********************************************************************************
*                         prj9_iov2_bootstrap.mlxtran                          *
*                          at                                                  *
*                         Monolix version : 2024R1                             *
********************************************************************************


ESTIMATION OF THE POPULATION PARAMETERS ________________________________________

Fixed Effects ----------------------------     se_lin     rse(%)   P2.5_lin  P97.5_lin      se_sa     rse(%)    P2.5_sa   P97.5_sa
ka_pop          :                     1.48     0.0807       5.46       1.33       1.64     0.0805       5.45       1.33       1.64
beta_ka_TREAT_B :                   0.0714     0.0415       58.1   -0.00996      0.153     0.0435       60.9    -0.0138      0.157
V_pop           :                    0.474     0.0132       2.79      0.449      0.501     0.0132       2.79      0.449      0.501
beta_V_TREAT_B  :                    -0.18      0.028       15.6     -0.235     -0.125     0.0288         16     -0.236     -0.123
Cl_pop          :                   0.0405    0.00128       3.17      0.038     0.0431    0.00129       3.18      0.038     0.0431
beta_Cl_TREAT_B :                   -0.205     0.0351       17.1     -0.274     -0.137     0.0353       17.2     -0.275     -0.136

Standard Deviation of the Random Effects -
omega_ka        :                    0.273     0.0387       14.2      0.208      0.359     0.0384       14.1      0.208      0.358
omega_V         :                    0.116     0.0214       18.5     0.0813      0.165     0.0521         45     0.0529      0.253
omega_Cl        :                    0.117     0.0273       23.4      0.075      0.181     0.0966       82.8     0.0347      0.393
gamma_ka        :                   0.0488     0.0611        125     0.0105      0.227     0.0272       55.7     0.0194      0.123
gamma_V         :                   0.0885     0.0152       17.2     0.0636      0.123     0.0716       80.9     0.0268      0.293
gamma_Cl        :                    0.129     0.0202       15.7     0.0952      0.174      0.106       82.5     0.0384      0.433

Correlations -----------------------------
corr1_V_Cl      :                     0.65      0.307       47.2     -0.259      0.948       1.37        210     -0.999          1
corr2_V_Cl      :                   -0.494      0.187       37.8     -0.772    -0.0573      0.801        162     -0.989      0.912

Error Model Parameters -------------------
a               :                    0.142     0.0376       26.5     0.0864      0.233      0.043       30.4      0.081      0.248
b               :                   0.0992    0.00862       8.69     0.0837      0.117    0.00946       9.54     0.0823      0.119

Elapsed time (seconds):      5.3
Exploratory phase iterations:      244 (Autostop)
Smoothing phase iterations:        112 (Autostop)

 _______________________________________________________________________________



ESTIMATION OF THE INDIVIDUAL PARAMETERS ________________________________________


Estimation of the individual parameters by Conditional Distribution ------------
               min            Q1        median            Q3           max  shrinkage(%)
ka :          0.89          1.33          1.53          1.94          2.69          4.82
V  :         0.319         0.395         0.447         0.473         0.589          27.6
Cl :        0.0222         0.032        0.0358        0.0428        0.0583         -3.12

Elapsed time (seconds):      1.1
Iterations:       70 (Autostop)

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Estimation of the individual parameters by Conditional Mode --------------------
               min            Q1        median            Q3           max  shrinkage(%)
ka :         0.873           1.3          1.47          1.89          2.55          6.11
V  :         0.316         0.389         0.442         0.473         0.578          27.6
Cl :        0.0224        0.0322        0.0361        0.0434        0.0588         -3.03

Elapsed time (seconds):    0.039

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 _______________________________________________________________________________



