$MIX and $CONTR

I wonder if someone can explain this item in the online NONMEM help guide for $MIX. $INPUT ... AGE ... $CONTR DATA=(AGE) Then AGE may be used on the right in $MIX. AGE and AGE(1) both refer to the value of AGE on the first observation record of the individual record. AGE(i) refers to the value of AGE on the i- th. observation record of the individual record. Assume there are 2 records for each subject like this ID AGE DV 1 0 10.506 1 50 10.331 2 0 10.039 2 50 10.99 3 0 9.3782 3 50 9.9395 4 0 98.438 4 50 99.411 5 0 10.598 5 50 9.6335 and this code is used to simulate with a different mixing fraction if AGE is less than 25 compared with AGE greater than or equal to 25: $PROB MIX $DATA agemix.csv $INPUT ID AGE DV $SIM (20070730) ONLYSIM NSUB=1 $THETA 0.25 ; PLT25 25% of young are non-responder 0.75 ; PGE25 75% of older are non-responder 10 ; NONRESPONDER 100 ; RESPONDER $OMEGA 0.01 $OMEGA 0.1 $SIGMA 1 $PRED IF (MIXNUM.EQ.1) THEN ; non-responder Y=THETA(3) + ETA(1) + EPS(1) ELSE ; responder Y=THETA(4) + ETA(2) + EPS(1) ENDIF $CONTR DATA=(AGE) $MIX NSPOP=2 IF (AGE.LT.25) THEN P(1)=THETA(1) ; young non-responder P(2)=1-THETA(1) ELSE P(1)=THETA(2) ; older non-responder P(2)=1-THETA(2) ENDIF $TABLE ID AGE DV NOAPPEND NOPRINT ONEHEADER FILE=agemix.fit I choose to define a response > 50 as a responder and <=50 as a non-responder. The simulated DV values (10,000 subjects) had 75% of non-responders (with the same proportion at both ages). I had expected 25% because AGE in $MIX is supposed to be the AGE on the first obs record i.e. AGE=0. I got identical results with NONMEM VI and NONMEM V. First question: Why is the proportion of simulated subjects different from what I expected? It seems like all the values are being simulated with AGE=50 instead of AGE=0. Second question: More generally, if we used AGE in other subroutines (e.g. $PK, $PRED) then AGE would change depending on the value in the current event record. Why doesn't this happen with $MIX? Third question: Is there a way to know the index of the observation record that is being used by $MIX? If I wanted to use AGE like I do in $PK it seems I must give the index of the current observation record. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand [EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:+64(9)373-7090 www.health.auckland.ac.nz/pharmacology/staff/nholford