********************************************************************************
*                        r01_warfarin_NODEs_IIV.mlxtran                        *
*                         at                                                   *
*                        Monolix version : 2024R1                              *
********************************************************************************


ESTIMATION OF THE POPULATION PARAMETERS ________________________________________

Fixed Effects ----------------------------     se_lin     rse(%)   P2.5_lin  P97.5_lin
Tlag_pop   :                         0.784      0.195       24.9      0.492       1.25
ka_pop     :                          1.42      0.534       37.6      0.724       2.79
V_pop      :                          7.93      0.325        4.1       7.32       8.59
Cl_pop     :                         0.132    0.00683       5.16       0.12      0.146
R0_pop     :                          95.9       1.07       1.11       93.8         98
W11_pop    :                        -0.528      0.359         68      -1.23      0.175
W12_pop    :                       -0.0481     0.0719        150     -0.189     0.0929
W13_pop    :                         0.105      0.189        181     -0.266      0.475
W14_pop    :                        -0.464       1.08        232      -2.57       1.65
W15_pop    :                         0.427      0.828        194       -1.2       2.05
b11_pop    :                         0.755      0.592       78.5     -0.406       1.92
b12_pop    :                         0.334      0.394        118     -0.439       1.11
b13_pop    :                         0.341      0.256       75.1      -0.16      0.841
b14_pop    :                         0.295       1.63        552       -2.9       3.49
b15_pop    :                         0.324      0.939        290      -1.52       2.16
W21_pop    :                        -0.504      0.377       74.8      -1.24      0.235
W22_pop    :                         0.183       0.22        120     -0.249      0.615
W23_pop    :                         0.304      0.389        128     -0.458       1.07
W24_pop    :                        0.0595      0.182        306     -0.298      0.417
W25_pop    :                        0.0948      0.178        188     -0.254      0.444
b21_pop    :                          0.28      0.162       57.8     -0.037      0.597
kout_pop   :                        0.0408   0.000896       2.19     0.0391     0.0426

Standard Deviation of the Random Effects -
omega_Tlag :                         0.574       0.18       31.4      0.322       1.02
omega_ka   :                         0.962      0.278       28.9      0.563       1.64
omega_V    :                          0.22     0.0302       13.7      0.169      0.287
omega_Cl   :                         0.287     0.0369       12.9      0.224      0.368
omega_R0   :                        0.0498    0.00954       19.2     0.0345     0.0718
omega_W11  :                         0.104      0.173        167     0.0179      0.604
omega_W12  :                        0.0511     0.0573        112      0.012      0.218
omega_W13  :                        0.0256      0.213        833    0.00142      0.463
omega_W14  :                         0.213       1.94        910     0.0112       4.06
omega_W15  :                        0.0797       0.93   1.17e+03     0.0036       1.77
omega_b11  :                         0.246      0.154       62.4     0.0902      0.671
omega_b12  :                         0.223      0.234        105     0.0551      0.903
omega_b13  :                         0.168      0.233        139     0.0332      0.847
omega_b14  :                         0.295       5.96   2.02e+03    0.00973       8.95
omega_b15  :                         0.337        1.4        414     0.0296       3.84
omega_W21  :                         0.124      0.241        195     0.0189      0.812
omega_W22  :                        0.0401      0.572   1.43e+03    0.00161          1
omega_W23  :                        0.0286      0.576   2.01e+03   0.000944      0.865
omega_W24  :                         0.201       0.13       64.8     0.0717      0.564
omega_W25  :                        0.0143      0.247   1.73e+03   0.000514      0.397
omega_b21  :                        0.0768     0.0914        119     0.0172      0.343
omega_kout :                        0.0758     0.0201       26.5     0.0462      0.124

Error Model Parameters -------------------
a1         :                         0.254     0.0438       17.3      0.182      0.354
b1         :                        0.0499    0.00876       17.6     0.0356     0.0698
a2         :                          3.44      0.247       7.17       2.99       3.96

