Bioequivalence and Bioavailability Forum

Non-informative “profiles” [General Sta­tis­tics]

posted by fno  – Belgium, 2014-03-11 16:52 (4064 d 14:15 ago) – Posting: # 12599
Views: 10,187

Dear Helmut, dear Ohlbe,

Thank you so much already for your feed-back!

❝ Fabrice stated that this was not a BE study. I think we need more information.

The context is the following:

• Phase IIa multiple-dose placebo-controlled study, so only one active treatment
  
• PK only as an exploratory objective (PD was the primary objective)
  
• Oral inhalation, resulting in quite high inter- and intra-patient PK variability
  
• Full PK profile obtained after 1^st dose and at steady-state, no accumulation at all: PK levels always decrease back below LLOQ between successive administrations, the PK levels were on average similar after single dose and at steady-state
  
• Low-concentration profiles observed both after 1^st dose and at steady-state; the one with all concentrations < LLOQ was after the 1^st dose

The study is thus not at risk from a PK point of view.
But I was nevertheless interested on what would be the suggestions to best handle such a situation from a pure statistical point of view.
For PK, the potential impact is on the steady-state vs single dose comparison, but you can also simply consider the computation of the descriptive geometric mean Cmax and AUC... how to best deal with a zero value?

As I already mentioned, it is not the first time I encounter this kind of issue.
I am therefore thinking to describe the handling of such cases in our SOPs, which we can refer to when nothing is specifically planned in the protocol or in the SAP .

Many thanks!

Complete thread:

• Log-transformation of "null" PK para­meters fno 2014-03-11 12:18 [General Sta­tis­tics] 
  • Non-informative “profiles” Helmut 2014-03-11 13:29
    • Non-informative “profiles” Ohlbe 2014-03-11 13:47
      • Non-informative “profiles” Helmut 2014-03-11 14:04
        • Non-informative “profiles”fno 2014-03-11 15:52
          • Non-informative “profiles” Helmut 2014-03-11 17:22
            • Non-informative “profiles” ElMaestro 2014-03-11 18:50
              • OT: log(0) - NaN, NA or what d_labes 2014-03-12 08:59
                • OT: log(0) - NaN, NA, ‘.’, –∞, or empty Helmut 2014-03-12 15:31
              • Non-informative “profiles” fno 2014-03-12 11:18
                • Non-informative “profiles” nobody 2014-03-12 13:18