Notes on testing carry-over effects in continuous data under an incomplete block crossover design

We consider hypothesis testing and estimation of carry-over effects in continuous data under an incomplete block crossover design when comparing two experimental treatments with a placebo. We develop procedures for testing differential carry-over effects based on the weighted-least-squares (WLS) method. We apply Monte Carlo simulations to evaluate the performance of these test procedures in a variety of situations. We use the data regarding the forced expiratory volume in one second (FEV₁) readings taken from a double-blind crossover trial comparing two different doses of formoterol with a placebo to illustrate the use of test procedures proposed here.     

Sample size determination for testing equality in frequency data under an incomplete block crossover design

When there are more than two treatments under comparison, we may consider the use of the incomplete block crossover design (IBCD) to save the number of patients needed for a parallel groups design and reduce the duration of a crossover trial. We develop an asymptotic procedure for simultaneously testing equality of two treatments versus a control treatment (or placebo) in frequency data under the IBCD with two periods. We derive a sample size calculation procedure for the desired power of detecting the given treatment effects at a nominal-level and suggest a simple ad hoc adjustment procedure to improve the accuracy of the sample size determination when the resulting minimum required number of patients is not large. We employ Monte Carlo simulation to evaluate the finite-sample performance of the proposed test, the accuracy of the sample size calculation procedure, and that with the simple ad hoc adjustment suggested here. We use the data taken as a part of a crossover trial comparing the number of exacerbations between using salbutamol or salmeterol and a placebo in asthma patients to illustrate the sample size calculation procedure.     

Notes on estimation of the intraclass correlation under the AB/BA crossover trial

Under the AB/BA crossover trial, we focus our attention on estimation of the intraclass correlation in normal data. We develop both point and interval estimators in closed form for the intraclass correlation. We employ Monte Carlo simulation to study the performance of these estimators in a variety of situations. We note that the estimators developed here for the intraclass correlation remain valid even when there are possibly unexpected carry-over effects.     

Notes on interval estimation of the proportion ratio under a three-treatment three-period crossover trial

When comparing two experimental treatments with a placebo, we focus our attention on interval estimation of the proportion ratio (PR) of patient responses under a three-period crossover design. We propose a random effects exponential multiplicative risk model and derive asymptotic interval estimators in closed form for the PR between treatments and placebo. Using Monte Carlo simulations, we compare the performance of these interval estimators in a variety of situations. We use the data comparing two different doses of an analgesic with placebo for the relief of primary dysmenorrhea to illustrate the use of these interval estimators and the difference in estimates of the PR and odds ratio (OR) when the underlying relief rates are not small.