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

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

posted by Helmut – Vienna, Austria, 2019-10-20 17:23 (1642 d 05:33 ago) – Posting: # 20710
Views: 9,242

Hi Nastia,

❝ Dear smart people!

^^^^ [image] Are you talking to me?

❝ should we try to keep as much data as possible for the analysis?

In principle yes – as long as the outcome is meaningful. ;-)

❝ 1). How would you advice to deal with subjects, who have only one (2,3..) points over LLOQ in one of the periods? […]

Tricky – IMHO, case by case (should be laid down in an SOP or the SAP, of course). IIRC, Health Canada had a rule that 1 (one!) concentration is sufficient for C_max and 3 (oh dear!) fo AUC. Gone with the wind. THX, HC.

❝ 2). What was the real reason for FDA to develop an algorithm for NTIDs with only complete data?

No idea. The same is applicable to all RSABE-methods of the FDA.

❝ […] theoretically it is possible to use all the data even with incomplete data.

Sure.

❝ Why then FDA just throw data of subjects with incomplete data to the bin?

Again – no idea.

❝ Is not it unethical? (I can't understand this point)

IMHO, it is and we are not alone with this conclusion.*

If SABE is applied, subjects with one missing R observation should be eliminated […]. This is unprecedented in our experience in a regulated bioequivalence setting. Traditionally, one does not exclude data unless there is a scientifically or clinically valid reason to do so. However, with the current draft guidance from FDA for progesterone bioequivalence, this appears to be the immediate approach to be applied for SABE.

Patterson SD, Jones B. Viewpoint: observations on scaled average bioequivalence. Pharmaceut Stat. 2012; 11(1):1–7. doi:10.1002/pst.498.

—
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Helmut Schütz

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Science Quotes

Complete thread:

Missing periods in replicate designs Helmut 2019-10-16 13:14 [RSABE / ABEL]
- 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