Elapsed time (seconds):       95
Exploratory phase iterations:      228 (Autostop)
Smoothing phase iterations:        169 (Autostop)

 _______________________________________________________________________________



ESTIMATION OF THE INDIVIDUAL PARAMETERS ________________________________________


Estimation of the individual parameters by Conditional Mode --------------------
                 min            Q1        median            Q3           max  shrinkage(%)
Tlag :         0.547         0.675         0.779         0.877          2.74          49.4
ka   :         0.278          1.15          1.39          1.55          3.46          49.8
V    :          5.08          7.06          8.05          8.95          12.5          5.23
Cl   :         0.073         0.109         0.128         0.164         0.291        -0.491
R0   :          87.2          92.6          97.8          98.9           101          16.1
W11  :        -0.549        -0.534        -0.528        -0.523        -0.446          79.6
W12  :       -0.0708       -0.0561       -0.0499        -0.047       -0.0384          84.8
W13  :         0.086        0.0995         0.104         0.109         0.123          69.6
W14  :        -0.485        -0.473        -0.465        -0.456        -0.416          93.2
W15  :         0.381         0.413         0.426         0.444         0.489          72.2
b11  :         0.681         0.746         0.758         0.782          1.09          66.7
b12  :         0.174         0.263          0.34         0.399         0.515          58.1
b13  :         0.153         0.304         0.358         0.409         0.463          51.6
b14  :         0.223         0.285         0.304         0.323          0.35          89.8
b15  :        0.0711         0.288         0.346         0.412         0.487          69.6
W21  :        -0.558         -0.51        -0.506          -0.5        -0.472          88.9
W22  :         0.178         0.182         0.185         0.188         0.199          86.9
W23  :         0.298         0.302         0.305         0.307         0.311          88.2
W24  :     -0.000431        0.0331        0.0576        0.0764         0.116          86.5
W25  :        0.0877        0.0928        0.0952        0.0976         0.104          76.7
b21  :         0.167          0.25         0.295         0.328         0.362          34.9
kout :        0.0359        0.0393        0.0409        0.0421         0.047            29

