Hello NONMEM users,
I am working on some target-mediated models. It is necessary to use
ADVAN8 because differential equations describe very fast and very slow
processes. The models run if I use option SLOW. If I do not use SLOW,
different models for different drugs fail. The message is
0PROGRAM TERMINATED BY OBJ
ERROR IN NCONTR WITH INDIVIDUAL 4 ID=XXXXXXXX
NUMERICAL HESSIAN OF OBJ. FUNC. FOR COMPUTING CONDITIONAL ESTIMATE
IS NON POSITIVE DEFINITE
MESSAGE ISSUED FROM ESTIMATION STEP
AT 0TH ITERATION, UPON EVALUATION OF GRADIENT WITH RESPECT TO OMEGA
0TRY SUBSTANTIALLY INCREASING "INITIAL ESTIMATE OF SIGMA"
OR DECREASING "INITIAL ESTIMATE OF OMEGA"
I tried to increase sigma, decrease omega, change the initial estimates, use
different data and models. Nothing works. Is there a way around it? Option
SLOW makes everything too slow.
Thanks!
Pavel
