Biomarkers, criteria

As developed in Chapter 6, workplace biomarker targets also provide context and a frame of reference for communicating general-population biomonitoring results. However, this raises a number of communication issues, given that workplace biomarker criteria are not directly relevant to the general public, for the reasons described previously and because the standards may be established with a different level of health protection than would be suitable for the general public. 

From these lines of evidence, it is apparent that the most likely reason for variability between interventional and medical management trials appears to be related to the frequency of early revascularization (100% in the former vs, <20% in the latter) and the utilization of periprocedural biomarker elevation criterion for Ml. Thus, treatment benefit associated with GPIIb/llla inhibitor is observed very early and is primarily driven by reduction in postprocedural biomarker elevation, the least robust but the most prevalent component of the composite endpoint with little benefit on death or Q-wave Ml. 

As for immunoassays for pharmaceutical proteins, in-study validation of biomarker assays should include one set of calibrators to monitor the standard curve as well as a set of QC samples at three concentrations analyzed in duplicate for the decision to accept or reject a specific run. Recommended acceptance criterion is the 6-4-30 rule, but even more lenient acceptance criteria may be justified based on statistical rationale developed from experimental data [14]. 

A criterion was recently proposed by Ferrari and coworkers that relied on MMP9 and TIMPl (Tissue Inhibitor of Metalloproteinase 1) as biomarkers for the EPR effect to select patients amenable to treatment with nanomedidnes [164]. Using FDA-approved PEGylated Liposomal Doxorubidn (Doxil , PLD) as the model nanomedidne, they analyzed the prominent parameters governing PLD accumulation and anticancer activity... 

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