Bioequivalence and Bioavailability Forum • Missing periods in replicate designs: save the data?

Missing periods in replicate designs: save the data? [RSABE / ABEL]

posted by Astea – Russia, 2019-10-20 16:46 (1642 d 20:28 ago) – Posting: # 20709
Views: 9,182

Dear smart people!

I've got two questions on this topic, that could be logically combined into the one philosophical: should we try to keep as much data as possible for the analysis?

1). How would you advice to deal with subjects, who have only one (2,3..) points over LLOQ in one of the periods? According to EMA it is possible to exclude subjects with AUC of reference product less than 5% of geometric mean AUC. Should we exclude all the data of such a subject or can we remain data from other periods?
Example: acetylcalycic acid (ASA) in enteric-coated form has a wide-range T_max in about 2 to 7 hours with extremely rapid conversion to salycic acid. So PK profiles look like "zero-zero-vertical line-zero-zero"... For catching it one has to plan a great number of sample points and use appropriate stabilization procedure. Even in these case there could be the uppermentioned problems.

2). What was the real reason for FDA to develop an algorithm for NTIDs with only complete data? As Helmut mentioned in the post, theoretically it is possible to use all the data even with incomplete data. Why then FDA just throw data of subjects with incomplete data to the bin? Is not it unethical? (I can't understand this point)

—
"Being in minority, even a minority of one, did not make you mad"

Complete thread:

Missing periods in replicate designs Helmut 2019-10-16 13:14
- Missing periods in replicate designs ElMaestro 2019-10-16 15:10
  - Missing samples Helmut 2019-10-17 10:22
    - Missing ambulatory samples M.tareq 2020-04-09 15:24
      - Missing ambulatory samples Helmut 2020-04-09 16:15
        
        Missing ambulatory samples M.tareq 2020-04-09 16:54
- Missing periods in replicate designs d_labes 2019-10-17 17:22
  - Missing periods in replicate designs ElMaestro 2019-10-17 20:17
    - Missing periods in replicate designs d_labes 2019-10-18 11:48
  - Missing periods in replicate designs Helmut 2019-10-19 14:30
    - Missing periods in replicate designs: save the data?Astea 2019-10-20 14:46
      - Missing periods in replicate designs: save the data? Helmut 2019-10-20 15:23
        
        Missing periods in replicate designs: kill the data? Astea 2019-10-21 01:59
        
        Meaningful data? Helmut 2019-10-21 11:37
- Missing periods in replicate designs Mahmoud 2019-11-06 11:41
  - Kenward-Roger? Helmut 2019-11-06 12:49
    - Kenward-Roger? PharmCat 2019-11-06 14:43
      - Kenward-Roger ≥ Satterthwaite Helmut 2019-11-08 20:57
        
        Kenward-Roger ≥ Satterthwaite PharmCat 2019-11-08 22:08
      - Kenward-Roger - links mittyri 2019-11-08 22:59
        
        Kenward-Roger - links PharmCat 2019-11-09 00:51
        degrees of freedom Helmut 2019-11-09 16:22
        
        degrees of freedom PharmCat 2019-11-09 19:11