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Clinicians and researchers alike are increasingly interested in how best to personalize interventions. A dynamic treatment regimen (DTR) is a sequence of pre-specified decision rules which can be used to guide the delivery of a sequence of…

Traditional phase I dose finding cancer clinical trial designs aim to determine the maximum tolerated dose (MTD) of the investigational cytotoxic agent based on a single toxicity outcome, assuming a monotone dose-response relationship.…

Methodology · Statistics 2024-11-14 Hao Sun , Hsin-Yu Lin , Jieqi Tu , Revathi Ananthakrishnan , Eunhee Kim

Dose-escalation trials in oncology drug development still today typically aim to identify 1-size-fits-all dose recommendations, as arbitrary quantiles of the toxicity thresholds evident in patient samples. In the late 1990s efforts to…

Category Theory · Mathematics 2025-07-03 David C. Norris

Drug combination trials are increasingly common nowadays in clinical research. However, very few methods have been developed to consider toxicity attributions in the dose escalation process. We are motivated by a trial in which the…

Methodology · Statistics 2018-08-23 Jose L. Jimenez , Mourad Tighiouart , Mauro Gasparini

Background. The DURATIONS design has been recently proposed as a practical alternative to a standard two-arm non-inferiority design when the goal is to optimise some continuous aspect of treatment administration, e.g. duration or frequency,…

Applications · Statistics 2023-04-20 Matteo Quartagno , Ehsan Ghorani , Tim P Morris , Michael J Seckl , Mahesh KB Parmar

Randomized controlled trials (RCTs) can be used to generate guarantees on treatment effects. However, RCTs often spend unnecessary resources exploring sub-optimal treatments, which can reduce the power of treatment guarantees. To address…

Computers and Society · Computer Science 2024-10-16 Santiago Cortes-Gomez , Naveen Raman , Aarti Singh , Bryan Wilder

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

Recent developments in artificial intelligence and automation support a new drug design paradigm: autonomous drug design. Under this paradigm, generative models can provide suggestions on thousands of molecules with specific properties, and…

There has been an increasing interest in using interval-based Bayesian designs for dose finding, one of which is the modified toxicity probability interval (mTPI) method. We show that the decision rules in mTPI correspond to an optimal rule…

Methodology · Statistics 2016-09-29 Wentian Guo , Sue-Jane Wang , Shengjie Yang , Suiheng Lin , Yuan Ji

Cluster randomized trials (CRTs) are studies where treatment is randomized at the cluster level but outcomes are typically collected at the individual level. When CRTs are employed in pragmatic settings, baseline population characteristics…

Methodology · Statistics 2023-06-22 Mary M. Ryan , Denise Esserman , Fan Li

The field of precision medicine aims to tailor treatment based on patient-specific factors in a reproducible way. To this end, estimating an optimal individualized treatment regime (ITR) that recommends treatment decisions based on patient…

Although optimal control theory has been used for the theoretical study of anti-cancerous drugs scheduling optimization, with the aim of reducing the primary tumor volume, the effect on metastases is often ignored. Here, we use a previously…

Tissues and Organs · Quantitative Biology 2013-06-21 Sebastien Benzekry , Philip Hahnfeldt

To promote precision medicine, individualized treatment regimes (ITRs) are crucial for optimizing the expected clinical outcome based on patient-specific characteristics. However, existing ITR research has primarily focused on scenarios…

Methodology · Statistics 2024-02-20 Chang Wang , Lu Wang

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

Group sequential designs (GSDs) are well established and the most commonly used adaptive design in confirmatory clinical trials with interim analyses. However, they remain underutilised, and their implementation involves unique theoretical…

Methodology · Statistics 2025-09-09 Zhangyi He , Suzie Cro , Laurent Billot

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

It is crucial to design Phase II cancer clinical trials that balance the efficiency of treatment selection with clinical practicality. Sargent and Goldberg proposed a frequentist design that allow decision-making even when the primary…

Methodology · Statistics 2025-05-15 Moka Komaki , Satoru Shinoda , Haiyan Zheng , Kouji Yamamoto

Multi-arm multi-stage trial designs can bring notable gains in efficiency to the drug development process. However, for normally distributed endpoints, the determination of a design typically depends on the assumption that the patient…

Methodology · Statistics 2017-10-11 Michael Grayling , James Wason , Adrian Mander

This study investigates the applicability of 3D dose predictions from a model trained on one modality to a cross-modality automated planning workflow. Additionally, we explore the impact of integrating a multi-criteria optimizer on adapting…

Medical Physics · Physics 2024-02-26 Gregory Szalkowski , Xuanang Xu , Shiva Das , Pew-Thian Yap , Jun Lian

Background. Designing trials to reduce treatment duration is important in several therapeutic areas, including TB and antibiotics. We recently proposed a new randomised trial design to overcome some of the limitations of standard two-arm…

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