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Oncology dose-finding trials are shifting from identifying the maximum tolerated dose (MTD) to determining the optimal biological dose (OBD), driven by the need for efficient methods that consider both toxicity and efficacy. This is…

Methodology · Statistics 2025-04-01 Hao Sun , Jieqi Tu , Revathi Ananthakrishnan , Eunhee Kim

Randomized experiments (often known as "A/B tests") are widely used to evaluate product and service innovations. We study how to allocate limited experimentation resources across M concurrent experiments in an experiment-rich regime.…

Methodology · Statistics 2026-03-19 Fenghua Yang , Dae Woong Ham , Stefanus Jasin

In this article, we propose a phase I-II design in two stages for the combination of molecularly targeted therapies. The design is motivated by a published case study that combines a MEK and a PIK3CA inhibitors; a setting in which higher…

Methodology · Statistics 2025-05-21 José L. Jiménez , Mourad Tighiouart

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

The primary objective of phase I oncology studies is to establish the safety profile of a new treatment and determine the maximum tolerated dose (MTD). This is motivated by the development of cytotoxic agents based on the underlying…

Applications · Statistics 2023-02-10 Yiding Zhang , Zhixing Xu , Hui Quan , Ji Lin

Identification of optimal dose combinations in early phase dose-finding trials is challenging, due to the trade-off between precisely estimating the many parameters required to flexibly model the possibly non-monotonic dose-response…

Methodology · Statistics 2024-02-13 James Willard , Shirin Golchi , Erica E. M. Moodie , Bruno Boulanger , Bradley P. Carlin

We developed a study design for rare disease clinical trials (RDTs) that efficiently evaluate treatments, promotes access to new treatments during treatment development, and optimizes healthcare resource utilization for future treatment…

Applications · Statistics 2016-07-04 Jian Yong , Sohaib H. Mohammad , Yan Yuan

There has been significant attention given to developing data-driven methods for tailoring patient care based on individual patient characteristics. Dynamic treatment regimes formalize this through a sequence of decision rules that map…

Methodology · Statistics 2022-02-22 Eric J. Rose , Erica E. M. Moodie , Susan Shortreed

We study the design of experiments with multiple treatment levels, a setting common in clinical trials and online A/B/n testing. Unlike single-treatment studies, practical analyses of multi-treatment experiments typically first select a…

Methodology · Statistics 2025-10-07 Jiachen Xu , Jian Qian , Zijun Gao

I study the minimax-optimal design for a two-arm controlled experiment where conditional mean outcomes may vary in a given set. When this set is permutation symmetric, the optimal design is complete randomization, and using a single…

Methodology · Statistics 2020-05-08 Nathan Kallus

Clinical randomized controlled trials (RCTs) collect hundreds of measurements spanning various metric types (e.g., laboratory tests, cognitive/motor assessments, etc.) across 100s-1000s of subjects to evaluate the effect of a treatment, but…

Machine Learning · Computer Science 2024-06-25 Sayeri Lala , Niraj K. Jha

Sequential Multiple Assignment Randomized Trials (SMARTs) are considered the gold standard for estimation and evaluation of treatment regimes. SMARTs are typically sized to ensure sufficient power for a simple comparison, e.g., the…

Breakthroughs in cancer biology have defined new research programs emphasizing the development of therapies that target specific pathways in tumor cells. Innovations in clinical trial design have followed with master protocols defined by…

Methodology · Statistics 2020-07-09 Alexander M. Kaizer , Joseph S. Koopmeiners , Nan Chen , Brian P. Hobbs

This work introduces the Burdened Bayesian Logistic Regression Model (BBLRM), an enhancement of the Bayesian Logistic Regression Model (BLRM) for dose-finding in phase I oncology trials. The BLRM determines the maximum tolerated dose (MTD)…

Methodology · Statistics 2025-08-18 Andrea Nizzardo , Luca Genetti , Marco Pergher

To accurately verify the dose of intensity-modulated radiation therapy (IMRT), we have used a global optimization method to investigate a new dose-verification algorithm. In practical application of this quality assurance (QA) procedure,…

Medical Physics · Physics 2007-05-23 Dong Hyun Park , Sung-Yong Park , Dahl Park , Tae-Hyun Kim , Kyung Hwan Shin , Dae Yong Kim , Kwan-Ho Cho

Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main…

Methodology · Statistics 2023-05-09 José L. Jiménez , Haiyan Zheng

In a sequential multiple-assignment randomized trial (SMART), a sequence of treatments is given to a patient over multiple stages. In each stage, randomization may be done to allocate patients to different treatment groups. Even though…

Methodology · Statistics 2024-01-09 Rik Ghosh , Bibhas Chakraborty , Inbal Nahum-Shani , Megan E. Patrick , Palash Ghosh

Longitudinal cluster randomized trials (L-CRTs) are increasingly used to evaluate the cost-effectiveness of healthcare interventions across multiple assessment periods, yet design methods for powering these trials remain underdeveloped.…

Methodology · Statistics 2026-03-20 Hao Wang , Jingxia Liu , Drew B. Cameron , Jiaqi Tong , Donna Spiegelman , Daniella Meeker , Fan Li

There are several different modalities, e.g., surgery, chemotherapy, and radiotherapy, that are currently used to treat cancer. It is common practice to use a combination of these modalities to maximize clinical outcomes, which are often…

Optimization and Control · Mathematics 2019-09-27 Kelsey Maass , Minsun Kim

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…

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