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Recently, the strategy for dose optimization in oncology has shifted to conduct Phase 2 randomized controlled trials with multiple doses. Optimal biologic dose selection from Phase 1 trial data to determine candidate doses for Phase 2…

Methodology · Statistics 2023-02-14 Masahiro Kojima

Monitoring treatment response in longitudinal studies plays an important role in clinical practice. Accurately identifying lesions across serial imaging follow-up is the core to the monitoring procedure. Typically this incorporates both…

Computer Vision and Pattern Recognition · Computer Science 2021-04-13 Jinzheng Cai , Youbao Tang , Ke Yan , Adam P. Harrison , Jing Xiao , Gigin Lin , Le Lu

Dynamic treatment regimes (DTRs) are used in medicine to tailor sequential treatment decisions to patients by considering patient heterogeneity. Common methods for learning optimal DTRs, however, have shortcomings: they are typically based…

Machine Learning · Statistics 2023-06-21 Theresa Blümlein , Joel Persson , Stefan Feuerriegel

Clinical diagnosis requires sequential evidence acquisition under uncertainty. However, most Large Language Model (LLM) based diagnostic systems assume fully observed patient information and therefore do not explicitly model how clinical…

Artificial Intelligence · Computer Science 2026-04-08 Xuyang Shen , Haoran Liu , Dongjin Song , Martin Renqiang Min

Combination drug therapies hold significant promise for enhancing treatment efficacy, particularly in fields such as oncology, immunotherapy, and infectious diseases. However, designing clinical trials for these regimens poses unique…

Methodology · Statistics 2025-06-04 Nan Miles Xi , Man Mandy Jin , Lin Wang , Xin Huang

In the pursuit of developing Large Language Models (LLMs) that adhere to societal standards, it is imperative to detect the toxicity in the generated text. The majority of existing toxicity metrics rely on encoder models trained on specific…

Computation and Language · Computer Science 2024-11-15 Hyukhun Koh , Dohyung Kim , Minwoo Lee , Kyomin Jung

Conventionally, a first-in-human phase I trial in healthy volunteers aims to confirm the safety of a drug in humans. In such situations, volunteers should not suffer from any safety issues and simple algorithm-based dose-escalation schemes…

As machine learning (ML)-based decision support tools proliferate in clinical practice, understanding how clinicians integrate personalized ML predictions alongside randomized controlled trial (RCT) evidence is critical. We designed a…

Human-Computer Interaction · Computer Science 2026-05-19 Zeshan Hussain , Barbara D. Lam , Fernando A. Acosta-Perez , Irbaz Bin Riaz , Maia Jacobs , Andrew J. Yee , David Sontag

Two useful strategies to speed up drug development are to increase the patient accrual rate and use novel adaptive designs. Unfortunately, these two strategies often conflict when the evaluation of the outcome cannot keep pace with the…

Methodology · Statistics 2018-07-24 Ruitao Lin , Ying Yuan

Dynamic treatment regimes (DTR) are sequential decision rules corresponding to several stages of intervention. Each rule maps patients' covariates to optional treatments. The optimal dynamic treatment regime is the one that maximizes the…

Methodology · Statistics 2023-10-10 Zhishuai Liu , Zishu Zhan , Jian Liu , Danhui Yi , Cunjie Lin , Yufei Yang

Radiotherapy (RT) is a critical cancer treatment, with volumetric modulated arc therapy (VMAT) being a commonly used technique that enhances dose conformity by dynamically adjusting multileaf collimator (MLC) positions and monitor units…

Medical Physics · Physics 2025-06-26 Stefanos Achlatis , Efstratios Gavves , Jan-Jakob Sonke

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

Conventional planning objectives in optimization of intensity-modulated radiotherapy treatment (IMRT) plans are designed to minimize the violation of dose-volume histogram (DVH) thresholds using penalty functions. Although successful in…

Medical Physics · Physics 2023-07-19 Lovisa Engberg , Kjell Eriksson , Anders Forsgren , Björn Hårdemark

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

Radiation therapy is considered to be one of important treatment protocols for cancers. Radiation therapy employs several beams of ionizing radiation to kill cancer tumors, but such irradiation also causes damage to normal tissues.…

Optimization and Control · Mathematics 2016-12-06 Shogo Kishimoto , Makoto Yamashita

Many drugs used therapeutically or recreationally induce tolerance: the effect of the substance decreases with repeated use. This phenomenon may reduce the efficacy of the substance unless dosage is increased beyond what is healthy for the…

Dynamical Systems · Mathematics 2024-03-19 Golrokh Nouri , Paul Tupper

Randomized discontinuation design (RDD) is an enrichment strategy commonly used to address limitations of traditional placebo-controlled trials, particularly the ethical concern of prolonged placebo exposure. RDD consists of two phases: an…

Methodology · Statistics 2025-06-03 Ayon Mukherjee , Oleksandr Sverdlov , Ngoc-Thuy Ha , Yu Deng

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

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

While cancer has traditionally been considered a genetic disease, mounting evidence indicates an important role for non-genetic (epigenetic) mechanisms. Common anti-cancer drugs have recently been observed to induce the adoption of…

Populations and Evolution · Quantitative Biology 2025-07-04 Einar Bjarki Gunnarsson , Benedikt Vilji Magnússon , Jasmine Foo
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