Clinical and Health Assessment

The accuracy of clinical diagnostic measurements is essential for reliable diagnosis and cost-effective treatment of disease. NIST's involvement includes reference methods, reference materials, and quality assurance programs to support the accuracy of health-related measurements.

NIST works closely with the community to identify and address reference material and methods needs, and to ensure that these Standard Reference Materials (SRMs) are commutable with routine clinical assays. NIST is continually expanding the range of SRMs available, including primary standards, calibration materials, and matrix matched validation materials. These reference methods and the associated SRMs provide critical traceability and help improve the reliability of routine clinical measurements.

Reference Methods and Reference Materials for Clinical Diagnostic Markers

NIST's involvement in reference methods and reference materials to support accuracy in health-related measurements began more than forty years ago. Reference measurement procedures and standard reference materials help ensure accuracy and comparability of routine clinical assays. In addition, this work allows U.S. clinical diagnostic manufacturers to comply with the European Union directive regarding in-vitro diagnostic medical devices (IVD MD), which requires that values assigned to calibrators and control materials be traceable to reference materials and reference measurement procedures of a higher order. The Joint Committee for Traceability in Laboratory Medicine (JCTLM) maintains a listing of these higher-order reference materials and methods. The SRMs also support accuracy in measurements performed as part of the National Health and Nutrition Examination Survey (NHANES) that is conducted by CDC.

Project Areas

Classical Clinical Metabolites/Markers

Assessment of health and disease status often requires the determination of clinical biomarkers and metabolites, measured in biofluids such as blood, serum, or urine. Accurate measurement of these analyte levels is critical.

NIST develops serum-based Standard Reference Materials (SRMs) that can be used as control materials by laboratories measuring clinical markers in human biofluids.

Nutritional Status Markers

A variety of nutrients are essential for normal functioning of the human body, and deficiencies can lead to serious illnesses. Accurate measurement of vitamin and vitamin metabolite levels is therefore critical for identifying individuals affected by nutritional deficiencies and for evaluating the potential health benefits associated with dietary supplementation. Assessment of nutritional status has been performed by a variety of techniques, including microbiological, enzymatic, immunoassay, and chromatographic approaches. Interlaboratory comparisons have revealed discrepancies in the results obtained by laboratories using different assay methods or even when different laboratories use the same assay for a given analyte. Such variation adds significant complexity to the identification of "normal" ranges for nutritional analytes, and reduces the reliability of vitamin deficiency diagnoses. To improve the accuracy and reliability of nutritional status assessments, NIST develops serum-based Standard Reference Materials (SRMs) that can be used as control materials by laboratories measuring nutritional status markers in human serum.

Reference Materials for Non-targeted Metabolomics, Lipidomics and Proteomics

The use of metabolite, lipid, and protein profiles for systems biology, biomedical research, and clinical applications has risen dramatically over recent years. Global profiling allows for the detection, identification and relative quantification of candidate biomarkers, or more specifically molecular markers, which discriminate disease processes, oxidative stress, injury, histopathological changes, pathophysiological mechanisms, drug effects, glycosylation, etc.  This technique has matured so that it is now possible to observe 1000s – 10,000s of unknown chemical compounds and different protein groups from cell lysates, bio-fluids and tissue samples, with the ability to gather simultaneous data of features much like RNA sequencing.  This non-targeted data analysis approach can highlight gross differences between sample groups and can be further queried by targeted quantitative analysis for specific proteins and/or biomarkers of interest.  However, due to the nature of detection, it is difficult if not impossible to relate data between instrument runs or amongst similar studies without a common internal standard or QC check.

Primary Standards for Clinical Metrology

NIST develops calibrants for organic chemical measurement that provide SI traceability through direct means and suitable for widely applicable clinical measurement procedures.

Quality Assurance Programs

NIST has extensive experience in the administration of interlaboratory comparisons and quality assurance programs (QAPs). These programs support the clinical measurement community by allowing participants to identify measurement challenges, improve the accuracy of their measurements, and demonstrate an effort to comply with various regulations. There is also the opportunity for laboratories to assess their in-house measurements, and, in conjunction with the use of SRMs, improve the comparability and precision of data over time.

The NIST Clinical Quality Assurance Program (ClinQAP) served two key functions in the clinical measurement community. The first was to support the long-term reliability of micronutrient, vitamin D metabolite, and fatty acid measurements in serum and plasma matrices through the Micronutrients Measurement Quality Assurance Program (MMQAP), the Vitamin D Metabolites Quality Assurance Program (VitDQAP), and the Fatty Acids in Human Serum and Plasma Quality Assurance Program (FAQAP), respectively. Results from the comparison studies helped participants to make accurate clinical and health-care decisions as well as to maintain and improve their measurement comparability. The second function of the ClinQAP was to monitor and support the emerging measurement needs of the clinical community and to expand the range of analytes and matrices studied.  The ClinQAP concluded in 2017, and parts of the ClinQAP community will now be served through the Health Assessment Measurements Quality Assurance Program (HAMQAP).

While quality assurance programs are conducted similarly to proficiency testing (PT), NIST programs are not PT and are not designed to pass strict evaluation of laboratory performance.  While proof of participation in NIST QAPs may be adequate to demonstrate proficiency in some communities, the use and distribution of each participant’s study results for this purpose will be at the discretion of the participant only.

CUSTOMERS/CONTRIBUTORS/COLLABORATORS

• American Association for Clinical Chemistry
• College of American Pathologists
• Centers for Disease Control and Prevention
• International Federation of Clinical Chemistry
• Mayo Clinic
• National Kidney Disease Education Program
• National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• New York State Department of Public Health
• Office of Dietary Supplements (ODS) at the National Institutes of Health