1536 Federal Register / Vol. 84, No.

23 / Monday, February 4, 2019 / Proposed Rules

DEPARTMENT OF HEALTH AND Stop C4–26–05, 7500 Security which the laboratory is certified under
HUMAN SERVICES Boulevard, Baltimore, MD 21244–1850. CLIA. PT referral was further addressed
For information on viewing public by enactment of the Taking Essential
Centers for Medicare & Medicaid comments, see the beginning of the Steps for Testing Act of 2012 (Pub. L.
Services SUPPLEMENTARY INFORMATION section. 112–202, December 4, 2012) (TEST Act)
FOR FURTHER INFORMATION CONTACT: and our implementing regulations (79
42 CFR Part 493 Sarah Bennett, CMS, (410) 786–3531; FR 25435 and 79 FR 27105). As of
[CMS–3355–P] Caecilia Blondiaux, CMS, (410) 786– January 2017, there were 246,143 CLIA-
2190; or Nancy Anderson, CDC, (404) certified laboratories, of which 36,777
RIN 0938–AT55 498–2741 Certificate of Compliance and Certificate
SUPPLEMENTARY INFORMATION: of Accreditation laboratories were
Clinical Laboratory Improvement required to enroll in a U.S. Department
Amendments of 1988 (CLIA) Inspection of Public Comments: All
comments received before the close of of Health and Human Services (HHS)-
Proficiency Testing Regulations approved PT program and comply with
Related to Analytes and Acceptable the comment period are available for
viewing by the public, including any the PT regulations.
Performance Testing has evolved significantly
personally identifiable or confidential
AGENCY: Centers for Medicare & business information that is included in since 1992, and technology is now more
Medicaid Services (CMS), HHS; Centers a comment. We post all comments accurate and precise than the methods
for Disease Control and Prevention received before the close of the in use at the time the PT regulations
(CDC), HHS. comment period on the following became effective for all laboratories in
website as soon as possible after they 1994. In addition, many tests for
ACTION: Proposed rule.
have been received: http:// analytes for which PT was not initially
SUMMARY: This proposed rule would required are now in routine clinical use.
www.regulations.gov. Follow the search
update proficiency testing (PT) For example, tests for cardiac markers,
instructions on that website to view
regulations under the Clinical such as troponins, and the hemoglobin
public comments.
Laboratory Improvement Amendments A1c test commonly used to monitor
of 1988 (CLIA) to address current Table of Contents glycemic control in persons with
analytes (that is, substances or I. Background
diabetes, were not routinely performed
constituents for which the laboratory II. Provisions of the Proposed Regulations prior to 1992. Recognizing these
conducts testing) and newer A. Proposed Changes for Microbiology PT changes, we are proposing revisions to
technologies. This proposed rule would B. Proposed Changes to PT for Non- our existing PT regulations in this
also make additional technical changes Microbiology Specialties and proposed rule.
to PT referral regulations to more Subspecialties As part of the process for developing
closely align them with the CLIA
C. Additional Proposed Changes our proposals to revise the PT
III. Collection of Information Requirements regulations, HHS requested input from
statute. IV. Response to Comments the Clinical Laboratory Improvement
DATES: To be assured consideration, V. Regulatory Impact Analysis Advisory Committee (CLIAC) regarding
comments must be received at one of A. Statement of Need
appropriate revisions to the regulations.
the addresses provided below, no later B. Overall Impact
C. Anticipated Effects CLIAC is the official federal advisory
than 5 p.m. on April 5, 2019. committee charged with advising HHS
D. Alternatives Considered
ADDRESSES: In commenting, please refer E. Accounting Statements and Table regarding appropriate regulatory
to file code CMS–3355–P. Because of F. Regulatory Reform Analysis Under E.O. standards for ensuring accuracy,
staff and resource limitations, we cannot 13771 reliability and timeliness of laboratory
accept comments by facsimile (FAX) G. Conclusion testing. Questions posed to CLIAC at the
transmission. I. Background September 2008 CLIAC meeting and
Comments, including mass comment their recommendations are documented
submissions, must be submitted in one On October 31, 1988, Congress in the meeting summary on the CLIAC
of the following three ways (please enacted the Clinical Laboratory website at https://ftp.cdc.gov/pub/
choose only one of the ways listed): Improvement Amendments of 1988 CLIAC_meeting_presentations/pdf/
1. Electronically. You may submit (Pub. L. 100–578) (CLIA’88), codified at CLIAC_Summary/cliac0908_
electronic comments on this regulation 42 U.S.C. 263a, to ensure the accuracy summary.pdf.
to http://www.regulations.gov. Follow and reliability of testing in all In response to our request for input,
the ‘‘Submit a comment’’ instructions. laboratories, including, but not limited CLIAC established a PT Workgroup that
2. By regular mail. You may mail to, those that participate in Medicare included laboratory experts,
written comments to the following and Medicaid, that test human representatives from accreditation
address ONLY: Centers for Medicare & specimens for purpose of providing organizations, state surveyors, and PT
Medicaid Services, Department of information for the diagnosis, program officials. The CLIAC PT
Health and Human Services, Attention: prevention, or treatment of any disease Workgroup provided information and
CMS–3355–P, P.O. Box 8016, Baltimore, or impairment, or the assessment of data to CLIAC for their deliberation in
MD 21244–8016. health, of human beings. The Secretary making recommendations to HHS
Please allow sufficient time for mailed established the initial regulations regarding appropriate revisions to
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comments to be received before the implementing CLIA on February 28, subparts H and I of the CLIA
close of the comment period. 1992 at 42 CFR part 493 (57 FR 7002). regulations. These recommendations
3. By express or overnight mail. You Those regulations required, among other addressed updating the list of required
may send written comments to the things, for laboratories conducting PT analytes; revising the scoring criteria
following address ONLY: Centers for moderate or high-complexity testing to for acceptable performance for current
Medicare & Medicaid Services, enroll in an approved proficiency and proposed analytes; changes to
Department of Health and Human testing (PT) program for each specialty, specialties or subspecialties, including
Services, Attention: CMS–3355–P, Mail subspecialty, and analyte or test for microbiology, that do not have required