Elapsed time (seconds):      6.8

 -------------------------------------------------------------------------------

 _______________________________________________________________________________



ESTIMATION OF THE FISHER INFORMATION MATRIX ____________________________________


Estimation of the Fisher information matrix by Linearization -------------------

Correlation Matrix :
  Tlag_pop         1
    ka_pop   0.23089         1
     V_pop  0.052435 -0.017105         1
    Cl_pop  0.029459 -0.043587 0.0021552         1
    R0_pop-0.0034361-5.1918e-05-5.3644e-05-0.0002512         1
   W11_pop  -0.01004 -0.020805-0.0041227-0.0011643-0.0085455         1
   W12_pop-0.0023297-0.0058184 -0.013347 0.0039058  0.004662 -0.018687         1
   W13_pop-0.0099275  0.0120533.6439e-05-0.0031706-0.0054867  -0.19292  -0.38411         1
   W14_pop-0.0072605 -0.028901 0.00154270.00040044-0.0051218   0.29365  -0.43023   0.04074         1
   W15_pop 0.0082938 -0.013308 0.0053839 0.0026243-0.0015749  0.087019   0.23233  -0.64718   0.10579         1
   b11_pop   0.01083  0.026513   0.00654-0.0029427 0.0079977  -0.96608-0.0030674   0.20814  -0.29256  -0.15334         1
   b12_pop-0.0023181 -0.010667  0.012509-0.0037971-0.0075561  0.037462  -0.88778   0.31567   0.47673  -0.18905 -0.023331         1
   b13_pop  0.015046  0.087406-0.0067591 -0.001805-0.0046527  0.064695  0.071135  0.055075 -0.040738 -0.023171   -0.1105 -0.014379         1
   b14_pop 0.0015422 0.0056427 0.0023427-0.00066029  0.012788  -0.25887  0.098011 -0.026874  -0.45655 -0.027232   0.18086 -0.096641 0.0072285         1
   b15_pop-0.0053192 0.00913010.000803520.000212570.00092796  -0.10974  -0.06054   0.12072  -0.26668  -0.22828   0.15743  0.093362  0.092048    0.2249         1
   W21_pop  0.010706  0.023646 0.0068712-0.0030611  0.016997  -0.83658  0.031636   0.19446    -0.238  -0.15766   0.90042 -0.048723  -0.12461  -0.12215   0.10148         1
   W22_pop 0.0068317 -0.013136-0.00027005 0.0014257-0.0054918 -0.092901    0.5854  -0.36414   -0.1943   0.43248  0.090906  -0.54175 0.0018843  0.036545  -0.27923   0.10774         1
   W23_pop-0.0071998 0.00721220.00056144-0.0014729-0.0082199  0.077593  -0.23724   0.21349   0.03643 -0.072046  -0.10181   0.14251 0.0015466 -0.040118   0.08039  -0.10595  -0.47799         1
   W24_pop-0.00520570.000648770.00090355-0.00043433-0.0082753   0.20084  -0.21259 -0.093268   0.49144   0.14979  -0.25123   0.22752  0.099136  -0.20317 -0.088458  -0.29926  -0.27495   0.18441         1
   W25_pop 0.0008728-0.00032121-0.0011567-0.00013636  0.003169  0.009914   0.11644  -0.19076  -0.12029  -0.49044  0.059138 -0.049269 -0.023147  0.062842  0.079819  0.077087   0.11348  -0.64414  -0.18154         1
   b21_pop 0.0046189 -0.044883-0.0079452 0.0058711  0.030585 -0.021922   0.24157  -0.17245    0.0716   0.27719  0.015726  -0.32297  -0.52493 -0.096472  -0.61501  0.045227   0.31595  -0.49164 -0.068703  0.092351         1
  kout_pop   0.21288-0.0024596  0.021716  0.010315   0.16468 -0.077843   0.10197  0.005512 -0.057753 -0.057818  0.080193 -0.096254 -0.039152  0.041411  0.017228   0.03551 -0.011027 -0.019771 -0.059432  0.029901  0.094518         1
omega_Tlag         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         1
  omega_ka         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0 -0.067155         1
   omega_V         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0-0.00070003-0.0016272         1
  omega_Cl         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0-0.00084809 -0.001776 0.0002552         1
  omega_R0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         00.00029412 0.0010795-1.2905e-057.5712e-07         1
 omega_W11         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         00.000347240.00079344-0.00033463-0.00034456  0.011626         1
 omega_W12         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         00.00087109-0.00091876-5.9716e-05-7.951e-06  0.025644  0.016797         1
 omega_W13         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0 0.0012772-0.00218680.00053018 4.343e-06-0.0003832 0.0041723  -0.10415         1
 omega_W14         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         00.00014172 0.0013921-7.7135e-05-1.3164e-05  0.010424   0.10926  0.091102 -0.010076         1
 omega_W15         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0-0.00056204 0.0014743-0.0014337 7.963e-05 0.0024358  0.008233  0.067727  -0.61757  0.020694         1
 omega_b11         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0-0.00013545-0.00163363.0582e-055.4546e-05 -0.006332  -0.69133 -0.063841  0.012464  -0.12986 -0.057208         1
