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Continuous Time Markov Model Data Structure

From: Jay Wen <wenxx164>
Date: Mon, 9 Aug 2021 20:53:32 -0700

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


Received on Mon Aug 09 2021 - 23:53:32 EDT

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