Sample size considerations for establishing clinical bioequivalence of allergen formulations.
Bioequivalence of formulations must be established by proving that the differences between the formulations are within a specified interval according to Equation 1, the Interval Hypothesis. Explicit estimates of sample size determined from Equation 8 and listed in Table 1 are qualitatively larger than those that would be determined from Equation 2, the Hypothesis of No Difference. Equation 8 was derived from the TOST procedure; other valid methods should yield comparable results. In any context, this discussion has illustrated that the failure to demonstrate a difference is not sufficient to demonstrate equivalence, and that a properly powered equivalence study of allergen formulations will generally demand many more than four study subjects.
Rabin
Ronald L
RL
US Food and Drug Administration, Center for Biologics Evaluation, 1401 Rockville Pike (HFM-422), Rockville, MD 20852, USA.
Slater
Jay E
JE
Lachenbruch
Peter
P
Pastor
Richard W
RW
D000485:Allergens / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002986:Clinical Trials as Topic; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D008962:Models, Theoretical; D018401:Sample Size; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration
D000485:Allergens