Crossover designs are widely accepted for use in clinical studies since each subject serves as his own control. Several incomplete Latin square designs are proposed and investigated for a bioavailability study that compares the individual components of a triple ingredient product with the coadministered components in all possible combinations to detect potential drug-drug interactions. The power of each design and the relative efficiency are evaluated. Finally, recommendations are made for this study based on a number of theoretical and practical criteria.
WestlakeWJ. The use of balanced incomplete block designs in comparative bioavailability trials. Biometrics1974;30: 319–327.
2.
MetzlerCM. Bioavailability — a problem in equivalence. Biometrics1974;30: 309–317.
3.
YoudenWJ. Use of incomplete block replications in estimating tobacco-mosaic virus. Contr. Boyce Thompson Inst.1937;9: 41–48.
4.
WilliamsEJ. Experimental designs balanced for the estimation of residual effects of treatments. Australian J. Sci. Res.1949;A2: 149–168.
5.
PattersonHD. The construction of balanced designs for experiments involving sequences of treatments. Biometrika.1952;39: 32–48.
6.
BoseRCClatworthyWHShrikhandeSS. Tables of partially balanced designs with two associate classes. Tech. Bul. No. 107. North Carolina Agricultural Experimental Station, 1954.
7.
CochranWGCoxGM. Experimental design. 2nd Edition, New York, NY: Wiley; 1957.
8.
JohnJA. Cyclical designs. New York, NY: Chapman and Hall; 1987.
9.
HedayatASJacrouxMMajumdarD. Optimal designs for comparing test treatments with controls. Stat. Sci.1988;3(4):462–476.
10.
KochGGAmaraIASimmonsPD. Multiple-period crossover designs for the comparisons of two or more active treatments and placebo. Proceedings of Biopharmaceutical Section of the American Statistical Association; 1988: 69–78.
11.
BechhoferRETamhaneAC. Comment on optimal designs. Stat. Sci.1988;3(4):477–480.
12.
GiovagnoliAVerdinelliI. Comment on optimal designs. Stat. Sci.1988;3(4):482–484.
13.
KieferJ. On the nonrandomized optimality and randomized nonoptimality of symmetrical designs. Ann. Math. Statist.1958;29: 675–699.
14.
KieferJ. Construction and optimality of generalized Youden designs. In: SrivastavaJ. ed. A survey of statistical design and linear models. Amsterdam: North Holland; 1975: 333–353.
