Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 3;81(3):ujaf043.
doi: 10.1093/biomtc/ujaf043.

Precision generalized phase I-II designs

Saijun Zhao  1 , Peter F Thall  2 , Ying Yuan  2 , Juhee Lee  3 , Pavlos Msaouel  4 , Yong Zang  5
Affiliations

Precision generalized phase I-II designs

Saijun Zhao et al. Biometrics. .

Abstract

A new family of precision Bayesian dose optimization designs, PGen I-II, based on early efficacy, early toxicity, and long-term time to treatment failure is proposed. A PGen I-II design refines a Gen I-II design by accounting for patient heterogeneity characterized by subgroups that may be defined by prognostic levels, disease subtypes, or biomarker categories. The design makes subgroup-specific decisions, which may be to drop an unacceptably toxic or inefficacious dose, randomize patients among acceptable doses, or identify a best dose in terms of treatment success defined in terms of time to failure over long-term follow-up. A piecewise exponential distribution for failure time is assumed, including subgroup-specific effects of dose, response, and toxicity. Latent variables are used to adaptively cluster subgroups found to have similar dose-outcome distributions, with the model simplified to borrow strength between subgroups in the same cluster. Guidelines and user-friendly computer software for implementing the design are provided. A simulation study is reported that shows the PGen I-II design is superior to similarly structured designs that either assume patient homogeneity or conduct separate trials within subgroups.

Keywords: Bayesian adaptive design; cell therapy; dose optimization; phase I-II clinical trials; precision medicine.

PubMed Disclaimer

Figures

Figure 1:
Figure 1:
Schematic for the PGen I-II design with three subgroups. N=n1+n2+n3 is the overall sample size for the whole trial.
See this image and copyright information in PMC

References

    1. Babb J, Rogatko A, and Zacks S (1998). Cancer phase I clinical trials: Efficient dose escalation with overdose control. Statistics in Medicine, 17, 1103–1120. - PubMed
    1. Chib S, and Greenberg E (1998). Analysis of multivariate probit models. Biometrika, 85, 347–361.
    1. Gooley TA, Martin PJ, Fisher LD and Pettinger M (1994) Simulating as a design tool for phase I/II clinical trials: an example from bone marrow transplantation. Controlled Clinical Trials, 15, 450–462. - PubMed
    1. Green PJ (1995). Reversible jump Markov chain Monte Carlo computation and Bayesian model determination. Biometrika, 82(4), 711–732.
    1. Guo B, and Yuan Y (2017). Bayesian phase I/II biomarker-based dose finding for precision medicine with molecularly targeted agents. Journal of the American Statistical Association, 112, 508–520. - PMC - PubMed

MeSH terms

LinkOut - more resources