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1537

PT analytes; and clarification of the PT minus) around the target value (as for the types of PT required for each
referral requirements. The questions defined in § 493.2), to propose for both microbiology subspecialty to allow
posed to CLIAC at the September 2010 new and existing required analytes. As flexibility for inclusion of new
CLIAC meeting and their a result of this work, we ultimately technologies.
recommendations are documented in decided to propose stating acceptance After deliberation, CLIAC made the
the meeting summary on the CLIAC limits as percentages whenever possible. following recommendations:
website at http://wwwn.cdc.gov/cliac/ We then again sought industry input. • A system for categorizing types of
pdf/cliac0910.pdf. For each analyte, we requested that PT service should be maintained in the
After the September 2010 CLIAC programs consider our potential new regulations to help laboratories
meeting, CMS and CDC met to review acceptance limits and provide data determine what PT they need to perform
and consider the recommendations. simulations using real PT data as a and assist surveyors in monitoring PT
Following this, the two agencies means of pilot testing our potential performance and patient testing.
collaborated to develop a process to acceptance limits. We received • The regulations should include four
revise the list of required PT analytes. simulation data from several PT categories of testing for each
That is, CMS and CDC reviewed current programs, which facilitated the microbiology subspecialty, as
analytes listed in subpart I to determine development of the acceptance limits applicable: Stain(s), susceptibility and
which analytes should be retained in proposed in this rule. We note that resistance testing, antigen and/or toxin
the regulations and which should be acceptance limits are intended to be detection, and microbial identification
deleted. In addition, CMS and CDC used for scoring PT performance by PT or detection.
examined analytes not currently listed programs and are not intended to be Based on these recommendations, we
in subpart I to determine if any used by individual laboratories to conducted a review of the PT modules
additional analytes should be added to satisfy the requirement at § 493.1253(b) offered by HHS-approved PT programs
subpart I. to establish performance specifications. and consulted with CDC microbiology
As discussed in section II of this
II. Provisions of the Proposed subject matter experts who concurred
proposed rule, a systematic approach
Regulations that not all four recommended
was taken in order to update the
categories above are applicable to each
required PT analytes, using various This section provides an overview of microbiology subspecialty nor do PT
factors in selecting candidate analytes. our proposed revisions to the CLIA
A variety of PT-related and test volume programs have PT available for each
definitions and PT requirements in category. If at some point in the future
data were subsequently collected from subpart A—General Provisions, § 493.2
HHS-approved PT programs and various PT becomes available, we may propose
Definitions; subpart H—Participation in to include additional categories of
sources as described below, and Proficiency Testing for Laboratories
analyzed by CMS and CDC. testing to microbiology subspecialties in
Performing Nonwaived Testing; and future rulemaking. Based on these
As discussed in section II.B.2. of this subpart I—Proficiency Testing Programs
proposed rule, CMS and CDC used those recommendations and our review, we
for Nonwaived Testing. are proposing to modify §§ 493.911
data and applied the criteria in a step-
wise approach to determine the analytes A. Proposed Changes to Microbiology through 493.919 to remove the types of
included in this proposed rule. PT services listed for each microbiology
Following selection of those candidate subspecialty and to add the
1. Categories of Testing recommended categories of testing for
analytes, CMS and CDC sought feedback
from PT programs on the following Subpart I of the CLIA regulations each microbiology subspecialty as
topics: Current PT program practices includes PT requirements for each described in the bullets below. We
using ‘‘peer grouping’’ to determine subspecialty of microbiology, §§ 493.911 believe that the revised microbiology PT
target values; the potential to include through 493.919, which describe ‘‘Types regulations would better reflect current
new analytes as required PT; of services offered by laboratories’’ for practices in microbiology.
mechanism for grading current of each subspecialty. In addition, since the • Section 493.911(a): For
analytes; possible changes to the criteria regulations do not specify required bacteriology, we are proposing that the
for acceptable performance; and analytes for microbiology as they do for categories required include, as
potential changes to microbiology other specialties, they include applicable: Gram stain including
subspecialties, including the descriptions of levels or extents (for bacterial morphology; direct bacterial
replacement of the types of service as example, identification to the genus antigen detection; bacterial toxin
outlined currently at §§ 493.911(a), level only, identification to the genus detection; detection and identification
493.913(a), 493.915(a), 493.917(a) and and species level) used to determine the of bacteria which includes one of the
493.919(a), with the candidate analytes type of laboratory for PT purposes. following: Detection of growth or no
and the replacement of the list of CLIAC discussed the usefulness and growth in culture media or
specific organisms for each limitations of the types of services listed identification of bacteria to the highest
microbiology subspecialty at the above in subpart I in helping laboratories level that the laboratory reports results
citations with our proposal to adopt a enroll properly or in helping surveyors on patient specimens; and antimicrobial
general list of types of microorganisms conduct laboratory inspections. It was susceptibility or resistance testing on
for each microbiology subspecialty. noted that the types of services listed in select bacteria.
Specifically, with CDC’s expertise and subpart I do not allow for reporting • Section 493.913(a): For
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assistance, we then developed an growth or no growth, presence or mycobacteriology, we are proposing that
approach and rationale, as discussed in absence, or presumptive identification the categories for which PT is required
section II.B.10. of this proposed rule, for of microorganisms on PT samples, include, as applicable: Acid-fast stain;
revising PT acceptance limits based which are common ways that physician detection and identification of
upon empirical data, including clinical office laboratories report patient results. mycobacteria which includes one of the
relevance. CMS and CDC worked to Based on input from the PT Workgroup, following: Detection of growth or no
determine the acceptance limits, that is, CLIAC suggested revision of the growth in culture media or
the symmetrical tolerance (plus and regulations to include broad categories identification of mycobacteria; and

