[Federal Register Volume 87, Number 131 (Monday, July 11, 2022)]
[Rules and Regulations]
[Pages 41194-41242]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-14513]
[[Page 41193]]
Vol. 87
Monday,
No. 131
July 11, 2022
Part II
Department of Health and Human Services
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Centers for Medicare & Medicaid Services
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42 CFR Part 493
Clinical Laboratory Improvement Amendments of 1988 (CLIA) Proficiency
Testing Regulations Related to Analytes and Acceptable Performance
Federal Register / Vol. 87 , No. 131 / Monday, July 11, 2022 / Rules
and Regulations
[[Page 41194]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Medicare & Medicaid Services
42 CFR Part 493
[CMS-3355-F]
RIN 0938-AT55
Clinical Laboratory Improvement Amendments of 1988 (CLIA)
Proficiency Testing Regulations Related to Analytes and Acceptable
Performance
AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS; Centers
for Disease Control and Prevention (CDC), HHS.
ACTION: Final rule.
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SUMMARY: This final rule updates proficiency testing (PT) regulations
under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to
address current analytes (that is, substances or constituents for which
the laboratory conducts testing) and newer technologies. This final
rule also makes technical changes to PT referral regulations to better
align them with the CLIA statute.
DATES: Effective August 10, 2022, except for the amendments to
Sec. Sec. 493.2 and 493.801 through 493.959 (amendatory instructions 2
and 5 through 21), which are effective July 11, 2024.
FOR FURTHER INFORMATION CONTACT: Sarah Bennett, CMS, (410) 786-3531; or
Nancy Anderson, CDC, (404) 498-2741.
SUPPLEMENTARY INFORMATION:
I. Background
On October 31, 1988, Congress enacted the Clinical Laboratory
Improvement Amendments of 1988 (Pub. L. 100-578) (CLIA '88), codified
at 42 U.S.C. 263a, to ensure the accuracy and reliability of testing in
all laboratories, including, but not limited to, those that participate
in Medicare and Medicaid, that test human specimens for the purpose of
providing information for the diagnosis, prevention, or treatment of
any disease or impairment, or the assessment of health, of human
beings. The Secretary established the initial regulations implementing
CLIA on February 28, 1992 at 42 CFR part 493 (57 FR 7002). Those
regulations required laboratories conducting moderate or high-
complexity testing to enroll in an approved proficiency testing (PT)
program for each specialty, subspecialty, and analyte or test for which
the laboratory is certified under CLIA. PT referral was further
addressed by enactment of the Taking Essential Steps for Testing Act of
2012 (Pub. L. 112-202, December 4, 2012) (TEST Act) and our
implementing regulations (79 FR 25435 and 79 FR 27105). As of January
2020, approximately 35,967 CLIA-certified laboratories were required to
enroll in a U.S. Department of Health and Human Services (HHS)-approved
PT program and comply with the PT regulations.
Participation in PT is required under the CLIA statute for
laboratories that perform moderate or high complexity testing. PT
evaluates a laboratory's performance by testing unknown samples just as
it would test patient samples. An HHS-approved PT program sends unknown
samples to a laboratory for analysis. After testing, the laboratory
reports its results to the PT program. The program grades the results
using the CLIA grading criteria and provides the laboratory with its
scores. PT is crucial to maintaining the quality of laboratory testing
because it independently verifies the accuracy and reliability of
laboratory testing, including the competency of testing personnel.
Testing has evolved significantly since 1992, and today's
technology is more accurate and precise than the methods used when the
PT regulations became effective in 1994. In addition, many tests for
analytes for which PT was not initially required are now in routine
clinical use. For example, tests for troponins, which are used to
diagnose myocardial infarction, and the hemoglobin A1c test commonly
used to monitor glycemic control in persons with diabetes were not
routinely performed prior to 1992. Recognizing these changes, we
proposed revisions to update the existing PT regulations in a proposed
rule entitled, ``Clinical Laboratory Improvement Amendments of 1988
(CLIA) Proficiency Testing Regulations Related to Analytes and
Acceptable Performance'', published in the February 4, 2019 Federal
Register (84 FR 1536) (hereinafter the proposed rule).
Generally, a final rule must be issued within 3 years of publishing
a proposed rule, except under exceptional circumstances. As discussed
in a notice entitled, ``Clinical Laboratory Improvement Amendments of
1988 (CLIA) Proficiency Testing Regulations Related to Analytes and
Acceptable Performance; Extension of Timeline for Publication of Final
Rule'', published in the January 19, 2022, Federal Register (87 FR
2736) (hereinafter the notice of extension), we could not meet the
February 4, 2022 deadline due to the necessary reallocation of
resources to respond to the COVID-19 public health emergency.
Therefore, in the notice of extension, we announced an extension of the
timeline to publish the final rule by 1 year until February 4, 2023.
As part of the process for developing the proposed rule, HHS
solicited input from the Clinical Laboratory Improvement Advisory
Committee (CLIAC), the official Federal advisory committee charged with
advising HHS regarding appropriate regulatory standards for ensuring
accuracy, reliability, and timeliness of laboratory testing. Taking
CLIAC's recommendations into account, CMS and CDC collaborated to
develop a process to revise the list of required PT analytes listed in
subpart I to determine which analytes should be retained, which should
be deleted, and which analytes not currently listed in subpart I should
be added to the regulations. Following the data-driven process and
step-wise criteria used to select the candidate analytes to be included
in the proposed rule, CMS and CDC sought feedback from PT programs on
the following topics: current PT program practices using ``peer
grouping'' to determine target values; the potential to include new
analytes as required PT; the mechanism for grading current analytes;
possible changes to the criteria for acceptable performance; and
potential changes to microbiology subspecialties, including the
replacement of the types of service as outlined currently at Sec. Sec.
493.911(a), 493.913(a), 493.915(a), 493.917(a) and 493.919(a), with the
proposed categories of required PT for each microbiology subspecialty
at the above citations and the replacement of the list of specific
organisms for each subspecialty with a proposed list of types of
microorganisms.
Based on empirical data and clinical relevance, CMS and CDC next
worked to determine or revise the acceptance limits (ALs) (as defined
in Sec. 493.2) for new and existing required analytes, respectively.
Whenever possible, we proposed ALs as percentages. For each analyte, PT
programs voluntarily provided data simulations using real PT data as a
means of pilot testing our potential ALs. As stated in the proposed
rule, ALs are intended to be used for scoring PT performance by PT
programs and are not intended to be used by individual laboratories to
satisfy the requirement at Sec. 493.1253(b) to establish performance
specifications.
II. Provisions of the Proposed Regulations
The proposed rule, if finalized, would amend the definitions and PT
[[Page 41195]]
requirements in subpart A--General Provisions, Sec. 493.2 Definitions;
subpart H--Participation in Proficiency Testing for Laboratories
Performing Nonwaived Testing; and subpart I--Proficiency Testing
Programs for Nonwaived Testing in the CLIA regulations.
A. Proposed Changes to Microbiology PT
1. Categories of Testing
Subpart I of the CLIA regulations includes PT requirements for each
subspecialty of microbiology, Sec. Sec. 493.911 through 493.919, which
describe ``Types of services offered by laboratories'' for each
subspecialty. In addition, since the regulations do not specify
required analytes for microbiology as they do for other specialties,
they include descriptions of levels or extents (for example,
identification to the genus level only, identification to the genus and
species level) used to determine the type of laboratory for PT
purposes. CLIAC discussed the usefulness and limitations of the types
of services listed in subpart I in helping laboratories enroll properly
or in helping surveyors conduct laboratory inspections. It was noted
that the types of services listed in subpart I do not allow for
reporting growth or no growth, presence or absence, or presumptive
identification of microorganisms on PT samples, which are common ways
that physician office laboratories report patient results. CLIAC
suggested revision of the regulations to include broad categories for
the types of PT required for each microbiology subspecialty to allow
flexibility for the inclusion of new technologies.
After deliberation, CLIAC made the following recommendations:
A system for categorizing types of service should be
maintained in the regulations to help laboratories determine what PT
they need to perform and assist surveyors in monitoring PT performance
and patient testing.
The regulations should include four categories of testing
for each microbiology subspecialty, as applicable: stain(s),
susceptibility and resistance testing, antigen and/or toxin detection,
and microbial identification or detection.
Based on these recommendations, we conducted a review of the PT
modules offered by HHS-approved PT programs and consulted with CDC
microbiology subject matter experts, who concurred that not all four
recommended categories above are applicable to each microbiology
subspecialty nor do PT programs have PT available for each category. If
at some point in the future PT becomes available, we may propose to
include additional categories of testing for microbiology
subspecialties in future rulemaking. Based on these recommendations and
our review, we proposed to modify Sec. Sec. 493.911 through 493.919 to
remove the types of services listed for each microbiology subspecialty
and to add the recommended categories of testing (that is, replace the
list with broader categories of organisms) for each microbiology
subspecialty as described in the bullets below. We believe that the
revised microbiology PT regulations would better reflect current
practices in microbiology.
++ Section 493.911(a): For bacteriology, we proposed that the
categories required include, as applicable: Gram stain including
bacterial morphology; direct bacterial antigen detection; bacterial
toxin detection; detection and identification of bacteria which
includes either: detection of growth or no growth in culture media or
identification of bacteria to the highest level that the laboratory
reports results on patient specimens; and antimicrobial susceptibility
or resistance testing on select bacteria.
++ Section 493.911(a)(3): We proposed that 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.
++ Section 493.913(a): For mycobacteriology, we proposed that the
categories for which PT is required include, as applicable: acid-fast
stain; detection and identification of mycobacteria which includes one
of the following: detection of growth or no growth in culture media or
identification of mycobacteria; and antimycobacterial susceptibility or
resistance testing.
++ Section 493.913(a)(3): For mycobacteriology, we proposed that
the annual program content must include Mycobacterium tuberculosis
complex and Mycobacterium other than tuberculosis (MOTT), if
appropriate for the sample sources.
++ Section 493.915(a): For mycology, we proposed the categories for
which PT is required include, as applicable: direct fungal antigen
detection; detection and identification of fungi and aerobic
actinomycetes which included one of the following: detection of growth
or no growth in culture media or identification of fungi and aerobic
actinomycetes; and antifungal susceptibility or resistance testing.
++ Section 493.915(a)(3): We proposed that annual 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, dimorphic fungi, hyaline hyphomycetes, and mucormycetes;
and aerobic actinomycetes.
++ Section 493.917(a): For parasitology, we proposed requiring PT
for direct parasite antigen detection and detection and identification
of parasites.
++ Section 493.917(a)(3): We proposed that the annual program
content must include intestinal parasites and blood and tissue
parasites, if appropriate for the sample source.
++ Section 493.919(a): For virology, we proposed requiring PT, as
applicable, for viral antigen detection; detection and identification
of viruses; and antiviral susceptibility or resistance testing.
++ Section 493.919(a)(3): We proposed that the annual program
content must include respiratory viruses, herpes viruses, enterovirus,
and intestinal viruses, if appropriate for the sample source.
We proposed revising the requirements for evaluating a laboratory's
performance at Sec. Sec. 493.911(b) through 493.919(b) to be
consistent with these categories. We did not propose to include antigen
and toxin detection in the mycobacteriology subspecialty because no PT
program currently offers applicable PT modules. We did not propose to
include stains and antiparasitic susceptibility or resistance testing
in the subspecialty of parasitology because no PT program offers
applicable PT modules. We invited the public to comment on these
proposals and specifically on the proposed categories of testing for
the subspecialties listed above. We stated that if public comments
indicate that applicable PT modules are available for antigen and toxin
detection or stains and antiparasitic susceptibility or resistance
testing, we may finalize their inclusion in the final rule, as
applicable. If PT becomes available at some point in the future for
mycobacteriology antigen and toxin detection testing, and stains and
antiparasitic susceptibility or resistance testing, we may propose to
include this category of testing for PT in future rulemaking. We
summarize and respond to the public comments on these proposals and
summarize our final policies in section III.E. of this final rule.
[[Page 41196]]
++ Sections 493.911(b)(1), 493.913(b)(1), 493.915(b)(1),
493.917(b)(1), and 493.919(b)(1): We proposed amending these provisions
to clarify that to achieve consensus, PT programs must attempt to grade
using both participant and referee laboratories \1\ before determining
that the sample is ungradable. We believe that this change will enhance
consistency among the PT programs when grading samples. The current
regulations noted above allow for scoring either with participants or
with referees before calling a sample ungradable. We summarize and
respond to the public comments we received on these proposals and
summarize our final policies in section III.D. of this final rule.
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\1\ https://www.ecfr.gov/current/title-42/chapter-IV/subchapter-G/part-493#493.2.
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2. Major Groups of Microorganisms
In the proposed rule (84 FR 1536, 1538), we proposed to remove the
lists of specific example organisms from each microbiology subspecialty
and add a more general list of organisms. This change clarifies that PT
programs are able to be flexible in selecting which samples to provide
to laboratories for PT, especially as new organisms are identified as
being clinically important.
Each subspecialty of microbiology, Sec. Sec. 493.911 through
493.919, currently includes a list of the types of microorganisms that
might be included in an HHS-approved PT program over time. Several PT
programs have suggested to HHS that the regulations should include a
more general list of types of organisms that must be included in
required PT instead of a specific list. CLIAC considered whether there
needs to be a more general list of organisms in the regulations to
ensure a variety of challenges are offered over the course of the year.
Following their deliberation, CLIAC made the following recommendation:
Require PT for a general list of types of organisms in
each subspecialty. For example, in bacteriology, the groups listed
should include Gram-negative bacilli, Gram-positive bacilli, Gram-
negative cocci, and Gram-positive cocci.
Generally, we have found that PT programs include only those
organisms listed in the current regulations, and do not include
additional organisms outside the current regulatory list. By
restructuring to a more general list of organisms, it will be more
apparent that PT programs are able to be flexible in selecting which
samples to provide to laboratories for PT, especially as new organisms
are identified as being clinically important. Therefore, we proposed to
remove the lists of specific example organisms from each microbiology
subspecialty, Sec. Sec. 493.911 through 493.919, and to add the
following list of types of organisms to each.
++ Section 493.911(a)(3): For bacteriology, we proposed that the
annual program content 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. The
more general list of types of organisms will continue to cover the six
major groups of bacteria currently listed in the regulations.
++ Section 493.913(a)(3): For mycobacteriology, we proposed that
the annual program content must include Mycobacterium tuberculosis
complex and Mycobacterium other than tuberculosis (MOTT), if
appropriate for the sample sources.
++ Section 493.915(a)(3): For mycology, we proposed that the annual
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, dimorphic fungi, hyaline hyphomycetes, and
mucormycetes; and aerobic actinomycetes.
++ Section 493.917(a)(3): For parasitology, we proposed that the
annual program content must include intestinal parasites and blood and
tissue parasites, if appropriate for the sample sources.
++ Section 493.919(a)(3): For virology, we proposed that the annual
program content must include respiratory viruses, herpes viruses,
enterovirus, and intestinal viruses, if appropriate for the sample
sources.
We summarize and respond to the public comments we received on
these proposals and summarize our final policies in section III.E. of
this final rule.
3. Declaration of Patient Reporting Practices
The PT requirements at Sec. 493.801(b) specify that laboratories
must examine or test, as applicable, the proficiency testing samples it
receives from the proficiency testing program in the same manner as it
tests patient specimens. CLIAC considered this requirement as applied
to microbiology and agreed that PT programs should instruct
laboratories to perform all testing as they normally would on patient
specimens, including reporting PT results for microorganism
identification to the same level reported on patient specimens. CLIAC
deliberated on this issue and made the following recommendation:
Laboratories should declare their patient reporting
practices for organisms included in each PT challenge. However, PT
programs should only gather this information as the inspecting agency
is responsible for reviewing and taking action if necessary.
We believe that laboratories should be instructed to report PT
results for microbiology organism identification to the ``highest''
level that they report results on patient specimens to ensure that they
do so to the ``same'' level that they report results on patient
specimens. As a result, we proposed to amend Sec. Sec. 493.801(b),
493.911(b), 493.913(b), 493.915(b), 493.917(b), and 493.919(b), to
state that laboratories must report PT results for microbiology
organism identification to the highest level that they report results
on patient specimens. If finalized, this proposal should address an
issue we identified during the PT program reapproval process in which
we found laboratories inappropriately deciding whether to participate
in a PT event based on the reporting criteria required by the PT
program. We believe that this change will enhance consistency among the
PT programs when grading samples.
We summarize and respond to the public comments we received on
these proposals and summarize our final policies in sections III.C. and
III.E. of this final rule.
4. Gram Stain PT
CLIAC considered whether the required PT for Gram stains should
include both stain reaction and morphology. CLIAC concluded it should
and recommended:
PT results for Gram stains should include both stain
reaction and morphology.
We agree with this recommendation because knowing the bacterial
morphology is essential for accurate identification of specific groups
of bacteria. Therefore, we proposed the following in Sec. 493.911:
++ Section 493.911(a): The addition of required morphology for Gram
stains.
++ Section 493.911(b): The evaluation of a laboratory's performance
would be modified to include bacterial morphology as one part of the
performance criterion for scoring the Gram stain.
We summarize and respond to the public comments on these proposals
[[Page 41197]]
and summarize our final policies in section III.E. of this final rule.
5. Mixed Culture Requirement
The current CLIA requirements for bacteriology Sec. Sec.
493.911(b)(1), mycobacteriology 493.913(b)(1), and mycology
493.915(b)(1) specify that at least 50 percent of the PT samples in an
annual program must be mixtures of the principal organism and
appropriate normal flora. This requirement aims to simulate the
findings that would occur with actual patient specimens. In
bacteriology, this 50 percent mixed culture requirement must be met for
two required sample types, those that require laboratories to report
only organisms that the testing laboratory considers to be a principal
pathogen that is clearly responsible for a described illness (excluding
immunocompromised patients) and those that require laboratories to
report all organisms present. The CLIA requirements for
mycobacteriology and mycology PT do not specify two sample types.
Still, they include the 50 percent requirement for cultures containing
a mixture of the principal organism and appropriate normal flora. None
of the 50 percent mixed culture requirements in these subspecialties
applies to samples that would only contain normal flora and no
reportable organisms.
CLIAC considered whether PT should include mixed cultures and
discussed the difficulties of having mixed cultures in challenges for
antimicrobial susceptibility testing. CLIAC considered lowering the
mixed culture requirement to 25 percent for all subspecialties in
microbiology. Upon deliberation, CLIAC made the following
recommendation:
Lower the mixed culture requirement from 50 percent to 25
percent for PT challenges of both sample types (those that require
laboratories to report only the principal pathogen and those that
require laboratories to report all organisms present).
We agree it is appropriate to lower the mixed culture requirement
from 50 percent to 25 percent for bacteriology, mycobacteriology, and
mycology to better reflect actual patient samples. As a result, we
proposed the following changes:
++ Section 493.911(a)(2): In bacteriology, we proposed to decrease
the required mixed cultures from 50 percent to 25 percent for culture
challenges that require laboratories to report only the principal
pathogen and those that require laboratories to report all organisms
present.
++ Sections 493.913(a)(2) and 493.915(a)(2): In mycobacteriology
and mycology, respectively, we proposed to decrease the mixed culture
requirement from 50 percent to 25 percent.
Since the requirements for parasitology and virology do not
currently include requirements for mixed cultures (or mixed PT
challenges), we did not propose to make any changes to these
subspecialties. We summarize and respond to the public comments we
received on these proposals and summarize our final policies in section
III.E. of this final rule.
6. Antimicrobial Susceptibility Testing
PT for antimicrobial susceptibility testing is currently required
for bacteriology at Sec. 493.911(b)(1) and mycobacteriology at Sec.
493.913(b)(1), but it is not required for mycology, parasitology, or
virology. For antimicrobial susceptibility testing in bacteriology at
Sec. 493.911(b)(3), at least one sample per testing event must include
one Gram-positive or Gram-negative sample, and for mycobacteriology at
Sec. 493.913(b)(3), at least one sample per testing event must include
a strain of Mycobacterium tuberculosis with a predetermined pattern of
susceptibility or resistance to the common antimycobacterial agents. In
some instances, laboratories appreciate the opportunity to participate
in additional susceptibility testing challenges as educational tools.
Under the current regulations, some laboratories may perform the
minimum required susceptibility testing on some organisms, such as
Gram-positive cocci. When CLIAC discussed this issue, the point was
made that by increasing the frequency and number of required
susceptibility testing PT challenges for different groups of organisms,
potential issues with patient testing in a laboratory may be detected
sooner. CLIAC considered recommending increasing the susceptibility
testing challenges to two per event and requiring one Gram-positive and
one Gram-negative organism in each bacteriology testing event. CLIAC
also considered whether PT should be required for resistance as well as
susceptibility testing and whether these requirements should be
extended to other microbiology subspecialties. Following this
deliberation, CLIAC made the following recommendations:
Required PT for antimicrobial susceptibility and/or
resistance testing should be increased to two challenges per event for
a total of six challenges per year in bacteriology and should include
one Gram-positive and one Gram-negative organism in each event.
PT should be required for laboratories that perform
susceptibility and/or resistance testing in all microbiology
subspecialties. It should include two challenges per event and should
include resistant organisms.
In considering these recommendations, we reviewed the modules
currently offered by PT programs that include susceptibility testing
and noted that there is a limited number of applicable PT modules
currently available for resistance testing. Also, no PT program
currently offers applicable PT modules for antiparasitic susceptibility
or resistance testing in the subspecialty of parasitology. We believe
it could be beneficial to increase the number of challenges per event
from one to two for each microbiology subspecialty to increase the
likelihood of detecting a problem in a laboratory. Antiparasitic
susceptibility or resistance testing is not included in the
subspecialty of parasitology because no PT program currently offers
applicable PT modules. Therefore, we proposed the following:
++ Section 493.911(a)(4): For bacteriology, we proposed requiring
at least two PT samples per event for susceptibility or resistance
testing, including one Gram-positive and one Gram-negative organism
with a predetermined pattern of susceptibility or resistance to common
antimicrobial agents.
++ Section 493.913(a)(5): For mycobacteriology, we proposed
requiring at least two PT samples per event for susceptibility or
resistance testing, including mycobacteria that have a predetermined
pattern of susceptibility or resistance to common antimycobacterial
agents.
++ Section 493.915(a)(4): For mycology, we proposed requiring at
least two PT samples per event for susceptibility or resistance
testing, including fungi that have a predetermined pattern of
susceptibility or resistance to common antifungal agents.
++ Section 493.919(a)(4): For virology, we proposed requiring at
least two PT samples per event for susceptibility or resistance
testing, including viruses that have a predetermined pattern of
susceptibility or resistance to common antiviral agents.
In each of these subspecialties, we also proposed to revise the
requirements for the evaluation of a laboratory's performance at
Sec. Sec. 493.911(b), 493.913(b), 493.915(b), and 493.919(b) to
account for the fact that PT would be required for susceptibility or
resistance
[[Page 41198]]
testing and that the scoring should be consistent with the testing
performed.
We summarize and respond to the public comments we received on
these proposals and summarize our final policies in section III.E. of
this final rule.
7. Direct Antigen Testing
PT for direct antigen testing is only required for bacteriology and
virology under Sec. Sec. 493.911(a) and 493.919(a), respectively, not
for the other microbiology subspecialties of mycobacteriology,
mycology, and parasitology. Since this type of testing is commonly used
for testing patient specimens, especially in mycology and parasitology,
CLIAC considered whether PT for direct antigen testing should be part
of all of the microbiology subspecialty requirements. CLIAC indicated
that direct antigen PT should be required in subspecialties where these
methods are used, and PT is available and made the following
recommendation:
PT for direct antigen testing should be required for all
microbiology subspecialties.
We reviewed the modules currently offered by PT programs and
determined that several modules include direct antigen testing for all
microbiology subspecialties except mycobacteriology, for which this
technology is not commonly used for testing patient specimens. In
addition, we recognized that in bacteriology, PT for direct antigen
testing to detect toxins produced by organisms such as Clostridioides
(formerly Clostridium) difficile is also commonly available. Based on
the information collected from the PT programs, availability of the
modules, and importance to the health and safety of the public, we
proposed to:
++ Retain the requirement for direct antigen detection for:
--Section 493.911(a)(1)(ii): Bacteriology.
--Section 493.919(a)(1)(i): Virology.
++ Add the requirement for direct antigen testing detection for:
--Section 493.915(a)(1)(i): Mycology.
--Section 493.917(a)(1)(i): Parasitology.
++ Require PT for bacterial toxin detection under Sec.
493.911(a)(1)(iii). No changes were proposed for mycobacteriology.
++ Add the evaluation criteria of a laboratory's performance for
two of the affected subspecialties under Sec. Sec. 493.911(b) and
493.917(b) to include performance and scoring criteria that address
direct antigen and toxin detection. Evaluation of a laboratory's
performance for direct antigen testing at Sec. 493.917(b) would align
with the other microbiology subspecialties and reflect current
microbiology practices in reporting patient results. Evaluation of a
laboratory's performance for bacterial toxin detection at Sec.
493.911(b) would reflect the current practice of reporting patient test
results (that is, absence or presence of bacterial toxin).
We summarize and respond to the public comments we received on
these proposals and summarize our final policies in section III.E. of
this final rule.
B. Proposed Changes to PT for Non-Microbiology Specialties and
Subspecialties
In addition to determining which analytes should be added or
deleted, CMS and CDC proposed to establish or change, if necessary, the
criteria for acceptable performance, which include the target value and
ALs, for the analytes. Currently, the CLIA regulations at Sec. Sec.
493.927(c)(2), 493.931(c)(2), 493.933(c)(2), 493.937(c)(2), and
493.941(c)(2) prescribe a variety of ALs, including: a multiple of the
standard deviation (SD) of results from the mean of all laboratories in
the peer group; fixed limit as a percentage of the assigned value;
fixed limit in concentration units; and a mixture of percentage and
concentration units, depending on the concentration of the analyte. As
discussed in section II.B. of the proposed rule, for all new and
currently required non-microbiology analytes, we proposed to amend
certain analytes in Sec. Sec. 493.927, 493.931, 493.933, 493.937, and
493.941 to include percentages with or without fixed ALs. Additionally,
we proposed to tighten ALs for certain current analytes in Sec. Sec.
493.927, 493.931, 493.933, 493.937, 493.941, and 493.959.
We summarize and respond to the public comments we received on
these proposals and summarize our final policies in section III.F. of
this final rule.
1. Analytes Proposed for Addition to Subpart I
The CLIA statute requires the PT standards established by the
Secretary to require PT for each examination and procedure for which
the laboratory is certified ``except for examinations and procedures
for which the Secretary has determined that a proficiency test cannot
reasonably be developed'' (42 U.S.C. 263a(f)(3)(A)). In determining
whether PT can reasonably be developed for a given analyte, we
considered whether the estimated cost of PT is reasonable in comparison
to the expected benefit. We attempted to maximize improvements to the
effectiveness of PT to improve accuracy, reliability and timeliness of
testing while minimizing costs to the laboratories. In addition, we
recognize that requiring PT for every analyte to derive benefits
generalizable to all test methods is unnecessary. For example,
systematic analytical problems on a multichannel analyzer might be
detected by participation in PT for any of the analytes tested.
Further, laboratories are already required under Sec. 493.1236(c)(1)
to verify the accuracy of any test or procedure they perform that is
not included in subpart I at least twice annually. Also, based on the
results of the national PT survey conducted by CDC and the Association
of Public Health Laboratories (APHL) in 2013, many laboratories
voluntarily purchased PT materials for many nonrequired analytes.
Keeping this in mind, as discussed in section II.B.2. of the proposed
rule, we proposed adding the most crucial analytes based upon the
following criteria:
(1) Current availability of PT materials and the number of PT
programs offering PT.
(2) Volume of patient testing performed nationwide.
(3) Impact on patient health and/or public health.
(4) Cost and feasibility of implementation.
2. Process for Ranking Analytes Proposed for Addition to Subpart I
We used a sequential process to narrow the list of eligible
analytes for addition based on each of the four criteria listed above.
a. Current Availability of PT Materials and the Number of PT Programs
Already Offering PT
We believe that the availability of these PT samples for a
particular analyte is an appropriate criterion for narrowing the list
of eligible analytes and that scaling up a program would be relatively
less difficult than creating a PT sample for a particular analyte that
had not previously been offered. For the reasons noted below, we
believe that at least three PT programs offering PT samples for a
particular analyte under consideration would provide a sufficient
number of programs to offer immediate access to PT by laboratories and
a reasonable starting point for the analytes under consideration. CMS
and CDC want to ensure that the laboratories could choose the best PT
program for the services that their laboratories offered as well as not
create a market advantage for a small number of PT programs. To
evaluate the current availability of PT materials and PT
[[Page 41199]]
programs offering PT samples for a particular analyte, we analyzed the
distribution of available PT programs for analytes for which PT is
currently not required by subpart I of the CLIA regulations. The
supporting data were collected from available sources, including data
from PT program catalogs and data routinely reported by PT programs,
including enrollment data. We examined the number of PT programs
offering these analytes at any number of events per year and any number
of challenges per event. We initially determined the number of analytes
under consideration for which PT was offered by at least two, three, or
four of the 11 existing PT programs. We determined that limiting the
analytes under consideration to those for which PT was offered by at
least three PT programs allowed a sufficient number of programs to
offer immediate access to PT by laboratories and provided a reasonable
starting point of 199 for the number of analytes under consideration
(96 in routine chemistry, 27 in endocrinology, 28 in toxicology, 25 in
general immunology, 21 in hematology, two for antibody identification).
