Faculty, Staff and Student Publications

Language

English

Publication Date

1-1-2026

Journal

Journal of Biopharmaceutical Statistics

DOI

10.1080/10543406.2024.2429481

PMID

39582234

PMCID

PMC12102293

PubMedCentral® Posted Date

1-8-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a Dirichlet-multinomial model to jointly model the distribution of toxicity and efficacy endpoints, making go/no-go decisions based on the posterior probability of toxicity and futility. In comparison to the original BOP2 and other existing designs, BOP2-TE offers the advantage of providing rigorous type I error control in cases where the treatment is toxic and futile, effective but toxic, or safe but futile, while optimizing power when the treatment is effective and safe. As a result, BOP2-TE enhances trial safety and efficacy. We also explore the incorporation of BOP2-TE into multiple-dose randomized trials for dose optimization, and consider a seamless design that integrates phase I dose finding with phase II randomized dose optimization. BOP2-TE is user-friendly, as its decision boundary can be determined prior to the trial’s onset. Simulations demonstrate that BOP2-TE possesses desirable operating characteristics. We have developed a user-friendly web application as part of the BOP2 app, which is freely available at www.trialdesign.org.

Keywords

Bayes Theorem, Humans, Clinical Trials, Phase II as Topic, Research Design, Dose-Response Relationship, Drug, Computer Simulation, Models, Statistical, Randomized Controlled Trials as Topic, Treatment Outcome, Bayesian design, phase II trials, dose optimization, go/no go decision, multiple-dose randomized trials

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.