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 1538 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

antimycobacterial susceptibility or microorganisms that might be included mucormycetes; and aerobic

resistance testing. in an HHS approved PT program over actinomycetes.
• Section 493.915(a): For mycology, time. Several PT programs have • § 493.917(a)(3): For parasitology, we
we are proposing that the categories for suggested to HHS that the regulations are proposing that the annual program
which PT is required include, as should include a more general list of content must include intestinal
applicable: Direct fungal antigen types of organisms that must be parasites and blood and tissue parasites,
detection; detection and identification included in required PT instead of a if appropriate for the sample sources.
of fungi and aerobic actinomycetes specific list. CLIAC considered whether • § 493.919(a)(3): For virology, we are
which includes one of the following— there needs to be a more general list of proposing that the annual program
detection of growth or no growth in organisms in the regulations to assure a content must include respiratory
culture media or identification of fungi variety of challenges are offered over the viruses, herpes viruses, enterovirus, and
and aerobic actinomycetes; and course of the year. Following their intestinal viruses, if appropriate for the
antifungal susceptibility or resistance deliberation, CLIAC made the following sample sources.
testing. recommendation:
• Section 493.917(a): For • Require PT for a general list of types 3. Declaration of Patient Reporting
parasitology, we are proposing that the of organisms in each subspecialty. For Practices
categories for which PT is required example, in bacteriology, the groups The PT requirements at § 493.801(b)
include, as applicable: Direct parasite listed should include gram-negative specify that laboratories must examine
antigen detection; and detection and bacilli, gram-positive bacilli, gram- or test, as applicable, the proficiency
identification of parasites which negative cocci, and gram-positive cocci. testing samples it receives from the
includes one of the following— Generally, we have found that PT proficiency testing program in the same
detection of the presence or absence of programs include only those organisms manner as it tests patient specimens.
parasites or identification of parasites. listed in the current regulations, and do CLIAC considered this requirement as
• Section 493.919(a): For virology, we
not include additional organisms applied to microbiology and agreed that
are proposing that the categories for
outside of the current regulatory list. By PT programs should instruct
which PT is required include, as
restructuring to a more general list of laboratories to perform all testing as
applicable: Viral antigen detection;
organisms, it will be clearer that PT they normally would on patient
detection and identification of viruses;
programs are able to be flexible in specimens, including reporting PT
and antiviral susceptibility or resistance
selecting which samples to provide to results for microorganism identification
testing.
In all of these subspecialties, as laboratories for PT, especially as new to the same level that would be reported
outlined in sections II.B.5., II.B.7., and organisms are identified as being on patient specimens. CLIAC
II.B.8. of this proposed rule, we are also clinically important. Therefore, we are deliberated on this issue and made the
proposing to revise the requirements for proposing to remove the lists of specific following recommendation:
evaluation of a laboratory’s performance example organisms from each • Laboratories should declare their
at §§ 493.911(b) through 493.919(b) to microbiology subspecialty, §§ 493.911 patient reporting practices for organisms
be consistent with these categories. through 493.919, and to add the included in each PT challenge.
We are not proposing to include following list of types of organisms to However, PT programs should only
antigen and toxin detection in the each. gather this information as it is the
mycobacteriology subspecialty because • § 493.911(a)(3): For bacteriology, we inspecting agency’s responsibility to
no PT program currently offers are proposing that the annual program review and take action if necessary.
applicable PT modules. We are not content must include representatives of We believe that laboratories should be
proposing to include stains and the following major groups of medically instructed to report PT results for
antiparasitic susceptibility or resistance important aerobic and anaerobic microbiology organism identification to
testing in the subspecialty of bacteria if appropriate for the sample the ‘‘highest’’ level that they report
parasitology because no PT program sources: Gram-negative bacilli; gram- results on patient specimens to ensure
offers applicable PT modules. We invite positive bacilli; gram-negative cocci; that they do so to the ‘‘same’’ level that
the public to comment on these and gram-positive cocci. The more they report results on patient
proposals and specifically on the general list of types of organisms will specimens. As a result, we are
proposed categories of testing for the continue to cover the six major groups proposing to amend §§ 493.801(b),
subspecialties listed above. If public of bacteria currently listed in the 493.911(b), 493.913(b), 493.915(b),
comments indicate that applicable PT regulations. 493.917(b), and 493.919(b), to state that
modules are available for antigen and • § 493.913(a)(3): For laboratories must report PT results for
toxin detection or for stains and mycobacteriology, we are proposing that microbiology organism identification to
antiparasitic susceptibility or resistance the annual program content must the highest level that they report results
testing, we may finalize their inclusion include Mycobacterium tuberculosis on patient specimens. If finalized, this
in the final rule, as applicable. If at complex and Mycobacterium other than proposal should address an issue we
some point in the future, PT becomes tuberculosis (MOTT), if appropriate for identified during the PT program
available for mycobacteriology antigen the sample sources. reapproval process in which we found
and toxin detection testing, and stains • § 493.915(a)(3): For mycology, we laboratories inappropriately deciding
and antiparasitic susceptibility or are proposing that annual program whether to participate in a PT event
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resistance testing, we may propose to content must include the following based on the reporting criteria required
include this category of testing for PT in major groups of medically important by the PT program.
future rulemaking. fungi and aerobic actinomycetes if
4. Gram Stain PT
appropriate for the sample sources:
2. Major Groups of Microorganisms Yeast or yeast-like organisms; molds CLIAC considered whether required
Each subspecialty of microbiology, that include dematiaceous fungi, PT for Gram stains should include both
§§ 493.911 through 493.919, currently dermatophytes, dimorphic fungi, stain reaction and morphology. CLIAC
includes a list of the types of hyaline hyphomycetes, and concluded it should and recommended:

