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We consider the problem of constructing optimal designs for model discrimination between competing regression models. Various new properties of optimal designs with respect to the popular $T$-optimality criterion are derived, which in many…

Statistics Theory · Mathematics 2009-08-14 Holger Dette , Stefanie Titoff

We consider the optimal design problem for identifying effective dose combinations within drug combination studies where the effect of the combination of two drugs is investigated. Drug combination studies are becoming increasingly…

Nonlinear regression models addressing both efficacy and toxicity outcomes are increasingly used in dose-finding trials, such as in pharmaceutical drug development. However, research on related experimental design problems for corresponding…

Methodology · Statistics 2016-01-06 Holger Dette , Katrin Kettelhake , Kirsten Schorning , Weng Kee Wong , Frank Bretz

The issue of determining not only an adequate dose but also a dosing frequency of a drug arises frequently in Phase II clinical trials. This results in the comparison of models which have some parameters in common. Planning such studies…

Methodology · Statistics 2017-11-16 Kirsten Schorning , Maria Konstantinou

Optimum experimental design theory has recently been extended for parameter estimation in copula models. However, the choice of the correct dependence structure still requires wider analyses. In this work the issue of copula selection is…

Methodology · Statistics 2016-01-29 Elisa Perrone , Andreas Rappold , Werner G. Müller

A common problem in Phase II clinical trials is the comparison of dose response curves corresponding to different treatment groups. If the effect of the dose level is described by parametric regression models and the treatments differ in…

Statistics Theory · Mathematics 2016-03-16 Chrystel Feller , Kirsten Schorning , Holger Dette , Georgina Bermann , Björn Bornkamp

Optimal designs are usually model-dependent and likely to be sub-optimal if the postulated model is not correctly specified. In practice, it is common that a researcher has a list of candidate models at hand and a design has to be found…

Statistics Theory · Mathematics 2023-03-29 Mingyao Ai , Holger Dette , Zhengfu Liu , Jun Yu

We construct optimal designs for estimating fetal malformation rate, prenatal death rate and an overall toxicity index in a toxicology study under a broad range of model assumptions. We use Weibull distributions to model these rates and…

Methodology · Statistics 2009-02-10 Holger Dette , Andrey Pepelyshev , Weng Kee Wong

Many chemical and biological experiments involve multiple treatment factors and often it is convenient to fit a nonlinear model in these factors. This nonlinear model can be mechanistic, empirical or a hybrid of the two. Motivated by…

Computation · Statistics 2018-10-09 Yuanzhi Huang , Steven Gilmour , Kalliopi Mylona , Peter Goos

Model-based experimental design is attracting increasing attention in chemical process engineering. Typically, an iterative procedure is pursued: an approximate model is devised, prescribed experiments are then performed and the resulting…

Optimization and Control · Mathematics 2021-01-25 Charlie Vanaret , Philipp Seufert , Jan Schwientek , Gleb Karpov , Gleb Ryzhakov , Ivan Oseledets , Norbert Asprion , Michael Bortz

This paper presents a quasi-sequential optimal design framework for toxicology experiments, specifically applied to sea urchin embryos. The authors propose a novel approach combining robust optimal design with adaptive, stage-based testing…

Methodology · Statistics 2025-03-04 Elvis Han Cui , Michael Collins , Jessica Munson , Weng Kee Wong

We consider the problem of constructing optimal designs for population pharmacokinetics which use random effect models. It is common practice in the design of experiments in such studies to assume uncorrelated errors for each subject. In…

Applications · Statistics 2010-11-16 Holger Dette , Andrey Pepelyshev , Tim Holland-Letz

Hierarchical random effect models are used for different purposes in clinical research and other areas. In general, the main focus is on population parameters related to the expected treatment effects or group differences among all units of…

Applications · Statistics 2021-04-07 Maryna Prus , Norbert Benda , Rainer Schwabe

We provide a systematic treatment of $D$-optimal design for binary regression and quantal response models in toxicology studies. For the two-parameter case, we provide an analytical equation (WC equation) for computing the $D$-optimal…

Applications · Statistics 2022-09-28 Elvis Han Cui

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

In this paper we consider the problem of constructing $T$-optimal discriminating designs for Fourier regression models. We provide explicit solutions of the optimal design problem for discriminating between two Fourier regression models,…

Methodology · Statistics 2015-12-24 Holger Dette , Viatcheslav B. Melas , Petr Shpilev

The problem of constructing optimal discriminating designs for a class of regression models is considered. We investigate a version of the $T_p$-optimality criterion as introduced by Atkinson and Fedorov [Biometrika 62 (1975a) 289-303]. The…

Statistics Theory · Mathematics 2013-06-07 Dietrich Braess , Holger Dette

The purpose of a phase I dose-finding clinical trial is to investigate the toxicity profiles of various doses for a new drug and identify the maximum tolerated dose. Over the past three decades, various dose-finding designs have been…

Methodology · Statistics 2021-11-25 Yunshan Duan , Shijie Yuan , Yuan Ji , Peter Mueller

In a recent paper Dette et al. (2014) introduced optimal design problems for dose fnding studies with an active control. These authors concentrated on regression models with normal distributed errors (with known variance) and the problem of…

Methodology · Statistics 2014-11-03 Holger Dette , Katrin Kettelhake , Frank Bretz

Interval designs are a class of phase I trial designs for which the decision of dose assignment is determined by comparing the observed toxicity rate at the current dose with a prespecified (toxicity tolerance) interval. If the observed…

Methodology · Statistics 2013-09-20 Suyu Liu , Ying Yuan
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