From: Tingjie Guo <*iam*>

Date: Tue, 05 Nov 2019 14:41:40 +0100

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

Received on Tue Nov 05 2019 - 08:41:40 EST

Date: Tue, 05 Nov 2019 14:41:40 +0100

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

Received on Tue Nov 05 2019 - 08:41:40 EST