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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

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