Continuous Time Markov Model Data Structure
Dear All,
I am currently working on a continuous time Markov Model to use
drug concentration as exposure to predict the toxicity (categorical
outcome). The dataset preparation and control stream is developed based on
Lu et al *CPT *2020 (PMID: 31877239
https://www.ncbi.nlm.nih.gov/pubmed/31877239) as it is somewhat easier to
construct the dataset compared to Schindler et al AAPS 2017 (PMID: 28634883
https://pubmed.ncbi.nlm.nih.gov/28634883/) or Lacroix et al* CPT* 2009
(PMID: 19626001 https://pubmed.ncbi.nlm.nih.gov/19626001/).
The dataset is structured as following:
ID TIME AMT EVID DV MDV CMT
1 1 . 0 1 0 2
1 1 . 3 . 1 .
1 1 615 1 . 1 1
1 8 . 0 1 0 2
1 8 . 3 . 1 .
1 8 607 1 . 1 1
1 22 . 0 1 0 2
1 22 . 3 . 1 .
1 22 607 1 . 1 1
The relevant control stream:
;; ---------Start
$MODEL
COMP=(CENTRAL) ; CMT1 DRUG
COMP=(EFFECT) ; CMT2
COMP=(PR0) ; CMT3 PR(TOXGR=0)
COMP=(PR1) ; CMT4 PR(TOXGR=1)
COMP=(PR2) ; CMT5 PR(TOXGR=2)
$PK
IF (NEWIND.NE.2) THEN
A1=0
A2=0
A3=0
A4=0
A5=0
PDV=0
ENDIF
IF (A_0FLG.EQ.1) THEN
A_0(1)=A1
IF (PDV.EQ.0) THEN
A_0(3)=1
A_0(4)=0
A_0(5)=0
ENDIF
IF (PDV.EQ.1) THEN
A_0(3)=0
A_0(4)=1
A_0(5)=0
ENDIF
IF (PDV.EQ.2) THEN
A_0(3)=0
A_0(4)=0
A_0(5)=1
ENDIF
ENDIF
$ERROR
IF (EVID.EQ.0) PDV=DV
Y=1E-16
IF (DV.EQ.0) Y=1E-16 + A(3)
IF (DV.EQ.1) Y=1E-16 + A(4)
IF (DV.EQ.2) Y=1E-16 + A(5)
A1=A(1)
PR0=A(3)
PR1=A(4)
PR2=A(5)
;; ---------End
*My question is:* to allow the preceding state to impact the probability of
the current state, should I be resetting the CMT at the same time as the
DV? Or I should be resetting the CMT until the next DV? In another word,
should I contructure the dataset as shown above or below? If there is any
difference, can someone kindly explain why?
ID TIME AMT EVID DV MDV CMT
1 1 . 0 1 0 2
1 1 615 1 . 1 1
1 8 . 3 . 1 .
1 8 . 0 1 0 2
1 8 607 1 . 1 1
1 22 . 3 . 1 .
1 22 . 0 1 0 2
1 22 607 1 . 1 1
Thank you for your time!
Best,
Ya-Feng (Jay)
--
Ya-Feng (Jay) Wen, Pharm.D. | Ph.D. Student
Experimental and Clinical Pharmacology
University of Minnesota College of Pharmacy
7-192 Weaver-Densford Hall, 308 Harvard Street SE
Minneapolis, MN 55455
Office: 612-624-9683 | Cell: 612-443-0511