Low AUC after reference product [Study As­sess­ment]

posted by Helmut Homepage – Vienna, Austria, 2018-03-14 17:38 (1839 d 06:25 ago) – Posting: # 18546
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Hi Gopinath,

❝ we have a done a BE study for GCC submission with two way crossover, here one subject shows less concentration in reference product and the T/R ratio for Cmax 2.43 and AUCt 2.35, …

The GCC-Guidelines are practically identical to the EMA’s when it comes to exclusion of subjects.

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).

❝ … because of this subject the study failed in border, if we excluded this as a outlier the 90% CI is within the acceptance limit.

❝ It is evident that something happen for this subject during clinical phase but the CRO failed to notify the incident.

Why is it evident? The staff of the CRO couldn’t look into the GIT of the subject. You cannot exclude a product failure.

❝ GCC just following EMA guidance so as per EMA this is failed study, …

Correct – if you didn’t state such a possible reason for exclusion it in the protocol. Post hoc exclusion (the study failed, let’s try something else) is rarely accepted.

❝ … but out of my curiosity Is there any way to scientifically justify and exclude this subject from statistical calculation.

No. You can only try to refer in the report to the GL and cross fingers.

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