# Handling missing values in bioequivalence studies? **URL:** \ **Category:** Modelling and Simulation\ **Created:** [April 12, 2016, 9:48am UTC](https://forum.certara.com/t/handling-missing-values-in-bioequivalence-studies/2955 "2016-04-12T09:48:16Z")\ **Posts on this page:** 3\ **Page:** 1
**Author:** ![simon.hutchings](https://avatars.discourse-cdn.com/v4/letter/s/a88e4f/32.png) [@simon.hutchings](https://forum.certara.com/u/simon.hutchings)\ **Post date:** [April 12, 2016, 9:48am UTC](https://forum.certara.com/t/handling-missing-values-in-bioequivalence-studies/2955/1 "2016-04-12T09:48:16Z")
Hi all, I have been scouring the relevant EMA/FDA guidance but haven’t come across anything too useful in relation to assessing the impact of missing samples in a bioequivalence study. The scenario is: 4 way cross BE study; test vs ref in fed and fasted states N = 22 HVs Tmax ~60 mins T1/2 ~120 min Sampling: 0, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 mins During one of the study periods a protocol non-compliance has resulted in the 480 min time point not being available for 2 out of 22 subjects. Given where the 480 h time point lies in the profile, my instinct tells me that the missing samples should have minimal/negligible impact on the study objectives (i.e. to test for bioequivalence) and should not introduce an unacceptable amount of bias into the estimation of AUCt for the 2 subjects in question. However, I would like to check if there are any guidelines/best practices etc that reinforce my ‘instinct’? Any thoughts most welcome! ---
**Author:** ![SimonDavis](https://avatars.discourse-cdn.com/v4/letter/s/d9b06d/32.png) [@SimonDavis](https://forum.certara.com/u/SimonDavis)\ **Post date:** [April 12, 2016, 11:27am UTC](https://forum.certara.com/t/handling-missing-values-in-bioequivalence-studies/2955/2 "2016-04-12T11:27:34Z")
I would tend to agree with you, if you say thalf is 2 hours as you should have enough points to interpolate OK, are all subjects quantifiable at 720 min? if not what is your typical Tlast currently? Personally, I would gauge the experiment on how well estimated AUC is for these 2 subjects compared to the rest, if they appear to be truncated then you might have problems, you may also consider asking on the BEBAC forum, there is a wealth of experience there. [http://forum.bebac.at/mix.php](http://forum.bebac.at/mix.php) In fact this one today explores just this sort of problem; [http://forum.bebac.at/mix\_entry.php?id=16182#top16182](http://forum.bebac.at/mix_entry.php?id=16182#top16182) Simon ---
**Author:** ![simon.hutchings](https://avatars.discourse-cdn.com/v4/letter/s/a88e4f/32.png) [@simon.hutchings](https://forum.certara.com/u/simon.hutchings)\ **Post date:** [April 12, 2016, 11:37am UTC](https://forum.certara.com/t/handling-missing-values-in-bioequivalence-studies/2955/3 "2016-04-12T11:37:25Z")
Thank you for the response Simon, and for suggesting the BEBAC forum (I wasn’t aware of that), much appreciated! Typical Tlast is 720 min (however bioanalysis is not complete yet); fingers crossed truncation won’t be an issue. Thanks again, Simon