Bioequivalence and Bioavailability Forum

Hi BE/proff,

❝ - Test and Reference are administered in 7 days; 8th day is a PK-session with blood sampling

❝ - Test is to be taken twice a day

❝ - Reference is to be taken 3 times a day

❝ - 2 period, cross-over study

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❝ Drug accountability done by a CRA showed several missed administrations of medications.

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❝ Is it possible to assess how missed administrations influenced on concentrations and therefore on PK-parameters?

Yes, most certainly this affects concentrations and affects the study outcome. How much etc. depends on a lot of ADME factors and you can probably simulate it but I guess it will be a waste of time. Assuming they ignored/forgot the study medication at random there's still hope.

It is an important lesson for you: Compliance in a trial is not necessarily good, but you can be fairly sure that even though some subjects forgot to take their medication, all of them will remember to pick up their compen$ation.
Be aware that issues with DA is an inspection trigger. I think most experienced assessors will understand that in an home setting an issue with DA is a regular compliance issues and not necessarily as serious as DA trouble with subjects housed within a CRO.

All sorts of solutions have been tried. More and better verbal and written communication. Daily email reminders. Text messages via phone or phone apps ("Dear Mr. 123, this message is sent to you from Dr. Quack. It is time for you take your medication. It will be in the dispensing bag labelled 123-06 Monday June 15, 2015" etc), but it will not necessarily get rid of the problem. Some subjects apparently don't want to be poisoned but just want to be rewarded.