Bioequivalence and Bioavailability Forum

❝ From a quick once over interesting topics included .

• 3-period 2-sequence full replicate as an example (is the bloody partial replicate design finally landing in the dustbin of history where it belongs?)
  
• Adaptive designs (yes, also simulation-based; EMA, are you reading this?)
  
• Sparse sampling – wow! I hope by ‘mean’ the FDA means the geometric mean. 
  
• Sensitivity of sample size estimation. THX, now in line with ICH E9 (of 1998!)
  
• The dreadful estimands enter the scene.
  
• ‘for a replicated PK BE study, if reference-scaled average BE is used, the applicant should ensure that the calculated intra-subject variability is not inflated due to extreme values or situations.’ That’s new but inline with all others (except ANVISA, still not requiring it)
  ’In the Random statement, TYPE=FA0(2) could possibly be replaced by TYPE=CSH or UNR.’ THX for CSH. Why not TYPE=FA0(1)?
  Instead of Satterthwaite’s degrees of freedom Kenward-Roger could be used (what does ‘possibly’ mean here?)
  
• Sorry folks, the CI inclusion approach ≠ TOST. Only the conclusions are the same.
  
• What’s the purpose of reporting arithmetic means additionally to geometric means?
  
• Covariates in parallel designs. THX!
  
• Details about studies in multiple groups or sites. Why equal sizes / group?
  
• How to deal in Higher-Order Crossover Designs with references from two regions (i.e., Two at a Time).
  
• Does anybody understand why carryover rose from the grave (Appendix A)? Any treatment-interaction in the model leads to an treatment effect which cannot be interpreted!