Actual vs. scheduled times [Study Performance]
❝ We have removed “magic” time allowance window (TAW) from our protocol. So every blood sampling deviation, will be reported in CRF and statistical analysis.
I think we disagree in terminology. Samples with deviations within the TAW don’t have to be commented in the CRF. However, the actual time point will always be recorded and used in PK. If you mandate to comment every deviation (even if considered irrelevant) you put stress on the clinical staff. They should concentrate on handling samples – not on prose.
❝ But one of our customer, ask us, to put TAW in our protocol. Since we can't justify the deviation, we can't accept the request.
I don’t understand. Can you elaborate?
❝ What I know from training, TAW will be specific for any kind of drug molecules, it can't 5%, more or less, depend on the impact to pharmacokinetic analysis.
Maybe, maybe not. I’m not aware of any paper exploring it. Papst wrote:
[…] only those time deviations will be of pharmacokinetic relevance in which the time interval between the preceding and the affected sample or the interval between the affected and the following sample was prolonged or shortened by, for example, more than 5%. In practice it has been proven acceptable to consider only those time deviations out of this specified range when calculating the AUC.
This procedure for calculating pharmacokinetic parameters by ignoring any time deviations of less than 5% of the shorter of the two time intervals surrounding the sample affected has been shown by simulations to lead to estimates that differ at the most by 1.5% from the theoretical value. In unfavourable circumstances (very few samples, all deviations in one direction) the relative error may increase to 3.6%). The simulation furthermore showed that a well-chosen design (e.g. with respect to sampling times) is more important than other factors (e.g. theoretical profile, analytical accuracy).
❝ But we don't how to decide the percentage of blood sampling deviation which can't make an effect to pharmacokintetic analysis.
Use the actual times.
❝ Would you mind to share how to decide the percentage of blood sampling which can't categorize as deviation, so TAW won't be "magic" again, but scientifically sound.
I would keep it at 5% (yes, arbitrarily!). The idea to comment on larger deviations is sumfink like this:
“Hhm, this concentration looks really weird. It is much lower than the ones before and after. Let’s have a look at the CRF. Ah, the venflow was blocked and it took the study nurse 10 minutes to rinse it with Ringer’s solution. Maybe she didn’t discard the first milliliters and the sample was diluted? I will go downstairs and ask her.”
BTW, things like this are pretty common. Train the staff not to reach for the stars. If a venflow cannot be opened quickly (say within two minutes), opt for venipuncure at this timepoint (make sure to mention it in the ICF). They can deal with the blockage later on.Dif-tor heh smusma 🖖🏼 Довге життя Україна!
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Helmut Schütz
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Science Quotes
Complete thread:
- Acceptable deviation of blood sampling time joy_fm 2015-08-10 08:50 [Study Performance]
- Time allowance windows? Helmut 2015-08-11 00:44
- Time allowance windows? joy_fm 2015-08-11 04:07
- Actual vs. scheduled timesHelmut 2015-08-11 13:09
- Actual vs. scheduled times joy_fm 2015-08-13 19:00
- Time allowance windows? Ohlbe 2015-08-17 17:51
- Actual vs. scheduled timesHelmut 2015-08-11 13:09
- Time allowance windows? joy_fm 2015-08-11 04:07
- Time allowance windows? Helmut 2015-08-11 00:44