# Additive error being bound to minimize the effect of the BLQ imputation **URL:** \ **Category:** Modelling and Simulation\ **Created:** [June 16, 2022, 10:43pm UTC](https://forum.certara.com/t/additive-error-being-bound-to-minimize-the-effect-of-the-blq-imputation/3615 "2022-06-16T22:43:39Z")\ **Posts on this page:** 7\ **Page:** 1
**Author:** ![davidq8](https://avatars.discourse-cdn.com/v4/letter/d/90ced4/32.png) [@davidq8](https://forum.certara.com/u/davidq8)\ **Post date:** [June 16, 2022, 10:43pm UTC](https://forum.certara.com/t/additive-error-being-bound-to-minimize-the-effect-of-the-blq-imputation/3615/1 "2022-06-16T22:43:39Z")
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 ---
**Author:** ![cradhakr](https://avatars.discourse-cdn.com/v4/letter/c/7feea3/32.png) [@cradhakr](https://forum.certara.com/u/cradhakr)\ **Post date:** [June 16, 2022, 11:19pm UTC](https://forum.certara.com/t/additive-error-being-bound-to-minimize-the-effect-of-the-blq-imputation/3615/2 "2022-06-16T23:19:06Z")
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](https://www.youtube.com/watch?v=xX-yCO5Rzag) Thanks and regards Chnadramouli ---
**Author:** ![davidq8](https://avatars.discourse-cdn.com/v4/letter/d/90ced4/32.png) [@davidq8](https://forum.certara.com/u/davidq8)\ **Post date:** [June 17, 2022, 3:08am UTC](https://forum.certara.com/t/additive-error-being-bound-to-minimize-the-effect-of-the-blq-imputation/3615/3 "2022-06-17T03:08:03Z")
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](https://forum.certara.com/uploads/short-url/jR3Bgl6piqZGPBiJwssiJYQmmeo.pdf) (1.86 MB)[NOMEM codes.pdf](https://forum.certara.com/uploads/short-url/cuzJzxe2xRGH5AbMfgZhGide28K.pdf) (1.47 MB) ---
**Author:** ![cradhakr](https://avatars.discourse-cdn.com/v4/letter/c/7feea3/32.png) [@cradhakr](https://forum.certara.com/u/cradhakr)\ **Post date:** [July 5, 2022, 5:43am UTC](https://forum.certara.com/t/additive-error-being-bound-to-minimize-the-effect-of-the-blq-imputation/3615/4 "2022-07-05T05:43:39Z")
Hi David, Apologies thought I had answered your question. With Phoenix you will be using the M3 method as mentioned in the link below [![](https://us1.discourse-cdn.com/certara/original/2X/f/f7468f0338ada49b1f7b6286a2702838b0b20a28.jpeg "Handling of LLOQ values in Phoenix") ](https://www.youtube.com/watch?v=xX-yCO5Rzag) Thanks Mouli [https://www.youtube.com/watch?v=xX-yCO5Rzag](https://www.youtube.com/watch?v=xX-yCO5Rzag) ---
**Author:** ![SimonDavis](https://avatars.discourse-cdn.com/v4/letter/s/d9b06d/32.png) [@SimonDavis](https://forum.certara.com/u/SimonDavis)\ **Post date:** [July 5, 2022, 10:51am UTC](https://forum.certara.com/t/additive-error-being-bound-to-minimize-the-effect-of-the-blq-imputation/3615/5 "2022-07-05T10:51:01Z")
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,)) ---
**Author:** ![davidq8](https://avatars.discourse-cdn.com/v4/letter/d/90ced4/32.png) [@davidq8](https://forum.certara.com/u/davidq8)\ **Post date:** [July 6, 2022, 7:42pm UTC](https://forum.certara.com/t/additive-error-being-bound-to-minimize-the-effect-of-the-blq-imputation/3615/6 "2022-07-06T19:42:46Z")
> [@cradhakr](#): > > Hi David, > > Apologies thought I had answered your question. With Phoenix you will be using the M3 method as mentioned in the link below > > [https://www.youtube.com/watch?v=xX-yCO5Rzag](https://www.youtube.com/watch?v=xX-yCO5Rzag) > > Thanks > > Mouli > > [https://www.youtube.com/watch?v=xX-yCO5Rzag](https://www.youtube.com/watch?v=xX-yCO5Rzag) Thanks Mouli for your explanation. ---
**Author:** ![davidq8](https://avatars.discourse-cdn.com/v4/letter/d/90ced4/32.png) [@davidq8](https://forum.certara.com/u/davidq8)\ **Post date:** [July 6, 2022, 7:44pm UTC](https://forum.certara.com/t/additive-error-being-bound-to-minimize-the-effect-of-the-blq-imputation/3615/7 "2022-07-06T19:44:33Z")
> [@sdavis](#): > > 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,)) Thanks, Simon, for providing me with text codes for PML, this is really helpful! Best