NONMEM troubleshooting

Published

August 30, 2025

Under construction

Troubleshooting

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EXIT OCCURS DURING SEARCH FOR ETA

0PRED EXIT CODE = 1
0INDIVIDUAL NO.       4   ID= 4.00000000000000E+00   (WITHIN-INDIVIDUAL) DATA 
REC NO.   2
THETA=
  1.00E-03   5.00E-01   1.00E+01   1.00E+01   1.00E-01   1.00E+01   1.00E+00
OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0
F OR DERIVATIVE RETURNED BY PRED IS INFINITE (INF) OR NOT A NUMBER (NAN).
 Elapsed estimation time in seconds:     0.00

This is a generic error message, nothing informative except indicates that there are some numerical problems. Often this is related to the outliers, so it helps to clean the data.

Things to try:

  • Change ADVAN (6 to 13, if this is differential equations model).
  • Change TOL in $SUBROUTINES record.
  • Change SIGL and NSIG in $ESTIMATION.
  • Change initial estimates
    • To something else within a realistic range.
    • To the values of the previous model.
    • If this is a complex model, try to start with something simpler, like linear, and use the output as initial estimates, and also look for outliers.
    • Increase initial estimate of RUV.
  • Sometimes MCETA=1000 in $ESTIMATION records helps with this message.
  • Add IIV on RUV.

(Credit: Leonid Gibiansky)

Terminology
  • Use “Disease modifying” instead of “protective” (Credit: Mats Karlsson)
  • Time varying covariate: Specify as “regressor”.

References