Re: Hessians of posterior density

From: Luann Phillips <luann.phillips@cognigencorp.com> Subject: Re: [NMusers] Hessians of posterior density Date: 7/1/2003 7:57 PM Justin, Given that the estimate of theta4 is approaching zero (or is zero) then the additive + constant CV error model simplifies to a constant CV error model (W=F). When coding the constant CV error model, I suggest using the following code to prevent division by zero for dose records (F=0 usually for first dose). IPRED=F IF(AMT.NE.0)W=1 IF(AMT.EQ.0)W=F IRES=DV-IPRED IWRES=IRES/W Changing the weight for DOSE records will not effect the MVOF. If you obtain a predicted concentration of zero on an observation record (run may terminate), you will need to determine how to handle that on a case by case basis. Maybe the concentration is obtained at a very late time after the dose and really shouldn't be observable (i.e., a dose time error or sample time error or assay error) and therefore could be deleted from the database. If you do want to keep the concentration then you could try something like the following: SCP=0.00001 IPRED=F IF(AMT.NE.0)W=1 IF((AMT.EQ.0).AND.(F.EQ.0)) IPRED=F+ SCP ;predicted conc=0 on obs. record IF((AMT.EQ.0).AND.(F.NE.0)) IPRED=F ;normal observation record If you choose to do this, I would suggest testing smaller and smaller values of SCP until you get the same value of the MVOF for 2 successive SCP values. This would ensure that the concentrations with the altered predicted values do not have undue influence on the MVOF. Incorporating the following 2 lines in your current code with theta4 fixed to zero may also work. In the current code, if you obtain a predicted of zero on a dose record then W=SQRT(0+theta5*0*0)=0 and IWRES=IRES/0 which might be the root of the error. IF(AMT.NE.0)W=1 IF(AMT.EQ.0)W=F Regards, Luann _______________________________________________________