Isotonic Phase I Cancer Clinical Trial Design Utilizing Patient-Reported Outcomes

Authors

Nolan A Wages
Ruitao Lin

Publication Date

1-1-2025

Journal

Statistics in Biopharmaceutical Research

DOI

10.1080/19466315.2023.2288013

PMID

40842959

PMCID

PMC12365655

PubMedCentral® Posted Date

8-25-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

This article considers the concept of designing Phase I clinical trials using both clinician- and patient-reported outcomes to adaptively allocate study participants to tolerable doses and determine the maximum tolerated dose (MTD) at the study conclusion. We describe a new isotonic patient-reported outcome (PRO-ISO) Phase I design with the flexibility of allocating patients to lower, more tolerable regimens if a large number of PRO-DLT events are seen at higher doses. We conduct simulation studies of the operating characteristics of the design and compared them to the patient-reported outcomes continual reassessment method (PRO-CRM). We illustrate that the PRO-ISO makes appropriate dose assignments during the study to give investigators and reviewers an idea of how the method behaves. In simulation studies, the PRO-ISO demonstrates comparable performance to the PRO-CRM in terms of recommending target doses and allocating patients to these doses. It also performs well relative to a nonparametric optimal benchmark applied to the PRO setting. Finally, we extend our methodology to account for the problem of late-onset toxicities.

Keywords

dose-finding, isotonic regression, patient-reported outcomes, late-onset toxicity

Published Open-Access

yes

Recommended Citation

Nolan A Wages and Ruitao Lin, "Isotonic Phase I Cancer Clinical Trial Design Utilizing Patient-Reported Outcomes" (2025). Faculty, Staff and Student Publications. 4752.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4752