Warning obtained while running SAEM

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