- Contemporary messages sorted: [ by date ] [ by thread ] [ by subject ] [ by author ] [ by messages with attachments ]

From: Ruben Faelens <ruben.faelens_at_gmail.com>

Date: Wed, 6 Nov 2019 14:13:26 +0100

Hi Tingjie,

You used METHOD=COND LAPLACE in the default posthoc estimate. Whether

INTERACTION is implied depends on your version of NONMEM. Could you check?

I do not entirely understand the following section:

$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,

Are you sure it should not be:

Y = LOG(VAR) + (DV-IPRED)**2 / VAR

Apart from that, it seems you should indeed end up with the same MLE

estimates.

Best regards,

Ruben

On Tue, Nov 5, 2019 at 2:53 PM Tingjie Guo <iam_at_tingjieguo.com> wrote:

*> 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 Wed Nov 06 2019 - 08:13:26 EST

Date: Wed, 6 Nov 2019 14:13:26 +0100

Hi Tingjie,

You used METHOD=COND LAPLACE in the default posthoc estimate. Whether

INTERACTION is implied depends on your version of NONMEM. Could you check?

I do not entirely understand the following section:

$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,

Are you sure it should not be:

Y = LOG(VAR) + (DV-IPRED)**2 / VAR

Apart from that, it seems you should indeed end up with the same MLE

estimates.

Best regards,

Ruben

On Tue, Nov 5, 2019 at 2:53 PM Tingjie Guo <iam_at_tingjieguo.com> wrote:

Received on Wed Nov 06 2019 - 08:13:26 EST