RE: Incorporating duplicate assays

From: "Hutmacher, Matt" Matt.Hutmacher@pfizer.com Subject: RE: [NMusers] Incorporating duplicate assays Date: Mon, 21 Nov 2005 12:40:45 -0500 Hello, Vladimir, let me be more specific about my response. As per your formulation below, let Yijk=Fij+EPS1ij+EPS2ijk and Var(EPS1ij)=s12, Var(EPS2ijk)=s22, where all the EPS are independent. Let Rijk=Yijk-Fij. For two replicates (i.e. k=1,2 for simplicity), the correlation of Rij1 and Rij2 is s12/(s12+s22) for this model, with a variance-covariance matrix (lower triangle), [s12+s22,s12,s12+s22]. So, even though the EPS are independent, the Rijk's are not. My indication that this is similar to a parent-metabolite correlation stems from the implication that the assay results all stem from one blood sample, which is the experimental unit for the replicate (analogous in some sense to a patient being the experimental unit for single blood samples). The variance structure (compound symmetric) in the case above is a special case of a more general $SIGMA block in which the variances can be different and the correlation is not tied to the variances. The formulation in Mats' paper is a very parsimonious model (and very cleverly developed given the coding in NONMEM which would be necessary for similar variances parameters with a general covariance), which might be very appropriate for PK replicates. This structure might not be appropriate for QT sampling replicates (temporally ordered) and could be tested relative to a general structure. Matt _______________________________________________________