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Phase II dose finding studies in clinical drug development are typically conducted to adequately characterize the dose response relationship of a new drug. An important decision is then on the choice of a suitable dose response function to…

Applications · Statistics 2015-08-04 Kirsten Schorning , Björn Bornkamp , Frank Bretz , Holger Dette

In clinical trials, the response of a given subject often depends on the selected treatment as well as on some covariates. We study optimal approximate designs of experiments in the models with treatment and covariate effects. We allow for…

Statistics Theory · Mathematics 2019-07-10 Samuel Rosa

We consider two problems that are attracting increasing attention in clinical dose finding studies. First, we assess the similarity of two non-linear regression models for two non-overlapping subgroups of patients over a restricted…

Methodology · Statistics 2017-09-12 Frank Bretz , Kathrin Möllenhoff , Holger Dette , Wei Liu , Matthias Trampisch

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

This paper discusses the problem of determining optimal designs for regression models, when the observations are dependent and taken on an interval. A complete solution of this challenging optimal design problem is given for a broad class…

Methodology · Statistics 2015-02-25 Holger Dette , Andrey Pepelyshev , Anatoly Zhigljavsky

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 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

Consider an experiment consisting of a set of independent trials for comparing a set of treatments. In each trial, one treatment is chosen and the mean response of the trial is equal to the effect of the chosen treatment. We examine the…

Statistics Theory · Mathematics 2016-12-21 Samuel Rosa

Optimal two-treatment, $p$ period crossover designs for binary responses are determined. The optimal designs are obtained by minimizing the variance of the treatment contrast estimator over all possible allocations of $n$ subjects to $2^p$…

Methodology · Statistics 2015-05-12 S. Mukhopadhyay , S. P. Singh , A. Dey

This paper addresses the problem of deciding whether the dose response relationships between subgroups and the full population in a multi-regional trial are similar to each other. Similarity is measured in terms of the maximal deviation…

Statistics Theory · Mathematics 2024-04-30 Holger Dette , Lukas Koletzko , Frank Bretz

In this paper, the tools provided by the theory of Optimal Experimental Design are applied to a nonlinear calibration model. This is motivated by the need of estimating radiation doses using radiochromic films for radiotherapy purposes. The…

Applications · Statistics 2020-05-20 Jesús López-Fidalgo , Mariano Amo-Salas

Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing…

Computation · Statistics 2025-03-11 Michael Sweeting , Daniel Slade , Dan Jackson , Kristian Brock

We characterize $D$-optimal designs in the two-dimensional Poisson regression model with synergetic interaction and provide an explicit proof. The proof is based on the idea of reparameterization of the design region in terms of contours of…

Statistics Theory · Mathematics 2021-06-17 Fritjof Freise , Ulrike Graßhoff , Frank Röttger , Rainer Schwabe

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

Optimal designs for generalized linear models require a prior knowledge of the regression parameters. At certain values of the parameters we propose particular assumptions which allow to derive a locally optimal design for a model without…

Statistics Theory · Mathematics 2019-06-26 Osama Idais

We present general results on D-optimal designs for estimating the mean response in repeated measures growth curve models with metric outcomes. For this situation, we derive a novel equivalence theorem for checking design optimality. The…

Statistics Theory · Mathematics 2023-01-23 Fritjof Freise , Heinz Holling , Rainer Schwabe

Suppose that we intend to perform an experiment consisting of a set of independent trials. The mean value of the response of each trial is assumed to be equal to the sum of the effect of the treatment selected for the trial, and some…

Statistics Theory · Mathematics 2016-12-21 Samuel Rosa , Radoslav Harman

This article discusses $A$-, $D$- and $E$-optimality results for multivariate crossover designs, where more than one response is measured from every period for each subject. The motivation for these multivariate designs comes from a $3…

Methodology · Statistics 2025-09-22 Shubham Niphadkar , Siuli Mukhopadhyay

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

Adaptive designs are commonly used in clinical and drug development studies for optimum utilization of available resources. In this article, we consider the problem of estimating the effect of the selected (better) treatment using a…

Statistics Theory · Mathematics 2023-01-24 Masihuddin , Neeraj Misra