Loky do
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Egypt,
2020-06-24 03:23

Posting: # 21570
Views: 1,183
 

 truncation issues [General Sta­tis­tics]

Hello Dears,

For certain products, ema product-specific bioequivalence guidance states that the main PK variables: AUC0-72,...etc (also stated in the study protocol), Is that mean any subject who miss 72 h will be excluded from AUC0-72 calculations? if yes, there will be around 25% of subjects missed this interval, is that will be acceptable?

Thanks in advance
Helmut
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Vienna, Austria,
2020-06-24 10:47

@ Loky do
Posting: # 21571
Views: 704
 

 EMA: AUC72 for all IR products

Hi Loky do,

» For certain products, ema product-specific bioequivalence guidance states that the main PK variables: AUC0-72,...etc (also stated in the study protocol),

Not only the ones in product-specific guidances but all IR products (BE-GL page 9):

A sampling period longer than 72 h is therefore not considered necessary for any immediate release formulation irrespective of the half life of the drug.


» Is that mean any subject who miss 72 h will be excluded from AUC0-72 calculations?

No. If you have a reliable estimate of λz (at least three concentrations), you may use an estimate – if the exact method is stated in the protocol. E.g., in Phoenix/WinNonlin specify pAUC72 and you are fine. There are many posts in the forum discussing the details.

» if yes, there will be around 25% of subjects missed this interval, is that will be acceptable?

In principle yes but as an assessor I would question the clinical performance of the CRO.

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Helmut Schütz
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pmohite
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India,
2020-06-24 12:08

@ Helmut
Posting: # 21573
Views: 668
 

 EMA: AUC72 for all IR products

Hello,

The Revised EMA Bioequivalence Guideline, Questions & Answers, Summary of the discussions held at the 3rd EGA Symposium on Bioequivalence, June 2010, London, Session 3 under question 12 states as follows:

In studies with a sampling period of 72 h, and where the concentration at 72 h is quantifiable, AUC(0-∞) and residual area do not need to be reported; it is sufficient to report AUC truncated at 72h, AUC(0-72h). A mixture of AUCt and AUC72 is acceptable as long as the sampling period allows for an adequate characterisation of AUCt. Of course, in the event samples were absent because of protocol violations on a mass scale then this would affect the acceptability of the study.


If there are around 25% of subjects missed this interval, then this will raise the acceptance of study.

Regards.


Edit: Document linked. [Helmut]
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