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From: Sam Liao <sliao>
Date: Fri, 20 Nov 2015 10:45:34 -0800

Dear Thierry,
External VPC would be a useful method to compare your data with the
published PPK model.

Best regards,
Sam Liao, Ph.D.
Pharmax Research, Inc.

On 11/20/2015 9:44 AM, Buclin Thierry wrote:
> Dear NMusers,
> We have a small series of some 100 blood measurements in 13
> neutropenic patients for a specific intravenous antibiotic. A
> population PK model for this antibiotic has already been published,
> based on about 300 patients, probably with very few neutropenic cases
> (neutropenia has not been tested as a covariate). The 2 compartment
> model includes 4 PK parameters (CL, V1, V2, Q), each with
> inter-individual variability, plus 7 coefficients applying to
> significant covariates and 1 residual variability.
> Rather than re-inventing a pop-PK model for our 13 neutropenic
> patients, we just wanted to check whether the model already published
> applied to them. Then we planned to use model-derived MAP values for
> AUC and Cmin. So we first ran the model on these 13 patients with all
> 16 parameters fixed/bound to their published reference value, and we
> obtained a value of the objective function (say OF_ref), along with
> estimates of AUC and Cmin. Thereafter, we estimated all parameters
> (except one that needed to be kept fixed) and we obtained another
> value of the objective function (say OF_fit). The parameter values
> obtained after fitting did not differ much from their published
> reference values, comprised in +/- 2SE for all except one; however,
> most SEs were of course large due to our small number of patients.
> PRED vs OBS scatter plots were not suggestive of bias; PRED_ref vs
> PRED_fit plots were well correlated. The fit decreased the objective
> function (OF_ref OF_fit) by about 40 points.
> We have a rather elementary question here : can this decrease in
> objective function be used to test statistically whether our 13
> neutropenic patients globally differ from the population PK profile
> described in the published reference model? Can we simply interpret
> the drop from OF_ref to OF_fit as following a Chi-square distribution
> with 15 degrees of freedom under the null hypothesis (i.e. neutropenic
> patients belong to the same population as the reference)? Or should we
> privilege more sophisticated approaches to answer this question? We
> searched the NMusers archive without finding much about this point.
> Thanks in advance
> Thierry Buclin, Aziz Chaouch
> University Hospital CHUV, Lausanne, Switzerland

Sam Liao
Pharmax Research Inc.
14 Upland,
Irvine, CA 92602
Phone: 201-9882043
efax: 720-2946783

Received on Fri Nov 20 2015 - 13:45:34 EST

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