Bioequivalence and Bioavailability Forum

Hi Ken Peh,

❝ We found out from sample analysis that there was no detection of drug in the plasma samples for one subject for both phases. During drug administration, this subject was observed to have swallowed the tablets.

Good. All is as it should be then.

❝ Can we consider this as outlier ?? Non-compliance ??

❝ What is the right way to present the case ?

Call it what it is: A sequence of BLQs.

❝ Is it right to confront the subject ? The subject argues that he swallowed. Nevertheless, the results of sample analysis will never lie.

You have asked the subject, he says he swallowed them. The issue could relate to bad extraction, bad chromatography / injection, IMP packaging, and much more. Do an audit to rule out eventualities, but absence of such cause does not mean you can conclude the subject did not swallow. It will just mean you don't know why the peaks are absent.

❝ Highly appreciate your comments and suggestion.

Next time, please consider a remedy that will increase your budget by 0.00000000000000000000000001 %. It's called a disposable tongue spatula - the PI or clinical staff staff will use it to confirm the IMP has been swallowed.

Dear Ken
If the subject swallowed the study medication or not can not be proven. You asked the subject but still have doubts. This is exact what you have to present in the study report. However, since the subject showed no plasma concentration in both phases there is no influence on the study result and consequently you do not have to exclude this subject as an outlier from statistical evaluation. The comparison of test and reference remains unaffected. Nevertheless you could present in paragraph 13 of the study report (discussion) mean values for AUC and Cmax with and without the subject under discussion.
I hope this helps.
Kind regards
Dr_Dan