Cost-efficient higher-order crossover designs for two-treatment clinical trials

Higher-order crossover designs have drawn considerable attention in clinical trials, because of their ability to test direct treatment effects in the presence of carry-over effects. The important question, when applying higher-order crossover designs in practice, is how to choose a design with both statistical and cost efficiencies from various alternatives. In this paper, we propose a general cost function and compare five statistically optimal or near-optimal designs with this cost function for a two-treatment study under different carry-over models. Based on our study, to achieve both statistical and cost efficiencies, a four-period, four-sequence crossover design is generally recommended under the simple carry-over or no carry-over models, and a three-period, two-sequence crossover design is generally recommended under the steady-state carry-over models.