Re: Warning obtained while running SAEM
Most likely, the parameter was reduced to the internal bound. Nonmem places the low bound equal to 1/100 (or 1/1000) of the initial value even if it is set to zero in the code. You may rerun with lower value of THETA(2) or put NOSIGMABOUND to the estimation record
Leonid
THETABOUNDTEST, OMEGABOUNDTEST, SIGMABOUNDTEST
With NONMEM VI, the estimation step sometimes terminates with the
message
PARAMETER ESTIMATE IS NEAR ITS DEFAULT BOUNDARY.
These options request that the "default boundary test" be per-
formed for THETA, OMEGA, and SIGMA, respectively. THETABOUNDTEST
may also be coded TBT or TBOUNDTEST; OMEGABOUNDTEST may also be
coded OBT or OBOUNDTEST; SIGMABOUNDTEST may also be coded SBT or
SBOUNDTEST. These options are the defaults.
NOTHETABOUNDTEST, NOOMEGABOUNDTEST, NOSIGMABOUNDTEST
Instructs NONMEM to omit the "default boundary test" for this
type of variable, i.e., to behave like NONMEM V in this regard.
Any option listed above may be preceded by "NO". The THETA,
OMEGA, and SIGMA choices are independent of each other. E.g., it
is possible to specify NOOBT (to prevent the "default OMEGA
boundary test") and permit both the "default THETA boundary test"
and "default SIGMA boundary test".
Quoted reply history
On 3/5/2024 8:08 AM, T. Preijers wrote:
> Dear NMusers,
>
> While running a simple 1-comp model in NONMEM using SAEM, we discovered a warning resulting from $ERROR. Using a SQRT( **2) describing a mixed error model resulted in zero gradients for the additive error (see Example error model 1 below).
>
> /*Example error model 1*/
>
> $ERROR
>
> IPRED = F
>
> IRES = DV-IPRED
>
> W = SQRT(THETA(1)**2 * IPRED**2 + THETA(2)**2)
>
> IF (W.EQ.0) W = 1
>
> IWRES = IRES/W
>
> Y = IPRED+W*ERR(1)
>
> However, when simplifying the $ERROR code omitting the use of SQRT() and THETA(x)**2 (see Example error model 2 below), a successful SAEM run was obtained.
>
> /*Example error model 2*/
>
> $ERROR
>
> IPRED = F
>
> IRES = DV-IPRED
>
> W = THETA(1) * IPRED + THETA(2)
>
> IF (W.EQ.0) W = 1
>
> IWRES = IRES/W
>
> Y = IPRED + W*ERR(1)
>
> Initial values for both THETAs were positive (TH1: 0.417, TH2: 0.545) and constrained with a lower boundary of 0. Moreover, the expected values for IPRED were ranged from 1-700 mg/L.
>
> Our interest lies in what has driven this error. Perhaps someone else has encountered this before?
>
> Looking forward to receiving any answers/comments!
>
> Kind regards,
>
> *Dr. T. Preijers, PharmD, PhD*
>
> /Hospital Pharmacist and Clinical Pharmacologist/
>
> Hospital Pharmacy Erasmus MC Rotterdam The Netherlands
>
> Rotterdam Clinical Pharmacometrics Group