Please post this Jointing Modeling of Dropout
I am trying to jointly model PD and dropout and I have few questions for
those who have experience with this model.
Does it matter if I use right or interval censored event model? What is
the advantage of using one over the other?
The dropout record should be the last record for each patient in a dataset,
isn’t it? If I want to do interval censored and I only know the last time
a subject is known to be in the trial, can I use the last time observed and
time of next scheduled visit for my interval? Or I only can do right
censoring in this case.
If dropout out data was not collected and I need to account for that, I can
develop criteria to define dropout after the fact that study is over, can’t
I? For example, subjects who did not show up for at least three visits
(first thee visits) are considered missing, or subjects who have been in
the study less than 14 days are considered missing. What if a subject made
it to the 1st and 5th visit but missed those in between? Any suggestions
how to do that?
When I run my joint model, I get the following error: ”SQUARED" WEIGHTED
INDIVIDUAL RESIDUALS IS INFINITE” or “NO. OF REQUIRED SIGNIFICANT DIGITS IN
SOLUTION VECTOR TO DIFFERENTIAL EQUATIONS, 5, MAY BE TOO LARGE”. I tried to
use different ADVAN (6,8,9) and reduce TOL (6,5,4,3,2,1) but that did not
solve the problem. Any idea what the problem is?
ID
TIME
DV
LOCF
DVID
CMT
1
0
37
0
1
1
1
14
18
37
1
1
1
30
14
18
1
1
1
58
7
14
1
1
*1*
*62*
*0*
*7*
*2*
*1*
2
0
22
0
1
1
2
0
0
0
3
2
2
25
23
22
1
1
*2*
*34*
*1*
*22*
*2*
*1*
$SUB ADVAN=6 TOL=9
$MODEL COMP=(HAZARD)
$PK
;;; PD COUNT MODEL ;;;
S0=THETA(1)*EXP(ETA(1))+THETA(10)*(SEX-1)
IF (REGION.EQ.6) THEN
REG=THETA(12)
ELSE
REG=0
ENDIF
IF (TX.EQ.1)
SSS=THETA(2)*EXP(ETA(2))+THETA(10)*(SEX-1)+REG+THETA(13)*MISSTOT
IF (TX.EQ.2)
SSS=THETA(3)*EXP(ETA(2))+THETA(10)*(SEX-1)+REG+THETA(13)*MISSTOT
IF (TX.EQ.3)
SSS=THETA(4)*EXP(ETA(2))+THETA(10)*(SEX-1)+REG+THETA(13)*MISSTOT
IF (TX.EQ.4)
SSS=THETA(5)*EXP(ETA(2))+THETA(10)*(SEX-1)+REG+THETA(13)*MISSTOT
IF (TX.EQ.1)
TPROG=THETA(6)*EXP(ETA(3))+(B_INF/25.86)**THETA(11)+REG+SEASON**THETA(13)
IF (TX.EQ.2)
TPROG=THETA(7)*EXP(ETA(3))+(B_INF/25.86)**THETA(11)+REG+SEASON**THETA(13)
IF (TX.EQ.3)
TPROG=THETA(8)*EXP(ETA(3))+(B_INF/25.86)**THETA(11)+REG+SEASON**THETA(13)
IF (TX.EQ.4)
TPROG=THETA(9)*EXP(ETA(3))+(B_INF/25.86)**THETA(11)+REG+SEASON**THETA(13)
;;; DROPOUT MODEL ;;;
BASE = THETA(14)
SHP = THETA(15)
LAM = BASE*SHP
BETA = SHP-1
BETA1 = THETA(16)
$DES
;;; PD COUNT MODEL ;;;
DCOUNT=S0+(SSS-S0)*(1-EXP(-LN2/TPROG*T))
;;; DROPOUT MODEL ;;;
IF(T.GT.0)THEN
DADT(1) = LAM*EXP(BETA*LOG(BASE*T)+DCOUNT*BETA1)
ELSE
DADT(1) = 0
ENDIF
$ERROR
COUNT=S0+(SSS-S0)*(1-EXP(-LN2/TPROG*TIME)) ;RENAME IPRED
CHZ = A(1) ;rename old cumulative hazard
SUR = EXP(-CHZ) ;survival probability
IF(TIME.GT.0)THEN
HAZNOW=LAM*EXP(BETA*LOG(BASE*TIME)+COUNT*BETA1)
ELSE
HAZNOW = 0
ENDIF
IF(DVID.EQ.1) THEN
F_FLAG=0
Y=COUNT+ERR(1) ;COUNT PREDICTION
ENDIF
IF(DVID.EQ.2.AND.DV.EQ.1) THEN
F_FLAG=1
Y=SUR*HAZNOW ;DROP OUT EVENT
ENDIF
IF(DVID.EQ.2.AND.DV.EQ.0) THEN
F_FLAG=1
Y=SUR ;RIGHT CENSORED EVENT
ENDIF
$EST MAXEVAL=9990 METHOD=COND LAPLACIAN
Thanks
Ali Alhadab, PharmD | PhD student
University of Minnesota College of Pharmacy
Department of Experimental & Clinical Pharmacology
E-mail: alhad...@umn.edu | Cell:541-740-7991
