Re: Different EBE estimation between original and enriched dataset with MDV=1

On 11/23/2012 11:08 AM, [email protected] wrote: > Dear NM-User community, > > I have a model with 2 differential equations and I use ADVAN6 TOL=5. In > $DES, I am using T the continuous time variable. The run converges, $COV > is OK, and the model gives a reasonable fit. In order to compute some > statistics which cannot be obtained analytically, I need to compute > individual predictions based on individual POSTHOC parameters and an > extended grid of time for interpolating the observed times. > > So I have > 1) added to my original dataset extra points regularly spaced with > MDV=1. To give you an idea, my average observation time is 25, with a > range going from 5 to 160. So my grid was set so that I have a dummy > observation every 1 unit of time. > 2) rerun my model using $MSFI to initialize the pop parameters, with > MAXEVAL=0 and POSTHOC options so that individual empirical Bayes > estimates (EBE) parameters for each patient would be first re-estimated, > then the prediction would be computed. > > Then I > 3) checked that my new predictions computed from the extended dataset > match the predictions of the original dataset at observed time points. I > had the surprise to see that for some individuals those predictions > match, for some others they slightly diverge, and for few others they > are dramatically different. I checked the EBEs and they were clearly > different between the original dataset and the one with the dummy points. > 4) I decided to redo the grid with only one dummy point every 1/4 of > time unit. The result was less dramatic, but still for most of my > individuals the EBEs predictions were diverging from the original ones > computed without the dummy times. > > Of course the solution for me is to estimate the EBEs from the original > dataset, export them in a table and reread them to initialize the > parameter of my individuals using only dummy time points and no > observations. > > This problem reminds me something that was discussed previously on > nm-user, but I could not recover the source in the archive. > > Anyway is this something known and predictable that when adding dummy > points with MDV=1 to your original dataset you sometimes get very > different EBEs ? Are there cases/models/ADVAN where the problem is > likely to happen? Is their a way to fix it it in NONMEM other than the > trick I used? > > Thanks for your replies! > > Kind regards, > > Pascal Girard, PhD > [email protected] > Head of Modeling & Simulation - Oncology > Global Exploratory Medicine > Merck Serono S.A. · Geneva > Tel: +41.22.414.3549 > Cell: +41.79.508.7898 > > This message and any attachment are confidential and may be privileged > or otherwise protected from disclosure. If you are not the intended > recipient, you must not copy this message or attachment or disclose the > contents to any other person. If you have received this transmission in > error, please notify the sender immediately and delete the message and > any attachment from your system. Merck KGaA, Darmstadt, Germany and any > of its subsidiaries do not accept liability for any omissions or errors > in this message which may arise as a result of E-Mail-transmission or > for damages resulting from any unauthorized changes of the content of > this message and any attachment thereto. Merck KGaA, Darmstadt, Germany > and any of its subsidiaries do not guarantee that this message is free > of viruses and does not accept liability for any damages caused by any > virus transmitted therewith. > > Click _ http://www.merckgroup.com/disclaimer_to access the German, > French, Spanish and Portuguese versions of this disclaimer.