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Back to the forum  Query: 2017-11-18 13:05 CET (UTC+1h)
 
rajasekhar
Junior

India,
2017-02-18 11:36

Posting: # 17080
Views: 1,129
 

 statistical evaluations [Regulatives / Guidelines]

Dear All,

My doubt is suppose participant completed entire period and he having the plasma samples for all time points but during bio analysis we got only 3 measurable concentrations. In this case is we can consider this data for PK and statistical evaluations.
Is there any regulation for minimum measurable concentrations to perform statistical analysis. please let me know is there any supportive guidelines for same.

Thank you in advance :-):-)
ElMaestro
Hero

Denmark,
2017-02-18 12:44

@ rajasekhar
Posting: # 17082
Views: 1,008
 

 statistical evaluations

Hi rajasekhar,

» Is there any regulation for minimum measurable concentrations to perform statistical analysis. please let me know is there any supportive guidelines for same.

This is where you need an SOP and not a guideline.
Wit three values above the LLOQ the profile for that subject's data is rubbish but in the absence of an SOP you may need to include it still. Perhaps the EMA's Cmax:LLOQ requirement comes to some degree of rescue.

I could be wrong, but…


Best regards,
ElMaestro

No, I still don't believe much in the usefulness of IVIVCs for OIPs when it comes to picking candidate formulations for the next trial. This is not the same as saying I don't believe in IVIVCs.
Ohlbe
Hero

France,
2017-02-20 11:59

@ rajasekhar
Posting: # 17091
Views: 888
 

 statistical evaluations

Dear Rajasekhar,

» My doubt is suppose participant completed entire period and he having the plasma samples for all time points but during bio analysis we got only 3 measurable concentrations. In this case is we can consider this data for PK and statistical evaluations.

If this happens in the period where the subject received the test product, you're in trouble...

To quote the EMA guideline, section 4.1.8:

Exclusion of data cannot be accepted on the basis of statistical analysis or for pharmacokinetic reasons alone, because it is impossible to distinguish the formulation effects from other effects influencing the pharmacokinetics.
The exceptions to this are:
1) A subject with lack of any measurable concentrations or only very low plasma concentrations for reference medicinal product. A subject is considered to have very low plasma concentrations if its AUC is less than 5% of reference medicinal product geometric mean AUC (which should be calculated without inclusion of data from the outlying subject). The exclusion of data due to this reason will only be accepted in exceptional cases and may question the validity of the trial.

Regards
Ohlbe
nobody
Senior

2017-02-20 14:35

@ Ohlbe
Posting: # 17092
Views: 894
 

 statistical evaluations

...I concur Ohle and want to add: an SOP for "PK outlier detection" won't buy you much in the light of the crystal clear guideline on this topic. Sometimes you loose, sometimes the others win ;-)

Kindest regards, nobody
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