Re: Combining L2-records configuration with M3 method
One simplistic solution would of course be to change the L2 variable so that if
one (or both) in a pair of observations is BLQ, then the L2 values are set to
different values, to ignore the correlation between the two analytes.
Since you only have a few BLQ records, perhaps this can be acceptable?
Best regards
Jakob
Jakob Ribbing, Ph.D.
Principal Consultant, Pharmetheus AB
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Quoted reply history
> On 19 Dec 2023, at 08:50, T. Preijers <[email protected]> wrote:
>
> Dear NMusers,
>
> Currently, I'm working on a project in which ceftriaxone measurements have
> been done for the free fraction and the total concentration. As both have
> been measured (almost) simultaneously, we've specified these as L2 records in
> our dataset. However, in a few records it occurs that one of the measurements
> (within one L2 record) may be below the LLOQ. Therefore, we've also included
> the M3 method to manage such measurements optimally.[1]
>
> Unfortunately, NONMEM is giving the following error:
> 0PROGRAM TERMINATED BY OBJ2
> WITH INDIVIDUAL 2 ID= 2.00000000000000E+00
> NONZERO VALUE OF F_FLAG CAN NOT BE USED WITHIN
> A MULTIPLE OBSERVATION L2 RECORD
>
> It seems that you cannot specify a F_FLAG of 1 within one of the L2 records.
> Therefore, the M3 method cannot be applied simultaneously with L2 records in
> your dataset.
>
> Although I can understand why this error occurs, I would like to know if
> there is a way to include both methods. We try to solve for the
> autocorrelation that may exist between the free (unbound) and the total
> concentration of ceftriaxone.
>
> Looking forward to receiving any answers/comments!
>
> Kind regards,
>
> Dr. T. Preijers PharmD, PhD
> Hospital Pharmacist and Clinical Pharmacologist
> Hospital Pharmacy
> Erasmus MC Rotterdam
>
> [1] Ahn JE, Karlsson MO, Dunne A, Ludden TM. Likelihood based approaches to
> handling data below the quantification limit using NONMEM VI. J Pharmacokinet
> Pharmacodyn. 2008 Aug;35(4):401-21.
>
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