Clinical Reference Laboratory

Fig. 1 Traceability system for the determination of the most important diagnostic markers in human body fluids in Germany. The clinical reference laboratories at the intermediate level providing calibration means to the routine medical laboratories are accredited as calibration laboratories in the framework of the German Calibration Service (DKD) and are firmly linked to the national metrology institute, PTB, by comparison measurements carried out on actual laboratory samples. Accreditation is in part required by the Federal Physicians Council (BAK) or is voluntary. The traceability system is still under development...

There are maii)7 methods for SNP genotyping and the method of choice depends on several factors, including turnaround time and throughput requirements. The necessities of high-volume genomic research are different from a clinical reference laboratory, a medical clinic, or the STAT laboratories of the future. 

The research formats presently used in clinical reference laboratories employ complex interpretation schemes, though they have been streamlined to be as decisive as is practical. Compatible with traditional interpretation, the first decision to be made is whether the test is valid through examination of the control results. PCR tests may include controls to test for sample preparation, amplification, and the detection of the amplified DNA. Additionally, for each patient specimen, an internal amplification control (e.g., for normal and mutant genes) may be included. Table 6 lists one interpretation scheme for an HIV assay wherein one primer pair and probe are used in the test and the decision is based on replicate testing. 

Fatty acid profiling by GC is routine in some clinical reference laboratories, particularly for identification of anaerobic bacteria. Fatty acids and lipids are bonded to proteins, carbohydrates, or other chemical entities in microbial cell walls and membranes. Fatty acids of chain length from Cg to C20 are useful for identifying Gram negative organisms at the species and genus levels. Perhaps the only automated GC-based microbial characterization system that is commercially available is a microbial analysis system based on derivatization GC of fatty acid methyl esters (Microbial ID, Inc., Newark, NJ). °... 

Hypertension caused by any of these conditions is referred to as secondary hypertension. Identification of a secondary cause of hypertension is often not initially pursued unless suggested by routine clinical and laboratory evaluation of the patient, or failure to achieve blood pressure control. 

Strindberg L, Lonnroth P. Validation of an endogenous reference technique for the calibration of microdialysis catheters. Scandinavian Journal of Clinical and Laboratory Investigation 2000, 60, 205-212. 

Most situations where proficiency evaluation is applied are rather narrowly defined as to scope. For example, clinical laboratories may be asked to demonstrate that they can determine certain constituents occurring in human serum with uncertainties not to exceed specific limits. Accrediting bodies will require successful participation in periodic proficiency tests conducted by a reference laboratory which they recognize. 

Table 1 Reference procedures developed in the reference laboratories of the German Society of Clinical Chemistry...

The National Glycohemoglobin Standardization Program (NGSP) used the CRMLN model to establish a reference laboratory network to standardize glycated hemoglobin (i.e., HbAlc) [33, 34], The purpose of the NGSP is to standardize HbAlc so that clinical laboratory results are comparable to the Diabetes Control and Complications Trial (DCCT) where relationships were established to mean blood glucose and risk for vascular complications. 

Nevertheless, manufacturers are interested in the further development of reference materials and reference measurement procedures suited for application in human serum for medical purposes. Therefore, industry appreciates the efforts started by the Joint Committee of Trace-ability and Laboratory Medicine (JCTLM), an initiative supported by the Bureau International des Poids et Mesures (BIPM) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) in order to develop suitable reference materials and measurement procedures, as well as to collect information on the activities of reference laboratories. In view of the limited resources and large efforts connected with these activities, clear priorities need to be set. Projects need to take into account the clinical importance of the analyte, consider the technical difficulties that must be overcome, and, most importantly, decide whether improvement of the metrological side is reflected in a gain of medically relevant information. 

Method-dependent measurements can be grouped by sector. For example, in the clinical fields there are cases where some higher order reference materials are required for IVD methods, such as for determination of glucose in human serum. It is also required of reference laboratories in specific measurement methods. These issues are now under the responsibility of JCTLM (Joint Committee on the Traceability of Laboratory Medicine of CCQM). CENAM has developed a reference material for glucose and cholesterol determination in human serum, and certified by IDMS, which is under review by JCTLM for the use by reference laboratories in any country applying a reference method. 

To improve measurement capability of field laboratories, CENAM has also been offering a PT scheme, not only because there are few PT providers in Mexico, but also due to the need to promote traceable measurement by the use of reference value provided by CENAM. Following the successful implementation of a PT program for environmental measurement laboratory assessment made by authorities of three local governments [8], similar efforts have been made to promote among laboratories who could be considered in the future as reference laboratories in food, petrochemical, clinical [9] and industrial sectors. 

In case of suspected terrorist act, misuse, intentional criminal, or any deliberate intentional suicidal ingestion, or when the amount ingested is either a large amount, or cannot be determined, the patient should be referred to a healthcare facility for clinical and laboratory assessment, and treatment if necessary (POISINDEX, 2007 Manoguerra and Cobaugh, 2005). 

Prevention and treatment Overview of clinical and laboratory studies References ... 

As is well known, the quality of a measurement result depends on different factors, such as sampling, the measurement method, the instrumentation and the reference materials used for the calibration, etc. This is why it is important that all critical parameters of the instrument and the reference materials should be calibrated and regularly controlled. Experience showed that some manufacturers may not offer sufficient field calibration and testing, and may not be willing to release calibration functions or allow access to raw measurement data. So, as the complexity of instruments increases, it is essential to establish other means to reliably calibrate and control instrumentation. On the other hand, as the instruments used in clinical chemistry laboratories are most diverse and have different degrees of... 

A large number of routine clinical chemistry laboratories perform analyses with multichannel analyzers of both the continuous-flow and the direct-sample type. Various types of spectrophotometric reference materials have been recommended to validate the photometric accuracy and linearity, wavelength accuracy or stray light radiation of photometric systems used for clinical analyses. In this respect, much has been done in the national area. The problem we are facing now concerns the required reference materials to be used for the validation of the concentration accuracy of this instrumentation, so widely used in clinical chemistry laboratories. 

This paper discusses a number of practical problems arising from the request for and use of clinical reference materials for the validation of the performance of photometric systems used in national clinical chemistry laboratories. It shows that uncertainties in the measurement step of photometric analysis have largely been ignored. Uncertainties associated with this step can and do contribute significantly to overall analytical uncertainty. Thus, for a knowledge of trueness and measurement uncertainty, an adequate certified reference materials system and an attempt at a traceability chain are of the utmost importance, since the quality of clinical chemistry results depends critically on the use of reliable reference materials and properly validated instruments. 

Figure 4-2 Typical EMF response of potassium selective membrane electrode to changes in the activity of potassium in the sample solution. Bracketed interval represents the normal reference interval of potassium concentration in blood. (From D Orazio R in Clinical chemistry laboratory management and ctinicai correlations, iewendrowski K, ed. Philadelphia Uppincott,Wiliiams and Wilkins, 2002 455.)...

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