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Dear All,
It was a cross over BE study with 24 subjects. All the subjects
completed the study.
During analysis, it was found that no drug levels were detectable in
one of the volunteers in both the periods. The analysis was repeated
suspecting it for an analytical error. The repeat analysis results
also reported No detectable drug levels. [as if the volunteer had not
ingested the drug!!!!!!]. It can be doubted that the volunteer was
smart enough not to swallow the medication. In such a situation are
there any implications on the integrity of the QA audit of the study?
How should this be treated in the pharmacokinetic analysis. Can it be
possible to do the PK calculations omitting this volunteer as such OR
need it undergo any systematic evaluation before omitting it as an
outlier?
We feel that In this case is may not be necessary to present results
including and excluding the results from the outlier especially since
no detectable levels are observed. Am i right in thinking so? What
are its regulatory implications?
I would be grateful if some one could comment on the above.
regards
KP
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dear kp,
as per my understanding the for QA point of view Investigation for
that subject of total study period should be prepared and audited.
second thing if there is no evidence found for the any situated
think , as per your in-house SOP of data deletion and outliers what
the suggested for the procedure with limit of concentration result
you have to look after for that and also as per Report preparation
guideline data sets analyzed you can excluded the subject but with
proper justification against with all the treatment group.
ref. E3 guideline Sec 11.1.
any one else with stat back ground can more specific comment on this.
regards,
paresh
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Dear KP
It's an interesting experience!!
It's possible that one intelligent subject (so called!) was in the
study. In one of the study that I know, the subject had taken out the
tablet from the mouth after dosing. [After that we had improved the
dosing procedures].
You may have to
1. do a systematic review of the procedures related to dosing to find
out a possible cause (as you have already checked the analytical part).
2. go through the literature and look for any pharmacokinetic
surprises (indications) with this drug. [If dosing is proper, it's
very rare not to find any concentration in the blood]. You can do a
confirmatory analysis by re-dosing the subject.
As there are no concentrations you can not do any PK or statistical
analysis for this subject. I think he cannot be called outlier, as
there is no data. As you have mentioned, you need to do a systematic
evaluation to account for the reason and document the same for
regulatory purpose. One has to apply the PK and stats for remaining
subjects.
Regards,
Vinay
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