Replicate Study designs [Outliers]

posted by Ohlbe – France, 2014-01-08 15:24 (3817 d 10:06 ago) – Posting: # 12146
Views: 13,792

Dear Balakotu,

❝ So, how can we justify those two subjects data as outliers/anomalous and how to perform statistical analysis in such a case?


For which authority ?

In the EMA guideline (§4.1.8.) the answer is clear:

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.


So looking at your case, the conclusion for an EU submission is simple: the study fails.

Regards
Ohlbe

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