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

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