User defined likelihood function in POSTHOC estimation

From: Tingjie Guo Date: November 05, 2019 technical Source: mail-archive.com
Dear NMusers, I would like to reproduce POSTHOC estimation with manually defined likelihood (LL) function. This is the control stream of a standard POSTHOC for which I want to reproduce: $PK CL = THETA(1) * CLCR/100 * EXP(ETA(1)) V = THETA(2) * WGT * EXP(ETA(2)) S1 = V $ERROR IPRED = F Y = IPRED + IPRED*EPS(1) + EPS(2) $THETA 4.58 ; TVCL (L/h) 1.53 ; TVV (L/kg) $OMEGA 0.151321 ; omega^2 CL 0.139876 ; omega^2 V $SIGMA 0.039601 ; Proportional 5.76 ; Additive $EST METHOD=COND LAPLACE MAXEVAL=0 NOABORT SIG=3 PRINT=1 And below is the control stream I used aiming to reproduce above POSTHOC estimation: $PK CL = THETA(1) * CLCR/100 * EXP(ETA(1)) V = THETA(2) * WGT * EXP(ETA(2)) S1 = V $ERROR IPRED = F ; Predicted DV ADDI = 5.76 ; Variance of additive error PROR = 0.039601 ; Variance of proportional error VAR = ADDI + PROR*IPRED**2 ; Variance of combined error Y = LOG(W) + (DV-IPRED)**2/VAR ; -2 log Likelihood, $THETA 4.58 ; TVCL (L/h) 1.53 ; TVV (L/kg) $OMEGA 0.151321 ; omega^2 CL 0.139876 ; omega^2 V $EST METHOD=COND LAPLACE -2LL MAXEVAL=0 NOABORT SIG=3 PRINT=1 The LL function was based on the minus twice log posterior distribution: -2LPosterior = log(Var) + SUM{(DV-IPRED)^2/Var} + ETA^2/OMEGA^2 I did not add eta/omega part (prior distribution) to the LL function in the code because NONMEM seems to apply them automatically in POSTHOC. The eta estimates using defined LL function were fairly close but not exactly same as what standard POSTHOC generated and I don't know why. Does anyone have ideas what might be going wrong in the code? Any input is appreciated! Yours sincerely, Tingjie Guo
Nov 05, 2019 Tingjie Guo User defined likelihood function in POSTHOC estimation
Nov 06, 2019 Shan Pan Re: User defined likelihood function in POSTHOC estimation
Nov 06, 2019 Ruben Faelens Re: User defined likelihood function in POSTHOC estimation
Nov 06, 2019 Tingjie Guo Re: User defined likelihood function in POSTHOC estimation