The expected impact on laboratories and PT programs was also considered
(for example, minimizing the cost of purchasing and providing samples)
when determining the minimum number of PT programs. Decreasing the
minimum PT programs to two rather than three would increase the number
of analytes under consideration to 303 but presumably decrease PT
program availability and access for a given analyte. Conversely,
increasing the minimum number of PT programs to four while presumably
increasing PT program availability and access for a given analyte
decreased the number of analytes under consideration to 164. This was
the first cut based upon available PT modules.
b. Volume of Patient Testing Being Performed Nationwide
For the second cut, we prioritized the remaining 199 analytes under
consideration based upon estimated national testing volumes. We decided
that an estimated national test volume of 500,000 per analyte annually
was an appropriate threshold as it was based upon testing volumes of
the majority (68 out of 81) of analytes currently listed in subpart I.
For comparison, of the analytes currently required under subpart I, 63
had a total national test volume above 1,000,000; five had national
test volumes between 500,000 and 1,000,000, and 13 had national test
volumes below 500,000. We used 500,000 annual tests as a preliminary
cut-off for retention on the list of analytes under consideration. We
also retained analytes below the 500,000 threshold that we determined
to be clinically important based on literature already footnoted in
section II.B.2.b. of the proposed rule and consultation with CDC health
experts. The following analytes with test volumes less than 500,000
that were retained are: carbamazepine, alpha-1-antitrypsin,
phenobarbital, hepatitis Be antigen, antibody identification,
theophylline, gentamicin, and tobramycin.
In estimating national testing volumes to rank the remaining 199
analytes under consideration in the proposed rule, we were unable to
identify a single source of available data for all patient testing
being performed nationwide. We had complete data for Medicare payment,
as well as the most current MarketScan Commercial Claims and Encounters
(CCAE) and MarketScan Medicaid Multi-state data sets \2\ and
extrapolated accordingly. We used data provided by an HHS-approved
accreditation organization, specifically a list of the number of their
accredited laboratories offering each test we considered for addition
to, or deletion from, subpart I to determine how many laboratories were
performing testing for the proposed analytes. We also considered
smaller representative data sets, including data sets obtained from a
large healthcare network, a large reference laboratory, and a
university hospital network, to evaluate the testing trends for the
proposed analytes. We analyzed national testing trends based upon
Medicare Part B payment data \3\ to determine the analytes in each
specialty that are increasingly used for patient diagnosis and/or
management. We concluded that the trends revealed in the data could
continue to show increases in payment for the proposed analytes.
---------------------------------------------------------------------------
\2\ 2009 Truven Health MarketScan[supreg] data, https://truvenhealth.com/your-healthcare-focus/life-sciences/data_databases_and_online_toolsMarkets/Life-Sciences/Products/Data-Tools/MarketScan-Databases.
\3\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698806/.
---------------------------------------------------------------------------
We estimated the 2009 national test volumes based upon two data
sets: (1) Medicare Part B payment statistics (excluding waived
testing); and (2) CCAE. For all analytes under consideration for the
addition to subpart I, we used Current Procedural Terminology (CPT)
codes from claims data. We identified all possible occurrences of a
particular analyte and combined them into one count. For example, if
bicarbonate could be performed in a panel and by itself, we included
all possible occurrences.
A complete count was available for the Medicare Part B data, and no
estimation of total counts was necessary for this sector. MarketScan
data, a sample of approximately 40 million covered individuals, was
necessary to estimate CCAE data and approximately 6.5 million covered
individuals for Medicaid data. Therefore, we estimated the total number
of tests in both categories for the entire United States. The Agency
for Healthcare Research and Quality (AHRQ) data showed that an
estimated total of 181.5 million covered individuals enrolled in CCAE
healthcare insurance; from this we derived a factor of 4.5 (181.5
million individuals/40 million individuals) by which to multiply the
MarketScan CCAE estimates to extrapolate estimates for the entire
United States. Similarly, for the Medicaid estimates, we knew from CMS
data that there were approximately 52.5 million individuals covered by
Medicaid, so we derived a factor of 8.0 (52.5 million individuals/6.5
million individuals) by which to multiply the MarketScan Medicaid
estimates to extrapolate estimates for the entire United States.
We note that these estimates did not account for some inpatient
testing that was paid through capitation arrangements for inpatient
testing. Testing paid directly by patients was also not counted
because, in these cases, CPT codes would not be captured in the data
because there was no request for reimbursement. Even with this
limitation, we believe that these estimates provide a relative sense of
the number of tests being performed annually per analyte. No other
accurate data were available to us.
As noted previously in this section, for the second cut, based upon
our estimates of national testing volumes, we decided that an estimated
national test volume of 500,000 per analyte annually was an appropriate
threshold as most of the analytes listed in subpart I had national
testing volumes above this threshold. Together with the above-described
analytes below the 500,000 threshold that we determined to be
clinically important, this narrowed our list of potential analytes
under consideration for addition to subpart I to 73, representing
analytes in five specialties or subspecialties
c. Impact on Patient and/or Public Health
For the third cut, we considered the evidence available related to
each analyte under consideration to assess patient and public health
impact of
[[Page 41200]]
testing. Because there was no standardized, generally accepted way to
assess this impact on clinical care and public health, we used the
following to get a relative sense of the importance of the analytes
under consideration: a review of published laboratory practice
guidelines (LPGs); a review of critical values; and a review of the
analyte's classification by the Food and Drug Administration (FDA).\4\
We accessed several data sources, including tests listed in the CDC
Guide to Community Preventive Services; \5\ National Healthcare
Priorities/Disparities reports; \6\ clinical practice guidelines
including the National Guideline Clearinghouse (NGC) database available
from AHRQ (https://www.guideline.gov/); critical values available in
publications; and (CAP) Q-Probes.
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\4\ http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfClia/Search.cfm.
\5\ https://www.thecommunityguide.org.
\6\ https://www.ahrq.gov/research/findings/nhqrdr/index.html.
---------------------------------------------------------------------------
In reviewing published LPGs, we hypothesized that if there were a
relatively large number of LPGs available for a particular analyte,
that analyte would be important for health testing. To estimate the
number of LPGs, we used the AHRQ's NGC database. For example, there
were 60 LPGs listed in the NGC for LDL cholesterol, 31 for hemoglobin
A1c, and 27 for troponin, all of which are proposed for addition in
Table 1. However, this approach did not differentiate analytes for
which there were conflicting recommendations. For example, there are
controversies about the value of screening men with prostate specific
antigen (PSA) testing, and there is an ongoing debate about the
prudence of testing vitamin D in asymptomatic adults (Kopes-Kerr,
2013).
To review critical values, which are pre-determined limits for
specific analytes that, when exceeded, may suggest that immediate
clinical intervention is required, we assessed analytes included in
published on ``critical values'' lists. This approach allowed us to
gauge the importance of an accurate result because an incorrect result
could lead to a life-threatening intervention or a failure to
intervene. We reviewed published literature and critical values posted
online from 16 institutions, including small hospitals, university
hospitals, and reference laboratories.
As mentioned earlier in this proposed rule, we also assessed the
clinical impact of an analyte by reviewing its medical device
classification (Class I, II, or III) as categorized by the Food and
Drug Administration's risk classification list. Similarly, we assessed
the public health importance of the eligible analytes by counting the
number of recommendations for testing the analytes from CDC's Morbidity
and Mortality Weekly Report, the Infectious Disease Society of America,
and the Council of State and Territorial Epidemiologists for
surveillance of health conditions related to the particular analyte
under consideration. We found supporting evidence for national
prioritization in some of the following: the U.S. Preventive Services
Task Force,\7\ the National Healthcare Quality and Disparities
Report,\8\ and the CDC Hormone Standardization Program.\9\ For some
analytes that are important to measure towards addressing health
disparities and have public health impact, such as blood lead, we
consulted with subject matter experts in CDC's National Center for
Environmental Health, which promotes national testing and/or has
standardization programs for some priority analytes, specifically
estradiol and testosterone. CMS and CDC used this information to help
determine which analytes should be included in the proposed rule.
---------------------------------------------------------------------------
\7\ https://www.uspreventiveservicestaskforce.org/Page/Name/recommendations.
\8\ https://www.ahrq.gov/research/findings/nhqrdr/index.html.
\9\ https://www.cdc.gov/labstandards/hs.html.
---------------------------------------------------------------------------
After assessing patient and public health impact on a case-by-case
basis for the third cut, we narrowed the analytes down to 34 for
consideration of addition to the proposed list of analytes in subpart
I.
d. Cost and Feasibility of Implementation
For the final analysis to determine whether an analyte would be
proposed for inclusion in subpart I of the CLIA regulations, we focused
on feasibility and costs of conducting PT for each of the remaining 34
analytes under consideration. We provided each of the HHS-approved PT
programs the opportunity to submit comments in writing related to:
inclusion/deletion of analytes, grading schemes, method(s) for
determining target values, evaluating data using peer groups, cost of
including new analytes, and structure of microbiology PT. Analytes for
which it would be difficult for the PT programs to scale up production
to meet the CLIA required frequency of three events per year with five
challenges per event were eliminated from consideration because we
believe that the costs passed down to laboratories to purchase the PT
would be overly burdensome. In other cases, the decisions were based on
the difficulty of finding any suitable PT materials. Some potential
analytes were eliminated because they were too unstable for product
development or shipping or because the testing methodology was not
sufficiently standardized to support PT, such as vitamin D testing.
After assessing the cost and feasibility of implementing PT on a case-
by-case basis, we made the final cut, narrowing the analytes down to 29
potential analytes for the proposed list of analytes in subpart I.
3. Specific Analytes Proposed for Addition to Subpart I
Based upon the sequential process described previously in this
final rule, information received from the PT programs, and consultation
between CDC and CMS, we narrowed the list down to 29 analytes that we
are proposing to add to subpart I of the CLIA regulations (Table 1).
BILLING CODE 4120-01-P
[[Page 41201]]
[GRAPHIC] [TIFF OMITTED] TR11JY22.000
BILLING CODE 4120-01-C
4. Analytes Proposed for Removal From Subpart I
Recognizing that changes in the practice of clinical medicine have
resulted in less frequent use of certain analytes, we used the same
process to review the existing list of analytes in subpart I to
determine which should be retained. In addition to requesting CLIAC's
recommendations, we generally used the same criteria for retention of
an analyte in subpart I as those used for determining which PT analytes
to propose adding; however, as such PT testing was already available on
the market, we did not consider the availability of PT material or the
feasibility of implementation; therefore, we believe that PT programs
already have the mechanism(s) in place to manufacture and ship PT for
these analytes.
5. Process for Ranking and Assessing Existing Analytes and Proposals
for Removal From Subpart I
a. Estimating Nationwide Testing Volume
We generally used the same rationale to select currently required
analytes to propose for deletion. Specifically, we used the same
threshold of 500,000 tests performed annually as an initial criterion
for considering PT analytes. Those estimated to be lower than this
threshold were considered for deletion from required PT. In particular,
we focused on PT for several therapeutic drugs (ethosuximide,
quinidine, primidone, and procainamide and its metabolite, N-acetyl
procainamide). New drugs that are more effective or safer have entered
the market since 1992 and may have replaced the use of therapeutic
drugs that were included in the 1992 regulations. If so, we would
expect to see a continued decline in the volume of testing for the use
of such drugs. In addition to identifying decreases in testing for
these drugs, we looked for probable causes of those decreases. These
decreases in testing could result from new and emerging tests,
including methodologies, replacing older tests, new technology, and
changes to the way that the medical community orders laboratory
testing. For example, the decrease in testing for LDH isoenzymes could
be explained by the increased reliance on better alternative cardiac
markers, especially troponin. For some anticonvulsant drugs, there may
have been changes in medical practice, including alternative drugs and
other treatments, possibly decreasing the need to measure them. We
identified 13 currently required analytes with national test volumes
less than our 500,000 annual test volume threshold.
b. Estimated Impact on Patient and Public Health
For any analyte still under consideration for removal, we performed
literature reviews to determine if testing for alternative analytes or
other diagnostic strategies had begun to supplant testing for the
considered analyte. We took into account testing trends over the past
10 years and we attempted to project
[[Page 41202]]
expected testing trends. We then assessed the critical importance of
candidates for deletion from subpart I based upon the number of
guidelines available in the AHRQ NGC and the same sources used for
considering inclusion in subpart I, bearing in mind that for all
analytes and tests that are not listed in subpart I, laboratories must
demonstrate accuracy twice per year as specified at Sec.
493.1236(c)(1). We also considered the potential impact of deleting
these analytes on clinical medicine and public health. Based on our
literature review and consultation with CDC health experts, we decided
not to propose the elimination of eight analytes based upon their
critical importance for patient testing: carbamazepine, alpha-1-
antitrypsin, phenobarbital, hepatitis B e antigen (HBeAg), antibody
identification, theophylline, gentamicin and tobramycin. These are used
for making important health decisions, for example, diagnosing
hepatitis B (HBeAg), performing crossmatching for blood transfusions
(antibody identification), or assessing compliance with medication for
critically ill asthmatic patients (theophylline).
6. Analytes Proposed for Deletion From Subpart I
Based upon the sequential process described previously in this
final rule, we proposed that the following analytes be deleted from
subpart I: at Sec. 493.931 LDH isoenzymes and at Sec. 493.937
ethosuximide, quinidine, primidone, and procainamide (and its
metabolite, N-acetyl procainamide).
7. Determining Criteria for Acceptable Performance
``Criteria for Acceptable Performance'', as that term is used in
Sec. Sec. 493.923, 493.927, 493.931, 493.933, 493.937, 493.941, and
493.959, is defined by the target value and acceptance limits. Criteria
for acceptable performance is meant for PT scoring only and not
intended to be used to set acceptability criteria for a laboratory's
verification or establishment of performance specifications.
8. Setting Target Values
Under Sec. 493.2, ``target value'' for quantitative tests is
currently generally defined as either the mean of all participant
responses after removal of outliers (those responses greater than 3
standard deviations from the original mean) or the mean established by
definitive or reference methods acceptable for use in the National
Reference System for the Clinical Laboratory (NRSCL) by the National
Committee for the Clinical Laboratory Standards (NCCLS). However, in
instances where definitive or reference methods are not available or a
specific method's results demonstrate bias that is not observed with
actual patient specimens, as determined by a defensible scientific
protocol, a comparative method or a method group (``peer'' group) may
be used. If the method group is less than 10 participants, ``target
value'' means the overall mean after outlier removal (as defined above)
unless acceptable scientific reasons indicate that such an evaluation
is inappropriate.
Based on input from PT programs, we recognize, that peer grouping
is generally the way that target values are set for most analytes.
Therefore, in the proposed rule, we proposed to continue allowing PT
programs to use peer grouping to set the target values. In addition, we
proposed removing the reference to the NRSCL and NCCLS, while retaining
the other options for setting target values.
9. Changing Acceptance Limits
Because there have been improvements in technology resulting in
better sensitivity, specificity, and precision, routinely using peer
grouping to set target values means that the AL that were originally
specified in each specialty and subspecialty of the CLIA `88
regulations in subpart I effectively allow for more tolerant acceptance
criteria for most analytes than would occur if targets were set by a
reference method or overall mean. Based on feedback from several HHS-
approved PT programs, we believe it would be appropriate to update the
ALs to reflect advancements in technology and analytical accuracy since
the PT regulations were implemented in 1992. While narrowing limits may
increase miss rates per challenge, we do not expect a high unsuccessful
rate based on the data simulations provided by the PT programs. We
expect the rates of unsatisfactory events would be low based on the
simulation data and that the rates of unsuccessful events (two
consecutive or two out of three testing events being unsatisfactory)
would be even lower; therefore, we believed it was reasonable to
propose tighter limits given current analytic accuracy. We used all
data available to us to minimize the negative consequences of the
proposed changes (for example, too many unsuccessful performances) to
acceptance limits, including simulations provided by PT programs.
10. Changes to Percentage Acceptance Limits (ALs)
a. Basis for Using Fixed Percentage PT ALs
Currently, the CLIA regulations at Sec. Sec. 493.927(c)(2),
493.931(c)(2), 493.933(c)(2), 493.937(c)(2), and 493.941(c)(2)
prescribe a variety of ALs, including: a multiple of the SD of results
from the mean of other participants in the peer group; fixed limit as a
percentage of the assigned value; fixed limit in concentration units;
and a mixture of percentage and concentration units, depending on the
concentration of the analyte. For all new and currently required non-
microbiology analytes, we proposed to use fixed ALs, preferably as
percentage limits rather than concentration units.
There are 53 analytes (existing or proposed) for which we proposed
a percentage-based AL, for which biological variability data were
published. There were no biological variability data for several
analytes (for example, therapeutic drugs). Where there were such data,
we used AL to get as close to, or below, an accuracy goal for the test
that was based on biological variability data. Then we simulated
several percentage-based ALs to see if their results would have passed
or failed at each simulation. We wanted to get miss rates (that is,
percent of laboratories that did not meet the criteria for acceptable
performance per PT challenge) of somewhere in the 1 to 2 percent range
as was observed in the data provided by the PT programs for current
ALs. Of the 53 analytes, 34 of the proposed ALs were tighter than or
equal to biological variability limits. For 19 analytes, the limits we
are proposing are looser (greater) than the limits required to meet
accuracy based upon biological variability. For these 19 analytes,
using ALs based on biological variability would be untenable because
the current analytical accuracy for such testing would not be expected
to meet such limits. White blood cell differential is the only
remaining analyte that would have ALs in SD. In this case there were no
biological variability data available.
In general, fixed ALs, either in percentages or concentration
units, are preferred to SDs for PT for several important reasons: they
can be tied directly to objective goals for performance, such as goals
for analytical accuracy and technical expectations; they are constant
in all PT events and do not vary because of statistical randomness,
masked outliers, or small sample size; they assure the same evaluation
criteria are used by all PT programs and discourage opportunities
[[Page 41203]]
for participants to ``shop'' for PT programs with less stringent
criteria for which it is easier to achieve acceptable performance; they
do not unfairly result in tighter effective ALs for peer groups that
use analyzers that have tighter analytical precision; they can combine
a fixed percentage and a fixed absolute concentration to allow for more
robust evaluation while also fairly evaluating low analyte
concentrations; and they are commonly used worldwide in other PT and
external quality assessment programs.
Our analysis of existing PT and external quality assessment
programs showed that ALs using two or three SDs have been used in PT in
a wide variety of settings for several reasons, such as: limited
experience with PT or matrix effects for a particular analyte; lack of
consensus on criteria for acceptable performance; inertia with no
compelling pressure for change; and analytical performance so poor that
multiples of the overall SD are considered to be the only fair
approach. We believe all of these reasons to some extent contributed to
initial reliance on SD limits for certain analytes when CLIA `88 was
implemented. We also note that while regulations promulgated under CLIA
`67 used ALs of three SD for several analytes, regulations finalized
under CLIA`88 replaced these with fixed limits and PT programs
successfully made the transition. Therefore, we believe it is likely
that the proposed changes from SD-based ALs to fixed ALs will not be
problematic.
Therefore, as discussed in section II.B. of the proposed rule, we
proposed to amend certain analytes in Sec. Sec. 493.927, 493.931,
493.933, 493.937, and 493.941 to include fixed ALs with or without
percentages. Three analytes have only concentration-based ALs (that is,
no percentage-based ALs): pH, potassium, and sodium.
b. Adding Fixed Concentration Units to Fixed Percentage Units
A percentage-based criterion can be unnecessarily stringent at low
concentrations--either because of technical feasibility or because
medical needs at the low concentration do not require such tight
precision. Thus, when percentage-based fixed criteria are used for ALs,
it may be necessary to place a minimum on the percentage as currently
occurs with the criterion for acceptable performance for glucose (Sec.
493.931) for which the AL switches from 10 percent to 6 mg/dL below a
concentration of 60 mg/dL. The combined ALs direct PT programs to score
with whichever of the specifications is more tolerant; at lower limits
of the analytical range this will be the fixed concentration limit.
Therefore, to allow for fairer and more realistic ALs, we proposed to
use combinations of percentage and concentration limits as appropriate.
These combination limits are similar to limits that already exist in
CLIA `88 regulations for glucose and other analytes.
Therefore, we proposed to amend certain analytes in Sec. Sec.
493.927, 493.931, 493.933, 493.937, 493.941, and 493.959 to include
percentage-based ALs with or without additional fixed ALs.
c. Establishing ALs Based on Analytical Accuracy Goals for Proposed New
and Several Current Analytes
For the newly proposed analytes and several current analytes for
which current ALs are in units other than percentages such as three SDs
or concentration units, we proposed to change the ALs to percentages.
Over the years, there have been many proposed criteria for establishing
goals for analytical performance. The various possible approaches were
reviewed and a hierarchy was established based on a 1999 consensus
conference. These strategies were reconsidered at the 2014 European
Federation of Clinical Chemistry and Laboratory Medicine Strategic
Conference in Milan. Participants in both conferences acknowledged that
the ability of a test method to meet clinical needs is the highest
priority, and the most defensible approach would be clinical trials in
which patient outcomes could be compared using different analytical
accuracy goals. This approach was not feasible for many reasons.
Although clinical outcomes studies would be the most rigorous basis for
establishing analytical performance goals, these are seldom possible,
leaving the natural dispersion of levels for each analyte (biological
variability) as the next best scientifically defensible approach for
establishing analytical accuracy goals. The less the biological
variability, the more stringent the analytical accuracy needs to be.
This approach makes sense for two of the most important reasons to
conduct patient testing: diagnosis of disease, that is, differentiating
an abnormal result from a normal one, and monitoring a patient's
progress during treatment. In the former case, we believe that the
``within-group'' biological variability is the important limiting
factor defining an appropriate error goal for a test method.
Furthermore, we believe the most important factor for monitoring
progress is the ``within individual'' variability. It was not possible
for us to differentiate how analytes are being used or will be used
clinically, with respect to diagnosis versus monitoring. Therefore, we
accounted for both needs and used an approach that accounted for both
kinds of biological variability to estimate analytical accuracy goals
as the basis for our proposals for acceptance limits in percentages.
The advantage of using analytical accuracy goals that are expressed in
terms of percentages is that they can be directly related to ALs in a
mathematical way expressed as percentages.
We have assumed that a laboratory that can meet the clinical needs
for test accuracy based upon biological variability should perform
successfully on PT most or all of the time. Therefore, whenever
possible, we have used publicly available estimates of allowed total
error based upon estimates of biological variability to approximate the
proposed AL. CDC has shown in a recent poster \10\ that it is possible
to design ALs based upon such accuracy goals, and it is possible to
simulate the ability of a PT program to identify laboratories that
cannot meet such goals, while minimizing the likelihood of
misidentifying laboratories that are meeting analytical accuracy goals
based upon biological variability.
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\10\ Astles, Tholen, and Mitchell, 2016, https://www.aacc.org/science-and-practice/annual-meeting-abstracts-archive.
---------------------------------------------------------------------------
Therefore, we proposed to amend ALs for certain current analytes as
well as establish ALs for analytes proposed for addition in Sec. Sec.
493.927, 493.931, 493.933, 493.937, 493.941 and 493.959 based on
analytical accuracy goals.
d. Tightening Existing Percentage ALs as Needed
There have been significant improvements in laboratories'
performance in PT for the great majority of analytes and PT
unsatisfactory rates have dropped for all types of laboratories. The
improvements are such that, for many analytes, laboratories that began
to use PT to comply with CLIA `88 now perform as well as the hospital
and independent laboratories that were previously required to perform
PT under CLIA `67. Howerton, et al., showed that for almost all
analytes examined, PT performance improved somewhat after CLIA `88 was
implemented, but the improvements were greater for laboratories that
were not previously required to perform PT. The rates of unsatisfactory
PT are now roughly the same for analytes listed in subpart I,
regardless of the laboratory type. This is consistent with CLIA's
intent to ensure accurate clinical testing regardless of the setting
where testing is performed. There are several factors
[[Page 41204]]
contributing to the improvements in PT performance, including improved
analytical methods being used in all settings, technological advances
resulting in improved precision, sensitivity and specificity, and
increased familiarity with handling preparation, and reporting of PT
samples. Therefore, for the reasons above as well as supporting
simulation data date from the PT programs, we proposed to make criteria
for acceptable performance for existing analytes listed in subpart I
(Sec. Sec. 493.927, 493.931, 493.933, 493.937, 493.941 and 493.959)
tighter, so they are in closer agreement with analytical accuracy goals
which are based upon biological variability and simulation data.
e. Simulating the Impact of New ALs on Unacceptable Scores for
Challenges and Unsatisfactory Rates for Events
We evaluated a very specific PT data set to help set appropriate
limits. The total simulations reproduced PT that covered 2 years,
representing 30 challenges (three events per year; five challenges per
event; 2 years) of each proposed new analyte and for the analytes for
which we propose to modify ALs. We reviewed the aggregated percentage
of unacceptable scores for each PT challenge using retrospective data.
We then reviewed the simulation data which applied two or three new ALs
for each of 84 analytes (consisting of 27 new analytes and 57 existing
analytes). Based on the simulation data, we were able to make informed
decisions to help us create or adjust the ALs.
Based upon our analysis of the simulation results, we further
refined the proposed ALs and added potential absolute concentrations in
lieu of percentage ALs, as was described previously in this final rule.
We then requested narrowly tailored data from PT programs as described
previously in this final rule using retrospective PT data and peer
group data for scoring, as they ordinarily would do. We focused on
unsatisfactory scores with the data so that we could calculate the
unsatisfactory rate per analyte among all participating laboratories
that might occur with each proposed AL. The final simulations were
conducted by several of the PT programs and this set of data was used
to determine the proposed ALs.
We compared the unacceptable scores for each challenge and each
proposed AL to determine at which concentrations it would be necessary
to switch to a fixed concentration AL. Using this approach, we were
able to identify an AL for each analyte and, in some cases, an
additional concentration-based AL. This approach enabled us to identify
an AL that would be sensitive enough to identify poor-performing
laboratories, yet not so sensitive that it will incorrectly identify
laboratories that likely meet requirements for accuracy.
f. Limitation in Our Ability To Predict the Number of New
Unsatisfactory and Unsuccessful Scores
It is not possible for us to predict the precise effect of the
proposed changes on the number of unsatisfactory and unsuccessful
scores. The occurrence of an unsatisfactory score for a PT event
depends upon at least two of five challenges being graded as
unacceptable or outside the criteria for acceptable for performance. PT
programs select different combinations of samples for each event and it
is impossible to predict how their selection could be modeled
statistically. Finally, the distribution of unsatisfactory and
unsuccessful PT scores is not randomly distributed across all
participants.
++ Sections 493.923(a), 493.927(a), 493.931(a), 493.933(a),
493.937(a), 493.941(a), and 493.959(b): We proposed to amend these
provisions to remove the option that PT samples, ``at HHS' option, may
be provided to HHS or its designee for on-site testing''.
++ Section 493.927: We proposed to amend the criteria for
acceptable PT performance to permit scoring of quantitative test
results for the following immunology analytes: antinuclear antibody;
antistreptolysin O; rheumatoid factor; and rubella. For these analytes,
we have determined that there are one or more test systems that
currently report results in quantitative units; therefore, we added ALs
based on percentages or target values in addition to retaining the
qualitative target values. We proposed to make this allowance in CLIA
for reporting PT which reflects current practice.
++ Section 493.931(b): We proposed making a technical change to the
description for creatine kinase isoenzymes to be CK-MB isoenzymes,
which may be measured either by electrophoresis or by direct mass
determination.
++ Section 493.933: We proposed adding the following analytes:
estradiol, folate (serum), follicle stimulating hormone, luteinizing
hormone, progesterone, prolactin, parathyroid hormone, testosterone,
and vitamin B12.
++ Section 493.937(a): We proposed revising this provision by
including the requirement that annual PT programs must provide samples
that cover the full range of values that could occur in patient
specimens. We proposed this amendment so that PT programs must provide
samples across a toxicology sample's entire reportable range rather
than just provide samples within a sample's therapeutic range.
++ Section 493.941: We differentiated the criteria for units of
reporting of the analyte prothrombin time. We proposed to amend the
criteria for acceptable performance to reflect both in seconds and/or
INR (international normalized ratio) and to add the requirement that
laboratories must report prothrombin time for PT the same way they
report it for patient results. We also proposed to add criteria for
acceptable performance for directly measured INR for prothrombin time.
Additionally, we proposed to require laboratories performing both cell
counts and differentials to conduct PT for both (that is, the ``or''
would be changed to an ``and''). Finally, we proposed changing the
criteria for acceptable performance for ``cell identification'' from 90
percent to 80 percent. We proposed this change as the requirement of
five samples per event does not allow for a score of 90 percent (that
is, five samples would allow for scores of zero percent, 20 percent, 40
percent, 60 percent, 80 percent, or 100 percent). PT for cell
identification is currently required in Sec. 493.941. Further, Sec.
