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Traditional health authority approval for oncology drugs is based on a clinical benefit endpoint, or a valid surrogate. In 1992 the FDA created the Accelerated Approval pathway to allow for earlier approval of therapies in serious…

Applications · Statistics 2026-02-26 Jane She , Xiaofei Chen , Malini Iyengar , Judy Li

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

Phase I dose-escalation trials must be guided by a safety model in order to avoid exposing patients to unacceptably high risk of toxicities. Traditionally, these trials are based on one type of schedule. In more recent practice, however,…

Methodology · Statistics 2020-08-18 Burak Kürsad Günhan , Sebastian Weber , Tim Friede

In multi-stage radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated mostly by radiobiological considerations, but also provides an approach to reduce normal tissue dose by…

An individualized dose rule recommends a dose level within a continuous safe dose range based on patient level information such as physical conditions, genetic factors and medication histories. Traditionally, personalized dose finding…

Methodology · Statistics 2020-07-21 Liangyu Zhu , Wenbin Lu , Michael R. Kosorok , Rui Song

This paper studies sample-size design for finite-population test-and-roll experiments, where a decision-maker first conducts an experiment on $m$ units and then assigns the remaining $N-m$ units to the treatment that performs better in the…

Econometrics · Economics 2026-05-05 Kentaro Kawato , Shosei Sakaguchi

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

In this paper we consider two-stage adaptive dose-response study designs, where the study design is changed at an interim analysis based on the information collected so far. In a simulation study, two approaches will be compared for these…

Methodology · Statistics 2016-02-08 Emma McCallum , Björn Bornkamp

The determination of the sample size required by a crossover trial typically depends on the specification of one or more variance components. Uncertainty about the value of these parameters at the design stage means that there is often a…

Methodology · Statistics 2018-03-28 Michael Grayling , Adrian Mander , James Wason

Large-batch training has become a cornerstone in accelerating the training of deep neural networks, yet it poses challenges in optimization and generalization. Existing optimizers like AdamW present performance degradation during language…

Machine Learning · Computer Science 2025-08-29 Yang Luo , Zangwei Zheng , Ziheng Qin , Zirui Zhu , Yong Liu , Yang You

We study the design of multi-armed parallel group clinical trials to estimate personalized treatment rules that identify the best treatment for a given patient with given covariates. Assuming that the outcomes in each treatment arm are…

Statistics Theory · Mathematics 2022-07-13 David Azriel , Yosef Rinott , Martin Posch

Several recent publications report advances in training optimal decision trees (ODT) using mixed-integer programs (MIP), due to algorithmic advances in integer programming and a growing interest in addressing the inherent suboptimality of…

Machine Learning · Computer Science 2020-11-09 Haoran Zhu , Pavankumar Murali , Dzung T. Phan , Lam M. Nguyen , Jayant R. Kalagnanam

Randomized controlled trials are often run in settings with many subpopulations that may have differential benefits from the treatment being evaluated. We consider the problem of sample selection, i.e., whom to enroll in a randomized trial,…

Methodology · Statistics 2024-06-26 Yuchen Hu , Henry Zhu , Emma Brunskill , Stefan Wager

Intensity Modulated Radiation Therapy is an effective cancer treatment. Models based on the Generalized Equivalent Uniform Dose (gEUD) provide radiation plans with excellent planning target volume coverage and low radiation for organs at…

We propose a multi-metric flexible Bayesian framework to support efficient interim decision-making in multi-arm multi-stage phase II clinical trials. Multi-arm multi-stage phase II studies increase the efficiency of drug development, but…

Applications · Statistics 2023-12-15 Suzanne M. Dufault , Angela M. Crook , Katie Rolfe , Patrick P. J. Phillips

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

Technological advancements in mobile devices have made it possible to deliver mobile health interventions to individuals. A novel intervention framework that emerges from such advancements is the just-in-time adaptive intervention (JITAI),…

Methodology · Statistics 2020-07-29 Jing Xu , Xiaoxi Yan , Caroline Figueroa , Joseph Jay Williams , Bibhas Chakraborty

The conventional phase II trial design paradigm is to make the go/no-go decision based on the hypothesis testing framework. Statistical significance itself alone, however, may not be sufficient to establish that the drug is clinically…

Methodology · Statistics 2021-12-22 Yujie Zhao , Daniel Li , Rong Liu , Ying Yuan

Minimizing the number of patients exposed to potentially harmful drugs in early onco logical trials is a major concern during planning. Adaptive designs account for the inherent uncertainty about the true effect size by determining the…

Applications · Statistics 2016-05-03 Kevin Kunzmann , Meinhard Kieser

Multistate process data are common in studies of chronic diseases such as cancer. These data are ideal for precision medicine purposes as they can be leveraged to improve more refined health outcomes, compared to standard survival outcomes,…

Methodology · Statistics 2022-11-28 Giorgos Bakoyannis