Testing Equality and Interval Estimation in Binary Responses When High Dose Cannot Be Used First Under a Three-Period Crossover Design

Abstract

When comparing two doses of a new drug with a placebo, we may consider using a crossover design subject to the condition that the high dose cannot be administered before the low dose. Under a random-effects logistic regression model, we focus our attention on dichotomous responses when the high dose cannot be used first under a three-period crossover trial. We derive asymptotic test procedures for testing equality between treatments. We further derive interval estimators to assess the magnitude of the relative treatment effects. We employ Monte Carlo simulation to evaluate the performance of these test procedures and interval estimators in a variety of situations. We use the data taken as a part of trial comparing two different doses of an analgesic with a placebo for the relief of primary dysmenorrhea to illustrate the use of the proposed test procedures and estimators.

Key Words:

• Binary data
• Crossover trial
• Equality
• Interval estimation
• Titration trial

ACKNOWLEDGMENTS

The authors wish to thank the associate editor and two reviewers for many valuable and useful comments to improve the clarity and contents of this article.