Statistical Efficiency in Multiple-to-One Comparison Trials with Optimal Allocation Ratio

Abstract

This paper discusses multiple-to-one comparison trials testing a multivalent vaccine product against multiple comparators with respect to immunologic responses. An optimal subject allocation ratio between the multivalent vaccine group and any of the comparators is introduced. This optimal ratio leads to higher statistical efficiency in terms of savings in sample size compared to equal allocation or any other allocation ratios. Several trial design scenarios are considered including assumptions of equal standardized effect size, unequal variance, and unequal standardized effect sizes of the multivalent vaccines versus the multiple comparators.

Key Words:

• Multiple-to-one comparison
• Multivalent vaccine
• Optimal allocation ratio
• Unequal variance

ACKNOWLEDGMENTS

We thank Tingting Yi and Micki Hultquist for their initial design of the quadrivalent influenza vaccine trial that motivated the work presented here. We also thank Dr. Gary Koch for his valuable comments and encouragement during a discussion in the early phase of this research.