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In a Phase II dose-finding study with a placebo control, a new drug with several dose levels is compared with a placebo to test for the effectiveness of the new drug. The main focus of such studies often lies in the characterization of the…

Methodology · Statistics 2020-07-14 Saswati Saha , Werner Brannath

An accurately identified maximum tolerated dose (MTD) serves as the cornerstone of successful subsequent phases in oncology drug development. Bayesian logistic regression model (BLRM) is a popular and versatile model-based dose-finding…

Methodology · Statistics 2021-05-17 Hongtao Zhang , Alan Y Chiang , Jixian Wang

With the development of novel therapies such as molecularly targeted agents and immunotherapy, the maximum tolerated dose paradigm that "more is better" does not necessarily hold anymore. In this context, doses and schedules of novel…

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

Cohort-based enrollment can slow down dose-finding trials since the outcomes of the previous cohort must be fully evaluated before the next cohort can be enrolled. This results in frequent suspension of patient enrollment. The issue is…

Applications · Statistics 2020-01-01 Tianjian Zhou , Wentian Guo , Yuan Ji

Clinical trials are an instrument for making informed decisions based on evidence from well-designed experiments. Here we consider adaptive designs mainly from the perspective of multi-arm Phase II clinical trials, in which one or more…

Methodology · Statistics 2021-08-31 Elja Arjas , Dario Gasbarra

Phase I dose-finding trials in oncology seek to find the maximum tolerated dose (MTD) of a drug under a specific schedule. Evaluating drug-schedules aims at improving treatment safety while maintaining efficacy. However, while we can…

Building state-of-the-art (SOTA) predictive models for drug discovery requires expensive search over tools, architectures, and training strategies. Current LLM-based agents can find SOTA solutions through extensive trial and error, but they…

Machine Learning · Computer Science 2026-05-18 Yikun Zhang , Xiwei Cheng , Tianyu Liu , Yuanqi Du , Wengong Jin

Drug discovery is a multi-stage process that comprises two costly major steps: pre-clinical research and clinical trials. Among its stages, lead optimization easily consumes more than half of the pre-clinical budget. We propose a combined…

Machine Learning · Computer Science 2020-11-30 Leili Zhang , Giacomo Domeniconi , Chih-Chieh Yang , Seung-gu Kang , Ruhong Zhou , Guojing Cong

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

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

Understanding treatment effect heterogeneity has become an increasingly popular task in various fields, as it helps design personalized advertisements in e-commerce or targeted treatment in biomedical studies. However, most of the existing…

Methodology · Statistics 2024-07-12 Waverly Wei , Xinwei Ma , Jingshen Wang

Diffusion models have achieved remarkable success in generative tasks but suffer from high computational costs due to their iterative sampling process and quadratic attention costs. Existing training-free acceleration strategies that reduce…

Machine Learning · Computer Science 2025-07-24 Ting Jiang , Yixiao Wang , Hancheng Ye , Zishan Shao , Jingwei Sun , Jingyang Zhang , Zekai Chen , Jianyi Zhang , Yiran Chen , Hai Li

Unsupervised domain adaptation has recently emerged as an effective paradigm for generalizing deep neural networks to new target domains. However, there is still enormous potential to be tapped to reach the fully supervised performance. In…

Machine Learning · Computer Science 2022-03-10 Binhui Xie , Longhui Yuan , Shuang Li , Chi Harold Liu , Xinjing Cheng , Guoren Wang

Safe exploration is critical for using reinforcement learning (RL) in risk-sensitive environments. Recent work learns risk measures which measure the probability of violating constraints, which can then be used to enable safety. However,…

Machine Learning · Computer Science 2021-12-08 Michael Luo , Ashwin Balakrishna , Brijen Thananjeyan , Suraj Nair , Julian Ibarz , Jie Tan , Chelsea Finn , Ion Stoica , Ken Goldberg

The traditional more-is-better dose selection paradigm, developed based on cytotoxic chemotherapeutics, is often problematic When applied to the development of novel molecularly targeted agents (e.g., kinase inhibitors, monoclonal…

Methodology · Statistics 2022-11-04 Liyun Jiang , Ying Yuan

We consider the procedure proposed by Bhandari et al. (2009) in the context of two-treatment clinical trials, with the objective of minimizing the applications of the less effective drug to the least number of patients. Our focus is on an…

Statistics Theory · Mathematics 2025-06-30 Sampurna Kundu , Jayant Jha , Subir Kumar Bhandari

The US Food and Drug Administration (FDA) launched Project Optimus and issued guidance to reform dose-finding and selection trials, shifting the paradigm from identifying the maximum tolerable dose (MTD) to determining the optimal…

Methodology · Statistics 2025-09-16 Kai Chen , Yixuan Zhao , Kentaro Takeda , Ying Yuan

Meta-learning is a popular approach for learning new tasks with limited data by leveraging the commonalities among different tasks. However, meta-learned models can perform poorly when context data is too limited, or when data is drawn from…

Machine Learning · Computer Science 2026-04-10 Young-Jin Park , Cesar Almecija , Apoorva Sharma , Navid Azizan

Consider an experiment, where a new drug is tested for the first time on human subjects - healthy volunteers. Such experiments are often performed as dose-escalation studies: a set of increasing doses is pre-selected, individuals are…

Statistics Theory · Mathematics 2016-08-17 Samuel Rosa , Radoslav Harman
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