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• PT results for Gram stains should percent to 25 percent for bacteriology, other microbiology subspecialties.
include both stain reaction and mycobacteriology, and mycology to Following this deliberation, CLIAC
morphology. better reflect actual patient samples. As made the following recommendations:
We agree with this recommendation a result, we are proposing changes as • Required PT for antimicrobial
because knowing the bacterial follows: susceptibility and/or resistance testing
morphology is essential for accurate • Section 493.911(a)(2): In should be increased to two challenges
identification of specific groups of bacteriology, we are proposing to per event for a total of six challenges per
bacteria. Therefore, we are proposing decrease the required mixed cultures year in bacteriology and should include
the following in § 493.911: from 50 percent to 25 percent for culture one gram-positive and one gram-
• Section 493.911(a): The addition of challenges that require laboratories to negative organism in each event.
required morphology for Gram stains. report only the principal pathogen and • PT should be required for
• Section 493.911(b): The evaluation those that require laboratories to report laboratories that perform susceptibility
of a laboratory’s performance would be all organisms present. and/or resistance testing in all
modified to include bacterial • Sections 493.913(a)(2) and microbiology subspecialties. It should
morphology as one part of the 493.915(a)(2): In mycobacteriology and include two challenges per event and
performance criterion for scoring the mycology, respectively, we are should include resistant organisms.
Gram stain. proposing to decrease the mixed culture In considering these
5. Mixed Culture Requirement requirement from 50 percent to 25 recommendations, we reviewed the
percent. modules currently offered by PT
The current CLIA requirements for Since the requirements for
bacteriology § 493.911(b)(1), programs that include susceptibility
parasitology and virology do not
mycobacteriology § 493.913(b)(1), and testing and noted that there is a limited
currently include requirements for
mycology § 493.915(b)(1) specify that at number of applicable PT modules
mixed cultures (or mixed PT
least 50 percent of the PT samples in an currently available for resistance testing.
challenges), we do not propose to make
annual program must be mixtures of the Also, no PT program currently offers
any changes to these subspecialties.
principal organism and appropriate applicable PT modules for antiparasitic
normal flora. The purpose of this 6. Antimicrobial Susceptibility Testing susceptibility or resistance testing in the
requirement is to simulate the findings PT for antimicrobial susceptibility subspecialty of parasitology. We believe
that would occur with actual patient testing is currently required for it could be beneficial to increase the
specimens. In bacteriology, this 50 bacteriology at § 493.911(b)(1) and number of challenges per event from
percent mixed culture requirement must mycobacteriology at § 493.913(b)(1), but one to two for each microbiology
be met for two required sample types, it is not required for mycology, subspecialty to increase the likelihood
those that require laboratories to report parasitology, or virology. For of detection of a problem in a
only organisms that the testing antimicrobial susceptibility testing in laboratory. Antiparasitic susceptibility
laboratory considers to be a principal bacteriology at § 493.911(b)(3), at least or resistance testing is not included in
pathogen that is clearly responsible for one sample per testing event must the subspecialty of parasitology because
a described illness (excluding immuno- include one gram-positive or gram- no PT program currently offers
compromised patients) and those that negative sample and for applicable PT modules. Therefore, we
require laboratories to report all mycobacteriology at § 493.913(b)(3), at are proposing the following:
organisms present. The CLIA least one sample per testing event must • Section 493.911(a)(4): For
requirements for mycobacteriology and include a strain of Mycobacterium bacteriology, we are proposing to
mycology PT do not specify two sample tuberculosis with a predetermined require at least two PT samples per
types, but include the 50 percent pattern of susceptibility or resistance to event for susceptibility or resistance
requirement for cultures containing a the common antimycobacterial agents. testing, including one gram-positive and
mixture of the principal organism and In some instances, laboratories one gram-negative organism with a
appropriate normal flora. None of the 50 appreciate the opportunity to participate predetermined pattern of susceptibility
percent mixed culture requirements in in additional susceptibility testing or resistance to common antimicrobial
these subspecialties applies to samples challenges as educational tools. Under agents.
that would only contain normal flora the current regulations, some • Section 493.913(a)(5): For
and no reportable organisms. laboratories may perform the minimum mycobacteriology, we are proposing to
CLIAC considered whether PT should required susceptibility testing on some require at least two PT samples per
include mixed cultures, and discussed organisms such as gram-positive cocci. event for susceptibility or resistance
the difficulties of having mixed cultures When CLIAC discussed this issue, the testing, including mycobacteria that
in challenges for antimicrobial point was made that by increasing the have a predetermined pattern of
susceptibility testing. CLIAC considered frequency and number of required susceptibility or resistance to common
lowering the mixed culture requirement susceptibility testing PT challenges for antimycobacterial agents.
to 25 percent for all subspecialties in different groups of organisms, potential • Section 493.915(a)(4): For
microbiology. Upon deliberation, CLIAC issues with patient testing in a mycology, we are proposing to require
made the following recommendation: laboratory may be detected sooner. at least two PT samples per event for
• Lower the mixed culture CLIAC considered recommending susceptibility or resistance testing,
requirement from 50 percent to 25 increasing the susceptibility testing including fungi that have a
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percent for PT challenges of both challenges to two per event and predetermined pattern of susceptibility
sample types (those that require requiring one gram-positive and one or resistance to common antifungal
laboratories to report only the principal gram-negative organism in each agents.
pathogen and those that require bacteriology testing event. CLIAC also • Section 493.919(a)(4): For virology,
laboratories to report all organisms considered whether PT should be we are proposing to require at least two
present). required for resistance as well as PT samples per event for susceptibility
We agree it is appropriate to lower the susceptibility testing and whether these or resistance testing, including viruses
mixed culture requirement from 50 requirements should be extended to that have a predetermined pattern of

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 1540 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

