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Inference in hierarchical nonlinear models needs careful consideration about targeting parameters that have either a conditional or population-average interpretation. For the special case of mixed-effects nonlinear sigmoidal models we…

Applications · Statistics 2017-07-11 Daniel Gerhard , Christian Ritz

Network meta-analysis (NMA) has been used to answer a range of clinical questions about the preferable intervention for a given condition. Although the effectiveness and safety of pharmacological agents depend on the dose administered, NMA…

This study examines the application of Bayesian approach in the context of clinical trials, emphasizing their increasing importance in contemporary biomedical research. While conventional frequentist approach provides a foundational basis…

Methodology · Statistics 2026-01-16 Paramahansa Pramanik , Arnab Kumar Maity , Anjan Mandal , Haley Kate Robinson

To investigate the structure of individual differences in performance on behavioral tasks, Haaf and Rouder (2017) developed a class of hierarchical Bayesian mixed models with varying levels of constraint on the individual effects. The…

Applications · Statistics 2022-10-24 Thomas J. Faulkenberry

The prediction interval has been increasingly used in meta-analyses as a useful measure for assessing the magnitude of treatment effect and between-studies heterogeneity. In calculations of the prediction interval, although the…

Methodology · Statistics 2021-07-14 Yuta Hamaguchi , Hisashi Noma , Kengo Nagashima , Tomohide Yamada , Toshi A. Furukawa

Throughout the different phases of a drug development program, randomized trials are used to establish the tolerability, safety, and efficacy of a candidate drug. At each stage one aims to optimize the design of future studies by…

Applications · Statistics 2021-02-08 Sebastian Weber , Andrew Gelman , Daniel Lee , Michael Betancourt , Aki Vehtari , Amy Racine

Subgroup analysis is a frequently used tool for evaluating heterogeneity of treatment effect and heterogeneity in treatment harm across observed baseline patient characteristics. While treatment efficacy and adverse event measures are often…

Applications · Statistics 2018-08-14 Nicholas C. Henderson , Ravi Varadhan

Dose-finding clinical trials in oncology aim to determine the maximum tolerated dose (MTD) of a new drug, generally defined by the proportion of patients with short-term dose-limiting toxicities (DLTs). Model-based approaches for such phase…

Methodology · Statistics 2020-12-08 Moreno Ursino , Lucie Biard , Sylvie Chevret

The use of drug combinations in clinical trials is increasingly common during the last years since a more favorable therapeutic response may be obtained by combining drugs. In phase I clinical trials, most of the existing methodology…

Methodology · Statistics 2020-02-17 José L. Jiménez , Sungjin Kim , Mourad Tighiouart

Phase I clinical trials are designed to test the safety (non-toxicity) of drugs and find the maximum tolerated dose (MTD). This task becomes significantly more challenging when multiple-drug dose-combinations (DC) are involved, due to the…

Machine Learning · Computer Science 2021-01-27 Hyun-Suk Lee , Cong Shen , William Zame , Jang-Won Lee , Mihaela van der Schaar

BACKGROUND: Random-effects meta-analysis within a hierarchical normal modeling framework is commonly implemented in a wide range of evidence synthesis applications. More general problems may even be tackled when considering meta-regression…

Computation · Statistics 2022-12-27 Christian Röver , Tim Friede

Dose-finding studies are frequently conducted to evaluate the effect of different doses or concentration levels of a compound on a response of interest. Applications include the investigation of a new medicinal drug, a herbicide or…

Applications · Statistics 2011-08-01 Björn Bornkamp , Frank Bretz , Holger Dette , José Pinheiro

Imaging in clinical oncology trials provides a wealth of information that contributes to the drug development process, especially in early phase studies. This paper focuses on kinetic modeling in DCE-MRI, inspired by mixed-effects models…

Applications · Statistics 2020-04-22 Volker J. Schmid , Brandon Whitcher , Anwar R. Padhani , N. Jane Taylor , Guang-Zhong Yang

In parametric Bayesian designs of early phase cancer clinical trials with drug combinations exploring a discrete set of partially ordered doses, several authors claimed that there is no added value in including an interaction term to model…

Methodology · Statistics 2022-08-12 Mourad Tighiouart , José L. Jiménez , Marcio A. Diniz , André Rogatko

An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…

Methodology · Statistics 2010-12-01 Peter F. Thall

We overview Bayesian estimation, hypothesis testing, and model-averaging and illustrate how they benefit parametric survival analysis. We contrast the Bayesian framework to the currently dominant frequentist approach and highlight…

Methodology · Statistics 2022-09-13 František Bartoš , Frederik Aust , Julia M. Haaf

The analysis of data from multiple experiments, such as observations of several individuals, is commonly approached using mixed-effects models, which account for variation between individuals through hierarchical representations. This makes…

Computation · Statistics 2026-03-05 Henrik Häggström , Sebastian Persson , Marija Cvijovic , Umberto Picchini

To investigate intervention effects on rare events, meta-analysis techniques are commonly applied in order to assess the accumulated evidence. When it comes to adverse effects in clinical trials, these are often most adequately handled…

Methodology · Statistics 2026-04-03 Christian Röver , Qiong Wu , Anja Loos , Tim Friede

Medical studies for chronic disease are often interested in the relation between longitudinal risk factor profiles and individuals' later life disease outcomes. These profiles may typically be subject to intermediate structural changes due…

Applications · Statistics 2023-08-22 Sandra Keizer , Zhuozhao Zhan , Vasan S. Ramachandran , Edwin R. van den Heuvel

Identification of optimal dose combinations in early phase dose-finding trials is challenging, due to the trade-off between precisely estimating the many parameters required to flexibly model the possibly non-monotonic dose-response…

Methodology · Statistics 2024-02-13 James Willard , Shirin Golchi , Erica E. M. Moodie , Bruno Boulanger , Bradley P. Carlin