PharmPK Discussion - 3-period-3-sequence replicate design in scaled average BE

• On 12 Nov 2009 at 16:53:47, ellen.schremmer.at.sandoz.com sent the message
  

  
  Dear Members,
  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?
  Best regards,
  Ellen Schremmer
  
  Hexal AG
  Sitz der Gesellschaft: Holzkirchen Amtsgericht: Muenchen HRB-Nr. 110375
  Vorstand: Hubert Hirzinger, Juergen Hoehne, Hubert Mayr
  Vorsitzender des Aufsichtsrates: Dr. Horst-Uwe Groh
  
  

  Back to the Top

Copyright 1995-2011 David W. A. Bourne (david@boomer.org)