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
[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford
