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Dear All,
I have a query it will be nice if someone could clarify it.
In a 2*2 crossover bioequivalence study there are 24+4 standby human
healthy volunteers participated in the study.
Clinical part:
Out of 28 volunteers 27 were participated in the study, volunteer
number 11 is windrow from the study during the first period but 6 blood
samples were selected.
And two more volunteers (number 5 and 18) they didn't turn up for
period 2, but volunteer number 11 is participated in the second period.
Query 1: Is it correct that we have taken the volunteer number 11 for
period2?
Analytical Part:
The protocol says that
"The first 24 subjects who completes both the period will be
analyzed, in case of dropouts, samples will be obtained from stand by
subjects,
following the same sequence of dosing as that of dropout will be
analyzed. In case of subsequent dropouts there will be no
replacements, in
such a condition an unequal number of subjects per sequence will be used
for statistical analysis."
During subject samples analysis the analyst has taken the fist 24
subjects who completed both the periods (excluding number 5 and 18),
instead
of volunteer 5 and 18 they have taken 25 & 26.
Where in which the sequence of 5 and 18 is TR. But the sequence of 25 &
26 is RT and TR
The sequence of 27 is TR.
Query 2: is it ok if we including the volunteer number 11 for analysis.
Because he had withdrawn from period one and again he participated in
the study.
Query 3: is it ok to include volunteers 25 and 26 instead of 26 and 27
the subject sample analysis.
PK and Statistical Part:
Query 4: During PK and statistical analysis of this study can we
include subject number 11? When we include the subject 11 the primary
pharmacokinetic parameters Cmax and AUC0-u where with in the acceptance
limits
of bioequivalence. But AUC0-t is not with in the acceptance limits
When we remove subject 11 all the three parameters are with in the
acceptance limits.
Thanks and Regards,
kanimozhi.A
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The following message was posted to: PharmPK
Dear Kanimozhi.A,
just my personal views:
>Query 1: Is it correct that we have taken the volunteer number 11 for
>period2?
>
No, since you have incomplete data on period 1, you are not be able
to run an intra-subject comparision of treatments for that subject.
>Query 2: is it ok if we including the volunteer number 11 for analysis.
>Because he had withdrawn from period one and again he participated in
>the study.
>
No. This does not make sense, since you have only inclomplete data
from period 1.
>Query 3: is it ok to include volunteers 25 and 26 instead of 26 and 27
>the subject sample analysis.
>
No, since you must follow the protocol:
"The first 24 subjects who completes both the period will be analyzed,
in case of dropouts, samples will be obtained from stand by subjects,
*following the same sequence of dosing as that of dropout* will
be analyzed..."
Subject 11 is also a drop out, therefore IMHO you have to include
the first two stand-by subjects with the sequence of subjects 5 and 11
(since you have not given the sequence of subject 11, I can't give you
the subject numbers).
>Query 4: During PK and statistical analysis of this study can we
>include subject number 11? When we include the subject 11 the primary
>pharmacokinetic parameters Cmax and AUC0-u where with in the acceptance
>limits of bioequivalence.
>But AUC0-t is not with in the acceptance limits
>When we remove subject 11 all the three parameters are with in the
>acceptance limits.
>
Now you are in trouble.
How did you calculate PK parameters of subject 11 based on only
6 samples from period 1?
Any regulator will be alert and get the impression you choose subjects
for inclusion based on the outcome of the BE analysis.
You have only p=0.05 to use it *once*; you may not post-hoc
"play around" with data to get the results you want.
best regards,
Helmut
--
Helmut Schutz
BEBAC
Consultancy Services for Bioequivalence and Bioavailability Studies
Neubaugasse 36/11
A-1070 Vienna/Austria
tel/fax +43 1 2311746
http://BEBAC.at Bioequivalence/Bioavailability Forum at
http://forum.bebac.at
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