Why is standardization of laboratory tests important?

Correct diagnosis, treatment, and prevention of diseases depend on accurate and reliable laboratory tests. Standardization, also known as harmonization, ensures that laboratory tests meet these requirements; if a test is standardized, this means that a thorough, independent assessment has demonstrated that its analytical performance meets defined analytical performance goals and clinical needs. With standardized laboratory tests, patients should receive the same diagnosis and treatment independent of where or how the measurements are made. In addition, it is more time and cost efficient for labs that use standardized tests to also use reference ranges and clinical decision levels defined by a standardized test.

What is the Centers for Disease Control and Prevention (CDC) doing to standardize laboratory tests?

The CDC Clinical Standardization Programs (CSP) ensure that the accuracy, precision, and other analytical performance parameters of a laboratory test are improved, verified, and maintained. To achieve this, CDC CSP maintain metrological reference laboratories, operate programs to standardize and harmonize assays, and monitor measurement performance in patient care and research. CDC CSP also work with partners and stakeholders, such as the Partnership for the Accurate Testing of Hormones (PATH), to define analytical performance criteria and reference ranges and generate biomarker data in the U.S. population.

Currently, CDC CSP reference laboratories provide reference measurements for eight analytes including total testosterone and estradiol. CDC CSP also operate standardization programs, including the Hormone Standardization Program (HoSt), the Vitamin D Standardization-Certification Program, and the Lipids Standardization Program, with more than 300 assay manufacturers and laboratories with laboratory-developed and commercial tests participating. CDC CSP are working with these participants to improve the accuracy and reliability of laboratory tests and achieve standardization for consistent and effective patient care.

What progress has CDC made with standardizing total testosterone and estradiol tests?

Since HoSt began in 2010, CDC has had more than 350 participants in 15 countries. Participants have shown measureable improvements for both total testosterone (TT) and estradiol (E2). Specifically, the among-laboratory bias has decreased from 16.5% in 2007 to 2.8% in 2017 for TT and from 54.8% in 2012 to 13.9% in 2017 for E2. Not only has bias improved, but data from proficiency testing programs also show that standardized testosterone assays are more accurate and consistent compared to non-standardized assays.

Recently, CDC CSP also collaborated with the Endocrine Society and PATH to develop reference ranges for testosterone in non-obese men ages 19-39 years old. These reference ranges are now part of an Endocrine Society clinical practice guideline and according to this guideline can be used by laboratory tests standardized to CDC’s criteria.

What are the next steps now that CDC has received additional funding from Congress for harmonization in 2018?

This is the first time CDC has received dedicated funding from Congress to improve the quality and reliability of diagnostic tests for hormones. With these funds, CDC CSP plan to increase in size and scope through the addition of new programs, such as the Accuracy-based Monitoring Program for routine laboratories, and new biomarkers such as parathyroid hormones, free thyroxine, and free testosterone. CDC CSP will continue to work with stakeholders and participants to reduce calibration bias and individual sample bias in order to enhance patient care and public health.

The author would like to thank Hubert W. Vesper, PhD, for his support with this article. CDC CSP would like to thank AACC, PATH, and the Endocrine Society for their support and assistance. 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.

Krista Poynter is a contract research chemist for CDC’s Clinical Standardization Programs in the Division of Laboratory Sciences at CDC in Atlanta, Georgia. +Email: [email protected]