What are the steps of CDC’s standardization process?

A: Standardization, as we define it at the Centers for Disease Control and Prevention (CDC), is a process in which the accuracy, precision, and other relevant analytical performance parameters of a laboratory test are assessed, improved, and maintained to meet certain clinical needs.

The CDC Clinical Standardization Program (CSP) for Cardiovascular Disease Biomarkers (CDC CVD Program) is doing that with three main components. First, the CDC Lipids Reference Laboratory (LRL) operates internationally recognized reference measurement procedures for total cholesterol, total glycerides, and HDL- and LDL-cholesterol that are traceable to SI in accordance with ISO 17511. Second, the certification program uses the serum materials characterized by LRL to maintain metrological traceability of the members of the Cholesterol Reference Method Laboratory Network (CRMLN). The CRMLN members work with assay manufacturers to establish and verify metrological traceability. Finally, CDC’s Lipids Standardization Program (LSP) monitors the analytical performance assays in clinical laboratories to ensure the accuracy achieved at the manufacturer level reaches patient care.

The LSP is different from external quality assurance (EQA) programs, as it collects weekly data from individual laboratories. In one example, this detailed data enabled CSP to detect a small shift in calibration with an assay manufacturer. CDC identified the source of the shift, and the manufacturer was able to correct the calibration before it affected patient care.

How are CVD programs evolving?

Clinical practice continues to change, and the CDC CVD program is continuing to adjust its program to meet the clinical laboratory community’s needs. Most notably, treatment targets for LDL-cholesterol are now much lower. However, analytical performance criteria for blood lipid measurements did not change accordingly. CDC does not define analytical performance criteria. It considers and adopts, where feasible, recommendations made by relevant stakeholders. For lipids, the last recommendations were developed more than 20 years ago. CDC is supporting stakeholders and experts who are revising current performance criteria to help support new practice guidelines.

With new data now available about limitations of LDL-C and HDL-C measurements, CDC introduced new requirements in its program, such as providing measurement data on samples from patients with certain diseases and conditions. Furthermore, CDC is changing its protocols to better assess analytical performance at lower lipids levels. Data from CDC’s CVD certification program show that establishing metrological traceability through appropriate calibration notably improves calibration bias. However, the bias observed in individual samples can still be high. This situation can only be addressed efficiently using individual donor specimens in the evaluation and certification process. The CDC CVD program is including bias of individual samples in its certification process.

The CDC CVD program is also addressing the need for traditional reference materials by collaborating and supporting the work conducted at the national and international Institute of Standards and Technology, France’s Laboratoire National de Métrologie et D’essais, and other metrology institutes.

What are the new CVD biomarkers that need standardization?

Measurements of traditional blood lipids do not fully capture CVD risk in all patients, and lipoproteins can provide more detailed information about a person’s risk for CVD. CDC CVD is responding to this need by including Lp(a), ApoB, and ApoA1 in its programs in close collaboration with the IFCC working group for Apolipoproteins by Mass Spectrometry.

The author thanks Hubert W. Vesper, PhD, director of the CDC Clinical Standardization Programs, for his contribution to the article. CDC CSP thanks the CRMLN Laboratories for their support with manufacturers standardization. The findings and conclusions in this article have not been formally disseminated by CDC and should not be construed to represent any agency determination or policy. Use of trade names and commercial sources is for identification only and does not constitute endorsement by the U.S. Department of Health and Human Services or CDC.

Uliana Danilenko, PhD, is the lead research chemist in the clinical chemistry branch at CDC in Atlanta. + Email: [email protected]