RE: Obj. function is infinite (error=136)

From: VPIOTROV@PRDBE.jnj.com Subject: RE: [NMusers] Obj. function is infinite (error=136) Date:Mon, 2 Jun 2003 12:09:21 +0200 Justin, What you described happens very often: FOCE is unstable in NONMEM V especially with dense data and complex models. Globomax/NONMEM Project Group promise to improve the algorith in the next version (NONMEM VI). However, in your control stream, there are a few strange things: 1. THETA(5) seems to be used twice: in $PK (for V) and in $ERROR 2. ETA(1) is used as a random effect in KA and ALAG. Individual values of these parameters can be correlated, but this has to be implemented via $OMEGA BLOCK unless the correlation coefficient is 1. In that case you can write ALAG1 = TALG * EXP(THETA(3) * ETA(1)) but not ALAG1 = TALG * EXP(THETA(3) + ETA(1)) which is quite unusual and can cause troubles with convergence 3. When you use log transformation, the additive error model has to be tested first, e.g.: $ERROR CALLFL=0 IPRE = LOG(.1) ; Protects from the stop caused by LOG domain error IF(F.GT.0) IPRE = LOG(F) Y = IPRE + ERR(1) The DV item in the data set should be the natural logarithm of concentration. All observations below LOQ should be skipped. So, there should be no zeros or "dots" in DV except dosing records! Best regards, Vladimir