493.851(a) states that ``failure to attain a score of at least 80
percent of acceptable responses for each analyte in each testing event
is unsatisfactory performance for the testing event.'' If the
requirement for acceptable performance remains at 90 percent, a
laboratory can only have satisfactory performance if they receive 100
percent; however, Sec. 493.851(a) allows satisfactory performance for
both 80 percent and 100 percent.
++ Section 493.959: We proposed changing the criteria for
acceptable performance for unexpected antibody detection from 80
percent accuracy to 100 percent accuracy. We proposed this change
because it is critical for laboratories to identify any unexpected
antibody when crossmatching blood in order to protect public health and
not impact patient care.
++ Sections 493.923(b)(1), 493.927(c)(1), 493.931(c)(1),
493.933(c)(1), 493.937(c)(1), 493.941(c)(1), and 493.959(d)(1): We
proposed amending these provisions to clarify that to achieve
consensus, PT programs must attempt to grade using both participant and
referee laboratories before determining that the sample is ungradable.
We believe that this change will enhance consistency among the PT
programs when grading samples. The current regulations noted previously
[[Page 41205]]
allow for scoring either with participants or with referees before
calling a sample ungradable.
C. Additional Proposed Changes
We proposed to amend Sec. 493.2 by modifying the definition of an
existing term and defining new terms as follows:
Target value: We proposed removing the reference to NRSCL
and NCCLS and retaining the other options for setting target values in
this final rule.
Acceptance Limit: We proposed defining this term to mean
the symmetrical tolerance (plus and minus) around the target value.
Unacceptable score: We proposed defining this term to mean
PT results that are outside the criteria for acceptable performance for
a single challenge or sample.
Peer group: We proposed defining this term as a group of
laboratories whose testing process utilizes similar instruments,
methodologies, and/or reagent systems and is not to be assigned using
the reagent lot number. PT programs should assign peer groups based on
their own policies and procedures and not based on direction from any
manufacturer.
We proposed the following revisions to the regulation text at
subpart A:
Sections 493.20 and 493.25: We proposed to amend the
regulations to reflect that if moderate and high complexity
laboratories also perform waived tests, compliance with Sec.
493.801(a) and (b)(7) are not applicable. However, we proposed to
continue to require compliance with Sec. 493.801(b)(1) through (6) to
align the regulations with the CLIA statute (42 U.S.C. 263a (i)(4)),
which does not exclude waived tests from the ban on improper PT
referral.
We proposed to revise the regulation text at subpart H:
Section 493.861: We proposed amending the satisfactory
performance criteria for failure to attain an overall testing event
score for unexpected antibody detection from ``at least 80 percent'' to
``100 percent.'' We proposed this change because it is critical for
laboratories to identify any unexpected antibody when crossmatching
blood to protect the public health and not impact patient care.
We proposed to revise the regulation text at subpart I:
Section 493.901(a): We proposed to require that each HHS-
approved PT program must have a minimum of 10 laboratory participants
before offering any PT analyte. We recognize that PT programs do not
grade results when there are fewer than 10 laboratory participants.
This would require the laboratory to perform additional steps to verify
the accuracy of their results. If at any time a PT program does not
meet the minimum requirement of 10 participating laboratories during
the reapproval process for an analyte or module, HHS may withdraw
approval for that analyte, specialty, or subspecialty. This change
reduces some burden on laboratories that have incurred the expense of
enrolling in a PT program but do not receive a score or receive an
artificial score requiring the laboratory to take additional steps to
verify the accuracy of the analyte as required by Sec. 493.1236(b)(2).
Section 493.901(c)(6): We proposed to add the requirement
that PT programs limit the participants' online submission of PT data
to one submission or that a method be provided to track changes made to
electronically reported results. Many PT programs currently allow
laboratories an option to report PT results electronically, while some
other PT programs only allow laboratories to report PT results
electronically with no other option such as facsimile or mailed PT
submission forms. However, at this time, the PT programs that do
participate in the online reporting have no mechanism to review an
audit trail for the submitted result. In some cases of PT referral, it
has been discovered that laboratories have sent PT samples to another
CLIA-certified laboratory for testing, received results from the other
laboratory, and then changed their online reported results to the PT
program since those results can be modified up until the PT event close
date. In an effort to assist in PT referral investigations and
determinations, an audit trail that includes all instances of reported
results would aid in determining if a laboratory compared PT results
obtained from another laboratory and changed their previously submitted
results.
Section 493.901(c)(8): We proposed to add to the
requirement previously found at Sec. 493.901 that contractors
performing administrative responsibilities as described in Sec. Sec.
493.901 and 493.903 must be a private nonprofit organization or a
Federal or State agency or nonprofit entity acting as a designated
agent for the Federal or State agency. Several PT programs have divided
their administrative and technical responsibilities into separate
entities or have had the administrative responsibilities performed by a
contractor. We were made aware that administrative responsibilities
were being performed by a for-profit entity. Because the CLIA statute
(42 U.S.C. 263a(f)(3)(C)) requires PT programs to be administered by a
private nonprofit organization or a State, we are proposing to amend
Sec. 493.901 to state that all functions and activities related to
administering the PT program must be performed by a private nonprofit
organization or State.
Section 493.901(e): We proposed the requirement that HHS
may perform on-site visits for all initial PT program applications for
HHS approval and periodically for previously HHS-approved PT programs
either during the reapproval process or as necessary to review and
verify the policies and procedures represented in its application and
other information, including, but not limited to, review and
examination of documents and interviews of staff.
Section 493.901(f): We proposed an additional requirement
to the regulation that specifies we may require a PT program to reapply
for approval using the process for initial applications if widespread
or systemic problems are encountered during the reapproval process. The
initial application for the approval as an HHS PT program requires more
documentation in the application process than that which is required of
PT programs seeking HHS reapproval.
Section 493.903(a)(3): It has come to our attention that
PT programs may have on occasion modified a laboratory's PT result
submission by adding information such as the testing methodology which
was inadvertently omitted by the laboratory. Therefore, we proposed
adding the requirement that PT programs must not change or add any
information on the PT result submission for any reason, including, but
not limited to, the testing methodology, results, data, or units.
Section 493.905: We proposed adding that HHS may withdraw
the approval of a PT program at any point in the calendar year if the
PT program provides false or misleading information that is necessary
to meet a requirement for program approval or if the PT program has
failed to correct issues identified by HHS related to PT program
requirements. We also proposed adding a requirement that the PT program
may request reconsideration should we determine that false or
misleading information was provided if the PT program has failed to
correct issues identified by HHS related to PT program requirements.
III. Analysis of and Responses to Public Comments
We received 107 public comments in response to the February 4,
2019,
[[Page 41206]]
proposed rule. The commenters represented individuals, PT programs,
accreditation organizations, laboratory professional organizations, and
businesses, including in vitro diagnostics manufacturers. Commenters
were generally supportive of the proposed changes, and some noted that
these changes would increase flexibility and be a positive change for
both laboratories and PT programs, especially in the specialty of
microbiology. A few commenters recommended clarification of proposed
changes or suggested specific changes, including alternative language,
to the proposed requirements. After analyzing the comments received, we
have modified or deleted several provisions in this final rule. A few
commenters raised issues that are beyond the scope of our proposals. We
are not summarizing or responding to those comments in this final rule.
However, we reviewed the comments to consider whether to take other
actions, such as revising or clarifying the CLIA program operating
instructions or procedures, based on the information or recommendations
in those comments. Our responses to specific comments are as follows:
A. Delayed Effective Date and Ongoing Process for Updating PT
Regulations (Sec. Sec. 493.2 and 493.801 Through 493.959)
Comment: Several commenters requested that there be a delayed
effective date or phase in approach for implementation of the updated
PT requirements to give all affected constituents time to accommodate
the changes. Two commenters suggested that CMS develop an ongoing
process to make changes to the PT regulations to ensure timely
implementation of the updates.
Response: We recognize that time will be needed for laboratories,
PT programs, accreditation organizations, exempt States, and surveyors
to adopt the updated PT requirements related to subparts H and I. As
such we are delaying the effective date of the revisions to Sec. Sec.
493.2 and 493.801 through 493.959 until 2 years after the publication
of this final rule in the Federal Register. The delayed effective date
reflects the timeframe that we believe PT programs will need to produce
the PT samples to meet the revised regulations and incorporate any
updates to PT reporting requirements. In addition, laboratories will
need to implement the new PT requirements after the samples are
available from the PT programs. We encourage laboratories to enroll in
the new and revised analytes prior to the delayed effective date. We
also appreciate the commenters' suggestions for a process to address
needed PT changes more quickly on an ongoing basis. We will consider
possible ways to streamline the process going forward in light of the
required timeframe for rulemaking. We note that the regulations related
to laboratories performing tests of moderate complexity and high
complexity testing that also perform waived testing and proficiency
testing enrollment, Sec. Sec. 493.20 and 493.25, respectively, will be
effective 30 days after the publication date of this final rule.
B. Definitions (Sec. 493.2)
Comment: A commenter stated that the term ``unacceptable score,''
as defined at Sec. 493.2, was confusing and should be replaced with
``unacceptable result.'' Other commenters pointed out that the
organization of sub-bullets under the definition of ``target value''
was incorrect as the content in (iv) does not belong under (1), but
should be included as (2) under the definition.
Response: We agree with commenters that the term ``unacceptable
score'' could be confusing because it could be interpreted to mean a
total analyte event score rather than the intended meaning of referring
to a single challenge or sample result. Since this term is not included
in the CLIA regulations except for the proposed amendments to Sec.
493.2, we are not finalizing this term in Sec. 493.2 in this final
rule. With respect to the proposed definition of ``target value'', we
agree with the commenter about the paragraphs included under that
definition and are making the recommended change in this final rule.
Comment: While several commenters supported the inclusion of a
definition for ``peer group'' in the proposed rule, other commenters
expressed concerns about our proposal. Three commenters approved of our
proposal to disallow peer-grouping to the reagent lot level, while two
commenters did not agree with the proposal. One commenter noted that
matrix effects, known to cause PT materials to behave differently from
unmodified patient samples, are the reason underlying the need to use
peer grouping to set target values and grade PT results. This commenter
was concerned that the final rule would not account for the existence
of matrix effects by not allowing peer grouping. One commenter
suggested we consider conducting a scientific study to assess the
contribution of calibration errors versus matrix effects in causing
differences in PT results.
Response: In response to the comments about peer-grouping to the
reagent lot level, PT is one of the important ways to detect problems
in FDA-cleared/approved test methods. Differences between reagent lots
used during testing may occur due to the manufacturing process.
Allowing peer grouping to the lot level may inhibit the detection of
these problems. We are not prohibiting PT programs from interacting
with manufacturers to discover problems with reagent lots. However, the
PT program has the responsibility for interpreting correct PT results.
If a PT program determines that a specific reagent lot failure
occurred, it should inform the affected laboratories and manufacturer.
Concerning the comment about matrix effects, currently CLIA requires PT
programs to demonstrate through a scientific protocol that bias, such
as matrix effects, existed in PT materials before allowing peer-
grouping to grade results. We are aware that PT programs have typically
not used a scientific approach to determine if a peer group should be
used as the process of demonstrating matrix effects is expensive and
time-consuming. This rule finalizes the proposed definitions for both
``peer group'' and ``target value'' and will continue to allow peer-
grouping for evaluation of PT results, without requiring prior
demonstration of matrix effects. We do not expect there will be a
change in how peer groups are identified by PT programs. Therefore,
there will be no change in how target values are determined based upon
the mean of peer group results. In response to the proposed study of
commutability to demonstrate differences in PT results based on
calibration errors, the comment is outside the scope of this final
rule.
Comment: Two commenters suggested that CLIA should not require
removal of outliers using a three standard deviation (3 SD) criterion
when grading PT, as required under the proposed definition of target
value in Sec. 493.2. One commenter noted that the requirement to
remove outliers was done to get a better estimate of the SD, which
would only apply to one analyte after the final rule is effective. The
other commenter stated that outlier removal using a 3 SD limit is not
recommended according to ISO 13528:2015. Both commenters noted the need
for robust methods to remove outliers, which can be especially
problematic when the PT peer group is very small, such as a group that
includes only 5 to 20 results.
Response: It is important that outliers be removed to set target
values. Because a spurious PT result, including one due to a
transcription error, could affect the peer group mean, especially when
the peer group has relatively few laboratory
[[Page 41207]]
participants, PT programs should continue to discard aberrant results
when calculating the peer group target. At this time, we do not have
sufficient information to provide additional or alternative options for
outlier removal. However, we recognize the need for PT programs to have
valid modern approaches for outlier removal. Therefore, we are
retaining the requirement to remove outliers as described in the
definition for target value, using a 3 SD criterion. Regarding the
comment referencing ISO requirements, we note that ISO standards do not
apply to CLIA.
Summary of Final Actions
We did not receive any comments on the proposed definition
of ``acceptance limit'' and are finalizing the definition with a
clarifying technical edit.
Based on the public comments received, we are finalizing
the proposed definition of ``peer group'' with a clarifying technical
edit.
We are revising and finalizing the proposed definition for
``target value.'' We have corrected the organization of the paragraphs
and have moved the content of subparagraph (iv) to paragraph (2).
We are not finalizing the proposed definition of
``unacceptable score.''
C. Enrollment and Testing of Samples (Sec. Sec. 493.20(c) and
493.25(d))
Comment: A number of commenters expressed concerns or requested
clarification about the proposal to amend Sec. Sec. 493.20(c) and
493.25(d) to reflect that if laboratories certified to perform moderate
and high complexity testing, respectively, also perform waived tests,
compliance with Sec. 493.801(a), which requires enrollment in PT, and
(b)(7), requiring PT for the primary method of patient testing, are not
applicable for the waived tests. However, as proposed, if laboratories
voluntarily enrolled in PT for their waived testing, Sec.
493.801(b)(1) through (6) would apply in cases of improper PT referral
for those tests. Commenters expressed that laboratories may be
discouraged from voluntarily enrolling in PT for waived tests if the
possibility of sanctions for referred PT existed. Two commenters
recommended that PT should be required for all testing, including
waived testing. One commenter requested clarification of whether
laboratories would need to verify the accuracy of waived tests twice
per year.
Response: Subsection (d)(2)(C) of the CLIA statute states that
subsections (f) and (g) shall not apply to a laboratory issued a
Certificate of Waiver. Subsection (f) is related to issuing standards
that, at a minimum, allow a laboratory to consistently perform testing
to ensure accurate and reliable test results, including the requirement
for all laboratories that perform nonwaived testing to enroll in an
approved PT program and to verify the accuracy of tests twice per year.
Subsection (g) speaks to inspecting laboratories for compliance with
subsection (f) and are generally done on a biennial basis. However,
sanctions related to PT referral are in subsection (i), which is not
limited to nonwaived laboratories but rather allows sanctions to be
taken against ``any laboratory'', including a Certificate of Waiver
laboratory, that intentionally refers PT samples to another laboratory.
Some Certificate of Waiver laboratories and other laboratories that
perform waived testing have voluntarily chosen to enroll in PT for
waived testing over the history of the CLIA program to ensure the
quality of their testing. We have no reason to believe these
laboratories will be discouraged from continuing their enrollment in
PT. As a result, we are finalizing the new requirements at Sec. Sec.
493.20(c) and 493.25(d) to ensure that the CLIA regulations align with
the statute.
Summary of Final Actions
We are finalizing the proposed revisions at Sec. Sec.
493.20(c) and 493.25(d).
We are finalizing the proposed revisions at Sec. Sec.
493.801 and 493.861. Section 493.801 will require laboratories to
report PT results for microbiology organism identification to the
highest level that they report results on patient specimens. Section
493.861 will amend the satisfactory performance criteria for failure to
attain an overall testing event score for unexpected antibody detection
from ``at least 80 percent'' to ``100 percent.'' We received no
comments on the proposed revisions at Sec. Sec. 493.801 and 493.861.
D. PT Program Approval and Administration (Sec. Sec. 493.901, 493.903,
493.905)
Comment: Two commenters urged CMS not to change the current codes
used for specific analytes when PT programs report PT results to CMS
and to create new codes for the analytes being added.
Response: We understand the commenters to be referring to certain
analyte-specific codes that are used as an internal data system
designation for PT programs to report PT analyte results to us.
Although these codes are not explicitly referenced in the regulations,
we agree with the commenters and note that the current analyte-specific
codes for PT will remain the same. New analyte-specific codes will be
generated for the newly required PT analytes.
Comment: Many commenters remarked on the requirement proposed at
Sec. 493.901(a) having at least 10 laboratory participants for an
analyte before a program is approved to offer that analyte. Commenters
stated that this requirement could inhibit development of new PT, and
be detrimental to both laboratories and PT programs, especially smaller
programs, which could find it harder to compete. Some commenters
pointed out that PT programs offering newly required analytes would
naturally have relatively fewer participating laboratories. One
commenter requested clarification on whether this requirement would
apply only to newly required analytes or to all PT analytes. Some
commenters pointed out that PT programs may not initially know how many
laboratories would enroll, and the programs would need time to develop
their market. One commenter stated that this requirement would be a
burden and result in more ungraded events.
Response: The requirement for at least 10 laboratory participants
would only apply for PT analytes required in subpart I, and therefore,
should not impact the development of PT for new or emerging analytes to
the extent that they are not listed in subpart I. We realize that PT
programs seeking HHS approval for the first time may not know how many
laboratories would enroll in their program, and we did not intend to
require at least 10 laboratory participants when PT programs apply for
initial approval. We intend to review the number of laboratory
participants for each program and each HHS-approved analyte during the
annual reapproval process. If a PT program has fewer than 10
participants, we may not reapprove the PT program for a specific
analyte. As a result of the comments, in this final rule, we are
clarifying the requirement at Sec. 493.901(a) to state ``for each
specialty, subspecialty, and analyte or test for which the proficiency
testing program is seeking reapproval'' to better reflect the PT
approval process.
Comment: A number of commenters representing several PT programs
and accreditation organizations commented on the requirement proposed
at Sec. 493.901(c)(6) that for those results submitted electronically,
a mechanism to track changes to any result reported to the proficiency
testing program and the reason for the change. There was general
opposition due to perceived burden and expense, both to PT
[[Page 41208]]
programs and laboratories, and possibilities for errors. Some
commenters stated that they are currently unable to know when every PT
result is entered or changed if done electronically based on the
technology used for laboratories to submit results. There were also
questions about the circumstances under which PT programs would be
required to provide audit trails. One commenter agreed with this
proposed change but recommended that we provide more guidance to
laboratories on how to meet this requirement.
Response: We appreciate the information provided by the commenters
expressing the challenges with meeting this requirement. We do require
laboratories to maintain documentation of their submissions to PT
programs (see Sec. 493.801(b)(5)). However, based on the comments
received, we are not finalizing the requirement proposed at Sec.
493.901(c)(6).
Comment: Several commenters expressed concerns about the
requirement proposed at Sec. 493.901(c)(9) that a contractor
performing administrative responsibilities as described in Sec. Sec.
493.901 and 493.903 must be a private nonprofit organization or a
Federal or State agency, or an entity acting as a designated agent for
the Federal or State agency. A commenter noted that many essential PT
program functions are currently performed by for-profit entities or
subcontractors. There was a general consensus among commenters that
many important administrative functions could not be performed without
contractual arrangements with for-profit entities, such as
transportation services.
Response: We recognize that some functions required as part of the
PT process, such as transportation services, are provided by for-profit
entities. Other business functions may also be provided by for-profit
contractors, such as obtaining and manufacturing the PT specimens/
products, initial testing to establish approximate target values as
prescribed by the PT program, aliquoting and labeling samples, testing
to assure homogeneity and stability of samples, long-term storage of
samples for use in future PT events, and storage of aliquoted PT
samples for additional testing as may be requested by the clients, or
required by us. Also, ``for-profit'' entities can be used or contracted
for distributing/mailing out the PT kits to the laboratories. This
proposed requirement was not intended to address those aspects of PT
program operations, but rather the technical and scientific
responsibilities as described in Sec. Sec. 493.901 and 493.903. These
technical and scientific responsibilities include, but are not limited
to, processes for selecting appropriate target values to be included in
challenges as part of the annual PT program or grading PT results,
determining target values, reporting scores to CMS, and determining
organisms included in microbiology PT samples. In an effort to clarify
the intent of the proposed requirement, we are changing
``administrative responsibilities'' to ``technical and scientific
responsibilities'' in the provision being finalized at Sec.
493.901(c)(8), previously proposed at Sec. 493.901(c)(9).
Comment: While commenters agreed with the requirement proposed at
Sec. Sec. 493.901(e) to allow HHS to require on-site visits as part of
the initial approval of PT programs, they indicated the need for
sufficient advance notice of an on-site visit. Also, there were two
suggestions to use an independent third party if on-site visits were to
be conducted.
Response: We would coordinate the timing of the visit with the PT
program and generally provide advance notice of the on-site visit. On-
site visits will be conducted by CMS, and not by a third party. As a
result, we are finalizing the new requirement at Sec. 493.901(e) as
proposed.
Comment: We received comments concerning the requirement proposed
at Sec. 493.901(f) that HHS may require a PT program to reapply for
approval using the process for initial applications if significant
problems are encountered during the reapproval process. While no
commenters disagreed with the proposed requirement, one commenter
requested that we use this option sparingly, and another commenter
requested clarification on when this option would be used.
Response: We intend to use this option cautiously and only when
issues arise that we consider be significant, for example, complaints
of quality issues related to the PT program. As a result, we are
finalizing the new requirement at Sec. 493.901(f).
Comment: Commenters suggested clarification was needed regarding
the requirement proposed at Sec. 493.903(a)(3) that PT programs must
not change or add any information on the PT result submission. They
requested clarification on what data could not be changed, noting that
some changes, such as adding or changing a method code, would not
necessarily affect test results submitted but would be important for
appropriate peer grouping. Commenters expressed concern that PT
programs would not be able to add a methodology if inadvertently left
off by the laboratory, thus affecting appropriate peer grouping.
Commenters questioned if exceptions might be made if errors were made
by the PT program and not the laboratory.
Response: As explained in the proposed rule (84 FR 1536, 1547), it
is not appropriate for a PT program to change or add information on the
PT result submission from a laboratory, including, but not limited to,
the testing methodology, results, data, or units. If a laboratory
inadvertently enters the wrong methodology or omits a methodology, the
PT program should not assume to know the correct methodology and make
that change or addition. We would consider it acceptable for the PT
program to enter the methodology in cases where the PT program form
does not include the methodology used by the laboratory for testing and
the laboratory has manually written the methodology on the result
submission form. This would also apply to units of measure. Under no
circumstances should a PT program change a laboratory's submitted
result. It is the laboratory's responsibility to provide correct and
complete information and to investigate and correct errors that lead to
PT failures. As a result, we are finalizing the requirement at Sec.
493.903(a)(3) as proposed.
Comment: Commenters expressed concerns regarding the potential
impact on laboratories and PT programs of the requirement proposed at
Sec. 493.905(a) allowing HHS to withdraw the approval of a PT program
at any point in the calendar year if the PT program provides false or
misleading information required for program approval or if the PT
program fails to correct issues identified by HHS related to PT program
requirements.
Response: We may withdraw approval of the PT program if HHS
determines the PT program fails to meet any of the required criteria
for approval. After we withdraw approval of a PT program, approval of
the PT program would remain in effect for 60 days from the date of
written notice to the PT program of this action. A PT program will be
required to notify all of its participating laboratories of our
withdrawal of approval within 30 days from the date of written notice
to the PT program. We believe the 30-day notification by the PT program
in this situation, and the additional 30 days before approval is
withdrawn, gives laboratories sufficient time to enroll in an
alternative PT program. PT programs may request reconsideration from us
in accordance with subpart D of part 488 regarding the
[[Page 41209]]
withdrawal of approval if the false or misleading information or issues
identified by us have been addressed within 60 days. We believe that
the 60-day timeframe gives the PT programs sufficient time to mitigate
any issues related to withdrawal of approval.
Summary of Final Actions
We are finalizing the proposed changes to Sec. Sec.
493.901(a), (c)(8), (e), (f), 493.903(a)(3), and 493.905.
Based on comments received, we are not finalizing the
proposed addition at Sec. 493.901(c)(6).
E. Proposed Changes to Microbiology PT (Sec. Sec. 493.911 Through
493.919)
Comment: Commenters suggested clarification is needed regarding
methods or platforms for which PT is proposed to be required,
specifically for laboratories that use molecular, nucleic acid
amplification, mass spectrometry testing or next generation sequencing
for microorganism identification and susceptibility testing in all
microbiology subspecialties. A commenter also questioned whether PT is
required only for FDA-cleared test systems. The commenters stated this
clarification would help prevent confusion among laboratories.
Response: PT is not required by method or specific technology for
microbiology subspecialties (Sec. Sec. 493.911 through 493.919),
including whether a test system is FDA-cleared, or analytes in non-
microbiology specialties or subspecialties (Sec. Sec. 493.921 through
493.959). Regardless of the method, a laboratory uses for microorganism
identification and susceptibility testing, PT is required for these
categories of microbiology testing. When CLIAC deliberated on
appropriate PT for microbiology, they suggested the inclusion of broad
categories of testing performed in microbiology, rather than the types
of services offered by laboratories, described in Sec. Sec. 493.911
through 493.919, to allow flexibility for the inclusion of new
technologies. Each laboratory needs to identify the method or test
system used when submitting PT results for programs to properly grade
the PT. If a laboratory performs microbiology testing for which PT is
not available or required, they need to verify the accuracy of those
procedures at least twice per year, as described at Sec.
493.1236(c)(1). If available, voluntary PT may be a way the laboratory
chooses to meet this requirement.
Comment: Commenters supported the removal of the types of services
offered by laboratories in each microbiology subspecialty and
replacement of the types of services with general categories of testing
for which PT is required. However, they had questions about the
proposed option in bacteriology for detection of growth or no growth in
culture media. They questioned whether this option was included or
relevant for all microbiology subspecialties and all specimen types and
whether it should be removed as an option under the category for
identification of bacteria since bacteria are not identified when only
growth is detected. A commenter also noted that this category may not
be appropriate for cultures from normally sterile sites or those that
are expected to contain normal flora. Another commenter requested for
clarification of how this category would apply to urine colony counts.
A commenter suggested changing the language in bacteriology to
``presence or absence of bacteria without identification,'' with
similar changes in other subspecialties. Another commenter suggested
changing the language in bacteriology to ``growth or no growth in
culture media or identification of bacteria to the highest level that
the laboratory reports results on patient specimens.'' Other language
changes suggested by commenters included revising this category to
``growth or no growth of acid-fast bacilli'' in mycobacteriology and
``growth of yeast, growth of mold, or specimen negative for fungi'' in
mycology.
Response: We recognize the need for clarification of this option
based on the comments received. The option was proposed in bacteriology
at Sec. 493.911(a)(1)(iv)(A); mycobacteriology at Sec.
493.913(a)(1)(ii)(A); and mycology at Sec. 493.915(a)(1)(ii)(A) under
the proposed categories for microorganism detection and identification.
Similar language proposed for parasitology at Sec.
493.917(a)(1)(ii)(A) specified detection of the presence or absence of
parasites. This option was not proposed for virology. Specimen types
are not included in any of the PT categories in microbiology and a
challenge for growth or no growth, or presence or absence, was not
proposed and may not be appropriate for all specimen types or sites, or
appropriate as a response for all laboratories. It is one of two
options included under the category of detection and identification of
bacteria, mycobacteria, fungi and aerobic actinomycetes, and parasites,
in the respective microbiology subspecialties. It was proposed as an
option for laboratories that perform limited microbiology testing to
detect the presence of microorganisms and then refer growth from
culture or specimens containing the microorganisms detected to another
laboratory for identification. In response to the question about
applicability of this option for laboratories that perform urine colony
counts, PT is not required for colony counts. If the laboratory
performs identification of the bacterial growth, PT is required for the
identification. If the laboratory performs the colony count only and
refers the isolate for identification, an appropriate result for the PT
challenge would be to report detection or growth of bacteria. In
response to the suggestions for revisions to the language for this
option in each of the subspecialties, after considering the suggestions
from commenters, for clarification in this final rule we have changed
the language at Sec. 493.911(a)(1)(iv)(A) to ``detection of the
presence or absence of bacteria without identification.'' We changed
the language at Sec. 493.913(a)(1)(ii)(A) to ``detection of the
presence or absence of mycobacteria without identification, ``and at
Sec. 493.915(a)(1)(ii)(A) to ``detection of the presence or absence of
fungi and aerobic actinomycetes without identification.'' In
parasitology, we added ``without identification'' to the end of the
phrase currently at Sec. Sec. 493.917(a)(1)(ii)(A) and 493.917(b)(1)
to be consistent with the other microbiology subspecialties. In these
subspecialties, we also revised the performance criteria at Sec. Sec.
493.911(b)(1), 493.911(b)(7)(i), 913(b)(1), 493.913(b)(5)(i),
493.915(b)(5)(i), and 493.917(b)(5)(i) to correspond to these changes.