susceptibility or resistance to common • To add the evaluation criteria of a mind, as discussed in section II.B.2. of
antiviral agents. laboratory’s performance for two of the this proposed rule, we are proposing to
In each of these subspecialties, we are affected subspecialties under add the most crucial analytes based
also proposing to revise the §§ 493.911(b) and 493.917(b) to include upon the following criteria:
requirements for evaluation of a performance and scoring criteria that (1) Current availability of PT materials
laboratory’s performance at address direct antigen and toxin and the number of PT programs offering
§§ 493.911(b), 493.913(b), 493.915(b), detection. Evaluation of a laboratory’s PT.
and 493.919(b) to account for the fact performance for direct antigen testing at (2) Volume of patient testing
that PT would be required for § 493.917(b) would align with the other performed nationwide.
susceptibility or resistance testing and microbiology subspecialties and reflect (3) Impact on patient health and/or
that the scoring should be consistent current microbiology practices in public health.
with the testing performed. reporting patient results. Evaluation of a (4) Cost and feasibility of
laboratory’s performance for bacterial implementation.
7. Direct Antigen Testing toxin detection at § 493.911(b) would 2. Process for Ranking Analytes
PT for direct antigen testing is only reflect the current practice of reporting Proposed for Addition to Subpart I
required for bacteriology and virology patient test results (that is, absence or
under §§ 493.911(a) and 493.919(a), presence of bacterial toxin). We used a sequential process to
respectively, not for the other narrow the list of eligible analytes for
B. Proposed Changes to PT for Non- addition based on each of the four
microbiology subspecialties of Microbiology Specialties and
mycobacteriology, mycology, and criteria listed above.
Subspecialties
parasitology. Since this type of testing is a. Current Availability of PT Materials
commonly used for testing patient 1. Analytes Proposed for Addition to and the Number of PT Programs Already
specimens especially in mycology and Subpart I Offering PT
parasitology, CLIAC considered whether The CLIA statute requires the PT We believe that the availability of
PT for direct antigen testing should be standards established by the Secretary these PT samples for a particular analyte
part of all of the microbiology to require PT for each examination and is an appropriate criterion for narrowing
subspecialty requirements. CLIAC procedure for which the laboratory is the list of eligible analytes and that
indicated that direct antigen PT should certified ‘‘except for examinations and scaling up a program would be
be required in subspecialties where procedures for which the Secretary has relatively less difficult than creating a
these methods are used and PT is determined that a proficiency test PT sample for a particular analyte that
available and made the following cannot reasonably be developed’’ (42 had not previously been offered. For the
recommendation: U.S.C. 263a(f)(3)(A)). In determining reasons noted below, we believe that at
• PT for direct antigen testing should whether PT can reasonably be
least three PT programs offering PT
be required for all microbiology developed for a given analyte, we
samples for a particular analyte under
subspecialties. considered whether the estimated cost
consideration would provide a
We reviewed the modules currently of PT is reasonable in comparison to the
sufficient number of programs to offer
offered by PT programs and determined expected benefit. Considering CLIAC’s
immediate access to PT by laboratories
there are a number of modules that recommendations regarding possible
and a reasonable starting point for the
include direct antigen testing for all changes to the analytes for which PT is
analytes under consideration. CMS and
microbiology subspecialties except required, we attempted to maximize
CDC want to ensure that the laboratories
mycobacteriology, for which this improvements to the effectiveness of PT
could choose the best PT program for
technology is not commonly used for to improve accuracy, reliability and
the services that their laboratories
testing patient specimens. In addition, timeliness of testing while minimizing
offered as well as not create a market
we recognized that in bacteriology, PT costs to the laboratories. In addition, we
advantage for a small number of PT
for direct antigen testing to detect toxins recognize that it is not necessary to
programs. To evaluate the current
produced by organisms such as require PT for every analyte to derive
availability of PT materials and PT
Clostridioides (formerly Clostridium) benefits generalizable to all test
programs offering PT samples for a
difficile is also commonly available. methods. For example, systematic
particular analyte, we analyzed the
Based on the information collected from analytical problems on a multichannel
distribution of available PT programs for
the PT programs, availability of the analyzer might be detected by
analytes for which PT is currently not
modules, and importance to the health participation in PT for any of the
required by subpart I of the CLIA
and safety of the public, we are analytes tested. Further, laboratories are
regulations. The supporting data were
proposing: already required under § 493.1236(c)(1)
collected from available sources,
• To retain the requirement for direct to verify the accuracy of any test or
including data from PT program
antigen detection for: procedure they perform that is not
catalogs, and data routinely reported by
++ Section 493.911(a)(1)(ii): included in subpart I at least twice
PT programs, including enrollment data.
Bacteriology. annually. Also, based on the results of
We examined the number of PT
++ Section 493.919(a)(1)(i): Virology. the national PT survey 1 conducted by
programs offering these analytes at any
And add the requirement for direct CDC and the Association of Public number of events per year and any
antigen testing detection for: Health Laboratories (APHL) in 2013, a number of challenges per event. We
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++ Section 493.915(a)(1)(i): large number of laboratories voluntarily initially determined the number of
Mycology. purchased PT materials for many analytes under consideration for which
++ Section 493.917(a)(1)(i): nonrequired analytes.2 Keeping this in PT was offered by at least two, three, or
Parasitology. four of the eleven existing PT programs.
• To require PT for bacterial toxin
1 Office of Management and Budget control

number 0920–0961. Expiration date 4/30/2015. We determined that limiting the

detection under § 493.911(a)(1)(iii). No 2 Earley, Marie C., J. Rex Astles, and Karen
changes are proposed for Breckenridge. Practices and Perceived Value of of Applied Laboratory Medicine 1, 4 (2017), pp.
mycobacteriology. Proficiency Testing in Clinical Laboratories. Journal 415–420.

