NONMEM Users Network Archive

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RE: Weight based dosing

From: Abu Helwa, Ahmad Yousef Mohammad - abuay010 <ahmad.abuhelwa >
Date: Wed, 9 Dec 2015 01:35:50 +0000

Hi Abdullah:

This depends on how you set your criteria for including covariates into the=
 model (the p-value, reduction in OFV, se of the estimated covariate parame=
ter etc).
Before starting running covariate models, it is always a good practice to p=
lot BSV (i.e. ETAs) against the available covariates your have (in your cas=
e: ETAs versus weight) then if you see biologically plausible covariate rel=
ationships then you start testing them. I usually use forward addition (p-=
value 0.05, delta reduction 3.84 or p-value 0.01, delta OFV 6.63 units) and=
 backward elimination (p-value 0.001, delta increase OFV 10.8 units) and se=
 should be < 51.2%. You don't need to stick with these criteria but you can=
 develop your own. If including a covariate passes all the criteria and is =
estimated precisely, then I think it should stay in the model. Reduction in=
 BSV > 5% may be significant.

There are various methods for including covariates in the literature, you m=
ay need to choose yours!

Ahmad Abuhelwa
University of South Australia
Adelaide, South Australia

From: owner-nmusers
 Behalf Of Sultan,Abdullah S
Sent: Wednesday, 9 December 2015 11:10 AM
To: nmusers
Subject: [NMusers] Weight based dosing

Hi everyone,

I am developing a POP PK model for an anti-infective drug, I am trying to d=
etermine if dosing should be weight based or not. The range of weight in th=
e study was 40-100 kg.

Weight was statistically significant for Cl/F but only explained 9% of the =
variability observed for Cl.

I used allometric scaling to describe weights effect on Cl/F and slope effe=
ct of weight was 0.58, and scaled to 60 kg (the median).

Based on the slope effect estimated, AUC is predicted to decrease by 15% fo=
r an 80 kg individual, and increase by 25% for an individual that weights 4=
0 kg compared to a 60 kg individual.

How much should I trust the slope effect determined by my study? and should=
 I rely on it to develop the dosing regimen?

if weight only explained 9% of variability observed with Cl/F, could that i=
ndicate that it is not clinically significant and weight based dosing is no=
t required?


Abdullah Sultan, PhD candidate

University of Florida

Received on Tue Dec 08 2015 - 20:35:50 EST

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