Bioequivalence and Bioavailability Forum

Dear Dirk
My experience is that if you interpret "Before bioanalysis” as “prior to availability of bioanalytical data” no assessor will care and ask for the evaluation of the study with the full data set. Of course you will then present a sensitivity analysis but it could be hard to convince the assessor that the exclusion of the subject was justified. I made several bad experiences especially with MHRA. Even if you proof that the allocation of subjects to analysis sets happened at a time point when the clinical and statistical teams had not seen the bioanalytical data, the assessor will insist on the full analysis. So if you think that a clinical event will influence the outcome of the study you have to exclude this subject before you start sample measurement. I do not think that bioanalysis has to wait more or less until DB lock. You could organize a data review meeting and decide which subject should be excluded due to clinical reasons and you have to document this properly. Therefore you should define that “Before bioanalysis” will be interpreted as “prior to start of any bioanalytical assessments”. Consequently you should not measure samples of an excluded subject as long as this is not necessary (e.g. AE suspected to be related to drug concentration level). CPMP/QWP/EWP/1401/98 Rev. 1 states "If available, concentration data and pharmacokinetic parameters from such subjects should be presented in the individual listings, but should not be included in the summary statistics." So itś better not to have these data and to avoid a sensitivity analysis.
I hope this helps.
Kind regards
Dan