Toxicity Monitoring Rule for a Two-Cohort Phase II Clinical Trial with Bivariate Beta Prior

TL;DR

This paper introduces a Bayesian toxicity monitoring rule for two-cohort Phase II clinical trials using a bivariate beta prior, balancing between independent and pooled cohort approaches.

Contribution

It develops an exact Bayesian method with a bivariate beta prior for joint toxicity monitoring, addressing heterogeneity between cohorts.

Findings

Joint monitoring balances safety and heterogeneity considerations.

Exact calculations of operating characteristics are feasible.

Examples show improved performance over existing methods.

Abstract

Toxicity monitoring is essential in Phase II clinical trials to ensure participant safety. While monitoring rules are well-established for single-arm trials, two-cohort trials present unique challenges because toxicities are expected to be similar between cohorts but may still differ. Current approaches either monitor the two cohorts independently, which ignores their similarity, or pool them together as a single arm, which neglects heterogeneity between cohorts. We propose a Bayesian method based on a bivariate beta prior that provides a compromise between these two approaches. The marginal posterior distribution is derived as a mixture of beta distributions, enabling exact calculations of the proposed method's operating characteristics. Examples demonstrate that joint monitoring offers a balanced approach between the independent and pooled methods. Keywords: Toxicity; Two-cohort; Phase II clinical trial; Monitoring rules; Bivariate Beta; Exact Operating characteristics