 omega_b12         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         00.00067917-0.0017097-0.000583684.1782e-05 0.0002671 -0.015796  -0.46579  0.040757  -0.17054  -0.11147  0.054459         1
 omega_b13         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0 0.0014626 -0.016243-2.1465e-053.0339e-05 0.0035645 -0.012257  0.035957  0.030557 -0.010212 -0.026555 -0.034761    0.0267         1
 omega_b14         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         00.00025213-0.0033439 8.295e-051.4511e-05-0.0051404  -0.47381 -0.023329 0.0052403  -0.22403-0.0080252   0.47221  0.018839 -0.011812         1
 omega_b15         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         00.00026914-0.0023251-0.00011032-0.00013489 0.0028088  0.019389 0.0043413   0.04089 -0.014098-0.0042016 -0.062142  0.072056  0.024546 -0.064063         1
 omega_W21         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0-0.00017539 0.0029206 1.805e-05-4.4316e-05 0.0011203   0.44036  0.018827-0.00010341   0.16889  0.022597  -0.54166 -0.013974  0.014062   -0.8066   0.07242         1
 omega_W22         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0 0.0011539-0.0048909-0.000524794.9489e-05  0.017077 0.0010615   0.12004  0.012632  0.049269  -0.21928 -0.066976  -0.20739  0.016361-0.0085084  -0.15619  0.016109         1
 omega_W23         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0-0.0013876 0.0010361 0.00108180.00010511 -0.013858-0.0069626  -0.15423   0.15346 -0.027995   0.30738-0.0013337  0.093539 -0.022073 0.0098711 -0.039715  0.014381   0.14314         1
 omega_W24         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0-2.4396e-05-0.0017035-1.8189e-051.7972e-05 0.0028161 -0.093405 -0.014562 -0.009165   -0.1134  0.027812   0.10215 0.0022479-0.0076527  0.075358  -0.19841  -0.12027 -0.061215 0.0020764         1
 omega_W25         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         00.00028515-0.000486320.00041729-0.00010821 0.0037986-0.0081079  0.031247  -0.17706-0.0054074   -0.6244  0.046299   0.06351 0.00806550.00033134 -0.014161 -0.026888    0.1523  -0.75792 -0.020429         1
 omega_b21         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0-0.00046506  0.010241-0.00050946-6.9396e-05-0.00044119 0.0039703   0.09533 -0.088642  0.057489   0.11462  0.037961  -0.29272  -0.51718  0.037053  -0.58264 -0.050182  -0.18124  -0.37027   0.14126   0.07634         1
omega_kout         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0 -0.030234-0.0024267-0.000931764.0757e-05 0.0085024 0.0097521  0.011853 0.0069982  0.014119 -0.030317  -0.00433 -0.015524-0.0093522-0.0094198-0.0078248 0.0086953  0.024653  0.013576 0.0045472   0.01509-0.0031705         1
        a1         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         00.00010069  0.036029 0.0021584-0.0083703-7.1581e-06 -0.010927-0.0017095 0.0016704-0.00051622-0.00068907 0.0002855 0.00112780.00022422-0.00042242-0.0020139-0.00013104-0.0026361 0.0020865-1.5952e-07-0.00084425-0.0019035-0.0011703         1
        b1         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0-0.0094851 -0.064375 -0.023521 0.0014196-3.3342e-05 0.0047208 0.0018422-0.00122390.00041176-0.00095427-0.00011768-0.00241330.000188140.000505090.00047663-2.0987e-05 0.0015968 0.00128929.4199e-050.000506514.8788e-050.00016859  -0.80293         1
        a2         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0         0 -0.004335-0.00654530.00024522-6.1308e-06  -0.16353 -0.057434  -0.15352 0.0048865 -0.063801 -0.020774  0.024901 0.0030551 -0.025483  0.018633-0.0091907 -0.031548  -0.10549  0.082611 -0.017686 -0.017575 -0.011658   -0.19670.000414510.00013549         1

                               min       max   max/min
Eigen values           :   0.00076       3.6   4.8e+03

Elapsed time (seconds):     0.47

 -------------------------------------------------------------------------------

 _______________________________________________________________________________



ESTIMATION OF THE LOG-LIKELIHOOD _______________________________________________

                                                           (lin)
-2 x log-likelihood                       (OFV) :        2538.79
Akaike Information Criteria               (AIC) :        2632.79
Corrected Bayesian Information Criteria  (BICc) :        2769.33
Bayesian Information Criteria             (BIC) :        2701.68

Elapsed time                          (seconds) :           0.17
CPU time                              (seconds) :           0.00

 _______________________________________________________________________________

DATASET INFORMATION
Number of individuals: 32
Number of observations (obsid 1): 247
Number of observations (obsid 2): 232
Number of doses: 32

