Bioequivalence and Bioavailability Forum

Hi Oiinkie,

❝ The reference product is known to have a low intra-subject variability, but a very high inter-subject variability.

CVs of the product? Do you have data of a replicate study?

❝ […] one of the aims of the pilot PK study would be to assess and compare inter-subject variability of test and reference product.

Hhm, why CV_inter? Speaking cross-over only CV_intra is relevant. I performed studies with CV_inter of ~60%, where BE was shown in 12 subjects (due to CV_intra ~10%). I have seen some anecdotal (!) reports that high standardization (i.e., inclusion criteria, sex, narrow BMI,…) reduced CV_intra as well. I’m somewhat skeptical. IMHO that would only work for high correlation between the variance components. I don’t see a physiological basis for that.

❝ What kind of setup would you recommend for such a study (e.g. standard 2x2 crossover)?

Still not clear to me whether and why you are interested in the CVs of the products. In order to get CV_WR and CV_WT you would need a fully replicated design (TRT|RTR or TRTR|RTRT). For CV_BR and CV_BT I guess you would have to perform the study in two groups. Don’t ask me for the model. Maybe some ideas by other members?

❝ What sample size would be appropriate?

Define appropriate.