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1541

analytes under consideration to those source of available data for all patient estimated total of 181.5 million covered
for which PT was offered by at least testing being performed nationwide. We individuals enrolled in CCAE healthcare
three PT programs allowed a sufficient had complete data for Medicare insurance; from this we derived a factor
number of programs to offer immediate reimbursements, as well as the most of 4.5 (181.5 million individuals/40
access to PT by laboratories and current MarketScan Commercial Claims million individuals) by which to
provided a reasonable starting point of and Encounters (CCAE) and MarketScan multiply the MarketScan CCAE
199 for the number of analytes under Medicaid Multi-state data sets (2009 estimates to extrapolate estimates for the
consideration (96 in routine chemistry, Truven Health MarketScan® data, entire U.S. Similarly, for the Medicaid
27 in endocrinology, 28 in toxicology, https://truvenhealth.com/your- estimates, we knew from CMS data that
25 in general immunology, 21 in healthcare-focus/life-sciences/data_ there were approximately 52.5 million
hematology, two for antibody databases_and_online_toolsMarkets/ individuals covered by Medicaid, so we
identification). Expected impact on Life-Sciences/Products/Data-Tools/ derived a factor of 8.0 (52.5 million
laboratories and PT programs was also MarketScan-Databases) and individuals/6.5 million individuals) by
taken into account (for example, extrapolated accordingly. We used data which to multiply the MarketScan
minimizing the cost of purchasing and provided by an HHS-approved Medicaid estimates to extrapolate
providing samples) when determining accreditation organization, specifically a estimates for the entire United States.
the minimum number of PT programs. list of the number of their accredited We note that these estimates did not
Decreasing the minimum PT programs laboratories offering each tests we account for some inpatient testing that
to two rather than three would increase considered for addition to, or deletion was paid through capitation
the number of analytes under from, subpart I in order to determine arrangements for inpatient testing.
consideration to 303, but presumably how many laboratories were performing Testing paid directly by patients was
decrease PT program availability and testing for the proposed analytes. We also not counted because, in these cases,
access for a given analyte. Conversely, also considered smaller representative CPT codes would not be captured in the
increasing the minimum number of PT data sets, including data sets obtained data because there was no request for
programs to four, while presumably from a large healthcare network, a large reimbursement. Even with this
increasing PT program availability and reference laboratory, and a university limitation, we believe that these
access for a given analyte, decreased the hospital network in order to evaluate estimates provide a relative sense of the
number of analytes under consideration the trends in performing testing for the numbers of tests being performed
to 164. This was the first cut, based proposed analytes. We analyzed annually per analyte. No other accurate
upon available PT modules. national trends in testing based upon data were available to us.
Medicare Part B reimbursement data As noted above, for the second cut,
b. Volume of Patient Testing Being based upon our estimates of national
(https://www.ncbi.nlm.nih.gov/pmc/
Performed Nationwide testing volumes, we decided that an
articles/PMC4698806/) to determine the
For the second cut, we prioritized the analytes in each specialty that are estimated national test volume of
remaining 199 analytes under increasingly used for patient diagnosis 500,000 per analyte annually was an
consideration based upon estimated and/or management. We concluded that appropriate threshold as most of the
national testing volumes. We decided the trends revealed in the data could analytes listed in subpart I had national
that an estimated national test volume continue to show increases in testing volumes above this threshold.
of 500,000 per analyte annually was an reimbursement for the proposed Together with the above-described
appropriate threshold as it was based analytes. analytes that were below the 500,000
upon testing volumes of the majority (68 We estimated the 2009 national test threshold that we determined to be
out of 81) of analytes currently listed in volumes based upon two data sets: (1) clinically important, this narrowed our
subpart I. For comparison, of the Medicare Part B reimbursement list of potential analytes under
analytes that are currently required statistics (excluding waived testing); consideration for addition to subpart I to
under subpart I, 63 had a total national and (2) CCAE. For all analytes under 73, representing analytes in five
test volume above 1,000,000; five had consideration for the addition to subpart specialties or subspecialties
national test volumes between 500,000 I, we used Current Procedural c. Impact on Patient and/or Public
and 1,000,000; and 13 had national test Terminology (CPT) codes from claims Health
volumes below 500,000. We used data. We identified all possible
500,000 annual tests as a preliminary occurrences of a particular analyte and For the third cut, we considered the
cut-off for retention on the list of combined them into one count. For evidence available as to patient and
analytes under consideration. We also example, if bicarbonate could be public impact for each analyte. There
retained analytes that were below the performed in a panel and by itself, we was no standardized, generally accepted
500,000 threshold that we determined to included all possible occurrences. way available to us to assess the relative
be clinically important based on A complete count was available for impact of testing for particular analytes
literature already footnoted in section the Medicare Part B data, and for this on clinical care and public health.
II.B.2.b. of this proposed rule and sector no estimation of total counts was Therefore, we used the following
consultation with CDC health experts. necessary. MarketScan data, which is a parameters to get a relative sense of the
The following analytes with test sample of approximately 40 million importance of the analytes under
volumes less than 500,000 that were covered individuals, was necessary to consideration: A review of published
retained are: Carbamazepine, alpha-1- estimate CCAE data and approximately laboratory practice guidelines (LPGs); a
amozie on DSK3GDR082PROD with PROPOSALS2

antitrypsin, phenobarbital, hepatitis Be 6.5 million covered individuals for review of critical values; and a review
antigen, antibody identification, Medicaid data. Therefore, we estimated of the analyte’s classification by the
theophylline, gentamicin, and the total number of tests in both of these Food and Drug Administration (FDA)
tobramycin. categories for the entire United States. (http://www.accessdata.fda.gov/scripts/
In estimating national testing volumes The Agency for Healthcare Research and cdrh/cfdocs/cfClia/Search.cfm). We
to rank the remaining 199 analytes Quality (AHRQ) 3 data showed that an accessed several data sources, including
under consideration in this proposed tests listed in the CDC Guide to
rule, we were unable to identify a single 3 https://meps.ahrq.gov/mepstrends/hc_ins/. Community Preventive Services

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 1542 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

(https://www.thecommunityguide.org); accurate result could be because an d. Cost and Feasibility of

