Error message: NO MORE THAN 20 ADDITIONAL AND/OR LAGGED DOSE RECORDS ~

From: BellyGom@aol.com Subject: [NMusers] Error message: NO MORE THAN 20 ADDITIONAL AND/OR LAGGED DOSE RECORDS ~ Date: 11/5/2003 10:38 AM Dear All, I have the following error message and hope that someone can help me to resolve this problem (without deleting datapoints.!.) NO MORE THAN 20 ADDITIONAL AND/OR LAGGED DOSE RECORDS ACTIVE AT ONE TIME I got rather common screen output (DOS) as follows: WARNINGS AND ERRORS (IF ANY) FOR PROBLEM 1 (WARNING 2) NM_TRAN INFERS THAT THE DATA ARE POPULATION 1 file(s) copied. Starting nonmem execution ... ITERATIONS ARE NOT OUTPUT TO CONSOLE FOR G77 1 file(s) copied. The following is the content of FREPORT NM-TRAN VERSION III LEVEL 1.1 SUBROUTINES FROM THE PREDPP LIBRARY: PRED PREDI CHECK SADVAN ADVAN6 SSS0 TRANS1 INFN DVERK1 FCN1 GENERATED DP SUBROUTINES: PK ERROR MODEL TOL DES NONMEM SUBROUTINES: ALL many thanks in advance, In-Sun

From: "Bachman, William (MYD)" bachmanw@iconus.com Subject: RE: [NMusers] Error message: NO MORE THAN 20 ADDITIONAL AND/OR LA GGED DOSE RECORDS ~ Date: 11/5/2003 11:02 AM This is a message that suggests that something is probably wrong with your model, not the data.

From: BellyGom@aol.com Subject: Subject: [NMusers] Error message: NO MORE THAN 20 ADDITIONAL AND/OR LAGGED DOSE RECORDS ~ Date: 11/5/2003 12:12 PM Dear Dr. Bachman, Thanks for your interest in the problem; do you have some idea what might be wrong with the model? It actually runs okay(??) after eliminating subjects causing the message at the bottom; the original data size is approx. 6000*20 and after eliminating those subjects, it is approx. 4000*20. I indeed have many dose/lagged dose records per subject since I have duplicated the multiple dosing events for comp. 1 (central) 4 times, for 4 additional lagged compartments; the amounts in the four comp.s characterises the drug effect. And samples are often Very sparse. I will be more than happy to provide further information to resolve this matter.... (I just don't know which is relevant...) Many many thanks, In-Sun MONITORING OF SEARCH: 0PRED EXIT CODE = 1 0INDIVIDUAL NO. 10 ID=0.16000000E+02 (WITHIN-INDIVIDUAL) DATA REC NO. 130 THETA= 1.44E+02 2.40E+02 1.00E+01 1.11E+01 3.16E+02 2.04E+00 2.05E+02 5.48E-01 1.00E+00 1.20E+00 2.91E-01 4.36E+01 NO MORE THAN 20 ADDITIONAL AND/OR LAGGED DOSE RECORDS MAY BE ACTIVE AT ONE TIME 0PROGRAM TERMINATED BY OBJ MESSAGE ISSUED FROM ESTIMATION STEP AT INITIAL OBJ. FUNCTION EVALUATION 1THERE ARE ERROR MESSAGES IN FILE PRDERR

From: "Bachman, William (MYD)" bachmanw@iconus.com Subject: RE: [NMusers] Error message: NO MORE THAN 20 ADDITIONAL AND/OR LA GGED DOSE RECORDS ~ Date: 11/5/2003 1:09 PM While IT IS possible to "legitimately" have too many add'l or lagged doses, in our experience this message usually represents a problem with the model which requires the model to modified. Since your model runs with the "offending subject(s)" removed, your model may actually be OK. It's not possible for me to tell you what is problematic with these subjects without seeing the full model and the data. I'm not really sure why you are giving lagged doses to the effect compartments. Can you elaborate?

From: BellyGom@aol.com Subject: Subject: [NMusers] Error message: NO MORE THAN 20 ADDITIONAL AND/OR LAGGED DOSE RECORDS ~ Date: 11/6/2003 1:47 PM Dear Professor Casabo, It is very good to hear from you; hope that you and Ricardo are doing fine. Thank you so much for your suggestion; so I should try to minimise the dataset by reducing the number of addled/lagged dose events in the dataset whereever possible, via ADDL, AMT and II? Best wishes, In-Sun _______________________________________________________

From: Dr. Vicente G. Casabo vicente.casabo@uv.es Subject: RE: [NMusers] Error message: NO MORE THAN 20 ADDITIONAL AND/OR LA GGED DOSE RECORDS ~ Date: 11/06/2003 18:11:15 GMT Standard Time I read the question, IMHO the problem is not the number of additional or lagged doses, the problem is the actual number of dose records, which are delayed or contain addl. This is the number of rows of this kind of data in data file. Try reduce the nuber of dose records at fixed times, converting the records in additional doses included on the same dose record that first, at each compartment. AMT and II and ADDL can approximate as possible the actual schedule of administration or incorporation into compartment, if no can be exact.