___________________________________________________________________
 |                                                                 |
 |                                PRIOR                            |
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 MEANING: PRIOR subroutine
 CONTEXT: User-supplied subroutine; replaces a NONMEM dummy routine

 USAGE:
 SUBROUTINE PRIOR (ICALL,CNT)
 INTEGER ICALL
 (If double precision is to be used):
 DOUBLE PRECISION CNT
 (If single precision is to be used):
 REAL CNT

 DISCUSSION:
 The user-written PRIOR subroutine allows a penalty function based on a
 frequency  prior  to  be  specified  and added to the -2log likelihood
 function (Gisleskog et al, JPP, 2002, p. 473-505).  This serves  as  a
 constraint  on  the estimates of THETA, OMEGA, and SIGMA and thus as a
                     ---------
 way for stable estimates to be obtained with insufficient data.

 When the Simulation Step is implemented, THETA and  OMEGA,  and  SIGMA
 may  also  be simulated (along with etas and epsilons, should any such
 appear in the model and have nonzero-variances) in the  PRIOR  subrou-
 tine  (See NMPR16).   However, this need not be done (simply execute a
 return in PRIOR at ICALL=4), in  which  case  the  values  for  THETA,
 OMEGA,  and  SIGMA  used in the simulation are the values given in the
 NONMEM control stream or input Model Specification File.

 Input argument:

  ICALL
      Similar to ICALL for PRED subroutine.
      Possible values: 0, 1, 2, and 4.
      In a multiple problem run, PRIOR is called with ICALL=1 only with
      the first problem.

 Output argument:

  CNT
      CNT is the penalty term.

 Other Inputs:

 Other inputs are available  to  PRIOR  in  NONMEM  read-only  commons.
 (See NONMEM_commons).

 NONMEM Utility Routines:

 PRIOR  may  call   NONMEM   utility   routines,   NWPRI   and   TNPRI.
 (See nwpri, tnpri).  E.g.,

       SUBROUTINE PRIOR (ICALL,CNT)
       DOUBLE PRECISION CNT
       NTHETA=3
       NETA=3
       NEPS=1
       NTHP=2
       NETP=2
       NEPP=1
       PLEV=0
       CALL NWPRI (NTHETA,NETA,NEPS,NTHP,NETP,NEPP,NPEXP,ITYP,PLEV,
      1            NSAM,ISS,CNT)
       RETURN
       END

 NWPRI and TNPRI compute particular types of penalty  functions.  NWPRI
 computes a function based on a frequency prior that has a multivariate
 normal form for THETA, and also, in the case of  population  data,  an
 inverse  Wishart  form  for  OMEGA  (independent  from  the normal for
 THETA).  When used during a Simulation  Step,  it  produces  a  random
 value  of  THETA and a random value of OMEGA from the frequency prior.
 The prior information is entered manually  into  the  control  stream.
 This  prior  is  especially useful for a subjective specification of a
 penalty function.  (See nwpri, tnpri).

 Model parameters may be constrained in various ways.  Those parameters
 whose  values  are  not  fixed are transformed to new parameters whose
 values are not at all constrained a priori (the "unconstrained parame-
 ters",  or  UCP).   TNPRI  computes a penalty function based on a fre-
 quency prior that has a multivariate normal form for  all  UCP.   When
 used  during a Simulation Step, it produces a random value of the vec-
 tor of all model parameters (whose values are not  fixed).  The  prior
 information  is found in an input model specification file, and it has
 been automatically stored there as part of  a  NONMEM  analysis  of  a
 prior  data set. (See $msfi, model specification file).  This prior is
 especially useful for an empirical specification of  a  penalty  func-
 tion.  (See TNPRI).

REFERENCES: Guide III Section VII.3.5.4
REFERENCES: Guide V Section 12.4.16


  
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