flexible infusion rate model

Dear all, Here comes a beginner modeler, who wants to share the problem with experts in the Group and looking for good solutions ;-) I try to model Pop-PK anticancer drug which was delivered by continuous venous infusion with several types of duration time such as 24 hours, 46 hours, 96 hours or 120 hours. Data came from four different studies; some patients were observed on more than 1 cycle; and sampling varied from 1 point/patient to 20 points/patient. Since I observed inconsistent infusion rates (especially at the end of infusion), which might be a potential factor for variability in PK parameter, then i try to include flexible infusion rates into the model. I made a control code but unfortunately NONMEM stopped running and had an error message: #METH: First Order Conditional Estimation with Interaction MONITORING OF SEARCH: 0PRED EXIT CODE = 1 0INDIVIDUAL NO. 1 ID= 1.00000000000000E+00 (WITHIN-INDIVIDUAL) DATA REC NO. 3 THETA= 1.00E-01 1.00E-01 1.00E-01 1.00E-01 1.00E-01 1.00E-01 1.00E-01 1.00E-01 2.72E+02 3.84E+01 4.21E-01 2.52E-02 OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0 PK PARAMETER FOR RATE IS NON-POSITIVE 0PROGRAM TERMINATED BY OBJ MESSAGE ISSUED FROM ESTIMATION STEP AT INITIAL OBJ. FUNCTION EVALUATION Elapsed estimation time in seconds: 0.28 #TERM: #TERE: 1THERE ARE ERROR MESSAGES IN FILE PRDERR Hereby i sent you a part of structure data set and my control stream (see attachment). Could anyone point it out for me what could be a problem and how to handle this? Thanks in advance. yours, -Tomi PhD Student Uni Bonn Structure of data set & control file of FIR_Model.docx Description: application/vnd.openxmlformats-officedocument.wordprocessingml.document