Dear NMusers, 1. I have some difficulties to find information on the ODE solver implemented in NONMEM. Can anyone tell me about the numerical integrator(s) implemented when using ADVAN6 (recommended for non-stiff) and ADVAN8 (stiff problems)? In particular, is the integrator able to switch automatically between stiff and non-stiff resolution techniques?
2. Then, still related to the ODE solver, I was also interested in a message I¹ve picked up from the archive (from Mark Sale, posted January 2005, see below), for which I couldn¹t find any answer from the group. Additional information on these items would be greatly appreciated. _______________________________________________________ From: [EMAIL PROTECTED] 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 _______________________________________________________ Thanks for your help in this matter. Benjamin Ribba Therapeutic Targeting in Oncology (EA3738) University Claude Bernard Lyon 1 Faculty of Medicine Lyon-Sud 165, chemin du grand revoyet 69921 Oullins cedex Tel: +33 4 26 23 59 57 / +33 6 66 06 15 21
