Bioequivalence and Bioavailability Forum

EMA - Exclusion of data [Regulatives / Guidelines]

posted by d_labes  – Berlin, Germany, 2012-01-24 12:09 (5267 d 08:24 ago) – Posting: # 7991
Views: 4,250

Dear All!

The EMA guideline states under Reasons for exclusion (page 14/27):
"Exclusion of data cannot be accepted on the basis of statistical analysis or for pharmacokinetic reasons alone, ...

The exceptions to this are:
1) A subject with lack of any measurable concentrations or only very low plasma concentrations for reference medicinal product. A subject is considered to have very low plasma concentrations if its AUC is less than 5% of reference medicinal product geometric mean AUC (which should be calculated without inclusion of data from the outlying subject)."
In implementing this I wonder about some peculiarities for distinct designs and/or settings:

• May this be applied also in the truncated Area setting?
  
• Is this also applicable for AUC(0-tau) in multiple dose studies?
  
• What is the geometric mean in replicate cross-over studies? Overall or calculated for each replicate?
  
• What to do in case of crossover design with more than one Reference?
  
• Should an algorithm implemented recursively (i.e. repeated after exclusion of identified outlier with respect to the 5% criterion in a first run)?

Any opinion out there?

Complete thread:

• EMA - Exclusion of datad_labes 2012-01-24 11:09 
  • EMA - Exclusion of data Helmut 2012-01-24 15:53
  • EMA - Exclusion of data ElMaestro 2012-01-24 16:47
    • LSMeans? d_labes 2012-01-26 08:34
      • LSMeans? ElMaestro 2012-01-26 13:22