Dear Dennis,
" NUMERICAL DIFFICULTIES WITH INTEGRATION ROUTINE.
MAXIMUM NO. OF EVALUATIONS OF DIFFERENTIAL EQUATIONS, 1000000,
EXCEEDED. "
This seem to indicate that is due to large gap from the first dose time
to the next, causing the difficulty in numerical integration. For these
subjects, can you try to add few dummy records with EVID=2 to resolve
this problem.
Best regards,
Sam
On 12/5/2024 11:21 AM, Dennis Fisher wrote:
Colleagues
I have encountered a problem during NONMEM execution.
Most subjects are dosed daily but a small number of subjects have large intervals
(> 30 days) between successive doses.
For subjects dosed daily, concentrations 24 hours after a dose are BQL and
there is no evidence of accumulation.
For the problem subjects, NONMEM either:
1. aborts (despite a NOABORT option) with an error message at the first dose
after the lengthy gap
2. or sends the following error message:
0PRED EXIT CODE = 1
0INDIVIDUAL NO. 103 ID= 3.11040000000000E+04 (WITHIN-INDIVIDUAL) DATA
REC NO. 56
THETA=
1.66E+02 1.15E-01 2.95E+01 1.81E+01 4.33E+01 3.01E+02 8.26E+00
0.00E+00 1.00E+00 0.00E+00
0.00E+00 1.00E+00 1.00E+00 1.00E+00 1.00E+00 1.00E+00 1.00E+00
OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0
NUMERICAL DIFFICULTIES WITH INTEGRATION ROUTINE.
MAXIMUM NO. OF EVALUATIONS OF DIFFERENTIAL EQUATIONS, 1000000, EXCEEDED.
The error occurs with METHOD=1 but NOT with METHOD=0.
For one subject in whom doses were administered on Days 1, 30, and 60 (followed
by daily dosing), I deleted the first two dosing records and the error no
longer occurs with METHOD=1. I speculate that the error might relate to the
predicted concentration becoming Infinitesimally small after a lengthy interval
between doses, However, I have no idea if this is the explanation. And I am
reluctant to change the dataset so I seek other solutions.
Any ideas as to an explanation or a work-around?
Dennis
Dennis Fisher MD
P < (The "P Less Than" Company)
Phone / Fax: 1-866-PLessThan (1-866-753-7784)
www.PLessThan.com
