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 |                                                                 |
 |                            TNPRI EXAMPLES                       |
 |_________________________________________________________________|

 These examples illustrate the use of the NONMEM utility routine  TNPRI  |
 by  the NM-TRAN $PRIOR record, and also by an equivalent user-supplied  |
 routine PRIOR.                                                          |
 For a discussion of PRIOR:  (See prior).   For  a  discussion  of  the
 TNPRI:  (See tnpri).

 Example 1
 ------- -

 Use of PRIOR and TNPRI and a control stream for population data:

 This example obtains parameter estimates from population data, using a
 two-compartment  PK  model, and it incorporates a frequentist prior of
 transformed normal form for all of THETA, OMEGA and SIGMA.  The  prior
 information is found in model specification file msf1.

 $PROB   READ THE MODEL SPECIFICATION FILE
 $DATA data
 $INPUT ID DOSE TIME DV WT
 $PRIOR TNPRI (PROBLEM 2)                                                |
 $PRED
 ;
 ;     THETA(1)=MEAN ABSORPTION RATE CONSTANT - MEAN ELIM. RATE CONSTANT (l/HR)
 ;     THETA(2)=MEAN ELIM. RATE CONSTANT (1/HR)
 ;     THETA(3)=SLOPE OF CLEARANCE VS WEIGHT RELATIONSHIP (LITERS/HR/KG)
 ;     DOSE=WEIGHT-ADJUSTED DOSE (MG/KG)
 ;
       IF (NEWIND.NE.2) THEN
          AMT=DOSE*WT
          W=WT
       ENDIF
       T0=THETA(1)*EXP(ETA(1))
       T2=THETA(2)*EXP(ETA(2))
       T1=T2+T0
       T3=THETA(3)*W*EXP(ETA(3))
       A=EXP(-T2*TIME)
       B=EXP(-T1*TIME)
       C=T1-T2
       D=A-B
       E=T3*C
       Y=AMT*T1*T2/E*D+EPS(1)
 $MSFI msf1 ONLYREAD

 $PROB POPULATION DATA WITH PRIOR ON THETA, OMEGA AND SIGMA
 $INPUT ID DOSE TIME DV WT
 $DATA data

 $THETA  (0,4,5) (0,.09,.5) (.004,.01,.9)
 $OMEGA BLOCK (3) .7 .04 .05 .02 .06 .08
 $SIGMA  .4

 $EST

 Instead of a $PRIOR record, the following may be used:                  |

 $SUBROUTINE PRIOR=prior                                                 |

 The prior routine is as follows:

       SUBROUTINE PRIOR (ICALL,CNT)
       DOUBLE PRECISION CNT
       IFND=0
       MODE=0
       PLEV=0
       IF (IPROB.EQ.2) CALL TNPRI (IFND,MODE,ITYP,PLEV,NSAM,ISS,IVAR,CNT)
       RETURN
       END

 Example 2
 ------- -

 Use of PRIOR and TNPRI and a control stream for population data:

 This example obtains parameter estimates from population data, using a
 two-compartment  PK  model, and it incorporates a frequentist prior of
 transformed normal form for all of THETA and OMEGA, but for  only  the
 first  element  of a diagonal SIGMA, which is a prior-specific parame-
 ter.  Prior information for these parameters is found in model specif-
 ication file msf1.

 $PROB   READ THE MODEL SPECIFICATION FILE
 $DATA data
 $INPUT ID DOSE TIME DV WT
 $PRIOR TNPRI (PROBLEM 2)                                                |
 $PRED
 ;
 ;     THETA(1)=MEAN ABSORPTION RATE CONSTANT - MEAN ELIM. RATE CONSTANT (l/HR)
 ;     THETA(2)=MEAN ELIM. RATE CONSTANT (1/HR)
 ;     THETA(3)=SLOPE OF CLEARANCE VS WEIGHT RELATIONSHIP (LITERS/HR/KG)
 ;     DOSE=WEIGHT-ADJUSTED DOSE (MG/KG)
 ;
       IF (NEWIND.NE.2) THEN
          AMT=DOSE*WT
          W=WT
       ENDIF
       T0=THETA(1)*EXP(ETA(1))
       T2=THETA(2)*EXP(ETA(2))
       T1=T2+T0
       T3=THETA(3)*W*EXP(ETA(3))
       A=EXP(-T2*TIME)
       B=EXP(-T1*TIME)
       C=T1-T2
       D=A-B
       E=T3*C
       Y=AMT*T1*T2/E*D+EPS(2)
 $MSFI msf1 ONLYREAD

