Assessing Dose–Region Profile of Drug Efficacy: A Multiregional Trial Strategy

Abstract

In this article, we try to address the optimal dosing issue using a multiregional trial. In this trial, in addition to the treatment group using a globally promising dose of study drug, we have another treatment group using a lower dose treatment with which the drug also shows substantial treatment effect in some of the regions, and both treatment groups share the same placebo (control) group. The incorporation of an additional low-dose treatment group in the multiregional trial can provide the following advantages: (i) The multiregional trial can establish the whole treatment effect profile over different regions as well as drug doses; (ii) the multiregional trial allows for sharing drug efficacy information across different regions; and (iii) the use of a common placebo (control) group for the high- and low-dose treatment groups in the multiregional trial results in logistical convenience. We also examine the regional sample size allocation in the proposed multiregional trial for ensuring a desired power in a local region, using the Bayesian approach we proposed previously for analyzing the multiregional trial data.

Key Words:

• Optimal dose
• Power
• Region–dose interaction
• Sample size allocation

ACKNOWLEDGMENTS

The contract/grant sponsor for this study was the National Science Council of ROC, contract/grant number NSC 98-2118-M-001-016-MY3.