Re: [NMusers] Non-influential Eta

Mahesh,

If you are using NONMEM VI then you are OK because the bug has been
fixed in the distributed source code.

If you are using NONMEM V and the source code has been patched as
recommended by Icon/Globomax/NONMEM Project group then the bug will not
affect you.

You only need to worry if you (or your IT support) have not paid
attention to the announcements made about NONMEM bugs and how to fix
them. The simplest and most reliable way to keep your system up to date
is to use NMQUAL for installation.
http://www.metruminstitute.org/downloads/nmqual/

Nick

Samtani, Mahesh [PRDUS] wrote:
>
> Dear NMusers,
> I am trying to sequentially model the PD of a drug that has a simple
> inhibitory Emax effect. There is a clear placebo response from the
> control group and placebo effect goes away once patients stop taking
> their placebo pills (Hence the TY code below). Both drug & placebo
> effect (decrease from baseline) are bigger in patients with higher
> baseline. I want the etas on placebo and drug parameters (C1 and SMAX)
> to be correlated with baseline (BS) eta, which is done using the Block
> Band matrix. I think this problem may have the non-influential eta bug
> (eta on Smax for placebo subjects???). When I run the code below, the
> model runs quite well. How do I know if I have been bit by the bug and
> how can I fix it.
>
> Kindly advice...Mahesh
>
> $SUBR ADVAN4 TRANS4
>
> $PK
> CALLFL = -2
>
> ; PK PARAMETERS DRUG SPECIFIC VALUES REMOVED
> KA = #
> CL = #
> Q = #
> V3 = #
> V2 = #
> F1 = #
> F2 = 1-#
> D2 = #
> ALAG1 = #
>
> L1 = THETA(1)*EXP(ETA(1))
> SC50 = THETA(2)*EXP(ETA(2))
> C1 = THETA(3)*EXP(ETA(3))
> DURA = THETA(4)
> BS = THETA(5)*EXP(ETA(4))
> SMAX = THETA(6)*EXP(ETA(5))
>
> $ERROR
>
> ; BS IS THE BASELINE
> ; TY IS THE PLACEBO RESPONSE
> ; HFN IS HILL FUNCTION FOR DRUG EFFECT
>
> IF (TIME.LE.DURA) THEN
> TY=C1/L1*(1-EXP(-L1*TIME))
> ELSE
> TY=C1/L1*(1-EXP(-L1*DURA))*EXP(-L1*(TIME-DURA))
> ENDIF
>
> HFN=(SMAX*F)/(F+SC50)
>
> EFF=BS-TY-HFN
> IPRE = -5
> IF (EFF.GT.0) IPRE=LOG(EFF)
> Y=IPRE+ERR(1)
>
> $OMEGA ; DRUG SPECIFIC VALUES REMOVED
> #
> #
>
> $OMEGA BLOCK(3) ; DRUG SPECIFIC VALUES REMOVED
> #
> # #
> 0 # #
>
>

--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
n.holford_at_auckland.ac.nz tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford


Received on Wed Apr 16 2008 - 01:43:38 EDT