+--------------------------------------------------------------------+
 |                                                                    |
 |                       NONMEM ERROR MESSAGES                        |
 |                                                                    |
 +--------------------------------------------------------------------+

 MEANING: Error messages
 CONTEXT: NONMEM output

 USAGE:

 DISCUSSION:
 This  is  not  a  complete list.  It includes only commonly seen error
 messages.

 Section I.  Errors in the control stream

 FILE RECORD MISSING
      There is something wrong with the NONMEM control file.   Probably
      it  is  an  NM-TRAN control file (starting with $PROBLEM), rather
      than the FCON file produced by NM-TRAN.
 TOT. NO. OF OBSERVATIONS IN INDIVIDUAL REC NO.    1 (IN INDIVIDUAL REC
 ORDERING) EXCEEDS  50
  SEE INSTALLATION GUIDE
      There are too many observation records in some individual record.
      To increase the limit beyond 50, NONMEM must be recompiled.   see
      Guide III, Section 2.7.

 INITIAL ESTIMATE OF OMEGA HAS A NONZERO BLOCK WHICH IS NUMERICALLY NOT
 POSITIVE DEFINITE
      Possible cause: initial estimates of the variance and  covariance
      terms in a block of OMEGA are not appropriate.  Try other initial
      estimates.  (Hint: it helps of the covariance estimates are small
      relative to the variance estimates.)

 USER  CCONTR ROUTINE NOT USED, BUT THERE ARE NO EPSILONS, AND ETAS ARE
 TO BE ESTIMATED
      This can happen when POSTHOC etas are requested, but the data are
      single-subject  data.   The  user  may  have included the POSTHOC
      option in error.

 UNABLE TO OBTAIN A SATISFACTORY INITIAL ESTIMATE  OF  VARIANCE-COVARI-
 ANCE COMPONENTS
 BLOCKS IN BLOCK SET 2 OF OMEGA ARE NUMERICALLY NOT POSITIVE DEFINITE
      This  message  is from the Initial Estimates Step.  It identifies
      certain parameters whose initial estimates could not be obtained.

 Part II.  Error in NONMEM tasks

 NUMBER OF CALLS TO SIMETA EXCEEDS NO. OF DATA RECORDS  FOR  INDIVIDUAL
 1 (IN INDIVIDUAL RECORD ORDERING)
      During  the  Simulation  Step,  an  excessive  number of calls to
      SIMETA have occurred.   It  may  be  that  the  users's  PRED  is
      attempting  to  obtain ETA from a truncated distribution but, due
      to some error, is rejecting all or virtually all values.  (Possi-
      bly, the NEW option was omitted from the random source.)

 Some  messages  are preceded by lines such as the following that iden-
 tify the NONMEM routine that has detected the error:
 PROGRAM TERMINATED BY OBJ
 PROGRAM TERMINATED BY OBJ, ERROR IN CELS
 PROGRAM TERMINATED BY OBJ, ERROR IN ELS
 PROGRAM TERMINATED BY PRRES, ERROR IN ELS
 PROGRAM TERMINATED BY FNLETA
      OBJ computes the objective function;
      ELS computes Extended Least-Squares contribution to the objective
      function from the data from a single individual ("L1") record.
      CELS  computes  the conditional contribution to the ELS objective
      function;
      PRRES prints final results.
      FNLETA computes subject-specific (posthoc) eta values.

 WITH INDIVIDUAL    1 (IN INDIVIDUAL RECORD ORDERING)
      A line such as this identifies the record.

 Here are some commonly seen error messages.
 INTRAINDIVIDUAL VARIANCE OF DATA FROM OBS RECORD  1 ESTIMATED TO BE 0
 VAR-COV OF DATA FROM INDIVIDUAL RECORD ESTIMATED TO BE  SINGULAR
      A possible cause is the use of a  proportional   intra-individual
      error  model  while  some predicted  values  for  actual observa-
      tions are zero or close to zero.  (For example, if the first dose
      is  an  infusion  and  there is  a  "base- line"  observation  at
      the start of the infusion, the predicted level will be zero.)

 MINIMIZATION TERMINATED DUE TO PROXIMITY OF NEXT ITERATION EST.  TO  A
 VALUE AT WHICH THE OBJ. FUNC. IS INFINITE
      NONMEM Theta-recovery has failed.

