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In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and efficacious that maximises some optimality criterion based on safety and efficacy. This is further complicated when…

Applications · Statistics 2022-03-31 Helen Barnett , Oliver Boix , Dimitris Kontos , Thomas Jaki

Basket trials in oncology enroll multiple patients with cancer harboring identical gene alterations and evaluate their response to targeted therapies across cancer types. Several existing methods have extended a Bayesian hierarchical model…

Methodology · Statistics 2024-12-17 Ryo Kitabayashi , Hiroyuki Sato , Akihiro Hirakawa

Accurate dose calculation is vitally important for proton therapy. Pencil beam (PB) model-based dose calculation is fast but inaccurate due to the approximation when dealing with inhomogeneities. Monte Carlo (MC) dose calculation is the…

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

Many phase II clinical trials have used survival outcomes as the primary endpoints in recent decades. Suppose the radiotherapy is evaluated in a phase II trial using survival outcomes. In that case, the competing risk issue often arises…

Applications · Statistics 2022-03-15 Jina Park , Wenjing Hu , Ick Hoon Jin , Hao Liu , Yong Zang

For many years Phase I and Phase II clinical trials were conducted separately, but there was a recent shift to combine these Phases. While a variety of Phase~I/II model-based designs for cytotoxic agents were proposed in the literature,…

Methodology · Statistics 2018-06-19 Pavel Mozgunov , Thomas Jaki

An important task in drug development is to identify patients, which respond better or worse to an experimental treatment. Identifying predictive covariates, which influence the treatment effect and can be used to define subgroups of…

Methodology · Statistics 2018-11-27 Marius Thomas , Björn Bornkamp , Katja Ickstadt

In precision medicine, identifying optimal sequences of decision rules, termed dynamic treatment regimes (DTRs), is an important undertaking. One approach investigators may take to infer about optimal DTRs is via Bayesian dynamic Marginal…

Methodology · Statistics 2022-06-09 Daniel Rodriguez Duque , David A. Stephens , Erica E. M. Moodie

In traditional dose-finding studies, dose-limiting toxicity (DLT) is determined within a fixed time observation window where DLT is often defined as a binary outcome. In the setting of oncology dose-finding trials, often patients in…

Applications · Statistics 2019-09-09 Lucie Biard , Bin Cheng , Gulam A. Manji , Shing M. Lee

A common problem faced in clinical studies is that of estimating the effect of the most effective (e.g., the one having the largest mean) treatment among $k~(\geq2)$ available treatments. The most effective treatment is adjudged based on…

Statistics Theory · Mathematics 2022-09-20 Masihuddin , Neeraj Misra

Biomarker-guided designs are increasingly used to evaluate personalized treatments based on patients' biomarker status in Phase II and III clinical trials. With adaptive enrichment, these designs can improve the efficiency of evaluating the…

Methodology · Statistics 2024-06-11 Kaiyuan Hua , Hwanhee Hong , Xiaofei Wang

We consider a formal statistical design that allows simultaneous enrollment of a main cohort and a backfill cohort of patients in a dose-finding trial. The goal is to accumulate more information at various doses to facilitate dose…

Applications · Statistics 2024-04-03 Jiaxin Liu , Shijie Yuan , B. Nebiyou Bekele , Yuan Ji

Random allocation models used in clinical trials aid researchers in determining which of a particular treatment provides the best results by reducing bias between groups. Often however, this determination leaves researchers battling ethical…

Applications · Statistics 2020-08-04 Albert. H. Lee , Edward L Boone , Roy T. Sabo , Erin Donahue

The next great leap toward improving treatment of cancer with radiation will require the combined use of online adaptive and magnetic resonance guided radiation therapy techniques with automatic X-ray beam orientation selection.…

Medical Physics · Physics 2019-08-14 Ryan Neph , Yangsibo Huang , Youming Yang , Ke Sheng

Mass Casualty Incidents can overwhelm emergency medical systems and resulting delays or errors in the assessment of casualties can lead to preventable deaths. We present a decision support framework that fuses outputs from multiple computer…

Artificial Intelligence · Computer Science 2026-04-24 Szymon Rusiecki , Cecilia G. Morales , Kimberly Elenberg , Leonard Weiss , Artur Dubrawski

We consider the optimal design problem for identifying effective dose combinations within drug combination studies where the effect of the combination of two drugs is investigated. Drug combination studies are becoming increasingly…

Self-driving laboratories (SDLs) are combining recent technological advances in robotics, automation, and machine learning based data analysis and decision-making to perform autonomous experimentation toward human-directed goals without…

Machine Learning · Computer Science 2025-12-18 Luca Torresi , Pascal Friederich

Protein language models (PLMs) are becoming practical tools for de novo protein design, yet their dual-use potential raises safety concerns. We show that domain adaptation to specific taxonomic groups can elicit toxic protein generation,…

Machine Learning · Computer Science 2026-03-05 Manuel Fernández Burda , Santiago Aranguri , Iván Arcuschin Moreno , Enzo Ferrante

This paper studies system identification for nonlinear state-space models, a problem that arises across many fields yet remains challenging in practice. Focusing on maximum likelihood estimation, we employ Bayesian optimization (BayesOpt)…

Systems and Control · Electrical Eng. & Systems 2026-03-30 Hao Tu , Jackson Fogelquist , Iman Askari , Xinfan Lin , Yebin Wang , Shiguang Deng , Huazhen Fang

Introduction: Joint models are increasingly used in clinical trials. An important part of model building is to properly assess the descriptive and predictive ability of these models. Normalised prediction discrepancies (npd) and normalised…