Interactive Software “Isotonic Design using Normalized Equivalent Toxicity Score (ID-NETS©TM)” for Cancer Phase I Clinical Trials

• Type of Material: Article
• Authors: Zhengjia Chen, Emory University; Zhibo Wang, Emory University; Haibin Wang, Cedars-Sinai Medical Center; Taofeek K Owonikoko, Emory University; Jeanne Kowalski, Emory University; Fadlo Khuri, Emory University
• Language: English
• Date: 2013-04-05
• Publisher: Bentham Open
• Publication Version: Final Published Version
• Copyright Statement: © Chen et al.; Licensee Bentham Open
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://benthamopen.com/ABSTRACT/TOMINFOJ-7-8
• Title of Journal or Parent Work: Open Medical Informatics Journal
• ISSN: 1874-4311
• Volume: 7
• Issue: 1
• Start Page: 7
• End Page: 17
• Grant/Funding Information: Supported in part by NIH/NCI Grants No. 1 P01 CA116676 (Z.C. and F.K.), 5 P50 CA128613 (Z.C., F.K. and J.K.).
• Keywords: software; normalized equivalent toxicity score; Isotonic design; dose limiting toxicity; maximum tolerated dose; cancer phase I clinical trial
• Research Categories: Biology, Bioinformatics; Health Sciences, Oncology; Biology, Biostatistics

Abstract

Isotonic Design using Normalized Equivalent Toxicity Score (ID-NETS) is a novel Phase I design that integrates the novel toxicity scoring system originally proposed by Chen et al. [1] and the original Isotonic Design proposed by Leung et al. [2]. ID-NETS has substantially improved the accuracy of maximum tolerated dose (MTD) estimation and trial efficiency in the Phase I clinical trial setting by fully utilizing all toxicities experienced by each patient and treating toxicity response as a quasi-continuous variable instead of a binary indicator of dose limiting toxicity (DLT). To facilitate the incorporation of the ID-NETS method into the design and conduct of Phase I clinical trials, we have designed and developed a user-friendly software, ID-NETS©™, which has two functions: 1) Calculating the recommended dose for the subsequent patient cohort using available completed data; and 2) Performing simulations to obtain the operating characteristics of a trial designed with ID-NETS. Currently, ID-NETS©™1.0 is available for free download at http://winshipbbisr.emory.edu/IDNETS.html.