 2024-04-24 Matthias Becher , Ludwig A. Hothorn , Frank Konietschke

Statistical methodology for the design and analysis of clinical Phase II dose response studies, with related software implementation, are well developed for the case of a normally distributed, homoscedastic response considered for a single…

Methodology · Statistics 2014-05-09 José Pinheiro , Björn Bornkamp , Ekkehard Glimm , Frank Bretz

Multivariate matched proportions (MMP) data appears in a variety of contexts including post-market surveillance of adverse events in pharmaceuticals, disease classification, and agreement between care providers. It consists of multiple sets…

Methodology · Statistics 2023-05-08 Mark J. Meyer , Haobo Cheng , Katherine Hobbs Knutson

This paper investigates the problem of simultaneously predicting multiple binary responses by utilizing a shared set of covariates. Our approach incorporates machine learning techniques for binary classification, without making assumptions…

Methodology · Statistics 2024-03-07 The Tien Mai

Estimating the model evidence - or mariginal likelihood of the data - is a notoriously difficult task for finite and infinite mixture models and we reexamine here different Monte Carlo techniques advocated in the recent literature, as well…

Computation · Statistics 2022-05-12 Adrien Hairault , Christian P. Robert , Judith Rousseau

Composite binary endpoints are increasingly used as primary endpoints in clinical trials. When designing a trial, it is crucial to determine the appropriate sample size for testing the statistical differences between treatment groups for…

Applications · Statistics 2019-01-15 Marta Bofill Roig , Guadalupe Gómez Melis

In this work we show a Bayesian quantile regression method to response variables with mixed discrete-continuous distribution with a point mass at zero, where these observations are believed to be left censored or true zeros. We combine the…

Methodology · Statistics 2015-11-19 Bruno Santos , Heleno Bolfarine

To claim similarity of multiple dose-response curves in interlaboratory studies in regulatory toxicology is a relevant issue during the assay validation process. Here we demonstrated the use of dose-by-laboratory interaction contrasts,…

Applications · Statistics 2020-09-28 Ludwig A. Hothorn , Dimitrios Spiliotopoulos

Accurate dose selection in Phase II trials is critical to the success of subsequent Phase III trials, but suboptimal choices remain a leading cause of trial failure and regulatory rejection. Although MCP-Mod is widely adopted and endorsed…

Methodology · Statistics 2025-09-30 Linxi Han , Qiqi Deng , Feng Yu , Zhangyi He

The comparison of different medical treatments from observational studies or across different clinical studies is often biased by confounding factors such as systematic differences in patient demographics or in the inclusion criteria for…

Methodology · Statistics 2025-05-15 Ekkehard Glimm , Lillian Yau

In lifetime data, like cancer studies, theremay be long term survivors, which lead to heavy censoring at the end of the follow-up period. Since a standard survival model is not appropriate to handle these data, a cure model is needed. In…

Methodology · Statistics 2024-01-31 Ana López-Cheda , M. Amalia Jácome , Ingrid Van Keilegom , Ricardo Cao

In confirmatory clinical trials with small sample sizes, hypothesis tests based on asymptotic distributions are often not valid and exact non-parametric procedures are applied instead. However, the latter are based on discrete test…

Methodology · Statistics 2018-02-22 Robin Ristl , Dong Xi , Ekkehard Glimm , Martin Posch

Matched case-control studies are commonly employed in epidemiological research for their convenience and efficiency. Analysis of secondary outcomes can yield valuable insights into biological pathways and help identify genetic variants of…

Methodology · Statistics 2026-02-24 Shanshan Liu , Guoqing Diao

In a Phase II dose-finding study with a placebo control, a new drug with several dose levels is compared with a placebo to test for the effectiveness of the new drug. The main focus of such studies often lies in the characterization of the…

Methodology · Statistics 2020-07-14 Saswati Saha , Werner Brannath

Finding effective ways to exploit parallel computing to accelerate Markov chain Monte Carlo methods is an important problem in Bayesian computation and related disciplines. In this paper, we consider the zeroth-order setting where the…

Computation · Statistics 2026-01-28 Francesco Pozza , Giacomo Zanella
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