Testing and estimation of proportion (or risk) ratio under the matched-pair design with multiple binary endpoints.

The proportion ratio (PR) of responses between an experimental treatment and a control treatment is one of the most commonly used indices to measure the relative treatment effect in a randomized clinical trial. We develop asymptotic and permutation-based procedures for testing equality of treatment effects as well as derive confidence intervals of PRs for multivariate binary matched-pair data under a mixed-effects exponential risk model. To evaluate and compare the performance of these test procedures and interval estimators, we employ Monte Carlo simulation. When the number of matched pairs is large, we find that all test procedures presented here can perform well with respect to Type I error. When the number of matched pairs is small, the permutation-based test procedures developed in this paper is of use. Furthermore, using test procedures (or interval estimators) based on a weighted linear average estimator of treatment effects can improve power (or gain precision) when the treatment effects on all response variables of interest are known to fall in the same direction. Finally, we apply the data taken from a crossover clinical trial that monitored several adverse events of an antidepressive drug to illustrate the practical use of test procedures and interval estimators considered here.