If you can extrapolate something to inf then why not to 72 hrs.
I'd go for option 3 (after all we are used to extrapolations when it comes to AUCinf and nobody has a problem with that. 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). I'm not even sure my opinion would be worth twopence here, but. 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". (Basically, if you remove the last sample, will the calculated half-life still be the terminal half-life ?). The question will be, how reliable is your estimate ? It will depend on the PK of the drug (mono- or multicompartmental), sampling times, etc. Option: Extrapolate to 72h (C(calc.)=5.69 using log-lin regression with * points) and calculate then AUC (result=595.85). And you might be suspected again of playing with the data. In a way you would introduce a bias by using an under-estimated AUC. I suppose you would do that for both treatments. They will be afraid that you may pretend to have broken a tube in order to remove a subject with "annoying" results. Whichever option you select, you can be sure there will be an Agency to say it was the wrong one. Option: Extrapolate to 72h (C(calc.)=5.69 using log-lin regression with * points) and calculate then AUC (result =595.85). Option: Extrapolate to 72h (C(calc.)=5.69 using log-lin regression with * points) and calculate then AUC (result=595.85).value at 72h is missing unfortunately (vial broken or so), what to do?ĪUC(0-48h) is 437.21, considerably lower than AUC(0-72), only 75%. Half live for this curve with no missings is 53.6 h (using points 12-72 h).ĪUC(0-72)=584.93 (linear trapezoidal rule for sake of simplicity). I have the vague suspicion that I have not explained my point precise enough. ĭon't lose heart! Getting old is not for sissies (Bette Davis) ! I have such a procedure since decades (oh, I’m getting old) in my protocols. Evaluation of a Scenario in Which Estimates of Bioequivalence Are Biased and a Proposed Solution: t last (Common). Fisher D, Kramer W, Burmeister Getz E.I wouldn’t start trying to get an estimate of C 72.
#Winnonlin acquisition price software#
LOQ (for all treatments), it should be possible to get an unbiased estimate of the T/R-ratio.* Unfortunately this method is not available in commercial software (at least not in the current versions of WinNonlin, Kinetica, EquivTest/PK). » How do you act in a truncated setting if the last sample is missing? Or if some subject has conc. » I would like to discuss this a bit further. Sorry for the late response – I was driven by discussions about the drafted European BE-Guideline.
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