[NMusers] Can you post this question?

From: Ali Alhadab <alhad009_at_umn.edu>
Date: Tue, 2 Aug 2016 08:51:58 -0400

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 la=
st 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" WEI=
GHTED
INDIVIDUAL RESIDUALS IS INFINITE” or “NO. OF REQUIRED SIGNI=
FICANT 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: alhad009_at_umn.edu | Cell:541-740-7991

Received on Tue Aug 02 2016 - 08:51:58 EDT

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