NONMEM Users Network Archive

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target-mediate model: numerical difficulties

From: nonmem
Date: Fri, 19 Sep 2008 19:34:24 +0000 (GMT)

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

Received on Fri Sep 19 2008 - 15:34:24 EDT

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