[NMusers] Non-influential Eta

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 # #



Received on Tue Apr 15 2008 - 23:54:13 EDT