Background
CLIA requires laboratories performing moderate or high complexity testing to participate in a proficiency testing program. This program was established as the best way to evaluate a laboratory’s performance by sending unknown specimen samples to the laboratory for analysis and then providing the laboratory with its test scores. These scores are reliable indicators of the accuracy and reliability of the laboratory’s testing process, and ultimately of the competency of its personnel.
Initial regulations were established in 1992, but laboratory testing has evolved significantly since then. Some tests that were not widely used in 1992 are now in routine clinical use, requiring an update to the regulations. Examples of these include troponins (used to diagnose heart attacks) and Hemoglobin A1c, used to monitor medium to long-term blood glucose levels in diabetics.
As a result, after careful evaluation of these changes, CMS implemented several updates to the CLIA ’88 regulations for proficiency testing, known as the Final Rule. These were published on July 11, 2022.
These revisions, including the addition and deletion of several analytes that require PT, as well as updates to the criteria for acceptable performance, take effect two years after the publication of these in the Federal Register, on July 11, 2024.
However, these revisions also include an update to the regulations that remove the exclusion of waived tests from the ban on improper PT referral. These go into effect much earlier.
These updated regulations pertaining to laboratories performing tests of moderate and high complexity that also perform waived testing and PT enrollment went into effect on August 10, 2022, 30 days after the date of the final rule’s publication in the Federal Register.
CMS issued a statement that the total financial cost for laboratories to participate in PT for analytes and tests under the Final Rule will increase, but that confidence in the laboratory profession will increase as well: “Although the effect of the changes will increase costs, implementation of these changes in this final rule will increase the confidence of laboratory professionals and the end-users of test results, including physicians and other health care providers, patients, and the public, in the reliability and accuracy of test results.”
Changes to Microbiology Proficiency Testing Specifically, CMS has modified the proficiency testing requirements applicable to microbiology subspecialties like bacteriology, mycobacteriology, mycology, parasitology, and virology to remove the types of services listed for each subspecialty and instead specify broad categories of tests (or categories of organisms) for each subspecialty which requires proficiency testing.
CMS believes this better reflects current practices in microbiology, and it will allow greater flexibility for new technologies that may be developed in the future.
1. Subspecialty Requirements:
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For bacteriology, the categories required include, as applicable: Gram stain including bacterial morphology; direct bacterial antigen detection; bacterial toxin detection; detection and identification of bacteria that includes one of the following: detection of the presence or absence of bacteria without identification, or identification of bacteria; and antimicrobial susceptibility testing of select bacteria.
o The bacteriology annual PT program content described must include representatives of the following major groups of medically important aerobic and anaerobic bacteria if appropriate for the sample sources: Gram-negative bacilli; Gram-positive bacilli; Gram-negative cocci; and Gram-positive cocci.
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For mycobacteriology, the categories for which PT is required include, asapplicable: acid fast stain; and detection and identification of mycobacteriawhich includes one of the following: detection of the presence or absence of mycobacteria without identification, or identification of mycobacteria.
o The annual mycobacteriology PT program content must include Mycobacterium tuberculosis complex and Mycobacterium other than tuberculosis (MOTT), if appropriate for the sample sources. In the final rule, CMS will not include antigen and toxin detection in the mycobacteriology subspecialty because no PT program offers applicable PT modules.
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For mycology, the categories for which PT is required include, as applicable: direct fungal antigen detection; and detection and identification of fungi and aerobic actinomycetes which includes one of the following: detection of the presence or absence of fungi and aerobic actinomycetes without identification, or identification of fungi and aerobic actinomycetes.
o The annual mycology PT program content must include the following major groups of medically important fungi and aerobic actinomycetes if appropriate for the sample sources: yeast or yeast like organisms; molds that include dematiaceous fungi, dermatophytes, hyaline hyphomycetes, and mucormycetes; and aerobic actinomycetes.
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For parasitology, the categories for which PT is required include, as applicable: direct parasite antigen detection; and detection and identification of parasites which includes one of the following: detection of the presence or absence of parasites without identification, or identification of parasites.
o The annual parasitology PT program content must include intestinal parasites and blood and tissue parasites, if appropriate for the sample sources. In the final rule, CMS will not include stains and antiparasitic susceptibility or resistance testing in the subspecialty of parasitology because no PT program offers applicable PT modules.
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For virology, the categories for which PT is required include, as applicable: viral antigen detection; and detection and identification of viruses.
o The annual virology PT program content must include respiratory viruses, herpes viruses, enterovirus, and intestinal viruses, if appropriate for the sample sources.
2. Miscellaneous microbiology requirements:
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Laboratories are required to report PT results for microbiology organism identification to the highest level that they report results on patient specimens.
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Bacterial morphology is required for Gram stains.
