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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

Phase 1-2 designs provide a methodological advance over phase 1 designs for dose finding by using both clinical response and toxicity. A phase 1-2 trial still may fail to select a truly optimal dose. because early response is not a perfect…

Applications · Statistics 2024-04-03 Cheng-Han Yang , Peter F. Thall , Ruitao Lin

Multi-arm multi-stage (MAMS) trials have gained popularity, due to their improved efficiency in evaluating multiple treatments. A traditional MAMS trial often decreases the expected sample size of the trial compared to just running a…

We propose to use Bayesian optimization (BO) to improve the efficiency of the design selection process in clinical trials. BO is a method to optimize expensive black-box functions, by using a regression as a surrogate to guide the search.…

Methodology · Statistics 2021-05-20 Jakob Richter , Tim Friede , Jörg Rahnenführer

Two useful strategies to speed up drug development are to increase the patient accrual rate and use novel adaptive designs. Unfortunately, these two strategies often conflict when the evaluation of the outcome cannot keep pace with the…

Methodology · Statistics 2018-07-24 Ruitao Lin , Ying Yuan

We consider the problem of designing experiments for the comparison of two regression curves describing the relation between a predictor and a response in two groups, where the data between and within the group may be dependent. In order to…

Statistics Theory · Mathematics 2021-01-15 Kirsten Schorning , Holger Dette

Recent works have proposed optimal subsampling algorithms to improve computational efficiency in large datasets and to design validation studies in the presence of measurement error. Existing approaches generally fall into two categories:…

Methodology · Statistics 2025-12-25 Jasper B. Yang , Thomas Lumley , Bryan E. Shepherd , Pamela A. Shaw

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

In oncology, phase II studies are crucial for clinical development plans as such studies identify potent agents with sufficient activity to continue development in the subsequent phase III trials. Traditionally, phase II studies are…

Methodology · Statistics 2023-08-08 Takuya Yoshimoto , Satoru Shinoda , Kouji Yamamoto , Kouji Tahata

In oncology phase I trials, model-assisted designs have been increasingly adopted because they enable adaptive yet operationally simple dose adjustment based on accumulating safety data, leading to a paradigm shift in dose-escalation…

Methodology · Statistics 2026-02-23 Kana Yamada , Hisato Sunami , Kentaro Takeda , Keisuke Hanada , Masahiro Kojima

This paper considers real-time control and learning problems for finite-dimensional linear systems under binary-valued and randomly disturbed output observations. This has long been regarded as an open problem because the exact values of…

Systems and Control · Electrical Eng. & Systems 2024-11-12 Lantian Zhang , Lei Guo

In this paper we introduce a binary search algorithm that efficiently finds initial maximum likelihood estimates for sequential experiments where a binary response is modeled by a continuous factor. The problem is motivated by switching…

Statistics Theory · Mathematics 2008-08-27 Juha Karvanen

The paper develops methods to construct a one-stage optimal design of dilution experiments under the total available volume constraint typical for bio-medical applications. We consider various design criteria based on the Fisher information…

Statistics Theory · Mathematics 2013-05-08 Maryam Zolghadr , Sergei Zuyev

We study the optimal design of stealthy attacks against partially observed linear control systems. We first propose a novel likelihood-based detection mechanism derived from the innovation process, based on which we quantify stealthiness…

Optimization and Control · Mathematics 2026-05-12 Haosheng Zhou , Ruimeng Hu

An important issue for many economic experiments is how the experimenter can ensure sufficient power for rejecting one or more hypotheses. Here, we apply methods developed mainly within the area of clinical trials for testing multiple…

Methodology · Statistics 2021-08-06 Sebastian Jobjörnsson , Henning Schaak , Oliver Mußhoff , Tim Friede

The use of historical controls offers a valuable alternative when traditional randomized controlled trials are not feasible. However, such approaches may introduce bias due to temporal changes in patient populations, diagnostic criteria,…

Methodology · Statistics 2025-12-24 Marco Ratta , Pavel Mozgunov , Sandrine Boulet , Moreno Ursino

Algorithms which compute locally optimal continuous designs often rely on a finite design space or on repeatedly solving a complex non-linear program. Both methods require extensive evaluations of the Jacobian Df of the underlying model.…

Methodology · Statistics 2021-01-18 Philipp Seufert , Jan Schwientek , Michael Bortz

In the development of new cancer treatment, an essential step is to determine the maximum tolerated dose (MTD) via phase I clinical trials. Generally speaking, phase I trial designs can be classified as either model-based or algorithm-based…

Applications · Statistics 2022-03-02 Huaqing Jin , Wenbin Du , Guosheng Yin

Simulation-based optimal design techniques are a convenient tool for solving a particular class of optimal design problems. The goal is to find the optimal configuration of factor settings with respect to an expected utility criterion. This…

Methodology · Statistics 2013-05-21 Markus Hainy , Werner G. Müller , Helga Wagner

Adaptive sampling algorithms are modern and efficient methods that dynamically adjust the sample size throughout the optimization process. However, they may encounter difficulties in risk-averse settings, particularly due to the challenge…

Optimization and Control · Mathematics 2025-02-17 Sandra Pieraccini , Tommaso Vanzan