Direkt zum Inhalt

Mozgunov, Pavel ; Paoletti, Xavier ; Jaki, Thomas

A benchmark for dose-finding studies with unknown ordering

Mozgunov, Pavel, Paoletti, Xavier and Jaki, Thomas (2021) A benchmark for dose-finding studies with unknown ordering. Biostatistics 23 (3), pp. 721-737.

Date of publication of this fulltext: 30 Sep 2025 06:01
Article
DOI to cite this document: 10.5283/epub.77859


Abstract

An important tool to evaluate the performance of a dose-finding design is the nonparametric optimal benchmark that provides an upper bound on the performance of a design under a given scenario. A fundamental assumption of the benchmark is that the investigator can arrange doses in a monotonically increasing toxicity order. While the benchmark can be still applied to combination studies in which ...

An important tool to evaluate the performance of a dose-finding design is the nonparametric optimal benchmark that provides an upper bound on the performance of a design under a given scenario. A fundamental assumption of the benchmark is that the investigator can arrange doses in a monotonically increasing toxicity order. While the benchmark can be still applied to combination studies in which not all dose combinations can be ordered, it does not account for the uncertainty in the ordering. In this article, we propose a generalization of the benchmark that accounts for this uncertainty and, as a result, provides a sharper upper bound on the performance. The benchmark assesses how probable the occurrence of each ordering is, given the complete information about each patient. The proposed approach can be applied to trials with an arbitrary number of endpoints with discrete or continuous distributions. We illustrate the utility of the benchmark using recently proposed dose-finding designs for Phase I combination trials with a binary toxicity endpoint and Phase I/II combination trials with binary toxicity and continuous efficacy.



Involved Institutions


Details

Item typeArticle
Journal or Publication TitleBiostatistics
Publisher:Oxford Academic, Oxford University Press
Volume:23
Number of Issue or Book Chapter:3
Page Range:pp. 721-737
Date4 January 2021
InstitutionsInformatics and Data Science > Department Machine Learning & Data Science > Lehrstuhl für Computational Statistics (Prof. Dr. Thomas Jaki)
Identification Number
ValueType
10.1093/biostatistics/kxaa054DOI
KeywordsBenchmark; Combination trial; Dose finding; Partial ordering; Power likelihood
Dewey Decimal Classification000 Computer science, information & general works > 004 Computer science
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgNo
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-778596
Item ID77859

Export bibliographical data

Owner only: item control page

nach oben