For example, in bacteriology this change now specifies that the
performance criterion is the correct detection of the presence or
absence of bacteria without identification. This may be achieved when
performing a culture and looking for bacterial growth or when using
another test method that detects the presence of bacteria without any
type of identification being performed.
Comment: Two commenters recommended clarification of the proposed
categories of direct antigen and toxin detection, with specific
questions about the applicability of this category and which antigens
or toxins are required in the subspecialties of bacteriology (Sec.
493.911), mycobacteriology (Sec. 493.913), and mycology (Sec.
493.915). One commenter questioned whether the intent of the proposal
was to require PT for only Clostridium difficile toxin or also for
other toxins in bacteriology. The same commenter requested
clarification on which direct antigen tests are proposed to be required
in mycology. Another commenter questioned whether antigen
[[Page 41210]]
detection was intended to be required for mycobacteriology, as it was
not proposed and no programs currently offer this PT.
Response: The requirement for PT for laboratories that perform
direct antigen testing has been part of the CLIA regulations in the
subspecialties of bacteriology and virology since PT was first required
in 1994 and it was included as one of the required categories of
microbiology PT in the proposed rule. As with other microbiology PT,
the microorganisms for which it is required are not specified in the
regulations. Rather, the regulations require that PT programs determine
the reportable bacteria or viruses to be detected using direct antigen
techniques. In this rule, required PT for direct antigen detection is
included in bacteriology at Sec. 493.911(a)(1)(ii); mycology at Sec.
493.915(a)(1)(i); parasitology at Sec. 493.917(a)(1)(i); and virology
at Sec. 493.919(a)(1)(i). Required PT for toxin detection is included
in bacteriology at Sec. 493.911(a)(1)(iii). As in the previous rule,
the microorganisms for which direct antigen or toxin detection are
required are not specified in the regulations. Rather, in all
subspecialties for which this category is required, the regulations
state the PT program determines the organisms to be reported by direct
antigen or toxin detection. PT for direct antigen or toxin detection
may be part of a combination module or offered as an individual five-
challenge module in each subspecialty. If a laboratory performs direct
antigen or toxin testing for which PT is not available, they are
required to verify the accuracy of those procedures at least twice per
year, as described at Sec. 493.1236(c)(1).
Comment: A few commenters addressed the proposed requirements for
microbiology stains, with agreement that Gram stain PT should require
bacterial morphology as well as gram-reaction. Commenters requested for
clarification regarding the level of detail required for bacterial
morphology as part of PT and whether Gram stain PT would be required
when a Gram stain is performed as part of organism identification.
Commenters also questioned the proposed inclusion of Gram stains and
acid-fast stains in bacteriology and mycobacteriology, but lack of
requirements for stain challenges in other microbiology subspecialties.
Response: In this rule, we are finalizing the proposed requirement
at Sec. 493.911(b)(1) that includes bacterial morphology when
performing Gram stain PT. This may apply to either a Gram stain
required as an individual challenge or as part of bacterial
identification. PT program instructions specify which tests are to be
performed on each sample, thus identifying which samples require Gram
stains. Morphology should include the basic shape and arrangement of
bacteria. However, as stated at Sec. 493.911(b)(1), the PT program
determines the reportable staining and morphological characteristics to
be interpreted by Gram stains. In response to the commenters who
questioned whether PT was proposed for stains in mycology and virology,
at this time, PT programs do not offer challenges for stains in these
subspecialties. Thus, they were not proposed. In parasitology, although
specific stains were not proposed as a required PT category, the sample
types required at Sec. 493.917(a)(2) include PVA (polyvinyl alcohol)
fixed specimens and blood smears, both of which are used in parasite
identification. Because a variety of stains are used by laboratories to
facilitate identification of intestinal, blood, and tissue parasites,
and in some cases, parasites can be identified directly in wet mounts
without using a stain, no stains were included for this microbiology
subspecialty. Each laboratory participating in PT for parasite
identification should follow the staining procedures they use for
patient specimens.
Comment: Commenters supported the removal of specific lists of
microorganisms from the microbiology subspecialty requirements and
replacement with general groups of organisms to be included over time.
In addition, commenters requested clarification of the required groups
in bacteriology, mycology, and virology. In bacteriology, one commenter
suggested expansion of the groups to include Gram-negative cocci or
coccobacilli, and another requested clarification of whether the groups
of cocci include coccobacilli or diplococci. A third commenter
suggested bacterial strains included in PT should be those routinely
encountered in specimens. In mycology, two commenters expressed concern
about inclusion of dimorphic fungi as a required category, noting that
the majority require handling in a biosafety level 3 laboratory and are
unable to be shipped. Comments pertaining to groups of organisms for
virology recommended viral groups that must be included, and one
organization questioned whether a PT program needed to offer all
viruses and all specimen sources to be approved for virology PT.
Specifically, the commenter questioned whether a program could offer PT
challenges for susceptibility or resistance testing based on a single
specimen source, such as urine. Another commenter requested for
clarification regarding appropriate specimen sources to be included in
virology modules and questioned whether combinations of viruses needed
to be incorporated in a single PT sample.
Response: The PT requirements for the microbiology subspecialties
specify that the organisms included are those that are commonly
occurring in patient specimens or are important emerging pathogens. The
groups identified for each of the five subspecialties are general
groups to be included over time and annually, if appropriate for the
sample sources. They are not intended to be the only groups that could
potentially be included. In bacteriology, Gram-positive or Gram-
negative coccobacilli or diplococci could be included as challenges in
addition to, or as more specific subgroups of the individual
morphologies listed for bacteriology at Sec. 493.911(a)(3). No changes
are being made in this final rule to the bacteriology groups that were
proposed. As stated by the commenters for mycology, dimorphic fungi
were proposed at Sec. 493.915(a)(3)(ii)(C) as a group of organisms to
be included in mycology over time and more specifically, required on an
annual basis. We recognize the commenters concerns with the proposed
inclusion of this group of fungi, some of which must be manipulated at
a biosafety level 3. In response to these concerns, we have removed the
dimorphic fungi from the groups of annually required organisms in
mycology. However, over time, we encourage PT programs to include a
variety of organisms in each subspecialty, as appropriate, to test a
laboratory's ability to detect and identify the spectrum of organisms
that might be found in patient specimens. In mycology, this may
occasionally include dimorphic fungi, such as Sporothrix schenckii,
that can be handled under biosafety level 2 conditions. In response to
the questions about the PT requirements for virology at Sec.
493.919(a)(3), the proposed rule did not specify that all viruses or
specimen sources needed to be included for a PT program to be approved.
However, it was proposed that if appropriate for sample sources
offered, the types of viruses included annually must be representative
of the groups of medically important viruses listed. Generally, with
this rule, PT programs must continue to offer the same types of
virology challenges and modules that have been offered in the past.
Lastly, PT
[[Page 41211]]
samples containing combinations of viruses were not proposed and are
not required in this final rule.
Comment: Several commenters indicated that the proposed requirement
in all microbiology subspecialties for laboratories to detect and
identify organisms to highest level performed on patient specimens was
unclear. One commenter recommended changing the description of the
category for identification of bacteria to ``the highest level that the
laboratory reports results on patient specimens.'' Two commenters
suggested identification needed to be clarified as to whether the
intent was presumptive or definitive identification and others
questioned how this requirement should be applied with respect to
identification at the genus or species level. The commenters stated
more specific and better-defined criteria are needed, as well as the
incorporation of language to allow for abbreviated reporting frequently
used in reporting mixed cultures. They also questioned whether this
information would need to be transmitted from PT programs to CMS and
State agencies and one noted it would take time to implement this
requirement. Another commenter stated it is the responsibility of
inspectors to review patient reporting practices and not that of PT
programs.
Response: We agree that the language proposed in all subspecialties
for identification of microorganisms to the highest level that it
performs procedures on patient specimens may be unclear, and we agree
that the revised description provided by the commenter earlier more
clearly specifies that this requirement refers to how a laboratory
reports results on patient specimens. As a result, we have incorporated
the change suggested by the commenter and made conforming changes in
this rule for all subspecialties at Sec. Sec. 493.911(b)(2),
493.913(b)(2), 493.915(b)(2), 493.917(b)(2), and 493.919(b)(2). We
expect that this will clarify that if a laboratory reports patient
results to the genus level, that is the expectation for PT. Similarly,
if a laboratory reports patient results to the species level, that
would be the expectation for reporting patient results. In response to
the question about incorporation of language to allow for reporting
abbreviated results, if this is the practice for reporting results to
the highest level on patient specimens, it may be an acceptable PT
practice as well. In all subspecialties, PT programs determine the
organisms that must be reported as part of their identification. We
believe the delayed implementation of specific portions of this final
rule will allow PT programs to incorporate updates needed for reporting
results to CMS. We agree with the commenters who stated that it is the
responsibility of laboratory inspectors to review patient reporting
practices and not the responsibility of PT programs and this was part
of a CLIAC recommendation made prior to the development of the proposed
PT rule. It was not our intent that PT programs take on this
responsibility and it was not included in the proposed rule.
Comment: Multiple commenters supported the proposed changes to
decrease the required percentage of mixed culture challenges from at
least 50 percent to at least 25 percent in bacteriology,
mycobacteriology, and mycology. The change, if finalized, would specify
that at least 25 percent of the PT samples must contain mixtures of the
principal organisms and appropriate normal flora.
Response: We agree with the commenters and appreciate their support
of these proposed changes. This is in alignment with a CLIAC
recommendation stating such and was proposed at Sec. Sec.
493.911(b)(1), 493.913(b)(1), 493.915(b)(1). We are finalizing these
changes in this rule.
Comment: Some commenters recommended changes to the microbiology
subspecialties for which susceptibility or resistance testing PT was
proposed to be required. A commenter noted that it would be difficult
to comply with the requirement for susceptibility or resistance testing
in mycology since samples are limited, there are few FDA-cleared
methods or breakpoints for fungi, and there is extensive variability in
the testing. Another commenter recommended that susceptibility or
resistance testing may not be added to required PT in mycology and may
be removed in mycobacteriology since few laboratories perform this
testing. A third commenter stated the value of requiring PT for M.
tuberculosis susceptibility testing is limited since programs often
send out the same strain that is susceptible to all drugs tested. With
respect to virology, a commenter disagreed with requiring
susceptibility or resistance testing in this subspecialty and proposed
requiring PT for viral loads. Another commenter indicated that since
only one PT program currently offers antiviral susceptibility testing,
that does not meet the specified criterion of requiring that three
programs offer PT for an analyte or test, and it may not be required in
virology. Finally, a commenter questioned whether a PT program should
be required to offer susceptibility or resistance testing PT in
virology if they offered other virology PT.
Response: We agree with the commenters' reasons for suggesting that
PT not be required for susceptibility or resistance testing in mycology
and virology at this time. Therefore, we are removing the proposed
requirements for inclusion of this category of required PT Sec.
493.915(a)(1)(iii) for mycology and at Sec. 493.919(a)(1)(iii) for
virology in this final rule. If this testing becomes less variable and
PT availability increases in these subspecialties in the future, we may
propose to include it in rulemaking at that time. In the meantime, if a
laboratory performs susceptibility or resistance testing on patient
specimens in mycology or virology, they are required to verify the
accuracy of those procedures at least twice per year, as described at
Sec. 493.1236(c)(1). Voluntary PT may be a way the laboratory chooses
to meet this requirement. With respect to the requirement for
susceptibility or resistance testing in mycobacteriology, we are aware
that small numbers of laboratories perform this testing and subscribe
to PT and that only one program currently offers susceptibility testing
PT in mycobacteriology. We also recognize that PT programs are less
likely to send out resistant strains of mycobacteria, especially M.
tuberculosis, due to biosafety concerns when shipping or working with
these organisms. For these reasons, in addition to the fact that
mycobacteriology is unique in that only two PT events per year are
required, we are removing the requirement at Sec. 493.913(a)(1)(iii)
for susceptibility or resistance testing in mycobacteriology in this
final rule. As stated previously, if a laboratory performs
susceptibility or resistance testing on patient specimens in
mycobacteriology, they are required to verify the accuracy of those
procedures at least twice per year, the same frequency as required PT
in this subspecialty. Laboratories may choose to subscribe to voluntary
PT as a way to meet the requirement or they may use another mechanism
to meet the requirement that does not include shipping strains of
organisms that require special precautions.
Comment: Commenters questioned or requested clarification of the
proposed requirements specified for antimicrobial susceptibility or
resistance testing, including clarification of the definition or intent
of resistance testing, questioning whether it meant testing for
resistance mechanisms or markers for specific organisms. One commenter
stated clarification was needed as to whether susceptibility testing is
optional if a laboratory performs
[[Page 41212]]
identification. Another commenter suggested the language for this
category of PT in bacteriology be clarified to state ``antimicrobial
susceptibility or resistance testing of select bacteria.''
Response: The category of antimicrobial susceptibility or
resistance testing was included in the proposed rule in for the
subspecialties of bacteriology at Sec. 493.911(a)(1)(v);
mycobacteriology at Sec. 493.913(a)(1)(iii); mycology at Sec.
493.915(a)(1)(iii); and virology at Sec. 493.919(a)(1)(iii).
Resistance testing was included in this proposed category as it was
previously recommended by CLIAC to be required along with
susceptibility testing. As discussed in the previous comment, the
proposed requirement for susceptibility or resistance testing in
mycobacteriology, mycology, and virology has been removed from this
final rule. With respect to the proposed requirement for this category
in bacteriology, we agree with the commenters that the interpretation
of ``resistance testing'' may not be clear, and that in some cases,
bacterial resistance may be determined as part of an organism
identification. For these reasons, we have removed resistance testing
from the required category proposed in bacteriology and in this final
rule we are requiring antimicrobial susceptibility testing of select
bacteria, as suggested by the commenter, at Sec. 493.911(a)(1)(v),
since antimicrobial susceptibility testing is not performed on every
bacterium that is isolated in a culture and PT programs specify which
challenges require that susceptibility testing be performed. This also
addresses the comment suggesting a change in the description of this
bacteriology category for clarification. If laboratories perform
resistance testing separate from bacterial identification, they are
required to verify the accuracy of those procedures at least twice per
year, as previously stated, and may enroll in voluntary PT to do so. In
response to the recommended clarification of whether susceptibility
testing is optional when a laboratory performs identification,
laboratories must follow PT program instructions when determining which
tests to perform on a microbiology sample. The programs must clearly
identify which samples require that susceptibility testing be performed
on bacteria that are identified and those results reported for PT
purposes.
Comment: Several commenters agreed with the proposed increase in
the number of required susceptibility or resistance testing challenges
from one to two per event in all microbiology subspecialties except
parasitology, where PT for susceptibility testing is not required. They
indicated that increasing the number of challenges and requiring one
Gram-positive and one Gram-negative challenge per event in bacteriology
would help identify issues with patient testing. Other commenters
disagreed with this proposed change, expressing concerns that this
requirement would provide too much information to laboratories about PT
sample content and make the PT results more predictable. One commenter
stated that including two susceptibility challenges per event lacked
value and relevance. Others suggested that requiring a mixture of
challenges throughout the year was preferred over the requirement to
include one Gram-positive and one Gram-negative challenge per event.
Response: We agree with the commenters who supported the proposed
change to increase the number of required susceptibility or resistance
challenges to two per event and are finalizing that change in this rule
at Sec. 493.911(a)(4). This change was recommended by CLIAC, and we
believe it will provide a better assessment of laboratory testing
performance over time. We also agree with the commenters who suggested
that we should not specify a predictable pattern of susceptibility
testing challenges in bacteriology, requiring that each event must
include one Gram-positive and one Gram-negative challenge. As a result,
in this rule, we are revising the requirement to indicate that each
year, a minimum of two samples per testing event of susceptibility
testing challenges must include a mixture of Gram-positive and Gram-
negative challenges.
Comment: A PT program commented on the proposed requirements to
change scoring for the microbiology subspecialties by including
separate category scores in addition to the overall subspecialty
scores. The program inquired about the intent of this proposed change
and suggested that it would increase the complexity of determining
scores and it may be especially challenging to score laboratories that
perform a mixture of detection and identification procedures. The
commenter also noted the proposed scoring method would give PT programs
discretion in the interpretation of the requirement which could result
in laboratories choosing the program that uses the most advantageous
method. The commenter advocated for simplifying the subspecialty
scoring process rather than increasing complexity for efficiency and
increasing the value to laboratories.
Response: The four categories of testing proposed for microbiology
PT were recommended by CLIAC to replace the types of laboratory
services that are part of the current regulations. The types of
services guided the scoring of microbiology subspecialties since there
are no specific analytes in this laboratory specialty. However, since
only a single score is given for each subspecialty, many times
representing a combination of results for different types of testing,
it is not possible for laboratory surveyors to readily determine if a
laboratory is having problems with one area of their microbiology
testing. No changes were made to the scoring process for microbiology
in the proposed rule other than aligning the requirements for
evaluation of a laboratory's performance at Sec. Sec. 493.911(b)
through 493.919(b) to be consistent with the categories of testing and
facilitate the identification of problems in any one of the categories.
Summary of Final Actions
We are finalizing the proposed revisions at Sec. Sec.
493.911 through 493.919 by removing the types of services listed for
each microbiology subspecialty and inserting a more general list of
organisms.
We are finalizing the proposed revisions at Sec. Sec.
493. 911(a), 493.913(a), and 493.915(a) that are related to growth or
no growth and mixed culture requirements (50 percent to 25 percent).
We are finalizing the proposed performance criteria
revisions at Sec. Sec. 493.911(b), 493.913(b), 493.915(b), 493.917(b),
and 493.919(b).
We are finalizing the proposed addition of ``without
identification'' to the end of the phrase currently in the subspecialty
of parasitology at Sec. 493.917(a)(1)(ii)(A) to be consistent with the
other subspecialties.
We are finalizing the proposed revised requirement at
Sec. Sec. 493.911(b)(2), 493.913(b)(2), 493.915(b)(2), 493.917(b)(2),
and 493.919(b)(2) to clarify and emphasize that laboratories should
detect and identify organisms to the highest level that they report
results on patient specimens.
We will amend Sec. Sec. 493.911(b)(1), 493.913(b)(1),
493.915(b)(1), 493.917(b)(1), 493.919(b)(1) to clarify that for the
purpose of achieving consensus, PT programs must attempt to grade using
both participant and referee laboratories before determining that the
sample is ungradable.
We are finalizing the proposed revisions to Sec.
493.911(a) through (b) related to Gram stains, direct antigen
detection, bacterial toxin detection, and performance and scoring
related to
[[Page 41213]]
direct antigen and bacterial toxin detection for the subspecialty of
bacteriology.
We are finalizing the proposed addition to Sec.
493.915(a) related to requiring direct antigen testing for the
subspecialty of mycology.
We are finalizing the proposed addition to Sec.
493.917(a) related to requiring direct antigen testing for the
subspecialty of parasitology.
We are finalizing the proposed revision to Sec.
493.919(a) related to requiring direct antigen testing for the
subspecialty of virology.
We are removing the reference to resistance testing in the
subspecialty of bacteriology and have removed references to
``resistance testing'' in the requirement for antimicrobial
susceptibility testing of select bacteria at Sec. 493.911.
We are not finalizing the proposed requirements for PT of
antimicrobial susceptibility and resistance testing in the
subspecialties of mycobacteriology, mycology, and virology and have
removed the requirement at Sec. Sec. 493.913, 493.915, and 493.919.
F. Proposed Changes to PT for Non-Microbiology Specialties and
Subspecialties (Sec. Sec. 493.921 Through 493.959)
1. Required Analytes
Comment: Several commenters agreed that the list of required
analytes should be updated. Some commenters stated that the process for
analyte inclusion and removal was thorough, understandable, and
transparent. One commenter stated the inclusion threshold for new
analytes that only included three PT programs, rather than four, could
result in an unfair market advantage, raise PT costs for laboratories,
or result in logistical difficulties in obtaining PT.
Response: In response to the comments, we reviewed our analyses and
determined that there were no proposed analytes that would not have
made the requirement for being offered by at least four PT programs, as
was suggested by the commenter. We believe that the fact that there are
already at least three programs available to choose from for each new
analyte or test gives laboratories several options and should not
result in increased costs or logistical difficulties in obtaining PT.
All PT programs received notification of the proposed analytes or tests
at the same time when the proposed rule was published. Whether a PT
program elects to offer a particular analyte is a business decision of
the PT program, and outside of our purview.
Comment: A small number of commenters mentioned concerns about the
possibility that either inclusion of the PT analytes or the ALs we
proposed would have a negative impact on access to testing. A few
commenters suggested that for the ALs proposed for some analytes, some
existing test systems would not meet the new requirements. For example,
one manufacturer stated that the proposed ALs for creatine kinase
isoenzymes may be challenging for some testing platforms to meet. A
similar comment was made for proposed ALs for troponin I and
hematocrit.
Response: During the phase in period, manufacturers will have time
to improve test accuracy, and laboratories will have time to switch to
higher accuracy test methods if those they use do not provide results
that are able to meet the criteria for acceptable performance specified
in the regulations. Clinicians and patients should be able to expect
accurate testing, and assuring overall accuracy is the goal of
performing PT. Therefore, these changes should drive the health care
system toward more accurate methods. We have no reason to believe that
access to testing will be impacted.
Comment: Several commenters supported the list of analytes that
were proposed for addition and deletion, and commenters supported the
process we used for determining the list of analytes for which PT is to
be required. No commenters questioned any of the proposed new analytes.
However, one commenter stated that a current analyte, T3 uptake, should
be deleted because it lacked clinical utility. An accreditation
organization and an individual commented that determination of creatine
kinase (CK) MB fraction by electrophoresis should be discouraged, and
therefore, it should be excluded from the required PT for creatine
kinase isoenzymes. Rather, the commenters noted that PT should only be
required for laboratories that use immunochemical methods when testing
for this analyte. Some commenters recommended inclusion of analytes
that we had considered but decided not to include. One commenter
suggested that we require PT for several immunosuppressant drugs for
which PT is not currently required.
Response: We had initially considered all the analytes that
commenters recommended for either inclusion or deletion, but the
suggested analytes did not meet one or more of our inclusion or
deletion criteria. Both the inclusion and deletion processes, which
were described in the proposed rule, were based upon per-analyte
estimates of the availability and the number of programs already
offering PT, the nationwide volume of patient testing, the impact on
patient or public health of offering PT, and the cost and feasibility
of PT implementation. We did not propose deletion of T3 uptake because
test volumes were above the threshold for consideration. With respect
to the suggestion to discourage laboratories from using electrophoretic
methods to test for CK-MB isoenzymes, the method used is not a basis
for requiring or not requiring PT for any test or analyte. Each
laboratory needs to identify the method or test system used when
submitting PT results for programs to properly grade the PT. To the
extent that test results are used for clinical decision making, the
test results should be accurate. The immunosuppressant drugs that were
suggested were not done in sufficient volumes to meet the threshold for
consideration in the proposed rule, so they were not proposed to be
required.
Comment: For a few analytes that can be detected or quantified in
more than one way, some commenters requested clarification concerning
which analyte would require PT. For example, a commenter questioned if
PT was proposed to be required whether LDL cholesterol was calculated
or measured directly. Several commenters requested clarification
concerning whether drugs were to be measured in total or free forms.
One commenter mentioned a need to specify the sample type that should
be tested if the analyte can be tested in more than one type of body
fluid.
Response: For LDL cholesterol, which can be measured both directly
and as an estimation based on other measured lipids, PT is only
required for directly measured (not calculated) LDL cholesterol. For
all drugs, we intend that the measured form must be total drug. For the
specialty of chemistry, in subpart I the sample types for which PT is
required are specified for each under each subspecialty, at Sec.
493.931(b) for general chemistry, Sec. 493.933(b) for endocrinology,
and Sec. 493.937(b) for toxicology. If a laboratory performs patient
testing on other sample types than those listed, they are required to
verify the accuracy of testing with those alternative sample types at
least twice per year, as described at Sec. 493.1236(c)(1). If
available, voluntary PT may be a way the laboratory chooses to meet
this requirement.
Comment: A few commenters requested clarification of what should be
considered high sensitivity C-reactive protein, as opposed to
traditional C-reactive protein, as included in the
[[Page 41214]]
proposed rule. A related comment suggested that we should require PT
for all assays for C-reactive protein.
Response: Although traditional C-reactive protein has been used as
a general marker of inflammation for many years, it did not meet the
threshold for inclusion as a required PT analyte. In this rule we are
finalizing the proposed PT requirement for high sensitivity C-reactive
protein and we appreciate the need to define which test methods would
be considered ``high sensitivity'' testing. High sensitivity C-reactive
protein concerns testing related to cardiac ischemia, either for frank
cardiac events or for risk stratification, which requires more
sensitive test methods to detect lower concentrations. We are deferring
to laboratories to know whether their assay is a high sensitivity
method used to detect cardiac pathology, or the traditional, less
sensitive C-reactive protein. PT programs must label their PT offerings
accordingly.
Comment: One commenter suggested that we should specify the N-
terminal region of pro-B-natriuretic peptide (BNP), which was included
as a required analyte in the proposed rule because this is the epitope
usually detected by antibodies used in most test methods.
Response: We agree with the commenter that the N-terminal region of
pro-B-natriuretic peptide (BNP) is the part of the peptide that is
usually measured, but we did not want to restrict the requirement for
PT. Therefore, in this rule we are finalizing the name as proposed:
proBNP.
2. Scoring and Acceptance Limits
Comment: With respect to scoring and ungradable samples, one
commenter requested clarification about how performance on an analyte
was determined for a PT event when one of the PT samples was not able
to be graded. The commenter questioned what the denominator of graded
samples would be. An accreditation organization agreed with our
proposal to require PT programs to attempt to reach consensus using
both laboratory and referee laboratories before deciding a sample is
ungradable due to lack of consensus.
Response: If a sample for a particular PT event is ungradable, for
example, because consensus could not be reached, it is still considered
to be part of the denominator of five PT samples for that event, and in
this case, the laboratory is given credit for passing the challenge.
Therefore, if one of the remaining PT samples in the event is missed,
the event score is 80 percent, and the event score is ``satisfactory''
for the majority of required PT.
Comment: Several commenters stated that the process used for
simulating the impact of scoring PT using several alternative ALs to
determine the optimal limit to require was unclear.
Response: As discussed in the proposed rule, we requested PT
programs to examine the impact of various ALs on their aggregated
sample failure rates, using the peer grouping approaches they had
previously used. A number of the PT programs provided simulated
results, applying various possible percentage-based ALs to actual
results from previous PT events, and were able to help us select
appropriate ALs. We selected ALs using a target miss rate (per sample)
in the 1 to 2 percent range. Our intent was to assure that the ALs
would work across the clinically important range and not
inappropriately fail results that were accurate for clinical decision
making. Therefore, we examined error rates at all concentrations that
PT programs used throughout the 2 years of PT data they shared with us.
Comment: We received a number of comments related to the proposal
to use percentage-based ALs whenever possible. While some commenters
supported the proposed changes, others suggested changes to specific
proposed ALs for both current and newly proposed analytes. Generally,
these comments concerned whether the proposed limits would be workable
across the clinically important measurement interval for all test
methods and platforms. In almost all cases, the comments recommended
less stringent ALs, either across the entire analytical measurement
range or specifically at low concentrations, where test methods are
generally less accurate. Commenters pointed out that unless there is
allowance for low concentrations, PT programs would be discouraged from
using PT samples with low concentrations, to the detriment of assuring
accurate testing across the analytical range. Supporting this, some
commenters stated that it is not clinically important to be as accurate
as the percentage-based limits would require. Commenters suggested that
we use a combination of a percentage and a concentration limit for
certain analytes, such that PT samples with relatively low
concentrations would be more fairly assessed. In some cases, commenters
recommended a concentration limit that differed from a concentration
limit we had proposed. A small number of commenters were generally
concerned about moving from familiar 3 SD-limits to percentage based
ALs for some currently required analytes.
Response: In response to commenters' concerns about the use of
percentage limits when scoring PT analytes at low concentrations, in
this final rule, we are including ``concentration limits'' such as are
already used for glucose and some other analytes for many newly
required analytes and some previously required analytes. When adding
concentration limits and using combined ALs, programs are directed to
score with whichever of the specifications is more tolerant, allowing
for fairer and more realistic ALs that will allow PT programs to cover
the clinically important range of results. We re-examined previously
acquired simulation data from PT programs and have added concentration
limits for 13 analytes. Specifically, we created concentration
thresholds for alanine aminotransferase, aspartate aminotransferase,
cholesterol (high density lipoprotein), CK-MB isoenzymes, glucose,
carcinoembryonic antigen, human chorionic gonadotropin, vitamin B12,
acetaminophen, carbamazepine, lithium, phenobarbital, and salicylate.
Concerning the switch from current 3 SD limits to percentage-based
limits, we believe that the new ALs will be workable, fair, and
clinically relevant. As stated in the proposed rule, ALs based on
analytical variability within a peer group, such as the use of 3 SD
limits, are ill-suited to know whether testing results are sufficiently
accurate for clinical purposes.
