Effect of changing the bioequivalence range from (0.80, 1.20) to (0.80, 1.25) on the power and sample size.
International harmonization of guidelines for bioequivalence assessment has led to a wide acceptance of the multiplicative model for the extent and rate characteristics AUC and Cmax and--in consistency with this--of the bioequivalence range (0.80, 1.25). The effect of this change from (0.80, 1.20) on the power of the two one-sided test procedure and the sample sizes based thereon is investigated as a function of the within-subject coefficient of variation (CV) and the ratio mu T/mu R of expected medians for test and reference. The relative reduction in sample size is practically zero for mu T/mu R < or = 0.9 and then gradually increases as mu T/mu R approaches 1.2. At mu T/mu R = 1, the reduction is up to 20%. For a fixed ratio mu T/mu R this reduction increases with the coefficient of variation, reaching a plateau at a CV of about 25%.
Steinijans
V W
VW
Department of Biometry, Byk Gulden Pharmaceuticals, Konstanz, Germany.
Hauck
W W
WW
Diletti
E
E
Hauschke
D
D
Anderson
S
S
D015233:Models, Statistical; D012015:Reference Standards; D012494:Sampling Studies; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration