Abstract
We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding in phase I. After identifying a set of admissible doses, we immediately move the entire set forward to phase II. We propose a novel adaptive randomization scheme to favor assigning patients to more efficacious dose-combination arms. Our adaptive randomization scheme takes into account both the point estimate and variability of efficacy. By using a moving reference to compare the relative efficacy among treatment arms, our method achieves a high resolution to distinguish different arms. We also consider groupwise adaptive randomization when efficacy is late-onset. We conduct extensive simulation studies to examine the operating characteristics of the proposed design, and illustrate our method using a phase I/II melanoma clinical trial.
Original language | English (US) |
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Pages (from-to) | 924-942 |
Number of pages | 19 |
Journal | Annals of Applied Statistics |
Volume | 5 |
Issue number | 2 A |
DOIs | |
State | Published - Jun 2011 |
Externally published | Yes |
Keywords
- Adaptive randomization
- Dose finding
- Drug combination
ASJC Scopus subject areas
- Statistics and Probability
- Modeling and Simulation
- Statistics, Probability and Uncertainty