# Covariate effect explanation

**URL:** <https://forum.certara.com/t/covariate-effect-explanation/3694>\
**Category:** Modelling and Simulation\
**Created:** [August 3, 2023, 10:59pm UTC](https://forum.certara.com/t/covariate-effect-explanation/3694 "2023-08-03T22:59:06Z")\
**Posts on this page:** 4\
**Page:** 1

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**Author:** ![davidq8](https://avatars.discourse-cdn.com/v4/letter/d/90ced4/32.png) [@davidq8](https://forum.certara.com/u/davidq8)\
**Post date:** [August 3, 2023, 10:59pm UTC](https://forum.certara.com/t/covariate-effect-explanation/3694/1 "2023-08-03T22:59:06Z")

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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

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**Author:** ![bwendt](https://avatars.discourse-cdn.com/v4/letter/b/f4b2a3/32.png) [@bwendt](https://forum.certara.com/u/bwendt)\
**Post date:** [August 4, 2023, 9:56am UTC](https://forum.certara.com/t/covariate-effect-explanation/3694/2 "2023-08-04T09:56:04Z")

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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

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**Author:** ![Samer\_Mouksassi](https://avatars.discourse-cdn.com/v4/letter/s/ce7236/32.png) [@Samer\_Mouksassi](https://forum.certara.com/u/Samer_Mouksassi)\
**Post date:** [August 4, 2023, 9:57am UTC](https://forum.certara.com/t/covariate-effect-explanation/3694/3 "2023-08-04T09:57:45Z")

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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](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](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

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**Author:** ![davidq8](https://avatars.discourse-cdn.com/v4/letter/d/90ced4/32.png) [@davidq8](https://forum.certara.com/u/davidq8)\
**Post date:** [September 19, 2023, 10:04pm UTC](https://forum.certara.com/t/covariate-effect-explanation/3694/4 "2023-09-19T22:04:41Z")

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Thanks Bernd and Samer for your answers!!