National Healthcare Priorities/ incorrect result could lead to a life- Implementation
Disparities reports (https:// threatening intervention or a failure to
www.ahrq.gov/research/findings/ intervene. We reviewed published For the final analysis to determine
nhqrdr/index.html); clinical practice literature 10 and critical values posted whether an analyte would be proposed
guidelines including the National online from 16 institutions including for inclusion in subpart I of the CLIA
Guideline Clearinghouse (NGC) small hospitals, university hospitals, regulations, we focused upon feasibility
database available from AHRQ (https:// and reference laboratories.11 and costs of conducting PT for each of
www.guideline.gov/); 4 critical values the remaining 34 analytes under
available in publications; 5 and (CAP) Q- Our final parameter for assessing the
consideration. We provided each of the
Probes.6 clinical impact of an analyte was
HHS-approved PT programs the
In order to assess patient and public reviewing its medical device
classification (Class I, II, or III) as opportunity to submit comments in
impact for each analyte, we considered writing related to: inclusion/deletion of
the evidence available related to each categorized by the Food and Drug
Administration’s risk classification list. analytes, grading schemes, method(s) for
analyte under consideration. To do so, determining target values, evaluating
our first parameter was a review of In a similar way, we assessed the public
health importance of the eligible data using peer groups, cost of including
published LPGs. We hypothesized that
analytes by counting the number of new analytes, and structure of
if there was a relatively large number of
LPGs available for a particular analyte, recommendations for testing the microbiology PT. Analytes for which it
that analyte would be important for analytes from CDC’s Morbidity and would be difficult for the PT programs
health testing. To estimate the number Mortality Weekly Report, the Infectious to scale up production to meet the CLIA
of LPGs, we used the AHRQ’s NGC Disease Society of America, and the required frequency of three events per
database. For example, there were 60 Council of State and Territorial year with five challenges per event were
LPGs listed in the NGC for LDL Epidemiologists for surveillance of eliminated from consideration because
cholesterol, 31 for hemoglobin A1c, and health conditions related to the we believe that the costs passed down
27 for troponin, all of which are particular analyte under consideration. to laboratories to purchase the PT would
proposed for addition in Table 1. We found supporting evidence for be overly burdensome. In other cases,
However, this approach did not national prioritization in some of the the decisions were based on the
differentiate analytes for which there following: the U.S. Preventive Services difficulty of finding any suitable PT
were conflicting recommendations. For Task Force (https://www.uspreventive materials. Some potential analytes were
example, there are controversies about servicestaskforce.org/Page/Name/ eliminated because they were too
the value of screening men with prostate recommendations), the National unstable for product development or
specific antigen (PSA) testing, and there Healthcare Quality and Disparities shipping or because the testing
is an ongoing debate about the prudence Report (https://www.ahrq.gov/research/ methodology was not sufficiently
of testing vitamin D in asymptomatic findings/nhqrdr/index.html), the CDC standardized to support PT, such as
adults (Kopes-Kerr, 2013).7 8 9 Hormone Standardization Program vitamin D testing. After assessing cost
Our second parameter was a review of (https://www.cdc.gov/labstandards/ and feasibility of implementing PT on a
critical values. Critical values are pre-
hs.html). For some analytes that have case-by-case basis, we made the final
determined limits for specific analytes
important public health impact, such as cut, narrowing the analytes down to 29
that when exceeded may suggest that
blood lead, we consulted with subject potential analytes for the proposed list
immediate clinical intervention is
matter experts in the CDC National of analytes in subpart I.
required. We assessed analytes included
Center for Environmental Health, which
on ‘‘critical values’’ lists to determine 3. Specific Analytes Proposed for
promotes national testing and/or has
the analyte’s relative importance in Addition to Subpart I
standardization programs for some
helping clinicians to make rapid life-
altering decisions. This approach priority analytes, specifically estradiol Based upon the sequential process
allowed us to gauge how important an and testosterone. CMS and CDC used
described above, information received
this information to help determine
from the PT programs and consultation
4 AHRQ’s National Guideline Clearinghouse which analytes should be included in
between CDC and CMS, we narrowed
website accessed for this proposed rule, however, this proposed rule.
no longer exists on the internet effective July 16,
the list down to 29 analytes that we are
2018.
Therefore, we used those parameters proposing to add to subpart I of the
5 Burtis, C. A., Ashwood, E. R., & Bruns, D. E. in an attempt to get a relative sense of CLIA regulations (Table 1).
(2012). Tietz Textbook of Clinical Chemistry and the patient and public health impact of
Molecular Diagnostics. London: Elsevier Health the analytes under consideration, but, TABLE 1—ANALYTES PROPOSED FOR
Sciences. using the data available to us, we found
6 Laboratory critical values policies and ADDITION TO SUBPART I
procedures: a college of American Pathologists Q-
no standardized, generally accepted way
Probes Study in 623 institutions. Howanitz PJ, to assess the relative impact of testing CLIA
Steindel SJ, Heard NV. Arch Pathol Lab Med. 2002 for particular analytes on clinical care Analytes
Regulation
Jun;126(6):663–9. and public health. After assessing
7 Barry, Micheael J. Screening for Prostate

Cancer—The Controversy That Refuses to Die. New

patient and public health impact on a General Immu- Anti-HBs, Anti-HCV, C-reac-
case-by-case basis for the third cut, we nology, tive protein (high sensi-
amozie on DSK3GDR082PROD with PROPOSALS2

England Journal of Medicine 360;13 (March 2009).

8 Eck, Leigh M. Should family physicians screen narrowed the analytes down to 34 for § 493.927. tivity).
for vitamin D deficiency? yes: targeted screening in consideration of addition to the
at-risk populations is prudent. American Family proposed list of analytes in subpart I.
Physician 87, 8 (2013), pp. 541b.Fr.
9 Kopes-Kerr, Colin. Should family physicians
10 Wagar, Friedberg, Souers, and Stankovic, 2007,
screen for vitamin D deficiency? no: screening is
unnecessary, and routine supplementation makes https://www.ncbi.nlm.nih.gov/pubmed/18081434.
more sense. American Family Physician 87, 8 11 www.mayomedicallaboratories.com/test-

(2013), pp. 540b. catalog/appendix/criticalvalues/index.html.