Comment: Two commenters noted that CLIA ALs have been used in ways
other than their intended purpose of identifying laboratories with
unacceptable performance. One commenter noted that ALs have been used
as goals for ideal performance, for example, setting quality control
acceptable limits. Another commenter pointed out that ALs have been
used for verifying analytical performance, for example, accuracy.
Response: We agree with the comments and reemphasize that ALs must
not be used as the criteria to establish performance goals in clinical
laboratories. Goals for accuracy and precision must be based upon
clinical needs and manufacturer's FDA-approved or -cleared labeling; PT
performance is not the best assessment of these. Proficiency testing is
intended to identify laboratories that are not performing with
acceptable analytic accuracy; it is not intended, nor suited, to
provide goals for analytical accuracy or clinical performance.
[[Page 41215]]
Comment: Many commenters stated the proposed AL for hemoglobin A1c
(HbA1c) was too loose and not reflective of the testing accuracy of
current test methods. Many individuals and organizations commented that
the AL should be 6 percent, and several recommended lowering the limit
to 5 percent. Several comments requested that CLIA ALs should not
``change'' from the current 6 percent, despite the fact that HbA1c is
currently not a CLIA-required PT analyte, and therefore, no ALs are
specified in the regulations. Many commenters expressed concerns that
using a threshold higher than 6 percent would in some way subvert the
substantial progress made by the National Glycohemoglobin
Standardization Program (NGSP), working collaboratively with test
method manufacturers, to improve accuracy of HbA1c testing. Commenters
suggested that manufacturers would allow the accuracy of their test
methods to deteriorate if CLIA added HbA1c with an AL as loose as 10
percent. A PT program proposed that we use an AL of 10 percent for non-
commutable PT materials and a limit of 6 percent for commutable
(accuracy-based) PT materials. Another PT program commented in favor of
a 10 percent limit, noting that non-commutable PT materials may be less
accurate with certain test methods and, moreover, PT is not intended to
directly reflect accuracy needed for clinical testing.
Response: We appreciate the importance of HbA1c for diagnosis and
monitoring patient management, and the need for testing accuracy that
is sufficient to meet clinical needs, and we support the progress that
continues to be made to improve the accuracy of HbA1c testing. As
mentioned in the previous comment, CLIA PT ALs are intended to
identify, and hopefully remediate, laboratories that are not providing
results as accurate as their peers. CLIA PT ALs should not be used as
accuracy goals by manufacturers or by standardization initiatives such
as the NGSP. CLIA should not impose a requirement that limits access to
critically important patient testing, especially if it is based on PT
results that may not reflect the accuracy of patient testing.
One PT program has demonstrated progressive improvements in
accuracy of testing by laboratories enrolled in their accuracy-based PT
program, which uses commutable patient samples. We are aware that, over
time, the program has incrementally tightened their ALs for the
accuracy-based PT. This progress has been possible without CLIA
requiring PT for HbA1c, and therefore, adding a PT requirement for
HbA1c should not impede further progress in the future. Accreditation
organizations have the flexibility to require their laboratories to
meet a more stringent requirement than CLIA. They also have the option
of using the CLIA limit and using a second, more stringent, AL for
educational purposes. Either approach would allow these organizations
to continue to tighten the limits for HbA1c for their accredited
laboratories. We acknowledge the importance of standardization
programs, like the NGSP, having the latitude to continuously adjust
their accuracy goals to monitor and encourage improvements in the
accuracy of HbA1c testing. We do not believe that a CLIA AL that is
looser than the limit in use by the accuracy-based PT program would
cause manufacturers to allow testing accuracy to deteriorate, as many
commenters have suggested.
The AL adopted in CLIA regulations must not be too tight for
laboratories that do not participate in an accuracy-based PT program
that uses commutable PT materials. In simulation studies performed
before issuing the proposed rule, laboratories using non-commutable PT
samples had poorer performance, especially when scoring using any AL
less than 10 percent. This might have occurred because laboratories not
enrolled in accuracy-based PT use different test methods or because the
PT they use is non-commutable. CLIA does not specify whether
laboratories are required to participate in PT based on whether it is
commutable or non-commutable. The same AL apply regardless of the PT
samples' commutability.
After analyzing the comments received in response to the proposed
rule, we requested the PT programs that offer HbA1c to simulate results
that would be obtained if they used 5 percent, 6 percent, 8 percent,
and 10 percent as the AL. We requested programs to indicate miss rates
and unsatisfactory rates based upon different HbA1c concentrations in
their materials, and to disclose performance based upon their testing
platform or peer groups used. Based upon these more recent simulated
results, we found that it will be possible to use a tighter AL than 10
percent. After this analysis, we are setting the AL for HbA1c at 8
percent in this final rule. The performance improvements we saw between
the first and later simulations may reflect improvements in the
accuracy of testing for HbA1c.
Comment: Commenters stated that rather than using the proposed AL
of 20 percent for LDL cholesterol, we should require an AL of 12
percent, which is the accuracy target used by the National Cholesterol
Education Program.
Response: Because the commenters suggested an AL tighter than was
proposed, we requested PT programs to simulate the impact of using that
limit. Based upon reanalysis of new data shared by PT programs, we
confirmed that the proposed AL of 20 percent is appropriate for scoring
PT for LDL cholesterol, and we are finalizing that limit in this rule.
Comment: With respect to PT for blood lead, we proposed a change
from the current AL of 4 mcg/dL or 10 percent (greater) to
2 mcg/dL or 10 percent (greater). One commenter supported
the proposed AL, consistent with efforts to improve the ability of
laboratories to detect very low concentrations of blood lead in patient
specimens. Conversely, another commenter stated that the reduction of
the concentration AL from 4 mcg/dL to 2 mcg/dL would result in more
instances of nonconsensus, which would result in more ungraded samples
and events. Another commenter expressed concerns about the impact of
the proposed limits on failures for certain testing platforms.
Response: We agree with the commenter who emphasized the public
health importance of the need for accuracy at low concentrations of
blood lead, to detect and prevent cases of childhood lead poisoning,
and are finalizing the proposed AL for blood lead at 2 mcg/dL 10 percent (greater) in this rule. We appreciate the commenters'
concerns, however, one outcome of more stringent ALs may be that
laboratories switch to test methods that are more accurate across the
range of testing and better able to meet clinical needs. We believe
that manufacturers of analytical platforms that may fail to achieve
consensus, or otherwise perform poorly, will improve their accuracy
during the phase-in period. To address concerns regarding unintended
consequences that may increase health disparities, we will monitor
changes in PT participation for all analytes after this rule becomes
effective as this is required as part of PT oversight under CLIA. This
includes the methods used for testing each PT analyte required by CLIA.
Comment: A few commenters provided suggestions related to the
addition of troponin I and troponin T as required analytes in routine
chemistry. One commenter was concerned that adding troponins to the
required list for PT may potentially limit access to point-of-care
cardiac triage testing of potential cardiac events in rural settings.
The
[[Page 41216]]
same commenter also suggested that the ALs for troponin I and troponin
T should be expanded to 40 percent, with no suggested
changes to the associated concentration limits. A couple of commenters
suggested that the same, percentage-based AL would work for both
generic and high sensitivity troponins. A small number of commenters
suggested that we should require PT for high sensitivity troponin
assays in addition to traditional troponin assays.
Response: Troponin I and troponin T are used to make decisions
about the use of lifesaving, yet not risk-free, interventions, such as
cardiac catheterization and therapeutic thrombolysis. Therefore, it is
important that such testing be both accessible and accurate. We believe
that requiring PT for the troponins is important and must not inhibit
access to testing. We reviewed our simulation data to see if the same
concentration limit would work for both troponin I and T. We determined
that we must use the proposed, different ALs, and, therefore, are
finalizing the AL for troponin I as 0.9 ng/mL or 30 percent
(greater) and for troponin T as 0.2 ng/mL or 30 percent
(greater). At the time we proposed these changes, troponin I and T were
not frequently tested as ``high sensitivity'' analytes, that is, at
very low limits of detection. Also, there were not enough PT program
offerings to meet our threshold for inclusion for high sensitivity
troponins. Therefore, we are not requiring PT for ``high sensitivity''
troponin I or T.
Comment: A few commenters stated that some proposed percentage-
based ALs were too tight, regardless of whether a concentration
threshold was included. Commenters stated that the proposed percentage
ALs for immunoglobulin A (15 percent), immunoglobulin E
(15 percent), amylase (15 percent), and
leukocyte count (5 percent) were too tight. The commenters
recommended ALs be set at 20 percent for immunoglobulin A,
25 percent for immunoglobulin E, and 10 percent
for leukocyte count. No recommendation was provided for amylase.
Response: We re-examined simulation data that had been submitted by
PT programs and revised percentage limits as appropriate. Specifically,
in this rule we are finalizing the AL for immunoglobulin A to 20 percent, amylase to 20 percent, and leukocyte
count to 10 percent. We determined that adding a
concentration limit for these analytes was not necessary or adequate to
make the AL workable at a lower concentration. For immunoglobulin E, we
did not determine that it was necessary to increase the AL to 25 percent; therefore, we are finalizing the AL for
immunoglobulin E in this rule at 20 percent.
Comment: Some commenters expressed concerns related to proposing
ALs based on allowable total error derived from estimates of biological
variability (BV). There was a comment that the use of BV data was in
flux at this time. One commenter noted that estimates of BV that we
used may be incorrectly wide due to errors in the way estimates were
made, specifically that they may overestimate BV because the results
are based upon analytical test methods that have inherent variability.
One commenter stated that BV cannot be directly related to clinical
outcomes. The same commenter stated that when setting ALs both BV and
state-of-the art performance should be considered.
Response: We appreciate the concerns expressed and note that the
ALs we proposed were not based strictly on estimates of BV. Moreover,
we are aware that the field of estimating BV data has changed in the
last few years. However, any impact of suboptimal estimations of BV on
the ALs we proposed was likely negligible because we always tested
potential ALs using simulations. ALs that were too tight to be workable
were eliminated even if they were not as stringent as our estimates of
BV might have suggested were necessary. In other words, consistent with
one of the comments, we used state-of-the-art performance, demonstrated
through simulations, to finalize the proposed ALs. In some cases, we
showed through simulations that it was possible to use ALs that are
tighter than the ``minimal'' threshold based upon estimates of BV and
in these cases we used a somewhat tighter AL, but only if the data from
PT programs supported the tighter limit. As a result, changes in the
estimates of BV we used would not have affected our proposed ALs.
After re-examining the literature, we reconfirmed that BV is the
only tenable approach to establishing new limits. We agree that
clinical outcomes may not be reflected in BV data, but the preferred
outcomes studies were not available to us.
Comment: Commenters generally favored the proposal to require
separate PT for cell identification and differentials rather than
including an option to participate in PT for one or the other. It was
pointed out that the results can be used for different purposes in
patient treatment. There were questions, however, questioning whether
there should be separate scores for cell identification and
differentials or if they should be averaged. One commenter recommended
that the three standard deviation criteria for acceptable performance
for differentials should be changed to a percentage-based criterion and
another suggestion was made to include 1.0 (whichever is
greater) for low target values or absolute values (that is, basophils).
An additional commenter requested clarification as to whether PT would
be required for both manual and automated flow through differentials
for laboratories that use platforms that can report flow through
differentials.
Response: We appreciate the support from commenters who recognized
the need to recognize cell identification and differentials as two
separate analytes and are finalizing that change in this rule. As
separate analytes they may be scored individually. We are finalizing
the criteria for acceptable performance for both analytes in this rule.
We are not changing the criterion for differentials to percentage-based
because we have no BV data on which to base that change. As such, we
are also not including the 1.0 option for low target
values. In response to the question regarding PT requirements for
laboratories that perform both manual and automated flow through
differentials, a laboratory should perform PT in the same manner as
they perform testing on patient specimens. PT is required for the
primary method of testing used for patient testing.
Comment: A few commenters supported the proposal to change the
consensus requirement for cell identification from 90 percent to 80
percent. One commenter requested for clearer justification for the
change.
Response: This change was proposed because it is not possible to
score 90 percent on a 5-challenge PT panel. We are finalizing the
change in this rule.
Comment: An accreditation organization made several suggestions
about how standard deviations should be calculated when they are
required as ALs for white blood cell differentials. For peer group
sizes of 20 or more, they recommended that we continue to require
elimination of outliers before calculation of the standard deviation.
The commenter stated that when the peer group size is between 5 and 19
laboratories, robust methods as described in ISO 13528, ISO Guide 35,
or ASTM E-691, should be used. They recommended that, alternatively,
the standard deviation could be an average standard deviation
determined from previous rounds of PT, calculated according to ISO
13528. They also noted that mention of 3 SD to set ALs should
[[Page 41217]]
be removed from parts of the regulation that no longer include 3 SD
limits.
Response: As mentioned by the commenter, this final rule includes
only one analyte with a three standard deviation limit. We agree that
this recommendation would allow more accurate estimates of 3 SD ALs for
relatively small peer group sizes. We also agree that robust
statistical methods must be used to calculate the standard deviations
when the peer group size is between 5 and 19 laboratories. However, we
are not specifying the statistical approach that needs to be used. We
appreciate the commenter's suggestion to remove reference to 3 SD ALs
in relevant sections of this final rule and have done so in Sec. Sec.
493.931(c)(2) and 493.933(c)(2).
Comment: A few commenters recommended that the international
normalized ratio (INR) should be listed as a separate analyte in the
specialty of hematology, the same way blood cell counts and white blood
cell differentials are separate analytes, rather than including INR as
a mechanism for reporting prothrombin time results, as was proposed.
The commenters agreed that laboratories should report prothrombin time
results in seconds, as an INR, or both as appropriate, in the same way
that they report patient results. Commenters also stated that
separating the prothrombin time and INR would allow for separate ALs
for each of them.
Response: It is important for laboratories to report PT results the
same way that they report patient results. If patient results are
reported in seconds or as INR results, laboratories should report the
same way to PT programs. If the laboratory reports patient results in
both seconds and as an INR, they should report both to PT programs. The
AL for prothrombin time at 15 percent is applicable for
both seconds and INR. When we referenced ``directly measured INR'' in
the preamble to the proposed rule, we were referring to those devices
that internally calculate and display the INR value rather than giving
a value in seconds. The 15 percent AL for INR applies regardless of how
it is derived.
Comment: Two commenters remarked on the proposed change to the
criteria for acceptable performance of unexpected antibody detection in
immunohematology from 80 percent to 100 percent accuracy. While one
commenter agreed with this proposed change, the other disagreed. The
opposition was concerned with the possibility that laboratories that
use less sensitive, but safe, methods could be penalized, and it could
limit patient access to care.
Response: We believe that the criteria for acceptable performance
for unexpected antibodies should be 100 percent rather than 80 percent.
We are finalizing this change because it is critical for laboratories
to detect any unexpected antibody when crossmatching blood to protect
the public health and not impact patient care. It is important that
antibodies are detected to lessen the possibly of a transfusion
reaction due to incompatible blood products.
Comment: Concerning appropriate units for reporting PT results or
some other aspect of the AL, some commenters noted that we
inadvertently deleted titers for some ALs. It was pointed out that for
some analytes we incorrectly suggested that the AL should be
qualitative. Some commenters noted inaccuracies in the units we used
for quantitative analytes.
Response: We appreciate the commenters careful examination of the
proposed limits and we made appropriate adjustments that are now
reflected in the final rule. In response to comments about proposed
units for reporting PT results, unintentional uses of incorrect units
have been corrected in this final rule.
Summary of Final Actions
We are finalizing the proposed revision at Sec. Sec.
493.923(a), 493.927(a), 493.931(a), 493.933(a), 493.937(a) and
493.941(a) to remove the option that PT samples ``at HHS option, may be
provided to HHS or its designee for on-site testing.''
We are finalizing the proposed addition of 29 analytes and
the deletion of five analytes. See section II of this final rule.
Additional analytes can be found in section II.B.1. of this final rule,
Table 1, and deleted analytes are listed in section II.B.6 of this
final rule.
We are amending Sec. Sec. 493.923(b)(1), 493.927(c)(1),
493.931(c)(1), 493.933(c)(1), 493.937(c)(1), 493.941(c)(1), and
493.959(d)(1) to clarify that for the purpose of achieving consensus,
PT programs must attempt to grade using both participant and referee
laboratories before determining that the sample is ungradable.
Section 493.927 (General Immunology)
++ We are correcting typographical or editorial errors in the
proposed criteria for acceptable performance for alpha-1-antitrypsin,
alpha-fetoprotein (tumor marker), complement C3, complement C4,
antinuclear antibody, antistreptolysin O.
++ We are modifying the proposed AL for immunoglobulin A (IgA) of
15 percent and finalizing the AL for IgA as 20
percent based on public comments.
++ We are finalizing the proposed criteria for acceptable
performance for antinuclear antibody, antistreptolysin O, rheumatoid
factor, and rubella.
Section 493.931 (Routine Chemistry)
++ We are finalizing the proposed ALs in the criteria for
acceptable performance.
++ We are correcting the units for prostate specific antigen
(total).
++ We are making a technical change to CK-MB isoenzymes to address
measurement by electrophoresis or direct mass determination.
++ We are also modifying the proposed criteria for acceptable
performance for hemoglobin A1c of 10 percent and finalizing
the AL for hemoglobin A1c to 8 percent based on public
comments.
Section 493.933 (Endocrinology)
++ We are finalizing the proposed percentage based ALs in the
criteria for acceptable performance.
Section 493.937 (Toxicology)
++ We are finalizing the proposed concentration limits and
percentage based ALs in the criteria for acceptable performance.
++ We are finalizing the proposed requirement that PT programs must
provide samples that cover the full range of samples that could occur
in patient specimens.
++ We are correcting the units for phenytoin and vancomycin.
Section 493.941 (Hematology)
We are finalizing the proposed AL for leukocyte count.
++ We are finalizing the proposed revision to units of reporting
for prothrombin time to include seconds and INR (international
normalized ratio) and that laboratories must report prothrombin time in
the same was as they report patient results.
++ We are finalizing the proposed requirement that laboratories
performing both cell counts and differentials must enroll and
participate in PT for both.
++ We are finalizing the proposed change to the criteria for
acceptable performance for ``cell identification'' from 90 percent to
80 percent.
Section 493.959 (Immunohematology)
++ We are finalizing the proposed change to the criteria for
acceptable performance for unexpected antibody detection from 80
percent to 100 percent.
[[Page 41218]]
IV. Collection of Information Requirements
Under the Paperwork Reduction Act of 1995, we are required to
provide 30-day notice in the Federal Register and solicit public
comment before a collection of information requirement is submitted to
the Office of Management and Budget (OMB) for review and approval. In
order to fairly evaluate whether an information collection should be
approved by OMB, section 3506(c)(2)(A) of the Paperwork Reduction Act
of 1995 requires that we solicit comment on the following issues:
The need for the information collection and its usefulness
in carrying out the proper functions of our agency.
The accuracy of our estimate of the information collection
burden.
The quality, utility, and clarity of the information to be
collected.
Recommendations to minimize the information collection
burden on the affected public, including automated collection
techniques.
We are soliciting public comment on each of these issues for the
following sections of this document that contain information collection
requirements (ICRs).
The requirements and burden will be submitted to OMB under (OMB
control number 0938-New).
A. Clarification for Reporting of Microbiology Organism Identification
We proposed to clarify a requirement at Sec. Sec. 493.801(b),
493.911(b), 493.913(b), 493.915(b), 493.917(b), and 493.919(b), to
emphasize the point that, as currently required, laboratories must
report PT results for microbiology organism identification to the
highest level that they report results on patient specimens. In
accordance with the implementing regulations of the PRA at 5 CFR
1320.3(b)(2), we believe the reporting of microbiology organism
identification is a usual and customary practice when reporting PT
results to PT programs. We are able to determine how many laboratories
provide services in microbiology; however, we are unable to determine
if the laboratories are enrolled in the appropriate PT outside of the
survey process, or if the microbiology PT samples for which the
laboratory is enrolled are required under subpart I. There are no data
systems that capture this information. We estimate the number of
laboratories that are not currently reporting microbiology organisms to
the highest level that they report results on patient specimens to be
about 10 percent of 34,113 laboratories which is 341 laboratories. We
estimate it would take 20 minutes for a laboratory to fill this
information on the PT submission form. Each laboratory would report
this information 3 times per year and would take approximately 1 hour.
The total annual burden is 341 hours (341 laboratories x 1 hour). A
Clinical Laboratory Technologists/Technicians (29-2010) would perform
this task at an hourly wage of $27.36 as published in 2021 by the
Bureau of Labor Statistics.\11\ The wage rate would be $54.72 to
include overhead and fringe benefits. The total cost would be $18,660
(341 hours x $54.72).
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\11\ https://www.bls.gov/oes/tables.htm.
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B. Optional On-Site Visits to PT Programs
At Sec. 493.901(e), we proposed to add the requirement that HHS
may require on-site visits for all initial PT program applications for
HHS approval and periodically for previously HHS-approved PT programs
either during the reapproval process or as necessary to review and
verify the policies and procedures represented in its application and
other information, including, but not limited to, review and
examination of documents and interviews of staff. There is no
collection of information requirements associated with this proposed
requirement because the documentation is already being collected and
maintained by the PT program as normal course of business and is a
usual and customary practice in accordance with implementing
regulations of the PRA at 5 CFR 1320.3(b)(2).
C. PT Program Reapproval
At Sec. 493.901(f), we proposed to specify that we may require a
PT program to reapply for approval using the process for initial
applications if widespread or systemic problems are encountered during
the reapproval process. If a PT program would need to reapply for
approval using the initial application process, we would estimate that
the cost would be 10 hours for document collection. The total burden is
90 hours (9 PT programs x 10 hour). However, this would not be an
annual burden, rather it would only occur under the circumstances
outlined above, and we believe that these would only occur rarely. An
Office/Administrative Support Worker (43-9199) would perform this task
at an hourly wage of $20.47 as published in 2021 by the Bureau of Labor
Statistics.\12\ The wage rate would be $40.94 to include overhead and
fringe benefits. The total cost would be $3,685 (90 hours x $40.94).
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\12\ https://www.bls.gov/oes/tables.htm.
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D. Withdrawal of Approval of a PT Program
At Sec. 493.905, we proposed to add that HHS may withdraw the
approval of a PT program at any point in the calendar year if the PT
program provides false or misleading information that is necessary to
meet a requirement for program approval or if the PT program has failed
to correct issues identified by HHS related to PT program requirements.
We also proposed to add a requirement that the PT program may request
reconsideration. We believe this is excepted because of it being an
administrative action per 5 CFR 1320.4(a)(2).
E. Submission of PT Data by Laboratories
At Sec. 493.901(c)(6), we proposed to add the requirement that PT
programs limit the participants' online submission of PT data to one
submission or that a method be provided to track changes made to
electronically reported results. As discussed in section II.C. of this
final rule, based on public comments from PT programs and laboratories
that this requirement would be burdensome and expensive, we are not
finalizing this proposal.
Table 2 reflects the total burden and associated costs for the
provisions included in this final rule.
[[Page 41219]]
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V. Regulatory Impact Analysis
A. Statement of Need
Proficiency testing (PT) has long been recognized as a critical
component of a quality management system. It was first required at a
national level for some clinical laboratories under CLIA `67. When CLIA
`88 was enacted, and its implementing regulations were finalized in
1992, all clinical laboratories that perform nonwaived testing became
subject to the CLIA PT requirements. Since that time, there have been
many changes in the practice of laboratory medicine and improvements in
the analytical accuracy of test methods, such that HHS decided to
assess the need to revise the PT regulations to ensure the accuracy and
reliability of testing currently being used for clinical decision-
making and improved patient outcomes. For example, a number of analytes
and tests now used for making clinical decisions were not recognized or
commonly used at the time the CLIA PT requirements were published on
February 28, 1992 at 42 CFR part 493 (57 FR 7002). Improvements in
analytical accuracy required revisions to the criteria for acceptable
performance to reflect the current practices and better assess clinical
laboratory performance. We based our decision to update the regulations
and incorporate the changes being finalized in this rule in part, as
discussed above, upon advice from the Clinical Laboratory Improvement
Advisory Committee (CLIAC), a Federal advisory committee charged with
providing recommendations to HHS on revisions needed to CLIA. The
members of CLIAC are knowledgeable about laboratory medicine and
quality.
B. Overall Impact
We have examined the impacts of this rule as required by Executive
Order 12866 on Regulatory Planning and Review (September 30, 1993),
Executive Order 13563 on Improving Regulation and Regulatory Review
(January 18, 2011), the Regulatory Flexibility Act (RFA) (September 19,
1980, Pub. L. 96-354), section 1102(b) of the Social Security Act,
section 202 of the Unfunded Mandates Reform Act of 1995 (March 22,
1995; Pub. L. 104-4), Executive Order 13132 on Federalism (August 4,
1999) and the Congressional Review Act (5 U.S.C. 804(2)).
Executive Orders 12866 and 13563 direct agencies to assess all
costs and benefits of available regulatory alternatives and, if
regulation is necessary, to select regulatory approaches that maximize
net benefits (including potential economic, environmental, public
health and safety effects, distributive impacts, and equity). Section
3(f) of Executive Order 12866 defines a ``significant regulatory
action'' as an action that is likely to result in a rule: (1) having an
annual effect on the economy of $100 million or more in any one year,
or adversely and materially affecting a sector of the economy,
productivity, competition, jobs, the environment, public health or
safety, or State, local or tribal governments or communities (also
referred to as ``economically significant''); (2) creating a serious
inconsistency or otherwise interfering with an action taken or planned
by another agency; (3) materially altering the budgetary impacts of
entitlement grants, user fees, or loan programs or the rights and
obligations of recipients thereof; or (4) raising novel legal or policy
issues arising out of legal mandates, the President's priorities, or
the principles set forth in the Executive Order. A regulatory impact
analysis (RIA) is required for economically significant regulatory
actions that are likely to impose costs or benefits of $100 million or
more in any given year. We prepared the RIA and found that this PT
final rule does not meet the threshold of section 3(f)(1) of the
Executive Order for a significant regulatory action. In addition, our
upper limit of estimated impact is under the threshold of $165 million
for the year of 2022 under the Unfunded Mandates Reform Act (UMRA).
Nevertheless, we have voluntarily performed an RIA, as would be
required for an economically significant regulation.
This rule revises the CLIA PT requirements and affects
approximately 35,967 clinical laboratories subject to participation in
PT, resulting in some cost implications (Table 5). In addition, as a
result of this final rule, the eight existing CLIA-approved PT programs
will incur some costs as they modify their programs to meet the
specified requirements. It will also have an effect on CLIA-exempt
States regarding State PT requirements.
The RFA requires agencies to analyze options for regulatory relief
of small entities, if a rule has a significant impact on a substantial
number of small entities. For purposes of the RFA, we assume that the
great majority of clinical laboratories and PT programs are small
entities, either by being nonprofit organizations or by meeting the
Small Business Administration definition of a small business (having
revenues of less than $8.0 million to $41.5 million in any 1 year). For
purposes of the RFA, we believe that approximately 82 percent of
clinical laboratories qualify as small entities based on their
nonprofit status as reported in the American Hospital Association Fast
Fact Sheet, updated January 2021 \13\ and 100 percent of PT programs
are nonprofit organizations. Individuals and States are not included in
the definition of a small entity. As its measure of significant
economic impact on a substantial number of small entities, HHS uses a
change in revenue of more than 3 to 5 percent. We do not believe that
this threshold will be reached by the requirements in this final rule.
Therefore, the Secretary has certified that this final rule will not
have a significant economic impact on a substantial number of small
entities. We have included several provisions in this rule to address
the requirements of the RFA and provide regulatory relief or minimize
burden for small entities such
[[Page 41220]]
as laboratories and PT programs. The first is incorporating a phase-in
period for implementation of this rule. This phase-in will provide time
for laboratories to identify PT programs offering the newly required PT
and subscribe to PT for any of the analytes or tests that they offer.
It will also provide the time needed by PT programs to add new analytes
and tests to their programs, which requires the identification of new
sources of PT materials and revision of administrative processes to
accommodate the revised requirements. Other changes that will decrease
burden, which are incorporated in this rule as a result of public
comments from laboratories and PT programs, were several proposed
revisions to microbiology PT. These proposed changes included adding PT
requirements for susceptibility or resistance testing in the
subspecialties of mycology and virology and adding a PT requirement for
resistance testing in bacteriology. Because public comments indicated
these requirements would be difficult to comply with due to limited
materials and variability in the testing, we are not finalizing those
changes in this rule, which mitigates burden that would have been
placed on both laboratories and PT programs. In addition, because of
similar public comments that questioned the value of currently required
PT for susceptibility testing in mycobacteriology, we are removing this
requirement in this final rule. These changes will provide regulatory
flexibility and reduce burden to small entities.
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\13\ https://www.aha.org/statistics/fast-facts-us-hospitals.
