Hi,
Experimental studies (rather than just opinion) can be found here:
1. Zhang L, Beal SL, Sheiner LB. Simultaneous vs. sequential analysis
for population PK/PD data I: best-case performance. J Pharmacokinet
Pharmacodyn. 2003;30(6):387-404.
2. Zhang L, Beal SL, Sheiner LB. Simultaneous vs. sequential analysis
for population PK/PD data II: robustness of methods. J Pharmacokinet
Pharmacodyn. 2003;30(6):405-16.
3. Proost JH, Schiere S, Eleveld DJ, Wierda JM. Simultaneous versus
sequential pharmacokinetic-pharmacodynamic population analysis using an
iterative two-stage Bayesian technique. Biopharm Drug Dispos.
2007;28(8):455-73.
My interpretation of these studies is that one should use a sequential
approach to build the model then try a simultaneous fit. If the PK part
of the model changes 'importantly' (subjective decision) with the
simultaneous fit then this can be a clue to model misspecification in
the link between the PK and PD parts of the model (see second paper by
Zhang et al).
Nick
Hussein, Ziad wrote:
Hi Alan,
I just had a very recent experience few weeks ago for a sequential PopPK
for parent and metabolite that was submitted to the FDA and they came
back and asked for simultaneous modelling.
Whether this is scientific or not the FDA view should be taken into
consideration.
Kind regards,
Ziad
-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of Xiao, Alan
Sent: 09 December 2008 16:02
To: [email protected]
Subject: [NMusers] Simultaneous vs sequential for modeling parent AND
metabolites in pop PK
Dear All,
I know this is an old topic but would like to see the statistics.
When you have to develop a pop PK model for both parent and active
metabolites, which approach do you prefer or have you used most:
simultaneous or sequential? Which way do you think is more scientific? I
heard comments saying that the simultaneous approach is not scientific.
Thanks,
Alan
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