Hello, I have a question about communicating the covariate impact to people who are unfamiliar with the Nonlinear mixed effect methodology used in PopPk analysis.
So, suppose we have body weight influencing drug (X) clearance, and an increase in body weight is associated with a decrease in CL, with the impact estimated by the model (- 0.5).
Can we say that increasing body weight by 10 kg intervals results in a 5% reduction in drug clearance?
Thanks
Hi David,
if you define your covariate relationship with a linear model, the reduction would be adjusted by -0.5*10 = -5
To determine a percentage reduction, you would need to know the typical value of clearance.
Bernd
Hi it depends how your wrote your equation and many times we have multiple covariate affecting the parameter
Also more often than not we want to compute the effects on PK parameters of interest: AUC and Cmax.
I wrote this tutorial:
https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/psp4.12829
and built this R package:
https://cran.r-project.org/web/packages/coveffectsplot/index.html
To help you with the process.
Suppose:
CL = 5 *(WT/70^0.75
the weight effect is a power function and is nonlinear so a 10 kg increase from 60 to 70 is not the same from 70 to 80
(50/70)^0.75
[1] 0.7769695
(60/70)^0.75
[1] 0.8908199
(80/70)^0.75
[1] 1.105335
(90/70)^0.75
[1] 1.20742
think of the above as multipliers as compared to the ref value of 70 kg ( ref = 1)
Bests,
Samer
Thanks Bernd and Samer for your answers!!