 OCCURS DURING SEARCH FOR ETA AT A NONZERO VALUE OF ETA
      An  error  occurred  while NONMEM was obtaining conditional esti-
      mates of eta.

 Section III.  Errors in PREDPP

 Errors in LSODA

 As of NONMEM 7, A differential equation solver  has  been  introduced,
 called  LSODA, and is accessed using ADVAN=13 or ADVAN13.  The code to
 the differential equation solver is  found  in  source\LSODA.f90.   On
 occasion,  coded  errors  will be displayed if the algorithm is having
 trouble integrating  the  equations.   These  errors  may  usually  be
 ignored,  unless the error shows up frequently, and ultimately results
 in failure for the problem to complete.   Typically the remedy  is  to
 increase  or decrease TOL, but for those who desire to understand what
 the error codes mean, there are well documented comments on  these  at
 the beginning of LSODA.f90.  They are printed here for convenience:

 !ISTATE=An index used for input and output to specify the the state of the calculation.
 !
 ! On input,the values of istate are as follows.
 ! 1  Means this is the first call for the problem (initializations will be done).
 !    See note below.
 ! 2  Means this is not the first call,and the calculation is to continue
 !    normally, with no change in any input parameters except possibly TOUT
 !    and ITASK. (If ITOL,RTOL,and/or ATOL are changed between calls with
 !    ISTATE=2,the new values will be used but not tested for legality.)
 ! 3  Means this is not the first call,and the calculation is to continue
 !    normally,but with a change in input parameters other than TOUT and ITASK.
 !    changes are allowed in NEQ,ITOL,RTOL,ATOL,IOPT,LRW,LIW,JT,ML,MU and any
 !    optional inputs except H0,MXORDN,AND MXORDS.
 !    (see IWORK description for ML and MU.)
 ! Note: A preliminary call with TOUT=T is not counted as a first call here,as
 ! no initialization or checking of input is done. (Such a call is sometimes
 ! useful for the purpose of outputting the initial conditions.) Thus the first
 ! call for which TOUT /= T requires ISTATE=1 on input.
 !
 ! On output,istate has the following values and meanings.
 !  1  Means nothing was done; TOUT=T and ISTATE=1 on input.
 !  2  Means the integration was performed successfully.
 ! -1  Means an excessive amount of work (more than MXSTEP steps) was done on
 !     this call,before completing the requested task,but the integration was
 !     otherwise successful as far as T. (MXSTEP is an optional input and is
 !     normally 500.) TO continue,the user may simply reset ISTATE to a value > 1
 !     and call again (the excess work step counter will be reset to 0).
 !     In addition,the user may increase MXSTEP to avoid this error return
 !     (see below on optional inputs).
 ! -2  Means too much accuracy was requested for the precision of the machine
 !     being used. This was detected before completing the requested task,but
 !     the integration was successful as far as T. To continue,the tolerance
 !     parameters must be reset,and ISTATE must be set to 3. The optional output
 !     TOLSF may be used for this purpose. (Note: If this condition is detected
 !     before taking any steps,then an illegal input return (ISTATE=-3) occurs
 !     instead.)
 ! -3  Means illegal input was detected,before taking any integration steps.
 !     See written message for details.
 !     Note: If the solver detects an infinite loop of calls to the solver with
 !     illegal input,it will cause the run to stop.
 ! -4  Means there were repeated error test failures on one attempted step,before
 !     completing the requested task,but the integration was successful as far as T.
 !     The problem may have a singularity,or the input may be inappropriate.
 ! -5  Means there were repeated convergence test failures on one attempted step,
 !     before completing the requested task,but the integration was successful as
 !     far as T. This may be caused by an inaccurate jacobian matrix, if one is
 !     being used.
 ! -6  Means EWT(I) became zero for some I during the integration. Pure relative
 !     error control (ATOL(I)=0.0) was requested on a variable which has now
 !     vanished. The integration was successful as far as T.
 ! -7  Means the length of RWORK and/or IWORK was too small to proceed,but the
 !     integration was successful as far as T. This happens when DLSODA chooses
 !     to switch methods but LRW and/or LIw is too small for the new method.
 !
 ! Note: Since the normal output value of ISTATE is 2, it does not need to be
 ! reset for normal continuation. Also,since a negative input value of ISTATE
 ! will be regarded as illegal, a negative output value requires the user to
 ! change it, and possibly other inputs,before calling the solver again.

REFERENCES: Guide I Section G
REFERENCES: Guide V Section 13


  
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