Re: Re: Weight based dosing
While it is important to look at the variability explained by the covariate,
your question is not really a statistical one. You need to evaluate the
clinical significance of the change in exposure by weight. For a given dose,
how does exposure change by weight and how will this affect the efficacy of the
antibiotic under various assumptions of bacterial sensitivity? Think about how
you can use your model to answer the clinical question - you won't find the
answer in p-values or objective function changes.
Mike Fossler
Quoted reply history
On Dec 8, 2015, at 9:28 PM, Sultan,Abdullah S
<[email protected]<mailto:[email protected]>> wrote:
Hi Rudy Gunawan,
Thanks for the helpful information,
I tried both methods, fixing the exponents at 0.75 and 1 and estimating them,
results for both models are similar, No other covariate (demographic variables
or lab test) showed any correlation with Cl/F.
my main question is how important is it to look at the variability explained by
a covariate? And can it be used to determine if a covrariate is not clinically
significant
Thanks,
Abdullah Sultan
________________________________
From: Rudy Gunawan <[email protected]<mailto:[email protected]>>
Sent: Tuesday, December 8, 2015 8:10 PM
To: Sultan,Abdullah S; [email protected]<mailto:[email protected]>
Subject: RE: Weight based dosing
Hi Abdullah Sultan,
Since your estimate is not too far from 0.75 exponent in Clearances, did you
try using the theoretical allometric scaling (0.75 in all clearances and 1.00
in volumes)? With these, it would be easier to justify. Once you include the
body size, I would suggest you check the matrix plots of ETA in CL or V versus
other covariates (demo, labs, etc) to see if there is any other info would help
explain the variability. Without knowing more of the nature of the drug, I
think these would help build the model.
Hope this helps,
Rudy
From: [email protected]<mailto:[email protected]>
[mailto:[email protected]] On Behalf Of Sultan,Abdullah S
Sent: Tuesday, December 08, 2015 4:40 PM
To: [email protected]<mailto:[email protected]>
Subject: [NMusers] Weight based dosing
Hi everyone,
I am developing a POP PK model for an anti-infective drug, I am trying to
determine if dosing should be weight based or not. The range of weight in the
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 effect
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% for an
80 kg individual, and increase by 25% for an individual that weights 40 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
indicate that it is not clinically significant and weight based dosing is not
required?
Thanks,
Abdullah Sultan, PhD candidate
University of Florida
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