From: mark.e.sale@gsk.com 
Subject: [NMusers] questions on ODE solver errors
Date: Wed, January 26, 2005 4:40 pm

If the NOABORT option is used for the ODE solvers, and the
ODE solver has "numerical difficulties", giving the message:

 NUMERICAL DIFFICULTIES WITH INTEGRATION ROUTINE.                                                                                     
 MAXIMUM NO. OF EVALUATIONS OF DIFFERENTIAL EQUATIONS, 100000, EXCEEDED.                                                       
0END OF PRED EXIT CODE MESSAGES FROM THE ESTIMATION STEP 

But, NONMEM continues to plod along. 
Does anyone know what NONMEM does instead?  I assume that the OBJ
contribution for that subject cannot be calculated, so, the gradient
for the dimension(s) requiring that OBJ cannot be calculated.  Seems
like an error to simply ignore the OBJ contribution from that person
(resulting in a lower OBJ for that function evaluation, and a bad
gradient and Hessian).  Is that function evaluation discarded, and
no gradient is generated for that dimension/iteration?  But I don't
see a 0 gradient anywhere in the output (I know, in NONMEM V, it
isn't as simple as one function evaluation per dimension (+1)) 

Thanks 


Mark Sale M.D.
Global Director, Research Modeling and Simulation
GlaxoSmithKline
919-483-1808
Mobile 
919-522-6668 
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