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We consider design issues for toxicology studies when we have a continuous response and the true mean response is only known to be a member of a class of nested models. This class of non-linear models was proposed by toxicologists who were…

Statistics Theory · Mathematics 2010-11-29 Holger Dette , Andrey Pepelyshev , Piter Shpilev , Weng Kee Wong

A general framework is proposed for Bayesian model-based designs of Phase I cancer trials, in which a general criterion for coherence (Cheung, 2005) of a design is also developed. This framework can incorporate both "individual" and…

Methodology · Statistics 2011-08-08 Jay Bartroff , Tze Leung Lai

Bayesian optimal experimental design is a sub-field of statistics focused on developing methods to make efficient use of experimental resources. Any potential design is evaluated in terms of a utility function, such as the (theoretically…

Machine Learning · Computer Science 2022-10-21 Noble Kennamer , Steven Walton , Alexander Ihler

We consider a Bayesian persuasion or information design problem where the sender tries to persuade the receiver to take a particular action via a sequence of signals. This we model by considering multi-phase trials with different…

Theoretical Economics · Economics 2021-11-24 Shih-Tang Su , Vijay G. Subramanian , Grant Schoenebeck

There has been an increasing interest in using interval-based Bayesian designs for dose finding, one of which is the modified toxicity probability interval (mTPI) method. We show that the decision rules in mTPI correspond to an optimal rule…

Methodology · Statistics 2016-09-29 Wentian Guo , Sue-Jane Wang , Shengjie Yang , Suiheng Lin , Yuan Ji

We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a…

Methodology · Statistics 2024-08-13 Kai Chen , Heng Zhou , J. Jack Lee , Ying Yuan

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

An objective of phase I dose-finding trials is to find the maximum tolerated dose; the dose with a particular risk of toxicity. Frequently, this risk is assessed across the first cycle of therapy. However, in oncology, a course of treatment…

Applications · Statistics 2021-05-03 Helen Barnett , Oliver Boix , Dimintris Kontos , Thomas Jaki

Adaptive approaches, allowing for more flexible trial design, have been proposed for individually randomized trials to save time or reduce sample size. However, adaptive designs for cluster-randomized trials in which groups of participants…

Methodology · Statistics 2022-01-10 Junwei Shen , Shirin Golchi , Erica E. M. Moodie , David Benrimoh

In oncology dose-finding trials, due to staggered enrollment, it might be desirable to make dose-assignment decisions in real-time in the presence of pending toxicity outcomes, for example, when the dose-limiting toxicity is late-onset.…

Methodology · Statistics 2023-03-13 Tianjian Zhou , Yuan Ji

This paper proposes a novel criterion for the allocation of patients in Phase~I dose-escalation clinical trials aiming to find the maximum tolerated dose (MTD). Conventionally, using a model-based approach the next patient is allocated to…

Methodology · Statistics 2018-07-17 Pavel Mozgunov , Thomas Jaki

The US Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection towards identifying the optimal biological dose that offers the best balance between benefit and risk, rather…

Methodology · Statistics 2023-09-13 Ying Yuan , Heng Zhou , Suyu Liu

Most Bayesian response-adaptive designs unbalance randomization rates towards the most promising arms with the goal of increasing the number of positive treatment outcomes during the study, even though the primary aim of the trial is…

Applications · Statistics 2018-07-02 Steffen Ventz , Matteo Cellamare , Sergio Bacallado , Lorenzo Trippa

Cohort-based enrollment can slow down dose-finding trials since the outcomes of the previous cohort must be fully evaluated before the next cohort can be enrolled. This results in frequent suspension of patient enrollment. The issue is…

Applications · Statistics 2020-01-01 Tianjian Zhou , Wentian Guo , Yuan Ji

Experimental design is crucial for inference where limitations in the data collection procedure are present due to cost or other restrictions. Optimal experimental designs determine parameters that in some appropriate sense make the data…

Machine Learning · Statistics 2016-03-11 Panagiotis Tsilifis , Roger G. Ghanem , Paris Hajali

It is crucial to design Phase II cancer clinical trials that balance the efficiency of treatment selection with clinical practicality. Sargent and Goldberg proposed a frequentist design that allow decision-making even when the primary…

Methodology · Statistics 2025-05-15 Moka Komaki , Satoru Shinoda , Haiyan Zheng , Kouji Yamamoto

Conventionally, a first-in-human phase I trial in healthy volunteers aims to confirm the safety of a drug in humans. In such situations, volunteers should not suffer from any safety issues and simple algorithm-based dose-escalation schemes…

Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants, use resources efficiently and allow clinically meaningful conclusions to be drawn. Adaptive…

Methodology · Statistics 2025-07-17 James M. McGree , Antony M. Overstall , Mark Jones , Robert K. Mahar

Recently, the strategy for dose optimization in oncology has shifted to conduct Phase 2 randomized controlled trials with multiple doses. Optimal biologic dose selection from Phase 1 trial data to determine candidate doses for Phase 2…

Methodology · Statistics 2023-02-14 Masahiro Kojima

The primary goal of a two-stage Phase I/II trial is to identify the optimal dose for the following large-scale Phase III trial. Recently, Phase I dose-finding designs have shifted from identifying the maximum tolerated dose (MTD) to the…

Methodology · Statistics 2025-01-16 Hao Sun , Jerry Li