Additive error being bound to minimize the effect of the BLQ imputation

Phoenix Certara Forums Modelling and Simulation
1

Hi,
I am working on a model with LLOQ concentrations being imputed. I found the following in a published PopPk analysis:

" Residual variability was assumed to have an additive and a proportional element, with the additive error being bound to be at least 20% of the LLOQ to minimize the effect of the BLQ imputation".

I question how to put such a bound on additive error using the PML or built-in faction?

Thanks

2

Hi David,

Thanks for contacting Certara. In regards to your question, I am not sure which publication you are referring to.

I have attached a link (Presentation on handling LLOQ) that may be of use to you.

https://www.youtube.com/watch?v=xX-yCO5Rzag

Thanks and regards

Chnadramouli

3

Thanks, Chnadramouli, for sharing the link. It is very helpful. I am quite familiar with handling LLOQ using NLME, but I still do not know how they applied the bound on the additive error to be at least 20% of the LLOQ .
I am attaching the study and NONMEM codes.
Thanks
ETH PopPk.pdf (1.86 MB)NOMEM codes.pdf (1.47 MB)

4

Hi David,

Apologies thought I had answered your question. With Phoenix you will be using the M3 method as mentioned in the link below

Thanks

Mouli

https://www.youtube.com/watch?v=xX-yCO5Rzag

5

The model seems somewhat complex but this can be done in Phoenix too.

AddErr and PropErr are the fixed effects and they are combined into W which is used as a coefficient for the sigma.

That could be used in PML too (create fixefs AddErr and PropErr and use them to build W).

Since AddErr has a low limit as 0.00626, I assume it is the constraint you/the authors are talking about.

Prop=C*PropErr

Add=AddErr

W= sqrt(Add^2 + Prop^2))

error(CEps = 1)

observe(CObs = C + W*CEps)

fixef(AddErr = c(0.0138181,0.00626,))

fixef(PropErr = c(,0.171622,))

6

Thanks Mouli for your explanation.

7

Thanks, Simon, for providing me with text codes for PML, this is really helpful!

Best