RE: Dual inhibitor synergy model
Dear Mads
If the purpose of your study is to understand the time course of effects of
drugs on various scores of PD then maintaining relatively constant score levels
will most likely yield low information in your design.
You should aim for finding a design where the score is most sensitive to your
study variable (dose, drug, drug combination, time etc). Generally designs
that allow you to learn about PKPD are not good for maintaining stable patient
outcomes. You may wish to consider a design that weights the desire for a good
therapeutic outcome against the ability to learn about the system.
Regards
Steve
--
Professor Stephen
http://pharmacy.otago.ac.nz/our-people/academic-staff/stephen-duffull
Chair of Clinical Pharmacy
School of Pharmacy
University of Otago
PO Box 56 Dunedin
New Zealand
E: [email protected]<mailto:[email protected]>
P: +64 3 479 5044
F: +64 3 479 7034
Design software: http://www.winpopt.com/
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Mads Kreilgaard
Sent: Wednesday, 7 March 2012 10:03 a.m.
To: [email protected]
Subject: [NMusers] Dual inhibitor synergy model
I am looking for an appropriate design and modeling strategy for inhibition of
levodopa-induced dyskinesia (LID) in a rat model of Parkinsons disease.
Dyskinesia (AIM) is scored categorically 0,1,2,3 or 4. The two active drugs by
them selves only have a minor maximum response in the model (reversal of AIMS),
but displays synergy when combined.
My intended PKPD study design is maintaining a relative constant dyskinesia
level with levodopa, and combine three doses each (low, medium, high) of the
inhibitory drugs A and B, in a total of 9 treatments in addition to a levodopa
baseline study.
With respect to the modeling strategy, my intention is to establish a baseline
model for levodopa-induced dyskinesia. Do you have suggestions/literature
references for models that could be applied to analyse the synergistic
inhibitory responses of drug A and B?
Best regards,
Mads