Cholesterol Reference Method Laboratory

Fig. 2 Results of manufacturer comparisons for total cholesterol performed from January 2000 through March 2003. Sixteen manufacturers performed 79 comparisons. Bias versus the Cholesterol Reference Method Laboratory Network (CRMLN) laboratory is plotted on the a-ax is and the coefficient of variation (CV) (%) is plotted on the y-axis. Vertical lines at -3% and +3% bias and the horizontal line at 3% CV indicate the National Cholesterol Education Program recommendations for accuracy and precision for clinical laboratories...

Kimberly MM, Leary ET, Cole TG, Waymack PP. Selection, validation, standardization, and performance of a designated comparison method for HDL-cholesterol for use in the cholesterol reference method laboratory network. Clin Chem 1999 45 1803-12. 

Table 1 Metrological properties of methods used by the Choles- CV coefficient of variation, HDLC high-density lipoprotein cho-terol Reference Method Laboratory Network (CKMLN). 2 KM lesterol, SD standard deviation, LDLC low-density lipoprotein Secondary reference method, DCM designated comparison meth- cholesterol, NA not available od, IDMS isotope dilution mass spectroscopy, AK Abell-Kendall,...

Table 2 Comparison of Cholesterol Reference Method Laborato- tute, NIST National Institute of Standards and Technology (US ry Network (CRMLN) traceability model to the International Or- NMI), IDMS isotope dilution mass spectrometry, ACL accredited ganization for Standardization (ISO) model. BIPM International calibration laboratory, AK Abell-Kendall Bureau of Weights and Measures, NMI National Metrology Insti-...

Myers GL, Kimberly MM, Waymack PP, Smith SJ, Cooper GR, Sampson EJ. A reference method laboratory network for cholesterol a model for standardization and improvement of clinical laboratory measurements. Clin Chem 2000 46 1762-72. 

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. 

First, in most of the large-scale clinical and epidemiological studies that established the (1) relationships between lipids, lipoproteins, (2) risk for CHD, and (3) efficacy of cholesterol lowermg, the measurements were made in standardized laboratories in which the accuracy of the measurements was traceable to CDC reference methods. This included studies such as the National Diet Heart Study in the 1960s, the various LRC program studies (early 1970s to 1990), Specialized Centers of Research in Atherosclerosis (early 1970s to present), and several NHANES studies conducted between 1960 and 1994, ... 

Reference methods are the gold standards or accuracy targets that have been developed for the more common analytes, such as cholesterol, triglycerides, LDL, and HDL cholesterol. The reference method for cholesterol is fully validated and credentialed through the National Reference System for the Clinical Laboratory. The other methods, although not formally credentialed, have been accepted by consensus. 

The reference method, demonstrated to be readily transferable to other laboratories, has been widely adopted by other reference laboratories and diagnostic manufacturers as the accuracy target and the basis for calibration in cholesterol measurements. 

The most extensive effort involves quality assurance. CDC provides common quality control (QC) materials and all members use standardized QC procedures. In addition, CDC regularly surveys the CRMLN laboratories to ensure they meet the required criteria. Initially, surveys were conducted monthly however, as the laboratories gained experience and performance improved, the survey schedule was changed to bimonthly. These surveys use CDC frozen serum secondary reference materials that have been prepared using NCCLS C37-A protocol [28], TC surveys include three levels analyzed in duplicate in two runs. HDLC surveys include four levels analyzed in duplicate in four runs. As an additional check on the quantitative step of the HDLC method, a low-total cholesterol material with cholesterol concentration <100 mg/dl is added to the TC survey. LDLC surveys include four levels analyzed in quadruplicate in four runs. 

---