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Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing…

Computation · Statistics 2025-03-11 Michael Sweeting , Daniel Slade , Dan Jackson , Kristian Brock

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

Adaptive sample size re-estimation, early stopping, and trial re-design at interim analyses can reduce expected sample sizes in randomised trials. Cluster randomised trials, in which groups of participants are randomly allocated to…

Methodology · Statistics 2026-03-09 Samuel I. Watson , James Martin

Technological advancements in the field of mobile devices and wearable sensors have helped overcome obstacles in the delivery of care, making it possible to deliver behavioral treatments anytime and anywhere. Increasingly the delivery of…

Applications · Statistics 2017-11-13 Walter Dempsey , Peng Liao , Santosh Kumar , Susan A. Murphy

In single-arm phase II oncology trials, the most popular choice of design is Simon's two-stage design, which allows early stopping at one interim analysis. However, the expected trial sample size can be reduced further by allowing…

Methodology · Statistics 2019-09-09 Martin Law , Michael J. Grayling , Adrian P. Mander

Breakthroughs in cancer biology have defined new research programs emphasizing the development of therapies that target specific pathways in tumor cells. Innovations in clinical trial design have followed with master protocols defined by…

Methodology · Statistics 2020-07-09 Alexander M. Kaizer , Joseph S. Koopmeiners , Nan Chen , Brian P. Hobbs

It is increasingly common for therapies in oncology to be given in combination. In some cases, patients can benefit from the interaction between two drugs, although often at the risk of higher toxicity. A large number of designs to conduct…

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

The question of selecting the "best" amongst different choices is a common problem in statistics. In drug development, our motivating setting, the question becomes, for example: what is the dose that gives me a pre-specified risk of…

Statistics Theory · Mathematics 2018-03-15 Pavel Mozgunov , Thomas Jaki

Multi-armed bandits (MAB) are extensively studied in various settings where the objective is to \textit{maximize} the actions' outcomes (i.e., rewards) over time. Since safety is crucial in many real-world problems, safe versions of MAB…

Machine Learning · Computer Science 2021-12-14 Ilker Demirel , Mehmet Ufuk Ozdemir , Cem Tekin

Platform trials are a more efficient way of testing multiple treatments compared to running separate trials. In this paper we consider platform trials where, if a treatment is found to be superior to the control, it will become the new…

Methodology · Statistics 2023-11-30 Peter Greenstreet , Thomas Jaki , Alun Bedding , Pavel Mozgunov

This paper introduces a novel multi-stage decision-making model that integrates hypothesis testing and dynamic programming algorithms to address complex decision-making scenarios.Initially,we develop a sampling inspection scheme that…

Systems and Control · Electrical Eng. & Systems 2025-03-11 Ziyang Liu , Yurui Hu , Yihan Deng

FDA's Project Optimus initiative for oncology drug development emphasizes selecting a dose that optimizes both efficacy and safety. When an inferentially adaptive Phase 2/3 design with dose selection is implemented to comply with the…

Applications · Statistics 2024-12-12 Cong Chen , Mo Huang , Xuekui Zhang

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

This paper studies empirical risk minimization (ERM) problems for large-scale datasets and incorporates the idea of adaptive sample size methods to improve the guaranteed convergence bounds for first-order stochastic and deterministic…

Machine Learning · Computer Science 2017-09-05 Aryan Mokhtari , Alejandro Ribeiro

Adaptive designs are commonly used in clinical and drug development studies for optimum utilization of available resources. In this article, we consider the problem of estimating the effect of the selected (better) treatment using a…

Statistics Theory · Mathematics 2023-01-24 Masihuddin , Neeraj Misra

Despite the enormous success of Hamiltonian Monte Carlo and related Markov Chain Monte Carlo (MCMC) methods, sampling often still represents the computational bottleneck in scientific applications. Availability of parallel resources can…

Computation · Statistics 2026-01-26 Jakob Robnik , Uroš Seljak

Adaptive designs for multi-armed clinical trials have become increasingly popular recently in many areas of medical research because of their potential to shorten development times and to increase patient response. However, developing…

Applications · Statistics 2017-03-16 Adam Smith , Sofia S. Villar

Optimizing doses for multiple indications is challenging. The pooled approach of finding a single optimal biological dose (OBD) for all indications ignores that dose-response or dose-toxicity curves may differ between indications, resulting…

Methodology · Statistics 2024-10-07 Shuqi Wang , Peter F. Thall , Kentaro Takeda , Ying Yuan

Group sequential designs drive innovation in clinical, industrial, and corporate settings. Early stopping for failure in sequential designs conserves experimental resources, whereas early stopping for success accelerates access to improved…

Methodology · Statistics 2025-11-27 Luke Hagar , Shirin Golchi , Marina B. Klein