+--------------------------------------------------------------------+
 |                                                                    |
 |                        SIMULATION_3 EXAMPLE                        |
 |                                                                    |
 +--------------------------------------------------------------------+

 This is an example of simulation and estimation within the same NONMEM
 run.  It is a continuation of Simulation Example 2.

 As in Simulation Example 2, values of the covariate WT  are  simulated
 during  the  Simulation Step. They also replace the original WT values
 in NONMEM's internal copy of the data set.  This transgeneration makes
 them available in the Estimation and Table Steps.

 There are two models for V, illustrating the use of diferent models in
 the Simulation and Estimation Steps:

   (simulated V)  VS = THETA(2) * EXP(ETA(3))
   (non-simulated V)  VN = THETA(3) + ETA(4)

 There are two epsilons in the $ERROR block, illustrating the use of an
 of  using  an initial estimate for estimation different from the value
 used to simulate.

 Because theta(2), eta(2), eta(3) and eps(1) are used only in the Simu-
 lation   Step,   the   FIXED  attribute  is  specified  for  theta(2),
 omega(2,2), omega(3,3) and sigma(1,1) during the Estimation Step.

 $PROBLEM Simulation of population data w/ covariates
 $INPUT ID TIME WT AMT DV
 $DATA SIMORIG IGNORE=#
 $SUBROUTINE ADVAN1
 $PK
      IF (ICALL.EQ.4) THEN
      WT=70+70*ETA(3)
      ENDIF
      CL=THETA(1)*WT*EXP(ETA(1))
      IF (ICALL.EQ.4) THEN
       V=THETA(2)*EXP(ETA(2))  ; Simulated V
      ELSE
       V=THETA(3)+ETA(4)       ; Non-simulated V
      ENDIF
      K=CL/V
      S1=V
 $ERROR
      IF (ICALL.EQ.4) THEN
       Y=F+F*EPS(1)
      ELSE
       Y=F+F*EPS(2)
      ENDIF
 $THETA  (0,.0625)  (10 FIX) (0,12)
 $OMEGA .09 (.05 FIX) (.04 FIX) 4
 $SIGMA (.01 FIX) .03
 $SIMULATION (9215690) SUBPROBLEMS=10
 $ESTIMATION
 $TABLE ID TIME WT AMT NOPRINT FILE=SIMDATA3 NOHEADER

REFERENCES: Guide IV Section III.B.13, IV.I
REFERENCES: Guide V Section 12.4.8
REFERENCES: Guide VI Section III.C, III.E, IV.B, IV.G.1


  
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