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 ... You've visited this page 5 times. Last visit: 1/15/19 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
