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

Hi Nastia,

❝ Dear smart people!

     ^^^^  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 Cmax 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 However, with the current draft guidance from FDA for progesterone bioequivalence, this appears to be the immediate approach to be applied for SABE.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.

Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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