The following study is described in Chinchilli, Schwab, and Sen (1989). The pain of angina is caused by a deficit in oxygen supply to the heart. Calcium channel blockers like verapamil will dilate blood vessels, increasing the supply of blood and oxygen to the heart. This controls chest pain—but only when used regularly. It does not stop chest pain once it starts. The research goal of the study was to assess if there was a difference in four commercial formulations of verapamil (denoted by A, B, C, and D). Twenty-six healthy male volunteers were randomly assigned to one of four treatment sequences (ABCD, BCDA, CDBA, or DABC). The study protocol required lengthy washouts between treatment periods, and, thus, it was thought that any drug carryover effects from previous time periods would be negligible. The response variable was the area under the plasma time curve (AUC), with values given in the following table.
a. Plot the formulation means (AUCs) by period for each sequence.
b. Does there appear to be evidence of a period effect?
c. Do the formulations appear to have different AUC means?