Bioequivalence and Bioavailability Forum

Hi Dan & all,

❝ […] but rather a re-dose study (you administer test and reference in a cross-over design in the outlying subjects together with a certain number of other study participants). However this is only possible for FDA submissions.

See FDA’s guidance, Section VII.C:

[…] deletion of outlier values is generally discouraged, particularly for nonreplicated designs. With replicated crossover designs, the retest character of these designs should indicate whether to delete an outlier value or not. Sponsors or applicants with these types of data sets may wish to review how to handle outliers with appropriate review staff.

I have strong doubts whether the FDA would accept a re-testing study following a replicate study. In Balakotu’s case Subject II might be excluded, but not Subject I. Don’t be tempted to try that without talking to the OGD’s review staff before – keep RTR in mind!
Only fully replicated 4-period studies (RTRT|TRTR) are “fool-proof”.

If you are interested in a statistical approach (not recommended for beginners):

Schall R, Endrényi L, Ring A. Residuals and Outliers in Replicate Design Crossover Studies. J Biopharm Stat. 2010;20(4):835–49. doi 10.1080/10543401003618876