BQL simulations

Hello everyone I have a simple question for a simple bicompartmental model where M3 method for estimating bql is used, because of that my predictions are overly inflated at the tail end of the treatment period (bql levels), which distorts my simulations. I used this line to get corrected predictions: IF(COMACT.EQ.1) PREDI=IPRED But that doesn't improve my simulated data at low concentrations, is there a way around it or should I use an other method to handle my bql values? Thank you in advance

Dear Hiba, What is your complete error model? The information you provide is too limited to be sure how to help you. However, assuming you used a proportional error model with an additive term for M3/BQL, you might get better results with an exponential error model. For this, you need to use a transform-both-sides approach (TBS) as explained on page 530 of https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1002/psp4.12404 , or the example provided in the tutorial part II, example 2 https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/psp4.12422 (*) which has both M3 and TBS included. The reason is with the exponential-M3 model you can simulate decreasing concentrations, with residual error, going down beyond the LLOQ - there is no transition involved as with the proportional+ additive/M3 method. Hope this helps, Jeroen *: Bauer, Robert J. "NONMEM tutorial part II: estimation methods and advanced examples." /CPT: pharmacometrics & systems pharmacology/ 8.8 (2019): 538-556. http://pd-value.com [email protected] @PD_value +31 6 23118438 -- More value out of your data!

For simulation, you can remove bql part, and simulate from the model. Simulated values below lloq can be treated as bqls, if you e.g. want to compare fraction of bqls in observed and simulated sets. Leonid