ETAPvalues

Dear Nonmem users, My question is about ETAPval. I am modelling a parent-metabolite data using the 2-stage approach. After modelling the parent drug alone, parameter estimates (for the parent) were fixed in the metabolite model and metabolite parameters were estimated. All ETAPvalules for metabolite parameters were acceptable > 0.2 and all metabolite model parameters were estimated precisely; however, some of the ETAPvalues of parent drug parameters became < 0.05 while they were acceptable when the parent drug was modelled alone. Should ETAPvalues for parent parameters stay above the acceptable limit even if the parameters are fixed or we care only about the ETAPvals for estimated parameters only? N.B. Simultaneous modelling of the parent-metabolite wasn't possible. Thank you, Ahmad Abuhelwa Email: [email protected]<mailto:[email protected]> Mobile: +61 413118743

Dear Ahmad, The ETA P-value is one of the diagnostics available for modelers. What it means and how important it is depends on your modeling objective and data. Having said that, in this case it seems that you have fixed thetas and omegas but left parent concentrations in the dataset. The lower ETA P-value indicates that the parent posthoc ETA distribution has shifted away from zero. This most likely means that your metabolite submodel has 'pulled' the parent posthoc away. You might want to look at the parent posthoc graphs to further investigate how the model shifted. Generally speaking this could mean that the metabolite model has some mismatch that is compensated by the parent etas. You might be able to update the metabolite (or parent) model to avoid this. If needed, you could also use a slightly different approach where you completely fix the parent model by appending your original posthocs to your dataset and apply them as a fixed input to the metabolite model and adjust. Afterwards you can see whether the updated model has improved ETA P-values. Hope this helps! Best regards, Jeroen http://pd-value.com [email protected] @PD_value +31 6 23118438 -- More value out of your data!