[NMusers] NONMEM6: BQL and YLO --> OBSERVATION IS OUTSIDE LIMITS

Thank you Tom and Jeroen.

I followed the YLO example on page 493 of Manual VIII:
1. BLQs were set to LOQ/2 in the dataset;
2. MDV was set to 1;
3. CMT was set to 2 (observation compartment). EVID=0; AMT=missing.
4. YLO was coded:
  IF (STU.EQ.1.OR.STU.EQ.2.OR.STU.EQ.3) YYY=0.222
  IF (STU.EQ.4) YYY=0.333
  IF (STU.EQ.5) YYY=0.444
  YLO=YYY
  PRB=PR_Y
  IPRE=F

The following error appears:
0PROGRAM TERMINATED BY OBJ
 ERROR IN CELS WITH INDIVIDUAL 7 ID=0.70104000E+05
 OBSERVATION IS OUTSIDE LIMITS
 MESSAGE ISSUED FROM ESTIMATION STEP
 AT INITIAL OBJ. FUNCTION EVALUATION

This subject has DV=LOQ/2.

Does someone know the reason for the error? According to the example, BLQs should be "OUTSIDE LIMITS".

Thank you very much,
Pavel




----- Original Message -----
From: "Elassaiss - Schaap, J. (Jeroen)"
Date: Tuesday, January 9, 2007 5:46 pm
Subject: RE: [NMusers] NONMEM6: BQL and YLO
To: "Ludden, Thomas (MYD)" , nonmem_at_optonline.net
Cc: nmusers_at_globomaxnm.com

> Dear Pavel,
>
> Your are apparently in luxorious position that you can lay your
> hand on
> the actual values in case of BQL values. Modeling using all data
> regardless of censoring is than possible, by inclusion of an additive
> error; this preserves more of the information contained in BQL
> samples.The resulting additive error might be viewed upon in
> terms of a
> detection limit (actually the squared standard deviation thereof),
> assuming an otherwise perfect model of course.
>
> Best regards,
> Jeroen
>
> -----Original Message-----
> From: owner-nmusers_at_globomaxnm.com
> [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of Ludden,
> Thomas (MYD)
> Sent: Monday, 08 January, 2007 15:30
> To: nonmem_at_optonline.net
> Cc: nmusers_at_globomaxnm.com
> Subject: RE: [NMusers] NONMEM6: BQL and YLO
>
>
> Dear Pavel and NONMEM6 users,
>
> I believe the example referred to implements Stuart Beal's
> strategy II (J. Pharmacokin. Pharmacodyn. 32:213-243,2005) described
> specifically on page 230-231 of that article as well as in a previous
> article (J. Pharmacokin. Pharmacodyn. 28:481-504, 2001). That
> approachinvolves deletion of the DV> the likelihood
> (MDV=1) and corrects the likelihood for all remaining
> observations in
> the data set. Examine the PR_Y values for observations that are above
> but near the LOQ. This is at least a somewhat better estimate
> of the
> likelihood for the data remaining in the data set. For the users
> information, Stuart allows the calculation of the probabilities
> associated with DV> but, as
> you note, these do not influence -2LL. In most data sets,
> DV> are not reported quantitatively.
>
> Hope this is helpful.
>
> Tom
>
> _____
>
> From: owner-nmusers_at_globomaxnm.com
> [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of
> nonmem_at_optonline.net Sent: Friday, January 05, 2007 9:12 PM
> To: nmusers_at_globomaxnm.com
> Subject: [NMusers] NONMEM6: BQL and YLO
>
>
>
> Hello NONMEM6 users,
>
> At one conference new features of NONMEM6 were presented. It
> was stated that NONMEM6 takes care of BQL values and improves
> likelihood. I tried to find information in the manuals and
> found the
> YLO example and the following statement: "Last observation record
> (below) has DV < LOQ (LOQ = 1) and MDV = 1. This observation
> does not
> contribute to the -2LL estimate. However, probability that DV is
> > LOQ
> can be tabled using PRB=PR_Y." Therefore (?), taking care of
> BQLs in
> the YLO examlpe does not improve the results.
>
> 1. Is there a way to utilize BQLs and improve likelihood?
>
> 2. How helpful is the estimate of PR_Y?
>
> Thank you!
>
> Pavel
>
>
>
>
>
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Received on Sat Jan 13 2007 - 05:58:10 EST