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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

We consider the optimization of an uncertain objective over continuous and multi-dimensional decision spaces in problems in which we are only provided with observational data. We propose a novel algorithmic framework that is tractable,…

Machine Learning · Statistics 2018-10-30 Dimitris Bertsimas , Christopher McCord

Applications of artificial intelligence (AI) in drug development continue to increase at a rapid pace. Regulatory authorities have provided increasingly clear perspectives on the use of AI in regulated applications, including recent draft…

Applications · Statistics 2026-05-25 Aaron M. Smith , Tala Fakhouri , Run Zhuang , Jonathan R. Walsh

Since early 2020, the world has been dealing with a raging pandemic outbreak: COVID-19. A year later, vaccines have become accessible, but in limited quantities, so that governments needed to devise a strategy to decide which part of the…

Populations and Evolution · Quantitative Biology 2022-04-13 Sander Tonkens , Paul de Klaver , Mauro Salazar

There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed…

Methodology · Statistics 2023-08-25 Peter Greenstreet , Thomas Jaki , Alun Bedding , Pavel Mozgunov

Multi-arm multi-stage (MAMS) trials have gained popularity, due to their improved efficiency in evaluating multiple treatments. A traditional MAMS trial often decreases the expected sample size of the trial compared to just running a…

Sampling is a basic operation in many inference-time algorithms of large language models (LLMs). To scale up inference efficiently with a limited compute, it is crucial to find an optimal allocation for sample compute budgets: Which…

Computation and Language · Computer Science 2024-10-31 Kexun Zhang , Shang Zhou , Danqing Wang , William Yang Wang , Lei Li

The keyboard design is a novel phase I dose-finding method that is simple and has good operating characteristics. This paper studies theoretical properties of the keyboard design, including the optimality of its decision rules, coherence in…

Methodology · Statistics 2017-12-20 Haitao Pan , Ruitao Lin , Ying Yuan

We are interested in in silico evaluation methodology for molecular optimization methods. Given a sample of molecules and their properties of our interest, we wish not only to train an agent that can find molecules optimized with respect to…

Machine Learning · Computer Science 2022-01-31 Hiroshi Kajino , Kohei Miyaguchi , Takayuki Osogami

Motivated by a clinical trial conducted by Janssen Pharmaceuticals in which a flexible dosing regimen is compared to placebo, we evaluate how switchers in the treatment arm (i.e., patients who were switched to the higher dose) would have…

Methodology · Statistics 2020-09-07 Kelly Van Lancker , An Vandebosch , Stijn Vansteelandt

Hierarchical random effect models are used for different purposes in clinical research and other areas. In general, the main focus is on population parameters related to the expected treatment effects or group differences among all units of…

Applications · Statistics 2021-04-07 Maryna Prus , Norbert Benda , Rainer Schwabe

Under two-phase designs, the outcome and several covariates and confounders are measured in the first phase, and a new predictor of interest, which may be costly to collect, can be measured on a subsample in the second phase, without…

Methodology · Statistics 2023-05-12 Jingjing Zou , Lori B. Daniels , Karen Messer , Daniel Rabinowitz

A multi-arm multi-stage trial is a multi-arm trial which includes interim analyses - analysing the data at certain specified points, generally discontinuing treatments which are concluded to not work and proceeding with the remainder. It is…

Methodology · Statistics 2022-11-14 Martin Law

We consider a model where an agent has a repeated decision to make and wishes to maximize their total payoff. Payoffs are influenced by an action taken by the agent, but also an unknown state of the world that evolves over time. Before…

Computer Science and Game Theory · Computer Science 2021-01-20 Nicole Immorlica , Ian Kash , Brendan Lucier

Practitioners conducting adaptive experiments often encounter two competing priorities: maximizing total welfare (or `reward') through effective treatment assignment and swiftly concluding experiments to implement population-wide…

Machine Learning · Computer Science 2024-07-31 Chao Qin , Daniel Russo

Treatment planning uncertainties are typically managed using margin-based or robust optimization. Margin-based methods expand the clinical target volume (CTV) to a planning target volume, generally unsuited for proton therapy. Robust…

The use of `backfilling', assigning additional patients to doses deemed safe, in phase I dose-escalation studies has been used in practice to collect additional information on the safety profile, pharmacokinetics and activity of a drug.…

Applications · Statistics 2022-04-22 Helen Barnett , Oliver Boix , Dimitris Kontos , Thomas Jaki

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

The commonplace description of phase 1 clinical trials in oncology as "primarily concerned with safety" is belied by their near universal adoption of dose-escalation practices which are inherently unsafe. In contrast with dose titration,…

Methodology · Statistics 2020-04-28 David C. Norris

Ecologists are interested in modeling the population growth of species in various ecosystems. Studying population dynamics can assist environmental managers in making better decisions for the environment. Traditionally, the sampling of…

Methodology · Statistics 2021-02-04 Rebecca E. Atanga , Edward L. Boone , Ryad A. Ghanam , Ben Stewart-Koster