Notes on the two-stage procedure under an incomplete block two-period crossover design

Abstract

Under an incomplete block crossover design with two periods, we derive the least-squares estimators for the period effect, treatment effects and carry-over effects in explicit formulae based on within-patient differences. Using the commonly-used strategy of searching a base model for making inferences in regression analysis, we define a two-stage test procedure in studying treatment effects. On the basis of Monte Carlo simulation, we evaluate the performance of the two-stage procedure for hypothesis testing, point and interval estimation of treatment effects in a variety of situations. We note that use of the two-stage procedure can be potentially misleading and hence one should not apply a test procedure to exclusively determine whether he/she needs to account for the carry-over effect in studying treatment effects. We use the double-blind crossover trial comparing two different doses of formoterol with placebo on the forced expiratory volume in 1 second (FEV₁) readings to illustrate the use of the two-stage procedure, as well as the distinction between use of two-stage procedure and the approach with assuming no carry-over effects based on one's subjective knowledge.

Keywords:

• Carry-over
• Coverage probability
• Efficiency
• Incomplete block
• Inflation in Type I error
• Two stage procedure

Acknowledgments

The author wishes to thank the two referees for many useful and valuable comments and suggestions to improve the clarity and contents of this paper.