Bioequivalence and Bioavailability Forum

Dear Stefano,

Answer to your question is NO. As far as bioequivalence studies for US-FDA are concerned, it is not necessary to keep the "sequence" effect in the model. But most of the time we keep this "sequence" effect in the model. Obviously if we remove the sequence effect, our total error variance will increase and consequently the intra-subject CV will rise which will further give us a wider 90% CI as compared to a model with "sequence" effect. So it is in our favor to keep “sequence” effect in a model especially for a BA/BE study.

Further, I have observed that in Phase-I trials some statisticians don't prefer to use sequence effect as they are more keen to test the "treatment" or "period" effects.

In my opinion, sequence effect should always be considered for a cross-over trial as the basic principle of ANOVA is to segregate the total variability into different components of known variability and "sequence" is not an exception in a cross-over trial.

Regards,
Pankaj Mishra

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Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]