The missing 72h [NCA / SHAM]

posted by Ohlbe – France, 2009-01-28 01:00 (5615 d 06:54 ago) – Posting: # 3148
Views: 26,234

Dear D. Labes,

❝ 1. Option: Exclude subject

❝ 2. Option: Use AUC(0-48)

❝ 3. Option: Extrapolate to 72h (C(calc.)=5.69 using log-lin regression with * points) and calculate then AUC (result =595.85).

Whichever option you select, you can be sure there will be an Agency to say it was the wrong one... (At least the French Agency, I guess ;-) )

❝ 1. Option: Exclude subject

They will hate that... They will be afraid that you may pretend to have broken a tube in order to remove a subject with "annoying" results...

❝ 2. Option: Use AUC(0-48)

I suppose you would do that for both treatments. In a way you would introduce a bias by using an under-estimated AUC... And you might be suspected again of playing with the data.

❝ 3. Option: Extrapolate to 72h (C(calc.)=5.69 using log-lin regression with * points) and calculate then AUC (result=595.85).

Introducing another bias. The question will be, how reliable is your estimate ? It will depend on the PK of the drug (mono- or multicompartmental), sampling times, etc. (Basically, if you remove the last sample, will the calculated half-life still be the terminal half-life ?). Probably closer to the truth than Option 2, but they may refer to the current EU guideline: "The exclusive use of compartmental based estimates are not recommended", and forget about "exclusive".

I'm not even sure my opinion would be worth twopence here, but... write in your protocol what you would do in such a situation, do it this way, and keep you fingers crossed, hoping for your file to be reviewed by an assessor with not more than 30 or 60 minutes on his hands (ElMaestro would say you have good chances).


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