Request for help about M-M kinetics

From: alison@c255.ucsf.EDU (ABoeckmann) Subject: Request for help about M-M kinetics Date: 17 Sep 1997 14:50:35 -0400 Dear folks, I've had second thoughts about the reply that I sent to Honghui Zhou. It may well be that the sign of the first term in DADT(2) was correct in his original control stream but that he made a mistake when he copied it to the email message. If that is the case, then I'd like to make this point about methodology in the use of NONMEM. He says: the message I got is MINIMIZATION SUCCESSFUL, but the PRED values are 10,000 times less than the DV. I tried very hard, but the problem still exists. Maybe something wrong with the scale factor. If there is any question that the model may be incorrect, DO NOT RUN THE ESTIMATION STEP!! He should delete the $ESTIMATION record, and compare PRED vs. DV with the initial estimates of theta. Maybe the initial thetas are so poor that NONMEM cannot find its way to the appropriate miniumim. Or maybe with initial thetas that are known to be reasonable, it is clear that there is some scaling error. Or maybe the PRED vs DV scatter looks good with initial estimates, but during the estimation, the thetas are changed so radically as to lead NONMEM to a false minimum, in which case carefully chosen bounds for one or more theta may help NONMEM stay in a reasonable area of theta-space. The point is: if the model is wrong, the final estimates of theta may be so distorted as to make it impossible to figure out why the predictions are so poor. Alison