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the FDA proposes (Haidar SH, Davit B, Chen ML, et al. Bioequivalence approaches for highly variable drugs and drug products. Pharm. Res. 15: 237-241 (2008)) that if the within-subject variation of the reference drug is >30%, then SABE (Scaled Average Bioequivalence) could be applied. Replicate-design crossover investigations should be undertaken.
The FDA recommends that three-period BE studies be performed in which the reference product [R] provided twice and the Test product [T] is given once. Consequently the possible sequences of drug administration are TRR, RRT, RTR.
Applying the proc mixed of the Appendix E of the Guidance for Industry, Statistical Approaches to Establishing Bioequivalence in a three-period , 3 sequences result in two i.e. Residual Estimates, i.e. one for treatment R and one treatment T.
But here is my problem, the Residual Estimates for T makes no sense i.e. intra-individual variability between T-T does not exist due to the random scheme and therefore I can not interprete the result.
Does anybody had this setting and experience here and knows what to do?
Sitz der Gesellschaft: Holzkirchen Amtsgericht: Muenchen HRB-Nr. 110375
Vorstand: Hubert Hirzinger, Juergen Hoehne, Hubert Mayr
Vorsitzender des Aufsichtsrates: Dr. Horst-Uwe Groh
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