Bioequivalence and Bioavailability Forum

Hi all,

❝ This was one of the possibilities I suspected. Let’s see whether our specialist for OIPs (ElMaestro) will join the party…

Your wish is my command, Helmut

❝ The study is thus not at risk from a PK point of view.

❝ But I was nevertheless interested on what would be the suggestions to best handle such a situation from a pure statistical point of view.

Pure BLQs are not informative in a quantitative way, only qualitative. As Helmut says, even though the protocol and SAPs did not predict this situation and thus did not make provisions for it other than setting to AUC and Cmax to 0 in which case you will have NaN's in the analysed data. If the software throws an error for the log step without executing a default solution, then I think it is justified to introduce NA's where the software can't logarithmise and then let the chips run their course. Otherwise it is a choice between analysing something or analysing nothing (which is unethical).
Imputation and that sorta stuff isn't a good idea unless the SAP has specifically mentioned it.

In addition, a phase II trial is really quite explorative in nature. No patient's rights or well-being will be violated by introducing NaN's or NA's; contrarily introducing NaN or NA's etc will allow some planning for phase III, and that is in everyone's interest regardless of what's in the SAP.

So, full tilt ahead with the data, and also remember to inform your QA that this issue merits a wee bit of preventive action: Future protocols and SAPs should include a clause describing better how to handle these BLQ situations. Setting them to zero is not an optimal solution (My girlfriend hasn't spoken to me for three weeks. Which means she hasn't expressed any anger. Which means she probably isn't angry with me....)