Log in
Register|
Averroes ☆ Spain, 2011-02-22 15:05 (5191 d 00:49 ago) Posting: # 6659 Views: 5,215 |
|
|
Dear colleagues, First of all I would like to give thanks for this forum, it seems very helpful. This is my first time writting, and I'm very naive in BA/BE studies. I would like some advice on how to justify pre-dose concentration in the 2nd period, as we found them in around 50 % of subjects. It's very clear that the wash-out period was insufficient, but I would like to report that in an elegant way. As far as I know it should not be critical as all of them are below 5% of Cmax. Both test and reference were affected equally. Any suggestion? Thanks, Averroes Edit: Category changed; see also this post #1. [Helmut] |
|
Helmut ★★★   Vienna, Austria, 2011-02-22 15:45 (5191 d 00:09 ago) @ Averroes Posting: # 6660 Views: 4,413 |
|
|
Dear Averroes! ❝ I would like some advice on how to justify pre-dose concentration in the 2nd period, as we found them in around 50 % of subjects. It's very clear that the wash-out period was insufficient, but I would like to report that in an elegant way. Well, nothing to justify here. Shit happens; just report it and learn from it for the next studies. A common mistake is to plan the washout on the mean half-life reported in literature. Remember that higher than expected pre-dose values may occur if there is high inter-subject variability (especially if the drug is subjected to polymorphism). Plan always for the worst case (see this presentation, slides 40-42). ❝ As far as I know it should not be critical as all of them are below 5% of Cmax. Both test and reference were affected equally. Right. Maybe you will see a slight period effect, which will be accounted for in the ANOVA anyway. Just give it a try: Take the data of any BE study and multiply all values in the second period by let's say 100. The outcome (PE, confidence interval) will be exactly the same – although you will notice a highly significant period effect. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
|
Averroes ☆ Spain, 2011-02-22 19:14 (5190 d 20:40 ago) @ Helmut Posting: # 6661 Views: 4,273 |
|
|
Dear HS, Thanks for your comments and for your quick reply!!! For sure I will take into account for the future. Do you think we will receive comments from regulatory authorities due to that? or as long as all concentrations are below 5% of Cmax it's OK. I have to say that I used Mean+SD reported in previous bioequivalence studies and SmPC to calculate washout, so as per your comments I shouldn't have %50 percent of subjects with pre-dose levels. On the other hand, I used a lower LLOQ, then I think pre-dose levels are due to flat part of the profile (pure elimination phase). I think I will use data on SmPC and literature to justify this fact, hoping that it has no impact on the assessment of the application. Thanks!!! |
Ing. Helmut Schütz