Bioequivalence and Bioavailability Forum • Justification for the lack of incurred sample reanalysis

irene
☆

Greece,
2017-02-13 08:58
(2622 d 01:56 ago)

Posting: # 17053
Views: 3,619

Justification for the lack of incurred sample reanalysis [Regulatives / Guidelines]

Hello,

in the EMA's "Questions & Answers: positions on specific questions addressed to the Pharmacokinetics Working Party (PKWP)" it states the lack of incurred sample reanalysis data for a bioequivalence study can be justified. One of the points that should be adreessed is

90% confidence interval:
As one element of such justification, if applicable, the applicant could also take into consideration the width of the 90% confidence interval and the ratio to possibly justify that a false positive outcome due to ISR problems has a low probability.

I would like to ask if someone has ever provided these data and how the probability of a false positive outcome can be calculated. I was thinking of using simulations but it is not clear which parameters should I vary and which distributions to use (i.e. mean and sd).

Thank you in advance,

Irene

Dr_Dan
★★

Germany,
2017-02-14 18:20
(2620 d 16:34 ago)

@ irene
Posting: # 17058
Views: 2,949

Justification for the lack of incurred sample reanalysis

Post reply

Dear Irene
Please search the forum and you will find a lot of discussion on ISR. The guideline put an expiry date on old studies. If you now submit a study without ISR then this study does not reflect current scientific knowledge and will be certainly rejected. IMHO you can not argue the absence of ISR with 90% confidence interval even if the study result is not borderline.

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Kind regards and have a nice day
Dr_Dan

irene ☆ Greece, 2017-02-15 08:56 (2620 d 01:58 ago) @ Dr_Dan Posting: # 17059 Views: 2,877	Justification for the lack of incurred sample reanalysis Post reply
	Dear Dr_Dan, thank you for your answer. Yes, the study is old, conducted in 2007, but the submission regards a RUP, and I was wondering whether the study can be accepted even though ISR is missing. Kind regards, Irene