BLQ handling in BE study where all values in one profile are BLQ [NCA / SHAM]

posted by Hutchy_7 – UK, 2019-11-28 15:17 (364 d 09:45 ago) – Posting: # 20887
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I am analyzing a 'simple' 2 way cross bioequivalence study of a generic oral capsule.

Our standard approach for BE studies is to replace BLQs with zero.

However, one subject has a profile for test product where all values are BLQ; their reference product profile is relatively in line with the rest of the dataset. If this was the other way around (reference profile all BLQ) the EMA BE guidelines would allow exclusion from the analysis; alas we are not in that position.

There are no other clinical/medical reasons to exclude this subject from the PK analysis set, however the zero values for Cmax and AUC cannot be log transformed and therefore this subject's data cannot included in the statistical analysis.

My initial thought would be to replace BLQ with LLOQ/2 for this subject only.

Does that seem like a logical solution?

Very grateful for anyone's thoughts/experiences from a regulatory acceptability perspective.

Simon


Edit: Category changed; see also this post #1[Helmut]

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