NONMEM 7.3. Overview - ICON plc

System RequirementsThe NONMEM ® computer program is written anddistributed in ANSI FORTRAN 95 code, and therefore,can be used with most hardware and operating systemsincorporating a Fortan 95 compiler adhering to the ANSIstandard. It has been shown to operate with Intel FortranCompiler 9.0 or greater for Windows or Linux, and gFortranfor Windows or Linux (Intel Fortran compiler is preferred).Since a NONMEM® run can take considerable CPU time,perhaps many hours, depending on the speed of thecomputer and the size of the problem, it is advisable to usea fast machine. At least 1 and preferably 2 GB of memoryshould be available for exclusive use of NONMEM ® andNMTRAN programs.LicensingThe NONMEM ® program is available on a CD ROM, whichtogether with the documentation and all updates andadditions to the program, will be delivered for a licenseroyalty fee to be paid annually. This fee is subject to changefrom year to year, and at each anniversary the licensee at itsoption may choose not to renew the license.NONMEM 7.3 will include the following enhancements1. More mixed effects levels, with random effects acrossgroups of individuals such as clinical site, may nowbe modeled. Sites themselves may be additionallygrouped, such as by country, etc.2. Easy to code inter-occasion variability. ETA’s canbe referenced by an index variable related to theinter-occasion data item.3. Symbolic reference to thetas, etas, and epsilons.4. Priors for SIGMA matrix. Prior information may beadded to SIGMA parameters (assumes inverse Wishartdistributed).5. Certain options may be optimized for Monte Carlo (MC)and Expectation-Maximization (EM) methods. ForSAEM and IMP, NONMEM assesses best ISAMPLEvalues for each subject. For IMP, NONMEM assessesbest IACCEPT and DF values for each subject.For BAYES and SAEM, NONMEM assesses bestCINTERVAL based on the degree of Markov chaincorrelation across iterations.6. An AUTO option determines best set of options for MC/EM methods.7. Perform Monte Carlo search of population parameters,and select the set that provides the lowest startingobjective function for an estimation.8. Perform Monte Carlo search for initial best estimatesof etas for each subject. Together with a MonteCarlo search of best initial population parameters, thisprovides a global search technique for the traditionalmethods, with less reliance on starting position forincidence of success.9. FOCE/Laplace and ITS may be assessed using onlynumerical eta derivatives for search of best etas and/oreta Hessian matrix assessment. This feature relaxes therequirement that analytic derivatives be computed forFOCE and Laplace by either NMTRAN or the user.10. Conditional Individual Weighted Residual (CIWRES)added to residual variance diagnostics. Includesevaluation for L2 correlated data as well.11. Boot-strap simulations may be performed in NONMEM.12. Example control stream files modeling populationdensities of individual parameters that are t-distributed.13. Nelder-Mead optimization option for best fit individualetas, particularly useful to improve robustness forimportance sampling.14. Option to use either eigenvalue square root or Choleskysquare root algorithms for assessing weighted residualdiagnostics.15. Option to have etabar and eta shrinkage informationinclude only subjects which influence the etas.16. Subscripted variables may be used in abbreviatedcode, with fewer restrictions on DOWHILE. Additionally,correlation of residual variables using CORRL2 maynow be written in abbreviated code.17. Enhanced non-parametric analysis methods, suchas extended grid of support points, use of an outsizeinter-subject variance to obtain support points that fitoutlier subjects better, and built-in bootstrap analysismethods for obtaining empirical confidence ranges tonon-parametric probability parameters.www.iconplc.com