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In addition, section 1102(b) of the Social Security Act requires us
to prepare a regulatory impact analysis if a rule may have a
significant impact on the operations of a substantial number of small
rural hospitals. This analysis must conform to the provisions of
section 604 of the RFA. For purposes of section 1102(b) of the Act, we
define a small rural hospital as a hospital that is located outside of
a metropolitan statistical area and has fewer than 100 beds. We do not
expect this final rule will have a significant impact on small rural
hospitals and we are unable to estimate the number of laboratories that
support small rural hospitals. Such hospitals often provide limited
laboratory services and may refer testing for the newly required
analytes to larger hospitals. For the small rural hospitals with
laboratories that perform testing for the new analytes, we expect they
are already performing PT for other analytes and minimal effort will be
required since they should already have PT policies and procedures in
place. Therefore, the Secretary has certified that this final rule will
not have a significant impact on the operations of a substantial number
of small rural hospitals.
Section 202 of the UMRA also requires that agencies assess
anticipated costs and benefits before issuing any rule whose mandates
require spending in any one year of $100 million in 1995 dollars,
updated annually for inflation. In 2022, that threshold is
approximately $158 million. This rule will not impose an unfunded
mandate on States, tribal governments, or the private sector of more
than $165 million annually and thus does not meet the UMRA threshold.
Executive Order 13132 establishes certain requirements that an
agency must meet when it promulgates a final rule that imposes
substantial direct requirement costs on State and local governments,
preempts State law, or otherwise has Federalism implications. The
changes in this rule will not have a substantial direct effect on State
and local governments, preempt State law, or otherwise have a
Federalism implication and there is no change in the distribution of
power and responsibilities among the various levels of government. This
rule will not impose substantial direct compliance costs on State and
local governments that are not required by statute. A significant
number of laboratories affected by this rule are not operated by State
or local governments. Therefore, promulgation of this rule will not
cause substantial additional costs to State and local governments.
C. Anticipated Effects
This final rule will impact approximately 35,967 clinical
laboratories (total of Certificate of Compliance and Certificate of
Accreditation laboratories, as of January 2020) required to participate
in PT under the CLIA regulations implemented by the February 28, 1992
final rule, eight current CLIA-approved PT programs, and to a lesser
extent, in vitro diagnostics (IVD) manufacturers, healthcare providers,
laboratory surveyors, and patients. Although complete data are not
available to calculate all estimated costs and benefits that will
result from the changes made in this rule, we are providing an analysis
of the potential impact based on available information and certain
assumptions. Implementation of these requirements will result in
changes that will have both quantifiable and non-quantifiable impacts
on laboratories, PT programs, and others mentioned above. In estimating
the quantifiable impacts, we separated the laboratory specialties into
two broad categories that include: (1) PT changes to the microbiology
specialty; and (2) PT changes to non-microbiology specialties. This was
done because the PT requirements differ for microbiology than for other
laboratory specialties and laboratories that are certified to perform
microbiology testing may be impacted differently than those that
perform non-microbiology clinical testing. In each microbiology
subspecialty, PT participation is required based on the types of
services offered by a laboratory, and an overall score is given per
that subspecialty, whereas in the other specialties and subspecialties,
PT participation is required and scores are given based on specific
required analytes listed in the regulations.
1. Quantifiable Costs for Laboratories
CDC receives catalogs from all CLIA-approved PT programs annually.
We estimated material costs for purchasing PT materials based on the
range of 2020 catalog prices from the eight CLIA-approved PT programs.
In estimating the labor costs for performing PT for all laboratory
specialties that will be affected by this regulatory change, we assumed
the average national clinical laboratory fee schedule \14\ as an
estimate of the cost the laboratory incurs when testing each sample (or
challenge). This amount represents the average reimbursement to
laboratories performing patient testing for that analyte or test. We
also assume the cost for testing patient samples is the same as the
cost for testing PT samples.
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\14\ CMS Clinical Laboratory Fee Schedule Files: https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/ClinicalLabFeeSched/Clinical-Laboratory-Fee-Schedule-Files.
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We calculated that, on average, the cost impact would be between
$695 and $2,511 per laboratory, with laboratories testing fewer
analytes bearing a smaller burden.
a. Costs of PT Changes to the Microbiology Specialty
Changes to the microbiology specialty include changes in each of
the subspecialties (bacteriology, mycobacteriology, mycology,
parasitology, and virology) that will replace the types of services
offered and the examples of organisms to be included over time with a
list of categories of tests and groups of microorganisms for which PT
is required. In addition, this rule finalizes other changes in the CLIA
regulations, Subpart I for each individual subspecialty. These changes
will have a cost impact on laboratories. As stated in
[[Page 41221]]
CLIA at Sec. 493.801(a)(2)(ii) and Sec. 493.1236(c)(1), for tests or
procedures performed by the laboratory that are not listed in Subpart
I, Proficiency Testing Programs for Nonwaived Testing, a laboratory
must verify the accuracy of that test or procedure at least twice
annually. Although we do not have a way to estimate how many
microbiology laboratories voluntarily enroll in PT to meet this
requirement, we assume the added burden of performing the newly
required PT would be minimal for those already performing voluntary PT.
For the 5,341 affected microbiology laboratories, the estimated cost of
the quantifiable changes to required PT for each microbiology
subspecialty follows.
To estimate the costs that will be incurred by laboratories to
purchase PT materials to meet the revised requirements for the
microbiology specialty, we compiled a range of PT material cost
estimates per each challenge using 2020 catalog pricing for each PT
program. For this analysis we refer to the PT catalog offerings as
``modules.'' In microbiology, PT programs offer different types of
modules. Individual modules such as stain(s), antigen detection, or
toxin detection are intended for reporting a result for a single type
of test. Many microbiology modules include challenges that address
different types of testing. These modules, such as urine culture, may
include individual PT challenges for Gram stain, bacterial
identification, and antimicrobial susceptibility testing. In many
cases, estimating the challenge cost was difficult because PT programs'
pricing varies and in some cases the PT challenge cost per microbiology
test depends upon whether the test is offered as an individual module
or as part of a collection of multiple types of PT challenges in a
module. In addition, to accurately estimate the challenge cost, we had
to account for differences in the frequency at which the PT programs
currently offer their modules and challenges. For example, one PT
program may offer an antigen detection module at a frequency of two
events per year, and three samples per event (six total samples per
year), while another offers a similar module at three events per year,
and five samples per event (15 total samples per year). Based upon the
module type and frequency, we estimated the total low and high
challenge cost for PT material using the range of 2020 catalog prices
from the eight CLIA-approved PT programs for microbiology. Details are
explained under each subsection. We acknowledge that these estimated
ranges may be higher than the actual costs of requiring additional PT
since laboratories may already voluntarily purchase PT to meet the
biannual CLIA requirement for verifying the accuracy of testing.
However, we do not have a way of estimating the number of laboratories
or the cost of this voluntary participation.
In estimating the number of microbiology laboratories that will be
impacted by each of the regulatory changes, we determined the numbers
of Certificate of Compliance (CoC) and Certificate of Accreditation
(CoA) laboratories for each microbiology subspecialty using the CMS
Quality Improvement and Evaluation System (QIES) database. To
categorize the laboratories as described below, the QIES database was
used to determine the accreditation organization for each CoA
laboratory.
We designated two laboratory categories when estimating the impact
of the final PT rule in microbiology:
Laboratories participating in a PT program for already
required microbiology PT (Category M1).
Laboratories not participating in a PT program for newly
required microbiology PT (Category M2).
Category M1: Laboratories Already Participating in Required
Microbiology PT
For changes or additions to required microbiology PT, we used data
from the PT program event summaries provided to CDC by the PT programs
to estimate the total number of laboratories performing the already
required PT. We then used that number to estimate how many laboratories
would be affected by proposed changes or additions to the required PT.
Category M2: Laboratories Not Participating in a PT Program for Newly
Required Microbiology PT
We used Certificate of Accreditation data to estimate the number of
laboratories that are subject to the microbiology PT requirements in
this rule and are not already participating in a PT program. Of the
seven CLIA-approved accreditation organizations, data were provided by
COLA showing how many of the 6,999 COLA-accredited laboratories offer
testing for the microbiology tests that are being added to the list for
required PT. We used these data to estimate the percentage of COLA-
accredited laboratories that provide testing for these microbiology
tests. We assumed that COLA-accredited laboratories are similar to
Certificate of Compliance laboratories and laboratories accredited by
deemed status organizations other than the College of American
Pathologists (CAP) (who did not provide data) with regard to test
volumes and the microbiology testing they provide. Therefore, we
assumed that the percentage of COLA-accredited laboratories that
perform a specific microbiology test could be used to approximate the
total number of laboratories that perform the test. For the newly
required microbiology PT, the number of CAP-accredited laboratories was
considered negligible because they are already required to purchase PT
for all testing performed and were not included in the total. We
analyzed each proposed change for the microbiology specialty for each
category and added our estimates to obtain the total projected impact
on all affected laboratories.
(1) Costs of the PT Changes in the Bacteriology Subspecialty
In the bacteriology subspecialty, the changes being finalized in
this rule that may have a cost impact include the determination of
bacterial morphology as part of the Gram stain module, the addition of
bacterial toxin detection as required PT, and the addition of a second
antimicrobial susceptibility testing challenge per year. Gram stain
reaction is currently required in the PT regulations and all PT
programs that offer a Gram stain PT module also offer the determination
of bacterial morphology as part of the same module. We know the numbers
of total laboratories enrolled in the PT program modules that require
Gram stain reporting from the PT program event summaries. To determine
the number of laboratories that will be impacted by this change, we
calculated the number currently enrolled in Gram stain PT. Since this
change will require that these laboratories report bacterial morphology
in addition to Gram stain reaction on each challenge, we estimate the
cost impact would be minimal. We estimated the range of costs by using
the number of category M1 laboratories that perform Gram stain; the
estimate of the cost the laboratory incurs when testing each challenge,
using the average national CMS clinical laboratory fee schedule; the
low price and high price per challenge for PT (based on PT program
catalog variations); and the number of challenges required per year
using one challenge for the low estimate (Table 3) and 15 challenges
for the high estimate (Table 4).
To evaluate the impact of requiring PT for bacterial toxin
detection, we determined the total number of category M2 laboratories
for bacteriology. Laboratories performing voluntary PT
[[Page 41222]]
for bacterial toxin detection are already meeting the new PT
requirements. Since CAP-accredited laboratories are already required to
perform PT if they perform bacterial toxin detection, we assumed they
are already meeting the new PT requirements and did not include them in
our estimate. The range of estimated costs was determined by using the
number of category M2 impacted laboratories that perform bacterial
toxin detection; the estimate of the cost the laboratory incurs when
testing each challenge, using the average national CMS clinical
laboratory fee schedule; the low price and high price per challenge for
PT (based on PT program catalog variations); and the number of
challenges required per year using one challenge for the low estimate
(Table 1) and 15 challenges for the high estimate (Table 3).
Currently, one sample or challenge per testing event is required
for antimicrobial susceptibility testing in bacteriology. To evaluate
the impact of increasing the required antimicrobial susceptibility
testing from one challenge per year to two challenges per year, we
calculated the total number of category M1 laboratories already
participating in PT for antimicrobial susceptibility testing. The range
of estimated costs was determined by using the number of category M1
laboratories that currently perform antimicrobial susceptibility
testing; the estimate of the cost the laboratory incurs when testing
each challenge, using the average national CMS clinical laboratory fee
schedule; the low price and high price per challenge for PT (based on
PT program catalog variations); and the number of challenges required
per year using one challenge for the low estimate (Table 3).
Considering all of the potential cost impacts, the range of estimated
impact for the proposed bacteriology subspecialty changes for the first
year is $169,128 to $1,058,207.
(2) Costs of the PT Changes in the Mycobacteriology Subspecialty
Changes to add a second antimycobacterial susceptibility or
resistance testing challenge per event were proposed for the
mycobacteriology subspecialty. However, as discussed in section III.E.
of this final rule, due to public comments, those changes are not being
finalized. In addition, due to the public comments received, the
requirement for susceptibility testing in mycobacteriology is being
removed altogether in this rule. Although there may be a cost savings
for the small number of laboratories that perform antimycobacterial
susceptibility testing, we are assuming that the majority of these
laboratories will continue to subscribe to PT for this test to meet the
requirement at Sec. Sec. 493.801(a)(2)(ii) and 493.1236(c)(1) to
verify the accuracy of testing twice per year. As such, we are not
anticipating a significant cost savings by removing this requirement
and are not able to estimate the impact.
(3) Costs of the PT Changes in the Mycology Subspecialty
In the mycology subspecialty, the changes being finalized in this
rule that may have a cost impact include the addition of required PT
for direct fungal antigen detection and detection of the presence or
absence of fungi and aerobic actinomycetes without identification. To
evaluate the impact of the required PT for direct fungal antigen
detection, we determined the total number of category M2 laboratories
for mycology. Laboratories performing voluntary PT for direct fungal
antigen detection are already meeting the new PT requirements. Since
CAP-accredited laboratories are already required to perform PT if they
perform direct fungal antigen detection, we assumed they are already
meeting the new PT requirements and did not include them in our
estimate. The range of estimated costs was determined by using the
number of category M2 impacted laboratories that perform direct fungal
antigen detection; the estimate of the cost the laboratory incurs when
testing each challenge, using the average national CMS clinical
laboratory fee schedule; the low price and high price per challenge for
PT (based on PT program catalog variations); and the number of
challenges required per year using one challenge for the low estimate
(Table 3) and 15 challenges for the high estimate (Table 4).
The newly required detection of the presence or absence of fungi
and aerobic actinomycetes without identification impacts laboratories
that are currently performing dermatophyte identification using
dermatophyte test medium to determine the presence or absence of
dermatophytes in a patient specimen. We calculated the impact using the
same methodology as was performed to determine the impact of the
proposal to include direct fungal antigen detection (Tables 1 and 2).
Considering the cost impact of this rule in the mycology subspecialty,
the range estimated for the first year is $3,288 to $61,940.
(4) Costs of the PT Changes in the Parasitology Subspecialty
In the parasitology subspecialty, the change being finalized in
this rule that may have a cost impact is the addition of required PT
for direct parasite antigen detection. To evaluate the potential impact
of this addition, we determined the total number of category M2
laboratories for parasitology. Laboratories performing voluntary PT for
direct parasite antigen detection are already meeting the new PT
requirement. Since CAP-accredited laboratories are already required to
perform PT if they perform direct parasite antigen detection, we
assumed they are already meeting the new PT requirement and did not
include them in our estimate. The range of estimated costs was
determined by using the number of category M2 impacted laboratories
that perform direct parasite antigen detection; the estimate of the
cost the laboratory incurs when testing each challenge, using the
average national CMS clinical laboratory fee schedule; the low price
and high price per challenge for PT (based on PT program catalog
variations); and the number of challenges required per year using one
challenge for the low estimate (Table 3) and 15 challenges for the high
estimate (Table 4). Considering the potential cost impact of this rule
in the parasitology subspecialty, the range estimated for the first
year is $8,098 to $458,136.
(5) Costs of the PT Changes in the Virology Subspecialty
In the virology subspecialty, the proposed change that would have
had a cost impact was the addition of two antiviral susceptibility or
resistance testing challenges per year. However, as a result of the
public comments received, that change is not being finalized in this
rule. Therefore, we do not estimate a cost impact resulting from this
rule in the subspecialty of virology.
BILLING CODE 4120-01-P
[[Page 41223]]
[GRAPHIC] [TIFF OMITTED] TR11JY22.002
[GRAPHIC] [TIFF OMITTED] TR11JY22.003
[[Page 41224]]
BILLING CODE 4120-01-C
b. Costs of PT Changes to the Non-Microbiology Specialties/
Subspecialties
The changes being finalized in this rule in specialties and
subspecialties other than microbiology include adding 30 new analytes
at the frequency of three events per year and five challenges per
event. According to CLIA, laboratories with Certificates of Compliance
and Certificates of Accreditation are required to perform PT. There are
35,967 clinical laboratories that will be affected (18,938 Certificate
of Compliance and 17,029 Certificate of Accreditation laboratories).
The changes to required PT will be a new burden for some laboratories,
but many laboratories are already paying for PT of these analytes. As
previously mentioned, in CLIA Sec. Sec. 493.801(a)(2)(ii) and
493.1236(c)(1), for tests or procedures performed by the laboratory
that are not listed in the CLIA regulations Subpart I, the laboratory
must verify the accuracy of that test or procedure at least twice
annually. Since laboratories may voluntarily enroll in PT as one way to
meet this requirement, we assume the added burden would be minimal. We
have evidence from laboratories that responded to our national PT
survey that of those who were not already required by the CAP to
perform PT on more than the CLIA-required analytes, 39 percent
purchased PT for 1 to 5 analytes, 17 percent for 6 to 10 analytes, 10
percent for 11 to 20 analytes, and 10 percent for more than 20
analytes. We estimated the costs for newly required analytes by
grouping all affected laboratories into four categories: (1) CAP
enrolled in CAP PT program, (2) CAP enrolled in 7 non-CAP PT Program,
(3) Non-CAP not enrolled in 7 non-CAP PT program, and (4) Non-CAP
enrolled in 7 non-CAP PT program), calculating the number of
laboratories in each category and calculating the costs using the
analyte price, test reimbursement rate and labor cost to update PT
policies and procedures. We also tightened ALs and added concentration
limits for several currently required analytes, which may have an
impact on laboratories, but the cost impact is not included in our
estimate. In addition, with this rule, we are finalizing the removal of
five required analytes (ethosuximide, LDH isoenzymes, primidone,
procainamide/NAPA, and quinidine) that are infrequently performed. As
such, we do not anticipate this being a substantial cost savings since
laboratories may continue to use PT voluntarily as a way of meeting the
biannual accuracy verification requirement.
Three issues had to be considered to estimate the costs for PT
materials for new analytes: PT programs may offer analytes as an
individual analyte or as part of a module that combines multiple
analytes; some of the new analytes may already be offered but at a
frequency other than the CLIA-required frequency (3 x 5 = 15 samples
per year); and the extent to which laboratories already use PT varies
that is, laboratories accredited by the CAP are required to enroll in
PT for each test they perform. For all these reasons, laboratories
enrolled in different PT programs will be impacted differently. Based
on this observation and our inability to make estimates at the level of
individual laboratories, we accounted for each of these variations when
calculating the costs incurred.
To account for the different prices each PT program charges for
different analytes, as an individual analyte or as part of a module, we
used a range of estimates based upon the PT programs' unit costs for PT
currently offered. We used two approaches to estimate the cost of
individual PT analytes. If the analyte was offered individually by the
PT program, we used that price. However, if the analyte was not offered
individually, we divided the panel price by the total number of
analytes in the panel to determine the cost per analyte, which is used
as individual analyte price. For the lower cost estimate, we selected
the lowest individual analyte price among all PT providers. For the
higher cost estimate, we used the highest individual analyte price. In
some cases, PT programs offer PT for the new analytes at different
frequencies, that is, different numbers of events per year and
different numbers of challenges per event. Therefore, to accurately
estimate future costs, we had to calculate the increased frequency for
each analyte in order to achieve three events/year with five challenges
per event.
Implementation of this final rule will have different impacts on
different laboratories mainly because laboratories either have a
Certificate of Compliance or a Certificate of Accreditation and may be
accredited by different accreditation organizations and purchase PT
from different PT programs. Our analysis starts with CAP-accredited
laboratories as CAP is not only a large accreditation organization but
also the largest PT program. In estimating the number of affected
laboratories as a result of this final rule, we acknowledged that any
CAP-accredited laboratory that offers patient testing for one of the
CAP PT program analytes must enroll in the relevant program for that
analyte. However, CAP-accredited laboratories are permitted to enroll
in PT from other CAP-approved PT programs. Laboratories not accredited
by the CAP may purchase PT materials from any CLIA-approved PT program,
including the CAP PT program. Therefore, we have designated four
categories to estimate the cost impact of this rule.
Category 1: Laboratories Accredited by the CAP That Purchase Material
From the CAP PT Program
The CAP provided us with the number of CAP-accredited laboratories
that are enrolled in their PT program for each new analyte.
The cost increase was calculated on a per analyte basis by
multiplying the cost per sample (PT material + CMS reimbursement
amount) by the increase in frequency of samples and the number of
laboratories that purchase PT from the CAP PT program. We estimate the
costs for laboratories accredited by CAP that purchase material from
the CAP PT program to be $4,498,535.
Category 2: CAP-Accredited Laboratories That Purchase PT Materials From
Other PT Programs
For the analytes we are adding in this rule, CAP-accredited
laboratories are required to enroll in a CLIA-approved PT program.
Ordinarily CAP-accredited laboratories enroll in the CAP PT program but
are permitted to enroll in PT from other CAP-approved PT programs.
Using the data the CAP provided, we calculated the total number of CAP-
accredited laboratories enrolled in one of the other PT programs
provided through PT Program A, PT Program D, PT Program E, or PT
Program G.
The cost increase in this category was calculated on a per analyte
basis. We were able to obtain the enrollment distribution of the CAP-
accredited laboratories in each of the non-CAP PT programs. The cost
increase was calculated on a per analyte basis by multiplying the cost
per sample (PT material + CMS reimbursement amount) by the increase in
frequency of samples and the number of laboratories that purchase PT
from the non-CAP PT program. We estimate the costs for CAP-accredited
laboratories that purchase PT materials from other PT programs will
range from $0 to $1,304,343.
Category 3: Laboratories Not Accredited by CAP That Are Not Already
Enrolled in Other PT Programs
To derive the minimum and maximum number of laboratories not
already enrolled in a PT program that may provide testing for the newly
required analytes, we began by
[[Page 41225]]
estimating that there are 22,119 laboratories that perform nonwaived
testing and are not accredited by the CAP in the US. To facilitate the
calculations, we presumed that laboratories not accredited by CAP will
not purchase CAP PT. From the QIES database, we derived the number of
laboratories not accredited by CAP that provide testing in each
specialty and reasoned that this was the maximum number of laboratories
not accredited by the CAP that might provide testing for each analyte.
COLA provided us with the percentages of the approximately 6,999
COLA-accredited laboratories that perform testing for each new analyte.
We determined that COLA-accredited laboratories are similar to CoC
laboratories in terms of their annual test volumes. Therefore, we
assumed that the percentage of COLA-accredited laboratories that test
each new analyte could be used to estimate the minimum number of CoC
and CoA (other than CAP- or COLA-accredited) laboratories that test
each analyte.
We used the percentage of CAP-accredited laboratories that
participate in PT for each new analyte to estimate the maximum number
of CoC and CoA (other than CAP and COLA) laboratories that test each
analyte. This percentage was much higher for many of the analytes when
compared to the laboratories accredited by organizations other than the
CAP. Since CAP-accredited laboratories are often either hospital-based
or commercial laboratories that already participate in PT for the
additional analytes, approximations for high estimates may
substantially overestimate the number of laboratories impacted.
Using the above information, we calculated low and high estimates
for the total number of CoC and non-CAP-accredited CoA laboratories
that may provide testing for each new analyte.
For each new analyte, we calculated the number of CAP-accredited
laboratories that buy from non-CAP PT programs by subtracting the CAP-
accredited laboratories enrolled in CAP PT from the total number of
CAP-accredited laboratories.
We derived a low estimate of the total number of laboratories not
accredited by CAP and not enrolled in one of the non-CAP PT programs
for each analyte. Negative estimates were taken as ``0.'' This
represents our low estimate of the number of laboratories that will
need to purchase PT for each analyte.
To obtain the high estimate for the number of laboratories not
accredited by CAP and not enrolled in one of the non-CAP PT programs,
we took the high estimate of CoC laboratories and CoA laboratories not
accredited by the CAP and subtracted the number of this subset of CoA
laboratories already known to be enrolled in PT. For the high estimate
of the number of laboratories not accredited by CAP and not enrolled in
one of the non-CAP PT programs, we also used an additional criterion of
the number of laboratories in the respective specialty from QIES to cap
the estimate at the number of laboratories in the specialty. If this
number was less than the high estimate of CoC laboratories and CoA
laboratories accredited by a program other than CAP, then the high
estimate was calculated by subtracting the number of laboratories not
accredited by CAP and not enrolled in one of the non-CAP PT programs
from the total number of laboratories in the specialty.
The cost increase in this category was calculated on a per analyte
basis. The minimum cost per sample that was the lowest across all seven
non-CAP PT programs and the maximum cost per sample that was the
highest across all seven non-CAP PT programs were used for these
calculations. The minimum cost increase was calculated by multiplying
the minimum cost per sample, including the CMS reimbursement amount, by
the number of laboratories that are not purchasing PT from any PT
program. The same calculation was made using the maximum cost per
sample for the maximum cost increase. We estimate the costs for
laboratories not accredited by CAP and not already enrolled in other PT
programs will range from $7,047,880 to $58,710,510.
Category 4: Laboratories Not Accredited by the CAP and Enrolled in PT
Programs Other Than the CAP PT Program
We obtained the number of laboratories enrolled in PT programs
other than the CAP PT program from the PT event summaries from each PT
program. The cost increase in this category was calculated on a per
analyte basis. The estimated cost increases were calculated for each of
the non-CAP PT programs for which information was available. The
minimum increase was calculated for each of the PT programs by
multiplying the cost per sample, including the CMS reimbursement
amount, by the increase in frequency of samples and the number of
laboratories that purchase PT from that individual program. To
determine the maximum increase, the same calculation was made using the
highest cost per analyte, including the CMS reimbursement amount. We
estimate the costs for laboratories not accredited by CAP and already
enrolled in non-CAP PT programs will be $1,051,614.
c. Costs for Laboratories, Deemed Accreditation Organizations, Exempt
States, and PT Programs To Update Policies and Procedures
We expect that the 35,967 CoC and CoA laboratories will incur costs
for the time needed to review the revised PT regulations and update
their policies, procedures, and information technology (IT) systems, as
needed, to be in compliance with the updated regulations. We assume a
one-time burden of 4 to 8 hours per laboratory will be needed for this.
A general management level employee (13-1111) would perform this task
at an hourly wage of $46.91 per hour as published in 2020 by the Bureau
of Labor Statistics (https://www.bls.gov/oes/current/oes_nat.htm). The
wage rate would be $93.82 to include overhead and fringe benefits.
Therefore, we estimate the one-time costs for CoC and CoA laboratories
will range from $13,497,696 to $26,995,392 ($93.82 x 35,967 x 4 or 8
hours). Similarly, seven approved accreditation organizations and two
exempt States will need to review the regulations and may need to
revise their survey policies and procedures to be consistent with the
updated requirements. We estimate a one-time burden of 10 to 15 hours
to review the revised regulations and to develop policies and
procedures needed to reflect the new PT requirements. We assume the
person performing this review will be a business management level
employee (11-1021) paid $60.45 per hour as published in 2020 by the
Bureau of Labor Statistics (https://www.bls.gov/oes/current/oes_nat.htm). The wage rate would be $120.90 to include overhead and
fringe benefits. Therefore, we estimate the one-time costs for
accreditation organizations and exempt States to update their policies
and procedures will range from $10,881 to $16,322. For PT programs, we
estimate a one-time burden of 30 to 35 hours for them to review the
updated regulations, revise their policies and procedures, and add new
analytes or microbiology tests that they choose to offer. We assume the
person performing this job will be a business management level employee
paid $60.45 per hour as published in 2020 by the Bureau of Labor
Statistics (https://www.bls.gov/oes/current/oes_nat.htm). The wage rate
would be $120.90 to include overhead and fringe benefits. Therefore, we
estimate the one-time costs for PT programs will range from $36,270 to
$42,315.
[[Page 41226]]
d. Results
We estimate that the overall impact of adding requirements for the
new analytes in the specialties and subspecialties other than
microbiology will range from approximately $13 to $66 million for the
first year (Table 5). Because of the larger number of non-CAP
accredited laboratories, and the fact that they tend not to enroll in
non-required PT as frequently as CAP-accredited laboratories do, we
estimate that non-CAP accredited laboratories that are not enrolled in
any PT program will have an impact between $7 and $59 million for the
first year. We also estimate that laboratories not accredited by CAP
that are enrolled in PT programs other than CAP will have a relatively
minor impact, $1 million for the first year (Table 5).
BILLING CODE 4120-01-P
[GRAPHIC] [TIFF OMITTED] TR11JY22.004
Table 6 shows the total estimated range of annual cost for the
changes (including both microbiology and non-microbiology) in
undiscounted 2020 dollars and discounted at 3 percent and 7 percent to
translate expected costs in any given future years into present value
terms. The base year is 2020 for the calculations displayed in Table 6
and we assume costs in future years to be the same as costs in the base
year.
[[Page 41227]]
[GRAPHIC] [TIFF OMITTED] TR11JY22.005
[[Page 41228]]
BILLING CODE 4120-01-C
d. Non-Quantifiable Costs
A number of non-quantifiable cost impacts will also result for PT
programs and laboratories when this rule becomes effective.
As with any required PT, implementation of this final regulation
does not require approved PT programs to offer additional analytes.
