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Dear Members,
This is regarding the above mentioned subject, I wanted to know about
the calculation of AUCt and AUC inf in case where there are
concentrations below LOQ in the elimination phase. How do you
calculate the AUCt and do statistical analysis if there are
concentrations below LOQ. As per current practice we make the values
below LOQ as zero and then calculate the AUCt and Auc inf. But then
what is the correct method of analysis.
Prompt reply will be highly appreciated.
Regards,
Ratnakar
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Most Bioanalytical labs (in house or out-source) will not report out any
concentration values below the LLOQ (assigning a "0" to them or, as release testing labs do, report out the
concentration value of the LLOQ.
If the PK/PD values are going to be part of a submission you should not
attempt to use values below LLOQ in any formal way.
If they are to be used for your information only... PK/PD folks
sometimes
forget this and get themselves and possibly the bioanalytical lab in
trouble.
Because raw response values can and will vary run to run you want to be
circumspect about taking the raw response values associated with the
LLOQ
and converting them to concentrations.
Roger Jellife suggests using the fisher information of a sample result
to
support inclusion or exclusion but this approach has not yet been widely
accepted in bioanalysis (LC or Ligand Binding) and may not be
applicable to
samples with only a single measure (routine LC).
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Thanks for your prompt reply, reporting the value as 'zero' or if we
don't
consider the values (excluding the values below LLOQ) from the
statistical
calculation affect the statistics of the AUCT and AUCINF. Therefore
which is
the correct method, should we exclude the values or report them as
zero at
the time of statistical analysis of AUCT & AUCINF in BA/BE/PK studies.
Regards,
Ratnakar
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Hi Ratnakar,
Your 'zero' values won't affect determination of half life since they
disappear on the log scale. AUCt is calculated to the last above-LLOQ
concentration. The 'zero' values after that concentration are not
included. If you have a 'zero' value before the last above-LLOQ
concentration, you should have an SOP to describe how to deal with it.
Some people choose to ignore these values in the AUCt calculation,
some people use zero, and some people use LLOQ/2. There are many
debates on the message board on how to deal with them. Select a
method, describe it in your SOP (or at least, protocol), and stick
with it.
Best,
-Dave
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The following message was posted to: PharmPK
Basically reporting the values less than LOQ as zero, and considering
that at the time of statistical analysis in BA/BE/PK studies.
Sripal
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