A note on point estimation and interval estimation of the relative treatment effect under a simple crossover design.

Abstract

To increase power or reduce the number of patients needed for a parallel groups design, the crossover design has been often used to study treatments for noncurable chronic diseases. However, in the presence of carry-over effect caused by treatments, the commonly-used estimator which ignores the carry-over effect leads to a biased estimator for estimating the treatment effect difference. A two-stage test approach aimed to address carry-over effect proposed was found to be potentially misleading. In this paper, we propose a weighted average of the commonly-used estimator and an unbiased estimator that uses only the first period of the data. We derive an optimal weight that minimizes the mean squared error (MSE) and its modified estimator. We apply Monte Carlo simulation to evaluate the performance of the proposed estimators in a variety of situations. In the simulations, we examine the estimated MSE (EMSE), percentile interval length, and coverage probability calculated from the percentile intervals among considered estimators. Simulation results show that our proposed weighted average estimator and its modified estimator lead to smaller EMSEs on average comparing to the two commonly used estimators. The coverage probabilities using our proposed estimators are reasonably close to the nominal confidence level and the interval lengths are shorter comparing to the use of the unbiased estimator that uses only the first period of the data. We apply an example that was to evaluate the efficacy of two type of bronchodilators for asthma treatment to demonstrate the use of the proposed estimators.