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Hi,
This is balaji.
we have come across a significant difference in the treatment effect
in Cmax and
treatment & period effect in Auct and Auci respectively.
the sample size for the analysis is 14.
But the intra subject variability is less than 6% for all the
parameters.
The power is also 100% for all the parameters .
Could you please let me know the reason for the significant
difference for the effects.
How could be the result interpreted.
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The following message was posted to: PharmPK
Dear Mr Balaji,
Treatment effect and period effect in your study could have appeared
due to the carryover effect and inadequate washout between the
periods. Please check for predose concentrations also.It can be
eliminated by providing adequte washout period .
Thanks
Manoj K
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The following message was posted to: PharmPK
Hi Balaji,
If you provide us with ratio of {(AUC 0-t )/ (AUC 0-inf)} we can help
you better
Khalil I M Al-Khamis, Ph.D
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The following message was posted to: PharmPK
Hi Balaji!
>
>we have come across a significant difference in the treatment effect
>in Cmax and
>treatment & period effect in Auct and Auci respectively.
>
Significant treatment (and period) effects do not count
in a properly conducted BE study.
>the sample size for the analysis is 14.
>
OK, now I am assuming you went for the minimum sample size
stated in many regulations (namely 12), and added 2 subjects
for potential drop outs.
>But the intra subject variability is less than 6% for all the
>parameters.
>
Yes, from a statistical point of view 6 subjects would
have been enough to show BE for a deviation of +/-5% from
unity and 80% power.
>The power is also 100% for all the parameters .
>
100% power simply does not exist, but I believe you,
that it's >99.9% ;-)
>Could you please let me know the reason for the significant
>difference for the effects.
>
<>Just the low variability and the sample size.
Your study is overpowered, therefore significant effects
are not unlikely.
>How could be the result interpreted.
>
Nothing to interpret here: BE is defined by inclusion of
the confidence interval of a particular PK parameter
within a predefinded acceptance range, nothing more (no
significance testing at all).
best regards,
Helmut
Final remark: in the last year a come across a couple
of deficiency letters from the German BfArM with exactly
this topic (extremely low variability causing significant
treatment effects in a sample size of 12).
But all of these letters could be answered in a few
sentences ;-)
--
Helmut Schuetz
BEBAC
Consultancy Services for Bioequivalence and Bioavailability Studies
Neubaugasse 36/11
1070 Vienna/Austria
tel/fax +43 1 2311746
http://BEBAC.at
Bioequivalence/Bioavailability Forum at http://forum.bebac.at
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)