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We propose a data-dependent early completion of dose finding trials for drug-combination. The early completion is determined when a beta-binomial probability for dose retainment with the trial data and the number of remaining patients is…

Methodology · Statistics 2022-02-10 Masahiro Kojima

One way to investigate the precision of estimates likely to result from planned experiments and planned epidemiological studies is to simulate a large number of possible outcomes and analyse the sets of possible results. This appears to be…

Computation · Statistics 2013-06-28 G. K. Robinson , L. M. Ryan

Incorporating historical data or real-world evidence has a great potential to improve the efficiency of phase I clinical trials and to accelerate drug development. For model-based designs, such as the continuous reassessment method (CRM),…

Methodology · Statistics 2020-06-11 Yanhong Zhou , J. Jack Lee , Shunguang Wang , Stuart Bailey , Ying Yuan

A common problem in Phase II clinical trials is the comparison of dose response curves corresponding to different treatment groups. If the effect of the dose level is described by parametric regression models and the treatments differ in…

Statistics Theory · Mathematics 2016-03-16 Chrystel Feller , Kirsten Schorning , Holger Dette , Georgina Bermann , Björn Bornkamp

Adaptive designs are increasingly used in clinical trials and online experiments to improve participant outcomes by dynamically updating treatment allocation as data accumulate. In practice, experimenters often consider multiple candidate…

Methodology · Statistics 2026-04-08 Wenxin Zhang , Aaron Hudson , Maya Petersen , Mark van der Laan

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

Optimization via simulation has been well established to find optimal solutions and designs in complex systems. However, it still faces modeling and computational challenges when extended to the multi-stage setting. This survey reviews the…

Optimization and Control · Mathematics 2023-12-08 Zhuo Zhang , Dan Wang , Haoxiang Yang , Shubin Si

Adaptive seamless designs combine confirmatory testing, a domain of phase III trials, with features such as treatment or subgroup selection, typically associated with phase II trials. They promise to increase the efficiency of development…

Methodology · Statistics 2019-01-25 Tim Friede , Nigel Stallard , Nicholas Parsons

Clinical trials with time-to-event endpoints, such as overall survival (OS) or progression-free survival (PFS), are fundamental for evaluating new treatments, particularly in immuno-oncology. However, modern therapies, such as…

Methodology · Statistics 2025-09-10 James Salsbury , Jeremy Oakley , Steven Julious , Lisa Hampson

Recently, numerous pharmaceutical sponsors have expressed a great deal of interest in the development of biosimilars, which requires clinical trials to demonstrate the equivalence of pharmacokinetics (PK) and clinical efficacy.…

Applications · Statistics 2017-05-16 Ryuji Uozumi , Chikuma Hamada

The landscape of dose-finding designs for phase I clinical trials is rapidly shifting in the recent years, noticeably marked by the emergence of interval-based designs. We categorize them as the iDesigns and the IB-Designs. The iDesigns are…

Methodology · Statistics 2017-06-15 Yuan Ji , Shengjie Yang

The paper presents an investigation of estimating treatment effect using different matching methods. The study proposed a new method which is computationally efficient and convenient in implication-'largest caliper matching' and compared…

Applications · Statistics 2018-06-07 Sharif Mahmood

Platform trials evaluate multiple experimental treatments against a common control group (and/or against each other), which often reduces the trial duration and sample size. Bayesian platform designs offer several practical advantages,…

Methodology · Statistics 2025-07-18 Luke Hagar , Lara Maleyeff , Shirin Golchi , Dick Menzies

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

Decision rules offer a rich and tractable framework for solving certain classes of multistage adaptive optimization problems. Recent literature has shown the promise of using linear and nonlinear decision rules in which wait-and-see…

Optimization and Control · Mathematics 2022-11-24 Said Rahal , Dimitri J. Papageorgiou , Zukui Li

Simulation offers a simple and flexible way to estimate the power of a clinical trial when analytic formulae are not available. The computational burden of using simulation has, however, restricted its application to only the simplest of…

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

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

The US FDA's Project Optimus initiative that emphasizes dose optimization prior to marketing approval represents a pivotal shift in oncology drug development. It has a ripple effect for rethinking what changes may be made to conventional…

Methodology · Statistics 2024-06-04 Yuhan Li , Yiding Zhang , Gu Mi , Ji Lin

The conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase…

Methodology · Statistics 2023-08-31 Peng Yang , Daniel Li , Ruitao Lin , Bo Huang , Ying Yuan