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Dear All,
I appreciate if anybody can provide suggestions on Ordinal
Categorical PD data modeling and derivation of minimum effective
concentration levels. How to correlate IC50 of parametric model to
Proportional odds in the logistic regression model? Also, what
probability level of a single out come can we consider for minimum
effective concentrations?
Thanks in advance.
Ayyappa
Ayyappa Chaturvedula
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The following message was posted to: PharmPK
> I appreciate if anybody can provide suggestions on Ordinal
> Categorical PD data modeling and derivation of minimum effective
> concentration levels.
First suggestion is to forget about 'minimum effective
concentrations'. This is a concept that has no theoretical basis in
receptor based pharmacology.
Given suitable software you can write the logistic in terms of a
pharmacodynamic model e.g. linear, emax, sigmoid Emax.
Intepretation of the logistic model is then up to you. You might wish
to predict the conc that gives me 10% probability of the outcome
event. This might be interpreted as the 'minimum effective
concentration' if you want to assume this criterion for being effective.
Nick
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
n.holford.aaa.auckland.ac.nz
www.health.auckland.ac.nz/pharmacology/staff/nholford
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The following message was posted to: PharmPK
Hi Ayyappa,
You can find a correlation between sigmoid Emax model (incl IC50) and
logistic regression model in:
Bol, C. J. J. G., Vogelaar, J. P. W., and Mandema, J. W. (1999).
Anesthetic profile of dexmedetomidine identified by stimulus-response
and continuous measurements in rats. J. Pharmacol. Exp. Ther. 291,
153-160.
Please note that if you use the sigmoid Emax model it is assumed that
the probability of no response at baseline is 0. If that's not the case
you have to add an E0 to your model.
Best regards,
Kees
Kees Bol, Ph.D.
--
Kinesis Pharma BV > Consultants in Drug Development
BREDA, The Netherlands
www.kinesis-pharma.com
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