Re: Mixture model at the IOV level?

From: LSheiner <lewis@c255.ucsf.edu> Subject: Re: Mixture model at the IOV level? Date: Thu, 17 May 2001 12:02:04 -0700 We recently had to do this. There is at present almost no way to take advantage of NONMEMs mixture model option to accomplish this. The most general solution is to write your own PRED or $PRED and compute the mixture likelihood yourself. Unfortunately this means you give up the ability to use any ADVANs ... To see our recent example, look in ftp://pkpd.icon.palo-alto.med.va.gov/nonmem.dir/COMPLIANCE2.dir/ If your mixture situation is very simple, you may be able to get away with the following, which does allow fukller use of NONMEMs capacities. For concreteness, I'll use the following example: A patient is seen on (at most) two occasions, and a dose of drug is given on each and the Cp followed. The patient can be "sick or "not sick" on any occasion (these are the 2 mixture classes), and this might affect his clearance of the dose administered on the occasion. In this simple case, one can define 4 mixture classes (NSPOIP=4) at the individual level: Individual Occasion Occasion Mixture class mixture class ------------- ---------- -------------- 1 1 not-sick 2 1 sick 3 2 not-sick 4 2 sick THEN 1. $PK might have code such as IF (MIXNUM.EQ.1.OR MIXNUM.EQ.3) THEN CL=THETA(1)*EXP(ETA(1)) ELSE CL=THETA(2)*EXP(ETA(2)) ENDIF 2. $MIX might have code such as $MIX NSPOP=4 P(1)=THETA(5) P(2)=1-THETA(5) P(3)=THETA(5) P(4)=1-THETA(5) In the end, MIXEST will be 1,2,3,4 according as the fit finds the sick/'not-sick status on the 2 occasions. Note that if you have m mixture classes and k occasions, this requires m**k separate individual-level micture clasaes, which quickly gets unweildy! -- _/ _/ _/_/ _/_/_/ _/_/_/ Lewis B Sheiner, MD (lewis@c255.ucsf.edu) _/ _/ _/ _/_ _/_/ Professor: Lab. Med., Bioph. Sci., Med. _/ _/ _/ _/ _/ Box 0626, UCSF, SF, CA, 94143-0626 _/_/ _/_/ _/_/_/ _/ 415-476-1965 (v), 415-476-2796 (fax)