Nolan A Wages1, Nikole Varhegyi1. 1. Division of Translational Research & Applied Statistics, Department of Public Health Sciences, The University of Virginia, Charlottesville, VA, USA.
Abstract
BACKGROUND/AIMS: In evaluating the performance of Phase I dose-finding designs, simulation studies are typically conducted to assess how often a method correctly selects the true maximum tolerated dose under a set of assumed dose-toxicity curves. A necessary component of the evaluation process is to have some concept for how well a design can possibly perform. The notion of an upper bound on the accuracy of maximum tolerated dose selection is often omitted from the simulation study, and the aim of this work is to provide researchers with accessible software to quickly evaluate the operating characteristics of Phase I methods using a benchmark. METHODS: The non-parametric optimal benchmark is a useful theoretical tool for simulations that can serve as an upper limit for the accuracy of maximum tolerated dose identification based on a binary toxicity endpoint. It offers researchers a sense of the plausibility of a Phase I method's operating characteristics in simulation. We have developed an R shiny web application for simulating the benchmark. RESULTS: The web application has the ability to quickly provide simulation results for the benchmark and requires no programming knowledge. The application is free to access and use on any device with an Internet browser. CONCLUSION: The application provides the percentage of correct selection of the maximum tolerated dose and an accuracy index, operating characteristics typically used in evaluating the accuracy of dose-finding designs. We hope this software will facilitate the use of the non-parametric optimal benchmark as an evaluation tool in dose-finding simulation.
BACKGROUND/AIMS: In evaluating the performance of Phase I dose-finding designs, simulation studies are typically conducted to assess how often a method correctly selects the true maximum tolerated dose under a set of assumed dose-toxicity curves. A necessary component of the evaluation process is to have some concept for how well a design can possibly perform. The notion of an upper bound on the accuracy of maximum tolerated dose selection is often omitted from the simulation study, and the aim of this work is to provide researchers with accessible software to quickly evaluate the operating characteristics of Phase I methods using a benchmark. METHODS: The non-parametric optimal benchmark is a useful theoretical tool for simulations that can serve as an upper limit for the accuracy of maximum tolerated dose identification based on a binary toxicity endpoint. It offers researchers a sense of the plausibility of a Phase I method's operating characteristics in simulation. We have developed an R shiny web application for simulating the benchmark. RESULTS: The web application has the ability to quickly provide simulation results for the benchmark and requires no programming knowledge. The application is free to access and use on any device with an Internet browser. CONCLUSION: The application provides the percentage of correct selection of the maximum tolerated dose and an accuracy index, operating characteristics typically used in evaluating the accuracy of dose-finding designs. We hope this software will facilitate the use of the non-parametric optimal benchmark as an evaluation tool in dose-finding simulation.
Authors: Philip Pallmann; Fang Wan; Adrian P Mander; Graham M Wheeler; Christina Yap; Sally Clive; Lisa V Hampson; Thomas Jaki Journal: Clin Trials Date: 2019-12-19 Impact factor: 2.486