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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

The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…

Methodology · Statistics 2025-09-03 Wei Zhang , Zhiwei Zhang , Aiyi Liu

Randomized saturation designs are a family of designs which assign a possibly different treatment proportion to each cluster of a population at random. As a result, they generalize the well-known (stratified) completely randomized designs…

Methodology · Statistics 2022-03-21 Chencheng Cai , Jean Pouget-Abadie , Edoardo M. Airoldi

We examine nonparametric dose-finding designs that use toxicity estimates based on all available data at each dose allocation decision. We prove that one such design family, called here "interval design", converges almost surely to the…

Methodology · Statistics 2012-02-22 Assaf P. Oron , David Azriel , Peter D. Hoff

Tie-breaker designs trade off a statistical design objective with short-term gain from preferentially assigning a binary treatment to those with high values of a running variable $x$. The design objective is any continuous function of the…

Methodology · Statistics 2022-10-20 Harrison H. Li , Art B. Owen

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

Traditional phase I dose finding cancer clinical trial designs aim to determine the maximum tolerated dose (MTD) of the investigational cytotoxic agent based on a single toxicity outcome, assuming a monotone dose-response relationship.…

Methodology · Statistics 2024-11-14 Hao Sun , Hsin-Yu Lin , Jieqi Tu , Revathi Ananthakrishnan , Eunhee Kim

Bayesian optimal design is considered for experiments where the response distribution depends on the solution to a system of non-linear ordinary differential equations. The motivation is an experiment to estimate parameters in the equations…

Methodology · Statistics 2019-05-02 Antony Overstall , David Woods , Ben Parker

There are multiple cluster randomised trial designs that vary in when the clusters cross between control and intervention states, when observations are made within clusters, and how many observations are made at that time point. Identifying…

Methodology · Statistics 2023-07-20 Samuel I. Watson , Alan Girling , Karla Hemming

We construct optimal designs for group testing experiments where the goal is to estimate the prevalence of a trait by using a test with uncertain sensitivity and specificity. Using optimal design theory for approximate designs, we show that…

Statistics Theory · Mathematics 2017-01-05 Shih-Hao Huang , Mong-Na Lo Huang , Kerby Shedden , Weng Kee Wong

Project Optimus, an initiative by the FDA's Oncology Center of Excellence, seeks to reform the dose-optimization and dose-selection paradigm in oncology. We propose a dose-optimization design that considers plateau efficacy profiles,…

Applications · Statistics 2025-04-22 Rebecca B. Silva , Bin Cheng , Shing M. Lee

For biological experiments aiming at calibrating models with unknown parameters, a good experimental design is crucial, especially for those subject to various constraints, such as financial limitations, time consumption and physical…

Applications · Statistics 2014-07-22 Xiao Lin , Gabriel Terejanu

Given covariates for $n$ units, each of which is to receive a treatment with probability $1/2$, we study the question of how best to correlate their treatment assignments to minimize the variance of the IPW estimator of the average…

Methodology · Statistics 2025-01-08 Tim Morrison , Art B. Owen

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

We consider the optimal design problem for a comparison of two regression curves, which is used to establish the similarity between the dose response relationships of two groups. An optimal pair of designs minimizes the width of the…

Methodology · Statistics 2014-11-19 Holger Dette , Kirsten Schorning

We propose Locally Optimal Restricted Designs (LORDs) for phase I/II dose-finding studies that focus on both efficacy and toxicity outcomes. As an illustrative application, we find various LORDs for a 4-parameter continuation-ratio (CR)…

Methodology · Statistics 2025-09-09 Oleksandr Sverdlov , Yevgen Ryeznik , Weng Kee Wong

Data-driven, machine learning (ML) models of atomistic interactions are often based on flexible and non-physical functions that can relate nuanced aspects of atomic arrangements into predictions of energies and forces. As a result, these…

Materials Science · Physics 2024-05-15 Bartosz Barzdajn , Christopher P. Race

Given n experiment subjects with potentially heterogeneous covariates and two possible treatments, namely active treatment and control, this paper addresses the fundamental question of determining the optimal accuracy in estimating the…

Machine Learning · Statistics 2024-11-13 Jiachun Li , David Simchi-Levi , Yunxiao Zhao

The interference model has been widely used and studied in block experiments where the treatment for a particular plot has effects on its neighbor plots. In this paper, we study optimal circular designs for the proportional interference…

Statistics Theory · Mathematics 2015-07-31 Kang Li , Wei Zheng , Mingyao Ai

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