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2016 (v.24 no.3)

Translational and Clinical Pharmacology

Korean Society for Clinical Pharmacology and Therapeutics
ISSN: 2289-0882

  • Tips for the choice of initial estimates in NONMEM

    Seunghoon Han, Sangil Jeon, Dong-Seok Yim

    TCP | v.24, no.3, pp.119-123, Sep, 2016


    The importance of precise information and knowledge on the initial estimates (IEs) in modeling
    has not been paid its due attention so far. By focusing on the IE, this tutorial may serve as a practical
    guide for beginners in pharmacometrics. A ‘good’ set of IEs rather than arbitrary values is required
    because the IEs where NONMEM kicks off its estimation may influence the subsequent objective
    function minimization. To provide NONMEM with acceptable IEs, modelers should understand
    the exact meaning of THETA, OMEGA and SIGMA based on physiology. In practice, problems
    related to the value of the IE are more likely to occur for THETAs rather than the random-effect
    terms. Because it is almost impossible for a modeler to give a precise IE for OMEGAs at the beginning,
    it may be a good practice to start at relatively small IEs for them. NONMEM may fail to
    converge when too small IEs are provided for residual error parameters; thus, it is recommended
    to give sufficiently large values for them. The understandings on the roles, meanings and implications
    of IEs even help modelers in troubleshooting situations which frequently occur over the whole
    modeling process.


    NONMEM, initial estimate, pharmacometrics, pharmacokineticpharmacodynamic model