+--------------------------------------------------------------------+
 |                                                                    |
 |                   INITIAL ESTIMATE (INITIAL EST)                   |
 |                                                                    |
 +--------------------------------------------------------------------+

 MEANING: Initial estimates of parameters THETA, OMEGA, SIGMA
 CONTEXT: NONMEM output

 DISCUSSION:
 Initial  estimates  of  parameters  are  required by NONMEM.  They are
 used, for example, to compute the initial value of the objective func-
 tion  (before NONMEM begins its search for final estimates).  The user
 may provide initial estimates.  Alternatively,  he  may  request  that
 NONMEM provide initial estimates.

 (NONMEM  may  also use as initial estimates the final estimates from a
 previous run, by means of a Model Specification File; (See model spec-
 ification file).   When an MSFI is used, the outputs described here do
 not appear.)

 NONMEM output reflects initial estimates provided by the user  on  its
 problem summary page as in this example:

      INITIAL ESTIMATE OF THETA:
      LOWER BOUND    INITIAL EST    UPPER BOUND
      0.0000E+00     0.1500E+03     0.1000E+07
      0.0000E+00     0.0000E+00     0.0000E+00
      0.1000E+00     0.3000E+00     0.1000E+02
      -0.1000E+07    -0.1000E-01    0.1000E+07
      INITIAL ESTIMATE OF OMEGA:
      0.2500E+00
      0.0000E+00   0.2500E+00
      INITIAL ESTIMATE OF SIGMA:
      0.2500E+00

      The above states that:

      1)   The  initial  estimate of theta(1) is 150, and the parameter
           is constrained to be greater than zero (no upper bound).

      2)   Theta(1) is fixed at zero.

      3)   The initial estimate of theta(3) is .3, and the parameter is
           constrained to lie between .1 and 10.

      4)   The  initial estimate of theta(4) is -.01, and the parameter
           is unconstrained.

      5)   OMEGA is 2x2 and constrained to be  diagonal  (signified  by
           the  0 value of the initial estimate of omega(2,1); the ini-
           tial estimates of omega(1,1) and omega(2,2) are .25.

      6)   SIGMA is 1x1 (a scalar), with initial estimate .25.

 If the initial estimate of an element of THETA  is  left  blank,  this
 indicates  that the user has requested that NONMEM provide the initial
 estimate, as in this example:

      INITIAL ESTIMATE OF THETA:
      LOWER BOUND    INITIAL EST    UPPER BOUND
      0.1000E+00                    0.1000E+02

 Similarly, if the initial estimate of all  or  part  of  OMEGA  and/or
 SIGMA  is not printed, this indicates that the user has requested that
 NONMEM provide the missing initial estimate(s).

 NONMEM performs a search for missing initial estimates  as  its  first
 task.  With NONMEM 7.4, when initial thetas are to be estimated, eval-
 uations can now be done for FOCE and Laplace, not just  for  FO.   The
 complete  set  of  initial  estimates (including those provided by the
 user and those provided by NONMEM) are  printed  on  a  separate  page
 under  the  heading  "INITIAL PARAMETER ESTIMATE", as in the following
 example.  The format is identical to  that  of  the  "FINAL  PARAMETER
 ESTIMATE"  page.   If  all initial parameter estimates are provided by
 the user, this page does not appear.

       ********************  INITIAL PARAMETER ESTIMATE   ***
       THETA - VECTOR OF FIXED EFFECTS PARAMETERS  **********
                  TH 1      TH 2      TH 3
               1.50E+00  1.02E-01  2.90E+01
       OMEGA - COV MATRIX FOR RANDOM EFFECTS - ETAS  ********
                  ETA1
       ETA1    1.50E+00

 This example is from a run involving single-subject data, so there  is
 no SIGMA matrix.

 (See final parameter estimate).

REFERENCES: Guide  IV Section III.B.9, III.B.10, III.B.11


  
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