I think we are making it more difficult than needed, especially for the people who just started using the NLME. It does not hurt to include statistically significant covariate in the model even if the actual effect is small and does no manifest itself on the standard diagnostic plots.

It make sense to check whether there is an error in the model code. Plots of random effects versus covariates of interest should help to see whether covariate model changed the individual random effects. If not (that is, random effects of the model with and without covariate effect are numerically identical) then the coding is wrong and should be checked.

Thanks
Leonid



On 10/29/2019 11:00 AM, Luann Phillips wrote:
Hi,

If _all_ of the individual predictions are the same for the model with the covariate and without the covariate, then it sounds like the original model is at a local minimum instead of a global minimum.

Best regards,

Luann

*From:* owner-nmus...@globomaxnm.com <owner-nmus...@globomaxnm.com> *On Behalf Of *Singla, Sumeet K
*Sent:* Tuesday, October 29, 2019 10:00 AM
*To:* nmusers@globomaxnm.com
*Subject:* [NMusers] Stepwise covariate modeling

Hi!

I am performing stepwise covariate modeling using PsN feature in Pirana. I am getting some covariates which are statistically reducing OFV significantly, however, when I include those covariates in the PK model, the results I am getting are exactly similar to what I am getting in my base model, i.e. there is no difference in individual predictions or pop predictions or any other diagnostic plots. So, does that mean I should move forward WITHOUT including those covariates as they don’t seem to be explaining inter-individual variability despite scm telling me that they are statistically significant?

Regards,

*Sumeet K. Singla*

*Ph.D. Candidate*

*Division of Pharmaceutics and Translational Therapeutics*

*College of Pharmacy | University of Iowa*

*Iowa City, Iowa*

*sumeet-sin...@uiowa.edu <mailto:sumeet-sin...@uiowa.edu>*

*518.577.5881*


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