Re: NONMEM

From: Justin Wilkins Date: September 14, 2006 technical Source: cognigencorp.com
From: Justin Wilkins justin.wilkins@farmbio.uu.se Subject: Re: [NMusers] NONMEM Date: Thu, 14 Sep 2006 13:40:08 +0200 Dear Ritu, The example you quote seems to be more suitable for producing a limited series of Monte Carlo simulations than for producing a truly optimal design. If you want to do it in the most appropriate way, you will need to use a tool designed specifically for the purpose. You will have to decide what your needs are (whether you need exact sampling times or sampling windows, which will inform your choice of approach - D- or ED-optimality, for example), and then select one of the several pieces of software available based on these requirements. Two that are commonly used for generating population designs are PopED - http://depts.washington.edu/rfpk/rd/software_popED.html PFIM - http://www.bichat.inserm.fr/equipes/Emi0357/download.html Each (there are others as well) has its own strengths and weaknesses but I have used PopED with some success in the past, and PFIM has a good reputation. Both packages require other software to run - PopED needs O-Matrix or Matlab, and PFIM needs R or S-PLUS. Both rely on minimization of the inverse of the Fisher information matrix with respect to some variable (time, in your case), but others on this group will probably be able to give you more detail about this than I can. $SUPER is a NONMEM control record used to program a series of problems for NONMEM to perform within a single file. As for the other NONMEM parameters you mention, EVID is the PREDPP event identification variable, is usually required, and has 5 possible values - 0 for observation events, 1 for dose events, 2 for 'other-type' events such as compartment resets, 3 for reset events (which re-initialize the PK kinetic system) and 4 for reset-and-dose events (a combination of 1 and 3). SS is the steady-state data item for PREDPP, and can have 4 possible values - 0, indicating that the dose is not a steady-state dose, 1, indicating a steady-state dose with reset, 2, indicating steady-state dose without reset, and 3, which is very similar to 1. The above is a (very) basic summary from the NONMEM online help, which is accessed by the commands >> nmhelp SUPER >> nmhelp EVID >> nmhelp SS from the command prompt. Have a look for more detail. COVA and RATD have no special meaning in NONMEM and appear to have been user-defined variables (covariates, perhaps) supplied by the author of the quoted code. Justin
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