Several programs already offer the analytes or tests that will be
required, and, in these cases, we expect there to be a minimal cost
impact on the PT programs. We expect there will initially be some
increased expenditures for PT programs to implement the changes, even
if they are only scaling up currently offered PT. We have included an
estimate of those costs in this RIA. At the same time, PT programs will
also increase revenue received if they increase the PT analytes or
tests they offer. We have no way to estimate how many programs may
choose to offer additional PT analytes or tests, but we assume that
most will implement the changes included in the final rule. For some
programs, this will mean offering an analyte or test for the first
time, while for others it will mean increasing the yearly number of
events and/or challenges per event. The costs will be relatively less
for the programs that are already offering the PT analytes or tests,
including those currently offering challenges at less than the PT
frequency required under CLIA. There are also differences in what the
PT programs charge laboratories for PT. In part, these differences
depend upon the total number of samples distributed per year and how
the PT is packaged; some PT is sold as modules that group several
related analytes together. Because CLIA-approved PT programs are
required to maintain non-profit status, any increased revenue that
results from an expanded PT menu will not be turned into profit. We
have attempted to account for the quantifiable impacts in our estimates
for laboratories.
When this rule becomes effective, some PT programs may cease
offering the analytes that are no longer required, others may continue
to offer them at a frequency less than that required under CLIA, and
still others may continue to offer them at the PT frequency required
under CLIA. For these reasons we are unable to estimate the cost impact
to PT programs for this change.
Although we cannot precisely predict how the changes may
qualitatively affect clinical laboratories, we do not expect there to
be major changes in how they function. We have quantified the costs we
expect laboratories to incur but there may be costs associated with
other administrative functions related to PT ordering, result
reporting, and record keeping that we are not able to estimate. For
those laboratories that currently purchase PT for the five analytes for
which PT is no longer required, we cannot estimate the lowered
expenditure for laboratories that stop buying PT materials and must
begin doing something else to verify accuracy. Based on our focus
groups and surveys, we know there are a variety of things laboratories
may do to externally verify accuracy, ranging from splitting samples
with other laboratories to purchasing PT materials voluntarily. Also,
we do not know the extent to which split samples are tested, or how
many patient samples might be tested in this way; there is no stated
minimum number of specimens that must be tested semi-annually to verify
accuracy. Therefore, we have not attempted to estimate the costs for
alternative approaches that may be adopted to verify accuracy for the
deleted analytes. Regardless of how laboratories might be impacted, we
expect that they will not spend more than what they currently spend on
PT for the analytes deleted, but we cannot estimate this. By not
attempting to estimate the number of laboratories that may stop buying
PT material for the deleted analytes, we may be slightly overestimating
the net impact.
e. Benefits
While we cannot quantify the benefits that implementation of this
final rule revising the PT requirements will bring, we believe that the
changes will improve the accuracy and reliability of testing and allow
for quicker identification of unacceptable practice in laboratories,
especially those laboratories that have not previously participated in
PT. Remediation after identification of problems should also occur more
quickly and clinical test results of marginal or inferior quality are
less likely to be used as analytical systems will improve. All of these
things will serve to minimize the potential adverse impact to patients
and will benefit physicians and healthcare providers while not
impacting access to testing.
PT performance partially reflects daily clinical laboratory
performance. Updating ALs will benefit laboratories by helping to
ensure the accuracy and reliability of testing and providing a
mechanism for laboratories to be held accountable for clinically
appropriate patient test results, which directly affects the public's
health. Both clinical laboratories and patients can benefit from
continued monitoring of PT to help assess the success of intervention
efforts to improve the overall quality of clinical laboratory testing.
Another benefit that may result from adding new PT analytes and
tests and updating the limits for acceptable PT performance under CLIA
includes the generation of additional information on test performance
and sources of errors that PT programs can share with laboratories.
Such information can also be used as a source of training and can help
to maintain the competency of testing personnel (Garcia, et al, 2014).
Last, while we do not anticipate that the changes in this final
rule will result in any costs on the IVD industry, we expect the IVD
industry to potentially benefit by the changes made in this rule, from
having the ability to track PT results for the added analytes to enable
better and faster detection of problems with product manufacturing,
including reagent problems. We are aware that some IVD manufacturers
enroll in PT and are able to track the performance of the peer groups
using their instruments in summary reports issued by the PT programs.
Ultimately, we believe that laboratories, healthcare providers,
patients, and the IVD industry will benefit from improved analytical
performance \5\ that is expected to occur when this final rule becomes
effective with this new rule.
D. Alternatives Considered
A number of alternatives were considered in finalizing the changes
in this rule. We considered the possibility of changing either the
required frequency of PT events per year or changing the number of
required PT challenges per event. Responses from our national survey
did not support changing either parameter nor did CLIAC recommend any
changes to the required PT frequency or number of challenges per event.
Similarly, public comments received in response to the proposed rule
did not suggest changes to required PT frequency or number of
challenges per event. We did not perceive a benefit from either
reducing or increasing the number of events per year. Reducing the
number of events to two per year and keeping all other factors the same
would cost less, but it would delay the potential time it takes to
identify a poor performing laboratory as ``unsuccessful'' to at least
12 months, instead of the current 8 months. Increasing the number of
events might help to identify a laboratory with testing issues slightly
earlier, but increasing the number of events would increase costs. In
this final rule, we will continue to require five challenges per event,
with a successful event score defined under
[[Page 41229]]
CLIA `88 as a minimum of four out of five challenges (80 percent)
falling within the criteria for acceptable performance.
For the microbiology specialty, we considered the possibility of
including required PT analytes in each subspecialty at a frequency of
three events per year with five challenges per event. We determined
that the increase in required PT would result in an additional cost
impact of more than five million dollars to laboratories who would be
required to perform susceptibility testing for 15 challenges per year.
For the non-microbiology specialties and subspecialties, we could have
opted not to add any new PT analytes but testing of the analytes we are
now adding in this rule is widespread and is important in clinical
decision-making and public health testing. We also considered adding
all analytes for which there was at least one existing PT program, but
this alternative would have been excessively burdensome as it would
mean adding hundreds of new required analytes which may not be
necessary to identify problematic laboratory performance. We could have
left the ALs as they were established in CLIA `88, but we rejected this
approach as outdated given advancements in technology. We considered
the option of enforcing the definition of peer group established in
CLIA `88, but we decided this would be too expensive and ultimately
unworkable because it would require PT programs to perform
commutability testing using analyzers from multiple peer groups every
time a new batch of PT materials was created.
E. Accounting Statement and Table
We have prepared the following accounting statement showing the
classification of expenditures associated with the provisions of this
rule.
BILLING CODE 4120-01-P
[[Page 41230]]
[GRAPHIC] [TIFF OMITTED] TR11JY22.006
[[Page 41231]]
BILLING CODE 4120-01-C
F. Conclusion
We estimate that the total cost for laboratories to participate in
PT for the analytes and tests in this rule will be between $26 and $94
million in 2020 dollars. 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 healthcare providers,
patients, and the public, in the reliability and accuracy of test
results.
We have determined that this rule will not have a significant
economic impact on a substantial number of small entities or a
significant impact in the operations of a substantial number of small
rural hospitals and for these reasons, we are not preparing analyses
for either the RFA or section 1102(b) of the Act. However, we described
actions being taken in finalizing this rule to reduce burden and
minimize the impact on small entities such as laboratories and PT
programs.
In accordance with the provisions of Executive Order 12866, this
regulation was reviewed by the Office of Management and Budget.
VI. Analysis of and Responses to Public Comments on the Paperwork
Reduction and Regulatory Impact Analysis
We have provided an analysis of the potential impact of this final
rule, based upon available information and certain assumptions. We have
prepared the Paperwork Reduction Act and the Regulatory Impact Analysis
representing the costs and benefits of the final rule based on analysis
of identified variables and data sources needed for this change. We
requested that commenters provide any additional data that would assist
us in the analysis of the potential impact of this regulation on CLIA-
certified laboratories, but we did not receive any additional data.
Therefore, based on our analysis and assessment of the overall
annual costs to the laboratories affected by this final rule, we are
finalizing the provisions in this rule. The comments and our responses
are set forth below:
Comment: As part of regulatory impact analysis for the proposed
rule, we described the benefits of PT and the need to update the
regulations. Commenters representing accreditation organizations and
laboratory professional organizations were supportive of the proposed
changes, especially the expansion of the list of required PT analytes.
The commenters noted that PT is a valuable quality indicator and
measure of laboratory performance and they emphasized that the accuracy
and reliability of laboratory testing is critical to patient safety and
the delivery of quality healthcare services. A few commenters stated
that PT is burdensome and expensive, one of them adding that the
benefits of PT in reducing testing errors has not been documented
through studies or other evidence.
Response: We appreciate the comments that expressed support for the
changes in the proposed rule and recognized the value of PT as a
measure of laboratory quality and a mechanism to detect and prevent
errors that can affect patient safety. However, we agree with the
commenters who stated that it is difficult to quantify the value of PT
and we recognize the financial and other resource costs associated with
performing PT. Based on the positive comments received and previously
published studies (7-10), we believe that PT is a useful adjunct to
identify poor-performing laboratories and to help laboratories ensure
the quality of their testing which directly affects patients, and
ultimately the public's health.
Comment: We received comments from accreditation organizations,
professional organizations, businesses, and individuals concerning our
estimate of the impact of the proposed rule. Several commenters stated
that we had underestimated the overall impact, including the impact on
individual laboratories and accreditation organizations, especially the
administrative burden of new PT. While one commenter stated our
methodology was correct, others disagreed, and one commenter stated
that we failed to consider bigger changes to the way PT is conducted
which could reduce costs. A few commenters suggested that we conduct a
more comprehensive impact analysis.
Response: We acknowledge that our analysis was limited by the
availability of data and our ability to estimate all aspects of the
proposed changes. In the proposed rule, we solicited comments and data
to facilitate the determination of quantifiable estimates of the impact
in the final rule. We did not receive any suggestions of alternative
methods or data on which to base our estimates. Therefore, in this
final rule we have used similar methodology to that used in the
proposed rule with exceptions as follows. We added a range of estimates
to cover the one-time costs that would be expected for CoC and CoA
laboratories subject to PT to review the updated regulations; modify
policies, procedures, and IT systems as needed; and enroll in
appropriate PT to be in compliance with the revised requirements. We
also modified the impact analysis to include estimation of the one-time
costs for the seven deemed accreditation organizations and two exempt
States to review the updated regulations and revise their survey
policies and procedures to be consistent with the new PT requirements.
Lastly, we added similar one-time estimates for PT programs to review
the updated regulations, modify policies and procedures, and determine
if they will choose to offer the new analytes or microbiology PT. We
recognize that there will be ongoing costs for laboratories, deemed
accreditation organizations, exempt States, and PT programs based on
the revised list of required analytes and changes to microbiology PT.
However, we are unable to project these costs since, although we do not
know the number, some laboratories are already participating in PT for
the new analytes and microbiology tests as a way of meeting the
requirement to verify the accuracy of testing twice per year. For these
laboratories, the ongoing additional costs may be minimal. Similarly,
the accreditation organizations and exempt States may already be
reviewing voluntary PT data for some of the newly required analytes and
tests. With respect to ongoing costs for PT programs, we are also
unable to estimate the costs. As previously described in this rule
regarding the criteria used to select new analytes and microbiology PT,
we are aware that at least three programs already offer PT for these
analytes and tests, and we are unsure how many additional programs will
choose to offer them since they are not required by CLIA to do so. For
those that already offer the additional PT, we expect the ongoing costs
to be minimal.
Comment: Several commenters recommended that the effects of the
recent Protecting Access to Medicare Act of 2014 (PAMA) regulations
should be considered as part of the regulatory impact analysis in light
of PAMA's impact on laboratory testing reimbursement under Medicare.
Response: We recognize the impact of PAMA on Medicare payment for
laboratory testing. However, PAMA was implemented in 2018 and those
changes were independent of the CLIA PT changes that are now being
finalized. We do not have data that would allow us to determine the
cumulative effects of the two rules that were implemented at two
separate points in time. We did use the CMS CLFS for 2020, which
included post-PAMA payment rates, as
[[Page 41232]]
one part of our estimate of the costs of performing PT, as no other
data sources were suggested by commenters.
Comment: A commenter noted that the RIA had not accounted for the
costs of disallowing the use of for-profit entities by PT programs for
conducting any part of their business and suggested that the final rule
should include this economic assessment.
Response: The proposed rule did not specify that for-profit
entities were disallowed for use by PT programs for conducting any part
of their business. In this final rule, we are clarifying that the
provision being finalized at Sec. 493.901(c)(8), previously proposed
at Sec. 493.901(c)(9), requires that technical and scientific
responsibilities, such as grading PT, must be carried out by nonprofit
organizations, Federal or State agencies, or entities acting as a
designated Federal or State agency. This is an inherent function of an
approved PT program and should not result in additional costs for the
programs. Contractors used to perform tasks such as manufacturing or
transportation of samples are not required to be non-profit entities.
Chiquita Brooks-LaSure, Administrator of the Centers for Medicare &
Medicaid Services, approved this document on June 21, 2022.
Rochelle P. Walensky, MD, MPH, Director of the Centers for Disease
Control and Prevention, approved this document on June 17, 2022.
List of Subjects in 42 CFR Part 493
Administrative practice and procedure, Grant programs-health,
Health facilities, Laboratories, Medicaid, Medicare, Penalties,
Reporting and recordkeeping requirements.
For the reasons set forth in the preamble, the Centers for Medicare
& Medicaid Services amends 42 CFR part 493 as set forth below:
PART 493--LABORATORY REQUIREMENTS
0
1. The authority citation for part 493 continues to read as follows:
Authority: 42 U.S.C. 263a, 1302, 1395x(e), the sentence
following 1395x(s)(11) through 1395x(s)(16).
0
2. Amend Sec. 493.2 by--
0
a. Adding the definitions of ``Acceptance limit'' and ``Peer group'' in
alphabetical order; and
0
b. Revising the definition of ``Target value''.
The additions and revision read as follows:
Sec. 493.2 Definitions.
* * * * *
Acceptance limit means the symmetrical tolerance (plus and minus)
around the target value.
* * * * *
Peer group means a group of laboratories whose testing process
utilizes similar instruments, methodologies, and/or reagent systems and
is not to be assigned using the reagent lot number level.
* * * * *
Target value for quantitative tests means:
(1) If the peer group consists of 10 participants or greater:
(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) unless acceptable scientific
reasons are available to indicate that such an evaluation is not
appropriate.
* * * * *
0
3. Amend Sec. 493.20 by revising paragraph (c) to read as follows:
Sec. 493.20 Laboratories performing tests of moderate complexity.
* * * * *
(c) If the laboratory also performs waived tests, compliance with
Sec. 493.801(a) and (b)(7) and subparts J, K, and M of this part is
not applicable to the waived tests. However, the laboratory must comply
with the requirements in Sec. Sec. 493.15(e), 493.801(b)(1) through
(6), 493.1771, 493.1773, and 493.1775
0
4. Amend Sec. 493.25 by revising paragraph (d) to read as follows:
Sec. 493.25 Laboratories performing tests of high complexity.
* * * * *
(d) If the laboratory also performs waived tests, compliance with
Sec. Sec. 493.801(a) and 493.801(b)(7) and subparts J, K, and M of
this part are not applicable to the waived tests. However, the
laboratory must comply with the requirements in Sec. Sec. 493.15(e),
493.801(b)(1) through (6), 493.1771, 493.1773, and 493.1775.
0
5. Amend Sec. 493.801 by--
0
a. Redesignating paragraphs (b)(3) through (6) as paragraphs (b)(4)
through (7), respectively; and
0
b. Adding new paragraph (b)(3).
The addition reads as follows:
Sec. 493.801 Condition: Enrollment and testing of samples.
* * * * *
(b) * * *
(3) The laboratory must report PT results for microbiology organism
identification to the highest level that it reports results on patient
specimens.
* * * * *
0
6. Amend Sec. 493.861 by revising paragraph (a) to read as follows:
Sec. 493.861 Standard; Unexpected antibody detection.
(a) Failure to attain an overall testing event score of at least
100 percent is unsatisfactory performance.
* * * * *
0
7. Amend Sec. 493.901 by--
0
a. Redesignating paragraphs (a), (b), (c), and (d) as paragraphs (b),
(c), (d), and (e), respectively;
0
b. Adding new paragraph (a);
0
c. In newly redesignated paragraph (c)(7) by removing ``;'' and adding
in its place ``; and'';
0
d. Adding new paragraph (c)(8);
0
e. Revising newly redesignated paragraph (e); and
0
f. Adding new paragraph (f).
The additions and revisions read as follows:
Sec. 493.901 Approval of proficiency testing programs.
* * * * *
(a) Require a minimum of 10 laboratory participants for each
specialty, subspecialty, and analyte or test for which the proficiency
testing program is seeking reapproval;
* * * * *
(c) * * *
(8) A contractor performing technical and scientific
responsibilities as described in this section and Sec. 493.903
(including, but not limited to, processes for selecting appropriate
target values to be included in challenges as part of the annual PT
program or grading PT results, determining target values, reporting
scores to CMS, and determining organisms included in microbiology PT
samples) must be a private nonprofit organization or a Federal or State
agency, or an entity acting as a designated agent for the Federal or
State agency.
* * * * *
(e) HHS may require on-site visits for all initial proficiency
testing program applications for CMS approval and
[[Page 41233]]
periodically or when problems are encountered for previously HHS-
approved proficiency testing programs either during the reapproval
process or as necessary to review and verify the policies and
procedures represented in its application and other information,
including, but not limited to, review and examination of documents and
interviews of staff.
(f) HHS may require a proficiency testing program to reapply for
approval using the process for initial applications if significant
problems are encountered during the reapproval process.
0
8. Amend Sec. 493.903 by--
0
a. In paragraph (a)(1) by removing the period and adding ``;'';
0
b. In paragraph (a)(2) by removing ``;'' and adding in its place ``;
and''; and
0
c. By adding new paragraph (a)(3).
The addition reads as follows:
Sec. 493.903 Administrative responsibilities.
* * * * *
(a) * * *
(3) Not change submitted laboratory data and results for any
proficiency testing event;
* * * * *
0
9. Section 493.905 is revised to read as follows:
Sec. 493.905 Nonapproved proficiency testing programs.
(a) Effect on approval status. If a proficiency testing program is
determined by HHS to fail to meet any criteria contained in Sec. Sec.
493.901 through 493.959 for approval of the proficiency testing
program, CMS will notify the program of its withdrawal of approval.
Approval of the PT program remains in effect for 60 days from the date
of notification. The proficiency testing program must notify all of its
participating laboratories of the withdrawal of approval within 30 days
from the date of notification. CMS may disapprove any proficiency
testing program that provides false or misleading information with
respect to any information that is necessary to meet any criteria
contained in Sec. Sec. 493.901 through 493.959 for approval of the
proficiency testing program.
(b) Request for reconsideration. Any proficiency testing program
that is dissatisfied with a determination to disapprove the program may
request that CMS reconsider the determination, in accordance with
subpart D of part 488.
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10. Section 493.911 is revised to read as follows:
Sec. 493.911 Bacteriology.
(a) Program content and frequency of challenge. To be approved for
proficiency testing for bacteriology, the annual program must provide a
minimum of five samples per testing event. There must be at least three
testing events provided to the laboratory at approximately equal
intervals per year. The samples may be provided to the laboratory
through mailed shipments. The specific organisms included in the
samples may vary from year to year.
(1) The annual program must include, as applicable, samples for:
(i) Gram stain including bacterial morphology;
(ii) Direct bacterial antigen detection;
(iii) Bacterial toxin detection; and,
(iv) Detection and identification of bacteria which includes one of
the following:
(A) Detection of the presence or absence of bacteria without
identification; or
(B) Identification of bacteria; and
(v) Antimicrobial susceptibility testing of select bacteria.
(2) An approved program must furnish HHS and its agents with a
description of samples that it plans to include in its annual program
no later than 6 months before each calendar year. The program must
include bacteria commonly occurring in patient specimens and other
important emerging pathogens. The program determines the reportable
isolates and correct responses for antimicrobial susceptibility testing
for any designated isolate. At least 25 percent of the samples must be
mixtures of the principal organism and appropriate normal flora. Mixed
cultures are samples that require reporting of one or more principal
pathogens. Mixed cultures are not ``negative'' samples such as when two
commensal organisms are provided in a PT sample with the intended
response of ``negative'' or ``no pathogen present.'' The program must
include the following two types of samples to meet the 25 percent mixed
culture criterion:
(i) Samples that require laboratories to report only organisms that
the testing laboratory considers to be a principal pathogen that is
clearly responsible for a described illness (excluding immuno-
compromised patients). The program determines the reportable isolates,
including antimicrobial susceptibility for any designated isolate; and
(ii) Samples that require laboratories to report all organisms
present. Samples must contain multiple organisms frequently found in
specimens where multiple isolates are clearly significant or where
specimens are derived from immuno-compromised patients. The program
determines the reportable isolates.
(3) The content of an approved program must vary over time, as
appropriate. The types of bacteria included annually must be
representative of the following major groups of medically important
aerobic and anaerobic bacteria, if appropriate for the sample sources:
(i) Gram-negative bacilli.
(ii) Gram-positive bacilli.
(iii) Gram-negative cocci.
(iv) Gram-positive cocci.
(4) For antimicrobial susceptibility testing, the program must
provide at least two samples per testing event. The program must
annually provide samples that include Gram-positive organisms and
samples that include Gram-negative organisms that have a predetermined
pattern of susceptibility or resistance to the common antimicrobial
agents.
(b) Evaluation of a laboratory's performance. HHS approves only
those programs that assess the accuracy of a laboratory's responses in
accordance with paragraphs (b)(1) through (9) of this section.
(1) The program determines the reportable bacterial staining and
morphological characteristics to be interpreted by Gram stain. The
program determines the bacteria to be reported by direct bacterial
antigen detection, bacterial toxin detection, detection of the presence
or absence of bacteria without identification, identification of
bacteria, and antimicrobial susceptibility testing. To determine the
accuracy of each of the laboratory's responses, the program must
compare each response with the response which reflects agreement of
either 80 percent or more of 10 or more referee laboratories or 80
percent or more of all participating laboratories. Both methods must be
attempted before the program can choose to not grade a PT sample.
(2) A laboratory must identify the organisms to highest level that
the laboratory reports results on patient specimens.
(3) A laboratory's performance will be evaluated on the basis of
the average of its scores for paragraph (b)(4) through (8) of this
section as determined in paragraph (b)(9) of this section.
(4) The performance criteria for Gram stain including bacterial
morphology is staining reaction, that is, Gram positive or Gram
negative and morphological description for each sample. The score is
the number of correct responses for Gram stain reaction plus the number
of correct responses for morphological description divided by 2 then
divided by the number of samples to be tested, multiplied by 100.
[[Page 41234]]
(5) The performance criterion for direct bacterial antigen
detection is the presence or absence of the bacterial antigen. The
score is the number of correct responses divided by the number of
samples to be tested, multiplied by 100.
(6) The performance criterion for bacterial toxin detection is the
presence or absence of the bacterial toxin. The score is the number of
correct responses divided by the number of samples to be tested
multiplied by 100.
(7) The performance criterion for the detection and identification
of bacteria includes one of the following:
(i) The performance criterion for the detection of the presence or
absence of bacteria without identification is the correct detection of
the presence or absence of bacteria without identification. The score
is the number of correct responses divided by the number of samples to
be tested multiplied by 100.
(ii) The performance criterion for the identification of bacteria
is the total number of correct responses for bacterial identification
submitted by the laboratory divided by the number of organisms present
plus the number of incorrect organisms reported by the laboratory
multiplied by 100 to establish a score for each sample in each testing
event. Since laboratories may incorrectly report the presence of
organisms in addition to the correctly identified principal
organism(s), the scoring system must provide a means of deducting
credit for additional erroneous organisms that are reported. For
example, if a sample contained one principal organism and the
laboratory reported it correctly but reported the presence of an
additional organism, which was not considered reportable, the sample
grade would be 1/(1+1) x 100 = 50 percent.
(8) For antimicrobial susceptibility testing, a laboratory must
indicate which drugs are routinely included in its test panel when
testing patient samples. A laboratory's performance will be evaluated
for only those antimicrobials for which susceptibility testing is
routinely performed on patient specimens. A correct response for each
antimicrobial will be determined as described in paragraph (b)(1) of
this section. Scoring for each sample is based on the number of correct
susceptibility responses reported by the laboratory divided by the
actual number of correct susceptibility responses determined by the
program, multiplied by 100. For example, if a laboratory offers
susceptibility testing using three antimicrobial agents, and the
laboratory reports correct responses for two of the three antimicrobial
agents, the laboratory's grade would be \2/3\ x 100 = 67 percent.
(9) The score for a testing event in bacteriology is the average of
the scores determined under paragraphs (b)(4) through (8) of this
section based on the type of service offered by the laboratory.
0
11. Section 493.913 is revised to read as follows:
Sec. 493.913 Mycobacteriology.
(a) Program content and frequency of challenge. To be approved for
proficiency testing for mycobacteriology, the annual program must
provide a minimum of five samples per testing event. There must be at
least two testing events provided to the laboratory at approximately
equal intervals per year. The samples may be provided through mailed
shipments. The specific organisms included in the samples may vary from
year to year.
(1) The annual program must include, as applicable, samples for:
(i) Acid-fast stain; and
(ii) Detection and identification of mycobacteria which includes
one of the following:
(A) Detection of the presence or absence of mycobacteria without
identification; or
(B) Identification of mycobacteria.
(2) An approved program must furnish HHS and its agents with a
description of the samples it plans to include in its annual program no
later than 6 months before each calendar year. At least 25 percent of
the samples must be mixtures of the principal mycobacteria and
appropriate normal flora. The program must include mycobacteria
commonly occurring in patient specimens and other important emerging
mycobacteria. The program determines the reportable isolates and
correct responses.
(3) The content of an approved program may vary over time, as
appropriate. The mycobacteria included annually must contain species
representative of the following major groups of medically important
mycobacteria, if appropriate for the sample sources:
(i) Mycobacterium tuberculosis complex; and
(ii) Mycobacterium other than tuberculosis (MOTT).
(4) The program must provide at least five samples per testing
event that include challenges that contain acid-fast organisms and
challenges that do not contain acid-fast organisms.
(b) Evaluation of a laboratory's performance. HHS approves only
those programs that assess the accuracy of a laboratory's response in
accordance with paragraphs (b)(1) through (6) of this section.
(1) The program determines the reportable mycobacteria to be
detected by acid-fast stain. The program determines the mycobacteria to
be reported by detection of the presence or absence of mycobacteria
without identification, and identification of mycobacteria. To
determine the accuracy of each of the laboratory's responses, the
program must compare each response with the response that reflects
agreement of either 80 percent or more of 10 or more referee
laboratories or 80 percent or more of all participating laboratories.
Both methods must be attempted before the program can choose to not
grade a PT sample.
(2) A laboratory must detect and identify the organisms to the
highest level that the laboratory reports results on patient specimens.
(3) A laboratory's performance will be evaluated on the basis of
the average of its scores for paragraph (b)(4) through (5) of this
section as determined in paragraph (b)(6) of this section.
(4) The performance criterion for acid-fast stains is positive or
negative or the presence or absence of acid-fast organisms. The score
is the number of correct responses divided by the number of samples to
be tested, multiplied by 100.
(5) The performance criterion for the detection and identification
of mycobacteria includes one of the following:
(i) The performance criterion for the detection of the presence or
absence of mycobacteria without identification is the correct detection
of the presence or absence of mycobacteria without identification. The
score is the number of correct responses divided by the number of
samples to be tested multiplied by 100.
(ii) The performance criterion for the identification of
mycobacteria is the total number of correct responses for mycobacterial
identification submitted by the laboratory divided by the number of
organisms present plus the number of incorrect organisms reported by
the laboratory multiplied by 100 to establish a score for each sample
in each testing event. Since laboratories may incorrectly report the
presence of mycobacteria in addition to the correctly identified
principal organism(s), the scoring system must provide a means of
deducting credit for additional erroneous organisms reported. For
example, if a sample contained one principal organism and the
laboratory reported it correctly but reported the presence of an
additional organism, which was not considered
[[Page 41235]]
reportable, the sample grade would be 1/(1+1) x 100 = 50 percent.
(6) The score for a testing event in mycobacteriology is the
average of the scores determined under paragraphs (b)(4) through (5) of
this section based on the type of service offered by the laboratory.
0
12. Section 493.915 is revised to read as follows:
Sec. 493.915 Mycology.
(a) Program content and frequency of challenge. To be approved for
proficiency testing for mycology, the annual program must provide a
minimum of five samples per testing event. There must be at least three
testing events provided to the laboratory at approximately equal
intervals per year. The samples may be provided through mailed
shipments. The specific organisms included in the samples may vary from
year to year.
(1) The annual program must include, as applicable, samples for:
(i) Direct fungal antigen detection; and
(ii) Detection and identification of fungi and aerobic
actinomycetes which includes one of the following:
(A) Detection of the presence or absence of fungi and aerobic
actinomycetes without identification; or
(B) Identification of fungi and aerobic actinomycetes.
(2) An approved program must furnish HHS and its agents with a
description of the samples it plans to include in its annual program no
later than 6 months before each calendar year. At least 25 percent of
the samples must be mixtures of the principal organism and appropriate
normal background flora. The program must include fungi and aerobic
actinomycetes commonly occurring in patient specimens and other
important emerging fungi. The program determines the reportable
isolates and correct responses.