 $PROB POPULATION DATA WITH PRIOR ON THETA AND OMEGA
 $INPUT ID DOSE TIME DV WT
 $DATA data

 $THETA  (0,4,5) (0,.09,.5) (.004,.01,.9)
 $OMEGA BLOCK (3) .7 .04 .05 .02 .06 .08
 $SIGMA  .4 FIX .5

 $EST

 Instead of a $PRIOR record, use the same $SUBROUTINE  record  and  the  |
 same subroutine prior as in Example 1.                                  |

 Example 3
 ------- -

 Use of PRIOR and TNPRI and a control stream for population data:

 This example simulates the THETA and  OMEGA  parameters  of  the  same
 two-compartment  population  PK  model, as well as the population data
 from this model.  As with Example 2, the first  element  of  SIGMA  is
 prior-specific,  and  so its value need not be simulated. The value .5
 is used for the value of the second element  of  SIGMA.   The  default
 variance-covariance  matrix  from  the  prior  problem is used for the
 hyperparameter variance-covariance matrix (IVAR=1).

 $PROB   READ THE MODEL SPECIFICATION FILE
 $DATA data
 $INPUT ID DOSE TIME DV WT
 $PRIOR TNPRI (PROBLEM 2) PLEV=.9999 IVAR=1                              |
 $PRED
 ;
 ;     THETA(1)=MEAN ABSORPTION RATE CONSTANT - MEAN ELIM. RATE CONSTANT (l/HR)
 ;     THETA(2)=MEAN ELIM. RATE CONSTANT (1/HR)
 ;     THETA(3)=SLOPE OF CLEARANCE VS WEIGHT RELATIONSHIP (LITERS/HR/KG)
 ;     DOSE=WEIGHT-ADJUSTED DOSE (MG/KG)
 ;
       IF (NEWIND.NE.2) THEN
          AMT=DOSE*WT
          W=WT
       ENDIF
       T0=THETA(1)*EXP(ETA(1))
       T2=THETA(2)*EXP(ETA(2))
       T1=T2+T0
       T3=THETA(3)*W*EXP(ETA(3))
       A=EXP(-T2*TIME)
       B=EXP(-T1*TIME)
       C=T1-T2
       D=A-B
       E=T3*C
       Y=AMT*T1*T2/E*D+EPS(2)
 $MSFI msf1 ONLYREAD

 $PROB POPULATION DATA WITH PRIOR ON THETA AND OMEGA
 $INPUT ID DOSE TIME DV WT
 $DATA data
 $THETA  (0,4,5) (0,.09,.5) (.004,.01,.9)
 $OMEGA BLOCK (3) .7 .04 .05 .02 .06 .08
 $SIGMA  .4 FIX .5

 $SIM (547676) ONLY

 Instead of a $PRIOR record, the following may be used:

 $SUBROUTINE PRIOR=prior

 The prior routine is as follows:

       SUBROUTINE PRIOR (ICALL,CNT)
       DOUBLE PRECISION CNT
       IFND=0
       MODE=0
       ITYP=0
       PLEV=.9999
       ISS=0
       IVAR=1
       IF (IPROB.EQ.2) CALL TNPRI (IFND,MODE,ITYP,PLEV,NSAM,ISS,IVAR,CNT)
       RETURN
       END

 REFERENCES: none.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     


  
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