Splines
I looked at a readme text posted on line (attached) that originated from
Icon some time ago:
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=6&cad=rja&uac
t=8&ved=2ahUKEwiQ4ozXuvLfAhWCZd8KHVW2DRIQFjAFegQIARAB&url=https%3A%2F%2Fnonm
em.iconplc.com%2Fnonmem%2Fconstrained%2520longitudinal%2520spline%2Freadme.t
xt&usg=AOvVaw07-r6tKLZsz_5GMOTYBMuM readme.txt ...
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=6&cad=rja&uac
t=8&ved=2ahUKEwiQ4ozXuvLfAhWCZd8KHVW2DRIQFjAFegQIARAB&url=https%3A%2F%2Fnonm
em.iconplc.com%2Fnonmem%2Fconstrained%2520longitudinal%2520spline%2Freadme.t
xt&usg=AOvVaw07-r6tKLZsz_5GMOTYBMuM
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=6&cad=rja&uac
t=8&ved=2ahUKEwiQ4ozXuvLfAhWCZd8KHVW2DRIQFjAFegQIARAB&url=https%3A%2F%2Fnonm
em.iconplc.com%2Fnonmem%2Fconstrained%2520longitudinal%2520spline%2Freadme.t
xt&usg=AOvVaw07-r6tKLZsz_5GMOTYBMuM
https://nonmem.iconplc.com/nonmem/constrained%20longitudinal%20spline/readme
.txt
1.
https://webcache.googleusercontent.com/search?q=cache:xWJ5Iy0lqgsJ: https://
nonmem.iconplc.com/nonmem/constrained%2520longitudinal%2520spline/readme.txt
+&cd=6&hl=en&ct=clnk&gl=us Cached
Nov 18, 1997 - The longitudinal splines are constrained to exhibit (i)
decreasing tail (ii) ... random effects denoted ETAj in NONMEM, where ETAj
is distributed ...
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When I tried to run the code for a single dose I got an error message. The
control and data (1 subject) are attached. The error message was that the
characters in error were:
Pack
$268 SUBROUTINES EEROR WHILE OPENING OR COPYING USED SUPPLIED SUBROUTINE
Control
$PROBLEM Fits the single-dose PK data with the CLS method
$DATA ..\SDSPLINE_DAT.CSV IGNORE=I
$INPUT ID TIME DV AMT MDV
$SUB OTHER=PACK OTHER=single ; on SUN/UNIX
$SUB OTHER=PACK.f OTHER=single.f ; on PC
$PRED
"FIRST
" double precision ggg(10),col(4),desp(20)
" character fname(4)*12
NB2=3
ORDER=4
NDESP=5
FRAC=.05
STEP=.1
TMAX=36
" DESP(1)=.5
" DESP(2)=2.26
" DESP(3)=3.58
" DESP(4)=5.91
" DESP(5)=10
" COL(1)=1
" COL(2)=2
" COL(3)=3
" COL(4)=5
" FNAME(1)='pred.rep'
" FNAME(2)='ipred.rep'
" FNAME(3)='mipk.rep'
" FNAME(4)='para.rep'
" call single(icall,newind,theta,datrec,frac,nb2,order,time,
" x eta,col,desp,ndesp,step,tmax,fname,cls,ggg,id,0,icro)
" do j=1,nb2-1
" g(j,1)=ggg(j)
" enddo
Y=CLS*(1+EPS(1))+EPS(2) ; any error model
; Enter nonzero values of H(i,j+1), j=1,nb2-1, when the INTERACTION
; option is used in $EST.
;
;" do j=1,nb2-1
;" h(1,j+1)=ggg(j)
;" enddo
JUNK=ETA(1)+EPS(1) ; NMTRAN requirement
$OMEGA .0625 .0625 ; diagonal
; dimension = NB2-1 due to the end-point constraint
$SIGMA .0625 .09
$EST MAX=9999 POSTHOC
$THETA
(0 FIXED) ; THETA(1) = 0 due to the end-point constraint
(0 2 INF) ; THETA(2)
(0 2 INF) ; THETA(3)
(0 2 INF) ; THETA(4)
(0 2 INF) ; THETA(5)
(0 2 INF) ; THETA(6)
;$SIMULATION(2792293 NEW) ONLYSIM SUBPROBLEMS=100
;$ESTIMATION MAX=5000,PRINT=5
;$COVARIANCE
$TABLE TIME ID Y DV
ONEHEADER NOPRINT FILE=MODEL1.fit
ID
TIME
DV
AMT
MDV
1
0
.
50
1
1
0.5
6.82
.
0
1
2.26
8.66
.
0
1
3.58
7.25
.
0
1
5.91
4.32
.
0
1
10
5.95
.
0