(3) The content of an approved program must vary over time, as
appropriate. The fungi included annually must contain species
representative of the following major groups of medically important
fungi and aerobic actinomycetes, if appropriate for the sample sources:
(i) Yeast or yeast-like organisms;
(ii) Molds that include;
(A) Dematiaceous fungi;
(B) Dermatophytes;
(C) Hyaline hyphomycetes;
(D) Mucormycetes; and
(iii) Aerobic actinomycetes.
(b) Evaluation of a laboratory's performance. HHS approves only
those programs that assess the accuracy of a laboratory's response, in
accordance with paragraphs (b)(1) through (6) of this section.
(1) The program determines the reportable fungi to be reported by
direct fungal antigen detection, detection of the presence or absence
of fungi and aerobic actinomycetes without identification, and
identification of fungi and aerobic actinomycetes. To determine the
accuracy of a laboratory's responses, the program must compare each
response with the response reflects agreement of either 80 percent or
more of 10 or more referee laboratories or 80 percent or more of all
participating laboratories. Both methods must be attempted before the
program can choose to not grade a PT sample.
(2) A laboratory must detect and identify the organisms to highest
level that the laboratory reports results on patient specimens.
(3) A laboratory's performance will be evaluated on the basis of
the average of its scores for paragraphs (b)(4) through (5) of this
section as determined in paragraph (b)(6) of this section.
(4) The performance criterion for direct fungal antigen detection
is the presence or absence of the fungal antigen. The score is the
number of correct responses divided by the number of samples to be
tested, multiplied by 100.
(5) The performance criterion for the detection and identification
of fungi and aerobic actinomycetes includes one of the following:
(i) The performance criterion for the detection of the presence or
absence of fungi and aerobic actinomycetes without identification is
the correct detection of the presence or absence of fungi and aerobic
actinomycetes without identification. The score is the number of
correct responses divided by the number of samples to be tested
multiplied by 100.
(ii) The performance criterion for the identification of fungi and
aerobic actinomycetes is the total number of correct responses for
fungal and aerobic actinomycetes identification submitted by the
laboratory divided by the number of organisms present plus the number
of incorrect organisms reported by the laboratory multiplied by 100 to
establish a score for each sample in each testing event. Since
laboratories may incorrectly report the presence of fungi and aerobic
actinomycetes in addition to the correctly identified principal
organism(s), the scoring system must provide a means of deducting
credit for additional erroneous organisms that are reported. For
example, if a sample contained one principal organism and the
laboratory reported it correctly but reported the presence of an
additional organism, which was not considered reportable, the sample
grade would be 1/(1+1) x 100 = 50 percent.
(6) The score for a testing event is the average of the sample
scores as determined under paragraphs (b)(4) through (5) of this
section.
0
13. Section 493.917 is revised to read as follows:
Sec. 493.917 Parasitology.
(a) Program content and frequency of challenge. To be approved for
proficiency testing for parasitology, the annual program must provide a
minimum of five samples per testing event. There must be at least three
testing events provided to the laboratory at approximately equal
intervals per year. The samples may be provided through mailed
shipments. The specific organisms included in the samples may vary from
year to year.
(1) The annual program must include, as applicable, samples for:
(i) Direct parasite antigen detection; and
(ii) Detection and identification of parasites which includes one
of the following:
(A) Detection of the presence or absence of parasites without
identification; or
(B) Identification of parasites.
(2) An approved program must furnish HHS and its agents with a
description of the samples it plans to include in its annual program no
later than 6 months before each calendar year. Samples must include
both formalinized specimens and PVA (polyvinyl alcohol) fixed specimens
as well as blood smears, as appropriate for a particular parasite and
stage of the parasite. The majority of samples must contain protozoa or
helminths or a combination of parasites. Some samples must be devoid of
parasites.
(3) The content of an approved program must vary over time, as
appropriate. The types of parasites included annually must be
representative of the following major groups of medically important
parasites, if appropriate for the sample sources:
(i) Intestinal parasites; and
(ii) Blood and tissue parasites.
(4) The program must provide at least five samples per testing
event that include challenges that contain parasites and challenges
that are devoid of parasites.
(b) Evaluation of a laboratory's performance. HHS approves only
those programs that assess the accuracy of a laboratory's responses in
accordance with paragraphs (b)(1) through (6) of this section.
[[Page 41236]]
(1) The program determines the reportable parasites to be detected
by direct parasite antigen detection, detection of the presence or
absence of parasites without identification, and identification of
parasites. It may elect to establish a minimum number of parasites to
be identified in samples before they are reported. Parasites found in
rare numbers by referee laboratories are not considered in a
laboratory's performance; such findings are neutral. To determine the
accuracy of a laboratory's response, the program must compare each
response with the response which reflects agreement of either 80
percent or more of 10 or more referee laboratories or 80 percent or
more of all participating laboratories. Both methods must be attempted
before the program can choose to not grade a PT sample.
(2) A laboratory must detect and identify or concentrate and
identify the parasites to the highest level that the laboratory reports
results on patient specimens.
(3) A laboratory's performance will be evaluated on the basis of
the average of its scores for paragraphs (b)(4) through (5) of this
section as determined in paragraph (b)(6) of this section.
(4) The performance criterion for direct parasite antigen detection
is the presence or absence of the parasite antigen. The score is the
number of correct responses divided by the number of samples to be
tested, multiplied by 100.
(5) The performance criterion for the detection and identification
of parasites includes one of the following:
(i) The performance criterion for the detection of the presence or
absence of parasites without identification is the correct detection of
the presence or absence of parasites without identification. The score
is the number of correct responses divided by the number of samples to
be tested, multiplied by 100.
(ii) The performance criterion for the identification of parasites
is the total number of correct responses for parasite identification
submitted by the laboratory divided by the number of parasites present
plus the number of incorrect parasites reported by the laboratory
multiplied by 100 to establish a score for each sample in each testing
event. Since laboratories may incorrectly report the presence of
parasites in addition to the correctly identified principal
organism(s), the scoring system must provide a means of deducting
credit for additional erroneous organisms that are reported and not
found in rare numbers by the program's referencing process. For
example, if a sample contained one principal organism and the
laboratory reported it correctly but reported the presence of an
additional organism, which was not considered reportable, the sample
grade would be 1/(1+1) x 100 = 50 percent.
(6) The score for a testing event is the average of the sample
scores as determined under paragraphs (b)(4) through (5) of this
section.
0
14. Section 493.919 is revised to read as follows:
Sec. 493.919 Virology.
(a) Program content and frequency of challenge. To be approved for
proficiency testing for virology, a program must provide a minimum of
five samples per testing event. There must be at least three testing
events at approximately equal intervals per year. The samples may be
provided to the laboratory through mailed shipments. The specific
organisms included in the samples may vary from year to year.
(1) The annual program must include, as applicable, samples for:
(i) Viral antigen detection; and
(ii) Detection and identification of viruses.
(2) An approved program must furnish HHS and its agents with a
description of the samples it plans to include in its annual program no
later than 6 months before each calendar year. The program must include
other important emerging viruses and viruses commonly occurring in
patient specimens.
(3) The content of an approved program must vary over time, as
appropriate. If appropriate for the sample sources, the types of
viruses included annually must be representative of the following major
groups of medically important viruses:
(i) Respiratory viruses;
(ii) Herpes viruses;
(iii) Enterovirus; and
(iv) Intestinal viruses.
(b) Evaluation of laboratory's performance. HHS approves only those
programs that assess the accuracy of a laboratory's response in
accordance with paragraphs (b)(1) through (6) of this section.
(1) The program determines the viruses to be reported by direct
viral antigen detection, and detection and identification of viruses.
To determine the accuracy of a laboratory's response, the program must
compare each response with the response which reflects agreement of
either 80 percent or more of 10 or more referee laboratories or 80
percent or more of all participating laboratories. Both methods must be
attempted before the program can choose to not grade a PT sample.
(2) A laboratory must detect and identify the viruses to the
highest level that the laboratory reports results on patient specimens.
(3) A laboratory's performance will be evaluated on the basis of
the average of its scores for paragraphs (b)(4) through (5) of this
section as determined in paragraph (b)(6) of this section.
(4) The performance criterion viral antigen detection is the
presence or absence of the viral antigen. The score is the number of
correct responses divided by the number of samples to be tested,
multiplied by 100.
(5) The performance criterion for the detection and identification
of viruses is the total number of correct responses for viral detection
and identification submitted by the laboratory divided by the number of
viruses present plus the number of incorrect virus reported by the
laboratory multiplied by 100 to establish a score for each sample in
each testing event. Since laboratories may incorrectly report the
presence of viruses in addition to the correctly identified principal
organism(s), the scoring system must provide a means of deducting
credit for additional erroneous organisms that are reported. For
example, if a sample contained one principal organism and the
laboratory reported it correctly but reported the presence of an
additional organism, which was not considered reportable, the sample
grade would be 1/(1+1) x 100 = 50 percent.
(6) The score for a testing event is the average of the sample
scores as determined under paragraphs (b)(4) and (5) of this section.
0
15. Amend Sec. 493.923 by revising paragraphs (a) and (b)(1) to read
as follows:
Sec. 493.923 Syphilis serology.
(a) Program content and frequency of challenge. To be approved for
proficiency testing for syphilis serology, a program must provide a
minimum of five samples per testing event. There must be at least three
testing events at approximately equal intervals per year. The samples
may be provided through mailed shipments. An annual program must
include samples that cover the full range of reactivity from highly
reactive to non-reactive.
(b) * * *
(1) To determine the accuracy of a laboratory's response for
qualitative and quantitative syphilis tests, the program must compare
the laboratory's response with the response that reflects agreement of
either 80 percent or more of 10 or more referee laboratories or 80
[[Page 41237]]
percent or more of all participating laboratories. Both methods must be
attempted before the program can choose to not grade a PT sample.
* * * * *
0
16. Amend Sec. 493.927 by revising paragraphs (a), (b), (c)(1), and
(2) to read as follows:
Sec. 493.927 General immunology.
(a) Program content and frequency of challenge. To be approved for
proficiency testing for immunology, the annual program must provide a
minimum of five samples per testing event. There must be at least three
testing events at approximately equal intervals per year. The annual
program must provide samples that cover the full range of reactivity
from highly reactive to nonreactive. The samples may be provided
through mailed shipments.
(b) Challenges per testing event. The minimum number of challenges
per testing event the program must provide for each analyte or test
procedure is five. Analytes or tests for which laboratory performance
is to be evaluated include:
Table 1 to Paragraph (b)--Analyte or Test Procedure
------------------------------------------------------------------------
-------------------------------------------------------------------------
Alpha-l antitrypsin.
Alpha-fetoprotein (tumor marker).
Antinuclear antibody.
Antistreptolysin O (ASO).
Anti-human immunodeficiency virus (HIV).
Complement C3.
Complement C4.
C-reactive protein (high sensitivity).
HBsAg.
Anti-HBc.
HBeAg.
Anti-HBs.
Anti-HCV.
IgA.
IgG.
IgE.
IgM.
Infectious mononucleosis.
Rheumatoid factor.
Rubella.
------------------------------------------------------------------------
(c) * * *
(1) To determine the accuracy of a laboratory's response for
quantitative and qualitative immunology tests or analytes, the program
must compare the laboratory's response for each analyte with the
response that reflects agreement of either 80 percent or more of 10 or
more referee laboratories or 80 percent or more of all participating
laboratories. The proficiency testing program must indicate the minimum
concentration that will be considered as indicating a positive
response. Both methods must be attempted before the program can choose
to not grade a PT sample.
(2) For quantitative immunology analytes or tests, the program must
determine the correct response for each analyte by the distance of the
response from the target value. After the target value has been
established for each response, the appropriateness of the response must
be determined by using either fixed criteria or the number of standard
deviations (SDs) the response differs from the target value.
Table 2 to Paragraph (c)(2)--Criteria for Acceptable Performance
------------------------------------------------------------------------
The criteria for acceptable
performance are-- Analyte or test Criteria for acceptable performance
------------------------------------------------------------------------
Alpha-1 antitrypsin............... Target value 20%.
Alpha-fetoprotein (tumor marker).. Target value 20%.
Antinuclear antibody (ANA)........ Target value 2 dilutions
or positive or negative.
Antistreptolysin O................ Target value 2 dilutions
or positive or negative.
Anti-Human Immunodeficiency virus Reactive (positive) or nonreactive
(HIV). (negative).
Complement C3..................... Target value 15%.
Complement C4..................... Target value 20% or
5 mg/dL (greater).
C-reactive protein (HS)........... Target value 30% or
1 mg/L (greater).
HBsAg............................. Reactive (positive) or nonreactive
(negative).
Anti-HBc.......................... Reactive (positive) or nonreactive
(negative).
HBeAg............................. Reactive (positive) or nonreactive
(negative).
Anti-HBs.......................... Reactive (positive) or nonreactive
(negative).
Anti-HCV.......................... Reactive (positive) or nonreactive
(negative).
IgA............................... Target value 20%.
IgE............................... Target value 20%.
IgG............................... Target value 20%.
IgM............................... Target value 20%.
Infectious mononucleosis.......... Target value 2 dilutions
or positive or negative.
Rheumatoid factor................. Target value 2 dilutions
or positive or negative.
Rubella........................... Target value 2 dilutions
or positive or negative or immune
or nonimmune.
------------------------------------------------------------------------
[[Page 41238]]
* * * * *
0
17. Amend Sec. 493.931 by revising paragraphs (a), (b), (c)(1) and (2)
to read as follows:
Sec. 493.931 Routine chemistry.
(a) Program content and frequency of challenge. To be approved for
proficiency testing for routine chemistry, a program must provide a
minimum of five samples per testing event. There must be at least three
testing events at approximately equal intervals per year. The annual
program must provide samples that cover the clinically relevant range
of values that would be expected in patient specimens. The specimens
may be provided through mailed shipments.
(b) Challenges per testing event. The minimum number of challenges
per testing event a program must provide for each analyte or test
procedure listed below is five serum, plasma or blood samples.
Table 1 to Paragraph (b)--Analyte or Test Procedure
------------------------------------------------------------------------
-------------------------------------------------------------------------
Alanine aminotransferase (ALT/SGPT).
Albumin.
Alkaline phosphatase.
Amylase.
Aspartate aminotransferase (AST/SGOT).
Bilirubin, total.
Blood gas (pH, pO2, and pCO2).
B-natriuretic peptide (BNP).
proBNP.
Calcium, total.
Carbon dioxide.
Chloride.
Cholesterol, total.
Cholesterol, high density lipoprotein.
Cholesterol, low density lipoprotein, (direct measurement).
Creatine kinase (CK).
CK-MB isoenzymes.
Creatinine.
Ferritin.
Gamma glutamyl transferase.
Glucose (Excluding measurements on devices cleared by FDA for home use).
Hemoglobin A1c.
Iron, total.
Lactate dehydrogenase (LDH).
Magnesium.
Phosphorus.
Potassium.
Prostate specific antigen (PSA), total.
Sodium.
Total iron binding capacity (TIBC) (direct measurement).
Total Protein.
Triglycerides.
Troponin I.
Troponin T.
Urea Nitrogen.
Uric Acid.
------------------------------------------------------------------------
(c) * * *
(1) To determine the accuracy of a laboratory's response for
qualitative and quantitative chemistry tests or analytes, the program
must compare the laboratory's response for each analyte with the
response that reflects agreement of either 80 percent or more of 10 or
more referee laboratories or 80 percent or more of all participating
laboratories. Both methods must be attempted before the program can
choose to not grade a PT sample.
(2) For quantitative chemistry tests or analytes, the program must
determine the correct response for each analyte by the distance of the
response from the target value. After the target value has been
established for each response, the appropriateness of the response must
be determined by using either fixed criteria based on the percentage
difference from the target value or the number of standard deviations
(SD) the response differs from the target value.
Table 2 to Paragraph (c)(2)--Criteria for Acceptable Performance
------------------------------------------------------------------------
The criteria for acceptable
performance are-- Analyte or test Criteria for acceptable performance
------------------------------------------------------------------------
Alanine aminotransferase (ALT/ Target value 15% or
SGPT). 6 U/L (greater).
Albumin........................... Target value 8%.
Alkaline phosphatase.............. Target value 20%.
Amylase........................... Target value 20%.
Aspartate aminotransferase (AST/ Target value 15% or
SGOT). 6 U/L (greater).
Bilirubin, total.................. Target value 20% or
0.4 mg/dL (greater).
Blood gas pCO2.................... Target value 8% or 5 mm Hg (greater).
Blood gas pO2..................... Target value 15% or
15 mmHg (greater).
[[Page 41239]]
Blood gas pH...................... Target value 0.04.
B-natriuretic peptide (BNP)....... Target value 30%.
Pro B-natriuretic peptide (proBNP) Target value 30%.
Calcium, total.................... Target value 1.0 mg/dL.
Carbon dioxide.................... Target value 20%.
Chloride.......................... Target value 5%.
Cholesterol, total................ Target value 10%.
Cholesterol, high density Target value 20% or
lipoprotein (HDL). 6 mg/dL (greater).
Cholesterol, low density Target value 20%.
lipoprotein (LDL), direct
measurement.
Creatine kinase (CK).............. Target value 20%.
CK-MB isoenzymes.................. Target value 25% or
3 ng/mL (greater) or MB
elevated (presence or absence).
Creatinine........................ Target value 10% or
0.2 mg/dL (greater).
Ferritin.......................... Target value 20%.
Gamma glutamyl transferase........ Target value 15% or
5 U/L (greater).
Glucose (excluding measurements Target value 8% or 6 mg/dL (greater).
use.).
Hemoglobin A1c.................... Target value 8%.
Iron, total....................... Target value 15%.
Lactate dehydrogenase (LDH)....... Target value 15%.
Magnesium......................... Target value 15%.
Phosphorus........................ Target value 10% or
0.3 mg/dL (greater).
Potassium......................... Target value 0.3 mmol/L.
Prostate Specific Antigen, total.. Target value 20% or
0.2 ng/mL (greater).
Sodium............................ Target value 4 mmol/L.
Total Iron Binding Capacity Target value 20%.
(TIBC). (direct measurement).
Total Protein..................... Target value 8%.
Triglycerides..................... Target value 15%.
Troponin I........................ Target value 30% or
0.9 ng/mL (greater).
Troponin T........................ Target value 30% or
0.2 ng/mL (greater).
Urea nitrogen..................... Target value 9% or 2 mg/dL (greater).
Uric acid......................... Target value 10%.
------------------------------------------------------------------------
* * * * *
0
18. Amend Sec. 493.933 by revising paragraphs (a), (b), (c)(1), and
(2) to read as follows:
Sec. 493.933 Endocrinology.
(a) Program content and frequency of challenge. To be approved for
proficiency testing for endocrinology, a program must provide a minimum
of five samples per testing event. There must be at least three testing
events at approximately equal intervals per year. The annual program
must provide samples that cover the clinically relevant range of values
that would be expected in patient specimens. The samples may be
provided through mailed shipments.
(b) Challenges per testing event. The minimum number of challenges
per testing event a program must provide for each analyte or test
procedure is five serum, plasma, blood, or urine samples.
Table 1 to Paragraph (b)--Analyte or Test
------------------------------------------------------------------------
-------------------------------------------------------------------------
Cancer antigen (CA) 125.
Carcinoembryonic antigen (CEA).
Cortisol.
Estradiol.
Folate, serum.
Follicle stimulating hormone.
Free thyroxine.
Human chorionic gonadotropin (HCG) (excluding urine pregnancy tests done
by visual color comparison categorized as waived tests).
Luteinizing hormone.
Parathyroid hormone.
Progesterone.
Prolactin.
Testosterone.
T3 Uptake.
Triiodothyronine.
Thyroid-stimulating hormone.
Thyroxine.
Vitamin B12.
------------------------------------------------------------------------
(c) * * *
(1) To determine the accuracy of a laboratory's response for
qualitative and quantitative endocrinology tests or analytes, a program
must compare the laboratory's response for each analyte with the
response that reflects agreement of either 80 percent or more of 10 or
more referee laboratories or 80
[[Page 41240]]
percent or more of all participating laboratories. Both methods must be
attempted before the program can choose to not grade a PT sample.
(2) For quantitative endocrinology tests or analytes, the program
must determine the correct response for each analyte by the distance of
the response from the target value. After the target value has been
established for each response, the appropriateness of the response must
be determined by using either fixed criteria based on the percentage
difference from the target value or the number of standard deviations
(SDs) the response differs from the target value.
Table 2 to Paragraph (c)(2)-Criteria for Acceptable Performance
------------------------------------------------------------------------
The criteria for acceptable
performance are-- Analyte or test Criteria for acceptable performance
------------------------------------------------------------------------
Cancer antigen (CA) 125........... Target value 20%.
Carcinoembryonic antigen (CEA).... Target value 15% or
1 ng/dL (greater).
Cortisol.......................... Target value 20%.
Estradiol......................... Target value 30%.
Folate, serum..................... Target value 30% or
1 ng/mL (greater).
Follicle stimulating hormone...... Target value 18% or
2 IU/L (greater).
Free thyroxine.................... Target value or 15% or
0.3 ng/dL (greater).
Human chorionic................... Target value 18% or
3
gonadotropin (excluding urine mIU/mL (greater) or positive or
pregnancy tests done by visual negative.
color comparison categorized as
waived tests).
Luteinizing hormone............... Target value 20%.
Parathyroid hormone............... Target value 30%.
Progesterone...................... Target value 25%.
Prolactin......................... Target value 20%.
Testosterone...................... Target value 30% or
20 ng/dL (greater).
T3 uptake......................... Target value 18%.
Triiodothyronine.................. Target value 30%.
Thyroid-stimulating hormone....... Target value 20% or
0.2 mIU/L (greater).
Thyroxine......................... Target value 20% or
1.0 mcg/dL (greater).
Vitamin B12....................... Target value 25% or
30 pg/mL (greater).
------------------------------------------------------------------------
* * * * *
0
19. Amend Sec. 493.937 by revising paragraphs (a), (b), (c)(1), and
(2) to read as follows:
Sec. 493.937 Toxicology.
(a) Program content and frequency of challenge. To be approved for
proficiency testing for toxicology, the annual program must provide a
minimum of five samples per testing event. There must be at least three
testing events at approximately equal intervals per year. The annual
program must provide samples that cover the full range of values that
could occur in patient specimens and that cover the level of clinical
significance for the particular drug. The samples may be provided
through mailed shipments.
(b) Challenges per testing event. The minimum number of challenges
per testing event a program must provide for each analyte or test
procedure is five serum, plasma, or blood samples.
Table 1 to Paragraph (b)--Analyte or Test Procedure
------------------------------------------------------------------------
-------------------------------------------------------------------------
Acetaminophen, serum.
Alcohol (blood).
Blood lead.
Carbamazepine, total.
Digoxin, total.
Gentamicin.
Lithium.
Phenobarbital.
Phenytoin, total.
Salicylate.
Theophylline.
Tobramycin.
Valproic Acid, total.
Vancomycin.
------------------------------------------------------------------------
(c) * * *
(1) To determine the accuracy of a laboratory's responses for
quantitative toxicology tests or analytes, the program must compare the
laboratory's response for each analyte with the response that reflects
agreement of either 80 percent or more of 10 or more referee
laboratories or 80 percent or more of all participating laboratories.
Both methods must be attempted before the program can choose to not
grade a PT sample.
(2) For quantitative toxicology tests or analytes, the program must
determine the correct response for each analyte by the distance of the
response from the target value. After the target value has been
established for each response, the appropriateness of the response must
be determined by using fixed criteria based on the percentage
difference from the target value.
[[Page 41241]]
Table 2 to Paragraph (c)(2)--Criteria for Acceptable Performance
------------------------------------------------------------------------
The criteria for acceptable
performance are-- Analyte or test Criteria for acceptable performance
------------------------------------------------------------------------
Acetaminophen..................... Target value 15% or
3 mcg/mL (greater).
Alcohol, blood.................... Target Value 20%.
Blood lead........................ Target Value 10% or
2 mcg/dL (greater).
Carbamazepine, total.............. Target Value 20% or
1.0 mcg/mL (greater).
Digoxin, total.................... Target Value 15% or
0.2 ng/mL (greater).
Gentamicin........................ Target Value 25%.
Lithium........................... Target Value 15% or
0.3 mmol/L (greater).
Phenobarbital..................... Target Value 15% or
2 mcg/mL (greater).
Phenytoin total................... Target Value 15% or
2 mcg/mL (greater).
Salicylate........................ Target Value 15% or
2 mcg/mL (greater).
Theophylline...................... Target Value 20%.
Tobramycin........................ Target Value 20%.
Valproic Acid, total.............. Target Value 20%.
Vancomycin........................ Target Value 15% or
2 mcg/mL (greater).
------------------------------------------------------------------------
* * * * *
0
20. Amend Sec. 493.941 by revising paragraphs (a), (b), (c)(1) and (2)
to read as follows:
Sec. 493.941 Hematology (including routine hematology and
coagulation).
(a) Program content and frequency of challenge. To be approved for
proficiency testing for hematology, a program must provide a minimum of
five samples per testing event. There must be at least three testing
events at approximately equal intervals per year. The annual program
must provide samples that cover the full range of values that would be
expected in patient specimens. The samples may be provided through
mailed shipments.
(b) Challenges per testing event. The minimum number of challenges
per testing event a program must provide for each analyte or test
procedure is five.
Table 1 to Paragraph (b)--Analyte or Test Procedure
------------------------------------------------------------------------
-------------------------------------------------------------------------
Cell identification.
White blood cell differential.
Erythrocyte count.
Hematocrit (excluding spun microhematocrit).
Hemoglobin.
Leukocyte count.
Platelet count.
Fibrinogen.
Partial thromboplastin time.
Prothrombin time (seconds or INR).
------------------------------------------------------------------------
(c) * * *
(1) To determine the accuracy of a laboratory's responses for
qualitative and quantitative hematology tests or analytes, the program
must compare the laboratory's response for each analyte with the
response that reflects agreement of either 80 percent or more of 10 or
more referee laboratories or 80 percent or more of all participating
laboratories. Both methods must be attempted before the program can
choose to not grade a PT sample.
(2) For quantitative hematology tests or analytes, the program must
determine the correct response for each analyte by the distance of the
response from the target value. After the target value has been
established for each response, the appropriateness of the response is
determined using either fixed criteria based on the percentage
difference from the target value or the number of standard deviations
(SD) the response differs from the target value.
Table 2 to Paragraph (c)(2)--Criteria for Acceptable Performance
------------------------------------------------------------------------
The criteria for acceptable
performance are: Analyte or test Criteria for acceptable performance
------------------------------------------------------------------------
Cell identification............... 80% or greater consensus on
identification.
White blood cell differential..... Target 3SD based on the
percentage of different types of
white blood cells in the samples.
Erythrocyte count................. Target 4%.
Hematocrit (Excluding spun Target 4%.
hematocrit).
Hemoglobin........................ Target 4%.
Leukocyte count................... Target 10%.
Platelet count.................... Target 25%.
Fibrinogen........................ Target 20%.
Partial thromboplastin time....... Target 15%.
------------------------------------------------------------------------
If a laboratory reports a prothrombin time in both INR and seconds, the
INR should be reported to the PT provider program.
------------------------------------------------------------------------
[[Page 41242]]
Prothrombin time (seconds or INR). Target 15%.
------------------------------------------------------------------------
* * * * *
0
21. Amend Sec. 493.959 by revising paragraphs (b), (d)(1) and (2) to
read as follows:
Sec. 493.959 Immunohematology.
* * * * *
(b) Program content and frequency of challenge. To be approved for
proficiency testing for immunohematology, a program must provide a
minimum of five samples per testing event. There must be at least three
testing events at approximately equal intervals per year. The annual
program must provide samples that cover the full range of
interpretation that would be expected in patient specimens. The samples
may be provided through mailed shipments.
(d) * * *
(1) To determine the accuracy of a laboratory's response, a program
must compare the laboratory's response for each analyte with the
response that reflects agreement of either 100 percent of 10 or more
referee laboratories or 95 percent or more of all participating
laboratories except for antibody identification. To determine the
accuracy of a laboratory's response for antibody identification, a
program must compare the laboratory's response for each analyte with
the response that reflects agreement of either 95 percent or more of 10
or more referee laboratories or 95 percent or more of all participating
laboratories. Both methods must be attempted before the program can
choose to not grade a PT sample.
(2) Criteria for acceptable performance. The criteria for
acceptable performance are--
Table 2 to Paragraph (d)(2)--Criteria for Acceptable Performance
------------------------------------------------------------------------
Analyte or test Criteria for acceptable performance
------------------------------------------------------------------------
ABO group......................... 100% accuracy.
D (Rho) typing.................... 100% accuracy.
Unexpected antibody detection..... 100% accuracy.
Compatibility testing............. 100% accuracy.
Antibody identification........... 80%+ accuracy.
------------------------------------------------------------------------
* * * * *
Dated: June 24, 2022.
Xavier Becerra,
Secretary, Department of Health and Human Services.
[FR Doc. 2022-14513 Filed 7-7-22; 4:15 pm]
BILLING CODE 4120-01-P