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The mixed culture requirement has been lowered from 50 percent to 25 percent for bacteriology, mycobacteriology, and mycology. There are no mixed culture requirements for parasitology or virology.
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Antimicrobial susceptibility testing
o Bacteriology: A least two PT samples per event for susceptibility testing. The program must annually provide samples that include Gram-positive organisms and Gram-negative organisms that have a predetermined pattern of susceptibility to common antimicrobial agents.
Changes to Proficiency Testing for Non-Microbiology Specialties and Sub-specialties
For non-microbiology specialties and subspecialties (endocrinology, general immunology, routine chemistry, toxicology), 29 analytes were added to those in subpart 1 of the CLIA regulations. In addition, criteria for acceptable performance including the target values and acceptance limits (AL) have been updated or established by CMS and CDC.
CMS also deleted certain analytes including LDH isoenzymes, ethosuximide, quinidine, primidone, procainamide, and N-acetyl procainamide. These revisions are largely due to changes in the types of testing that have become more or less frequently used in clinical practice.
In addition to testing volume, CMS also based its revisions on the availability of proficiency testing materials, the number of proficiency testing programs that can provide the analytes, the impact on public health and patient health, and the cost and feasibility of implementation.
The 29 New Analytes Finalized in subpart 1 of the CLIA regulations:
General Immunology
§ 493.927
Analytes:
Anti-HBs
Anti-HCV
C-reactive protein (high sensitivity)
Routine Chemistry
§ 493.931
Analytes:
B-natriuretic peptide (BNP)
ProBNP
Cancer antigen (CA) 125
Carbon dioxide
Carcinoembryonic antigen
Cholesterol, low density lipoprotein, direct measurement
Ferritin
Gamma glutamyl transferase
Hemoglobin A1c
Phosphorus
Prostate specific antigen, total
Total iron binding capacity (TIBC), direct measurement
Troponin I
Troponin T
Endocrinology
§ 493.933
Analytes:
Estradiol
Folate, serum
Follicle stimulating hormone
Luteinizing hormone
Progesterone
Prolactin
Parathyroid hormone
Testosterone
Vitamin B12
Toxicology
§ 493.937
Analytes:
Acetaminophen, serum
Salicylate
Vancomycin
B. Definitions
CMS is finalizing new definitions to clarify terms used in proficiency testing to align with current practices and stakeholder comment. The definition for “acceptance limit” was accepted, the definition of “peer group” was clarified with a technical edit, the definition of “target value” was revised, and the proposed definition of “unacceptable score” was removed:
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Acceptance limit means the symmetrical tolerance (plus and minus) around the target value.
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Peer group means a group of laboratories whose testing process utilizes similarinstruments, methodologies, and/or reagent systems.
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Target value for quantitative tests means:
(1) If the peer group consists of 10 participants or more:
(i) The mean of all participant responses after removal of outliers (that is,those responses greater than three standard deviations from the original mean, as applicable);
(ii) The mean established by a definitive method or reference methods; or
(iii) If a definitive method or reference methods are not available, the mean of a peer group; or
(2) If the peer group consists of fewer than 10 participants, the mean of all participant responses after removal of outliers (as defined in paragraph (1) of this definition)
The final rule can be downloaded from the Federal Register at: https://www.federalregister.gov/.
References
1. CMS: Center for Clinical Standards and Quality/Quality, Safety & Oversight Group
Ref: QSO-22-21-CLIA DATE: July 11, 2022
TO: State Survey Agency Directors
FROM: Director, Quality, Safety & Oversight Group (QSOG)
SUBJECT: Final Rule – Clinical Laboratory Improvement Amendments of 1988 (CLIA) Proficiency Testing – Analytes and Acceptable Performance Final Rule (CMS3355-F)
https://www.cms.gov/files/document/qso-22-21-clia.pdf
2. Wichmann, C. Changes to the Clinical Laboratory Improvement Amendments. MLO.
July 20, 2022. https://www.mlo-online.com/management/regulatory/article/21274186/changes-to-the-clinical-laboratory-improvement-amendments-clia
3. CMS Fact Sheet. Clinical Laboratory Improvement Amendments of 1988 (CLIA) Proficiency Testing Regulations Related to Analytes and Acceptable Performance.
https://www.cms.gov/files/document/clia-1988-proficiency-testing-regulations-related-analytes-and-acceptable-performance-cms-3355-f.pdf
4. Telcor. CMS Releases Final Rule on CLIA Proficiency Testing Regulations. https://telcor.com/cms-releases-final-rule-on-clia-proficiency-testing-regulations/.
5. Bass Berry Sims. Recent Updates to CLIA Proficiency Testing and Proposed Changes to Fees, Sanctions, and Other Requirements. September 14, 2022. https://www.bassberry.com/news/clia-proficiency-testing/