ESTIMATION OF THE FISHER INFORMATION MATRIX ____________________________________


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

Correlation Matrix :
         ka_pop         1
beta_ka_TREAT_B  -0.39587         1
          V_pop   0.18568  -0.24324         1
 beta_V_TREAT_B   -0.1842   0.45469  -0.51777         1
         Cl_pop -0.046678  0.060985  0.051084   0.22352         1
beta_Cl_TREAT_B  0.041926 -0.098836   0.20283  -0.39385  -0.56298         1
       omega_ka         0         0         0         0         0         0         1
        omega_V         0         0         0         0         0         0 -0.019278         1
     corr1_V_Cl         0         0         0         0         0         0  0.014428  -0.18055         1
       omega_Cl         0         0         0         0         0         0-0.0011657  0.067524  -0.31511         1
       gamma_ka         0         0         0         0         0         0  -0.13349  0.060432 -0.047646 0.0044117         1
        gamma_V         0         0         0         0         0         0  0.028697  -0.27152   0.31314  -0.06223  -0.19672         1
     corr2_V_Cl         0         0         0         0         0         0 0.0041517  0.045127  -0.35335  0.081266 -0.025704    -0.163         1
       gamma_Cl         0         0         0         0         0         0 0.0014491 -0.038641   0.38642  -0.40246  0.014572   0.15227  -0.20353         1
              a         0         0         0         0         0         0 0.0012981 -0.015668  0.034632-0.0077494  -0.13309  0.012377  0.057128  -0.11021         1
              b         0         0         0         0         0         0 -0.005432 0.0035975 -0.024204 0.0065731  0.041137 -0.027454 -0.072665  0.074938  -0.88583         1

                               min       max   max/min
Eigen values           :      0.11       2.3        21

Elapsed time (seconds):    0.018

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Estimation of the Fisher information matrix by Stochastic Approximation --------

Correlation Matrix :
         ka_pop         1
beta_ka_TREAT_B  -0.39115         1
          V_pop   0.18666  -0.24624         1
 beta_V_TREAT_B  -0.20095   0.50305  -0.51687         1
         Cl_pop -0.059156  0.085545  0.035081   0.23673         1
beta_Cl_TREAT_B  0.062228  -0.15638   0.21987  -0.42177  -0.56187         1
       omega_ka 0.0094634 -0.020894-0.0044551 -0.018703 0.0082896  0.011488         1
        omega_V  0.040342  -0.13543-0.0027262 -0.084733  0.065964 0.0077397   0.20705         1
     corr1_V_Cl  -0.04921   0.14872 -0.006107  0.089186 -0.079817-0.0033188  -0.13157  -0.83509         1
       omega_Cl  0.056271   -0.1544  0.014751 -0.092802  0.078872-0.00078141   0.11783   0.78897  -0.95557         1
       gamma_ka  -0.15741   0.41327 -0.083178    0.2023  0.025753 -0.083391  -0.13256 -0.083786  0.071969 -0.074897         1
        gamma_V -0.016744  0.061833 0.0094015   0.04592 -0.087096  0.004079  -0.10661  -0.80167   0.93785  -0.89154-0.0094415         1
     corr2_V_Cl  0.067652  -0.18913   0.02285  -0.11382  0.072538  0.012732   0.12521   0.79061  -0.96306   0.94164  -0.11874  -0.90026         1
       gamma_Cl -0.054728   0.15015 -0.013524  0.090697 -0.084089 0.0025941  -0.12194  -0.79361   0.97198  -0.97321  0.067122   0.90913  -0.96104         1
              a -0.026753   0.10462 0.0077298  0.054569 -0.014295 -0.059173  -0.08949  -0.38871   0.44675  -0.41836  0.087095   0.43399  -0.41273   0.40712         1
              b  0.019825 -0.070246-0.0040322 -0.029585  0.014535  0.052811  0.044955   0.28556  -0.34013   0.31727 -0.052279  -0.33907   0.30109  -0.30996  -0.90422         1

                               min       max   max/min
Eigen values           :     0.019         6   3.2e+02

Elapsed time (seconds):      1.3
Iterations:       50 (Autostop)

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

 _______________________________________________________________________________



ESTIMATION OF THE LOG-LIKELIHOOD _______________________________________________

                                                            (is)
-2 x log-likelihood                       (OFV) :        1642.97
Akaike Information Criteria               (AIC) :        1674.97
Corrected Bayesian Information Criteria  (BICc) :        1720.13
Bayesian Information Criteria             (BIC) :        1711.39

Elapsed time                          (seconds) :           5.41
CPU time                              (seconds) :           5.00
MonteCarlo size (is):    10000 (Fixed number of iterations)


[Importance Sampling] Standard error        : 0.221
                      Sampling distribution : T-distribution with 5 degrees of freedom

 _______________________________________________________________________________

DATASET INFORMATION
Number of individuals: 36
Number of subjects-occasion: 72
Number of observations (Y): 720
Number of doses: 72