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1543

TABLE 1—ANALYTES PROPOSED FOR the market since 1992, and may have phenobarbital, hepatitis Be antigen
ADDITION TO SUBPART I—Continued replaced use of the therapeutic drugs (HBeAg), antibody identification,
that were included in the 1992 theophylline, gentamicin and
CLIA regulations. If so, we would expect to tobramycin. These are used for making
Analytes
Regulation see a continued decline in the volume important health decisions, for example,
of testing for the use of such drugs. In diagnosing hepatitis B (HBeAg),
Routine Chem- B-natriuretic peptide (BNP), addition to identifying decreases in performing crossmatching for blood
istry, ProBNP, Cancer antigen
testing for these drugs, we looked for transfusions (antibody identification), or
§ 493.931. (CA) 125, Carbon dioxide,
Carcinoembryonic antigen, probable causes of those decreases. assessing compliance with medication
Cholesterol, low density These decreases in testing could be a for critically ill asthmatic patients
lipoprotein, Ferritin, result of new and emerging tests, (theophylline).
Gamma glutamyl trans- including methodologies, replacing
6. Analytes Proposed for Deletion From
ferase, Hemoglobin A1c, older tests, new technology, and
Subpart I
Phosphorus, Prostate spe- changes to the way that the medical
cific antigen, total, Total community orders laboratory testing. Based upon the sequential process
iron binding capacity, For example, the decrease in testing for described above, we propose that the
Troponin I, Troponin T. LDH isoenzymes could be explained by following analytes be deleted from
Endocrinology, Estradiol, Folate, serum, Fol- subpart I: At § 493.931 LDH isoenzymes
the increased reliance on better
§ 493.933. licle stimulating hormone, and at § 493.937 ethosuximide,
Luteinizing hormone, Pro- alternative cardiac markers, especially
gesterone, Prolactin, Para- troponin.12 For some of the quinidine, primidone, and
thyroid hormone, Testos- anticonvulsant drugs, there may have procainamide (and its metabolite, N-
terone, Vitamin B12. been changes in medical practice, acetyl procainamide).
Toxicology, Acetaminophen, serum, Sa- including alternative drugs and other 7. Determining Criteria for Acceptable
§ 493.937. licylate, Vancomycin. treatments, possibly decreasing the need Performance
to measure them.13 We identified 13
4. Analytes Proposed for Removal From currently required analytes with ‘‘Criteria for Acceptable
Subpart I national test volumes that were less Performance’’, as that term is used in
than our 500,000 annual test volume §§ 493.923, 493.927, 493.931, 493.933,
Recognizing that changes in the
threshold. 493.937, 493.941, and 493.959, is
practice of clinical medicine have
defined by the target value and
resulted in less frequent use of certain b. Estimated Impact on Patient and acceptance limits. Criteria for acceptable
analytes, we used the same process to Public Health performance is meant for PT scoring
review the existing list of analytes in
For any analyte still under only and not intended to be used to set
subpart I to determine which should be
consideration for removal, we acceptability criteria for a laboratory’s
retained. In addition to requesting
performed literature reviews to verification or establishment of
CLIAC’s recommendations, we generally
determine if testing for alternative performance specifications.
used the same criteria for retention of an
analytes or other diagnostic strategies
analyte in subpart I as those used for 8. Setting Target Values
had begun to supplant testing for the
determining which PT analytes to Under § 493.2, ‘‘target value’’ for
considered analyte. We took into
propose adding, however, as such PT quantitative tests are currently generally
account testing trends over the past 10
testing was already available on the defined as either the mean of all
years 14 and we attempted to project
market, we did not consider the participant responses after removal of
expected testing trends. We then
availability of PT material or the outliers (those responses greater than 3
assessed the critical importance of
feasibility of implementation; therefore, standard deviations from the original
candidates for deletion from subpart I
we believe that PT programs already mean) or the mean established by
based upon the number of guidelines
have the mechanism(s) in place to definitive or reference methods
available in the AHRQ NGC and the
manufacture and ship PT for these acceptable for use in the National
same sources used for considering
analytes. Reference System for the Clinical
inclusion in subpart I, bearing in mind
5. Process for Ranking and Assessing that for all analytes and tests that are not Laboratory (NRSCL) by the National
Existing Analytes and Proposals for listed in subpart I, laboratories must Committee for the Clinical Laboratory
Removal From Subpart I demonstrate accuracy twice per year as Standards (NCCLS). However, in
specified at § 493.1236(c)(1). We also instances where definitive or reference
a. Estimating Nationwide Testing methods are not available or a specific
Volume considered the potential impact on
clinical medicine and public health of method’s results demonstrate bias that
We generally used the same rationale deleting these analytes. Based on our is not observed with actual patient
to select currently required analytes to literature review and consultation with specimens, as determined by a
propose for deletion. Specifically, we CDC health experts, we decided not to defensible scientific protocol, a
used the same threshold of 500,000 tests propose the elimination of eight comparative method or a method group
performed annually as an initial analytes based upon their critical (‘‘peer’’ group) may be used. If the
criterion for considering PT analytes. importance for patient testing: method group is less than 10
Those estimated to be lower than this carbamazepine, alpha-1-antitrypsin, participants ‘‘target value’’ means the
amozie on DSK3GDR082PROD with PROPOSALS2

threshold were considered for deletion overall mean after outlier removal (as
from required PT. In particular, we 12 Shahangian, Alspach, Astles, Yesupriya, and defined above) unless acceptable
focused on PT for several of the Dettwyler, 2014, https://www.ncbi.nlm.nih.gov/ scientific reasons are available to
therapeutic drugs (ethosuximide, pmc/articles/PMC4698806/. indicate that such an evaluation is not
13 Krumholz, et al, 2015) (NICE, 2012, https://
quinidine, primidone, and appropriate.
www.nice.org.uk/guidance/cg137).
procainamide and its metabolite, N- 14 Shahangian, Alspach, Astles, Yesupriya, and We recognize, based on input from PT
acetyl procainamide). New drugs that Dettwyler, 2014 https://www.ncbi.nlm.nih.gov/ programs, that peer grouping is
are more effective or safer have entered pmc/articles/PMC4698806/. generally the way that target values are

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 1544 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

set for most analytes. Therefore, in this percentage limits rather than have been used in PT in a wide variety
rule, we are proposing to continue concentration units. of settings for several reasons, such as:
allowing PT programs to use peer There are 53 analytes (existing or Limited experience with PT or matrix
grouping to set the target values. In proposed) for which we are proposing a effects for a particular analyte; lack of
addition, we propose removing the percentage-based AL, for which consensus on criteria for acceptable
reference to the NRSCL and NCCLS, biological variability data were performance; inertia with no compelling
while retaining the other options for published. For several analytes (for pressure for change; and analytical
setting target values. example, therapeutic drugs) there were performance so poor that multiples of
no biological variability data because the overall SD are considered to be the
9. Changing Acceptance Limits these analytes do not occur naturally in only fair approach. In our opinion, all
Because there have been the body. Where there were such data, of these reasons to some extent
improvements in technology resulting we used AL to get as close to, or below, contributed to initial reliance on SD
in better sensitivity, specificity, and an accuracy goal for the test that was limits for certain analytes when CLIA’88
precision, routinely using peer grouping based on biological variability data, and was implemented. We also note that
to set target values means that the then we simulated several percentage- while regulations promulgated under
acceptance limits (AL) that were based ALs to see if their results would CLIA’67 used ALs of three SD for
originally specified in each specialty have passed or failed at each simulation. several analytes, regulations finalized
and subspecialty of the CLIA’88 We wanted to get miss rates (that is, under CLIA’88 replaced these with fixed
regulations in subpart I effectively allow percent of laboratories that did not meet limits and PT programs were able to
for a more tolerant acceptance criteria the criteria for acceptable performance successfully make the transition.
for most analytes than would occur if per PT challenge) of somewhere in the Therefore, we believe it is likely that the
targets were set by a reference method 1 to 2 percent range as was observed in proposed changes from SD-based ALs to
or overall mean. Based on feedback from the data provided by the PT programs fixed ALs will not be problematic.
several HHS-approved PT programs, we for current ALs. Of the 53 analytes, 34
Therefore, as discussed in section II.B.
believe that it would be appropriate to of the proposed ALs were tighter than
of this proposed rule, we are proposing
update the ALs to reflect advancements or equal to biological variability limits.
to amend certain analytes in §§ 493.927,
in technology and analytical accuracy For 19 analytes, the limits we are
493.931, 493.933, 493.937, and 493.941
since the PT regulations were proposing are looser (greater) than the
to include fixed ALs with or without
implemented in 1992. While narrowing limits required to meet accuracy based
upon biological variability. For these 19 percentages. Three analytes have only
limits may increase miss rates per concentration-based ALs (that is, no
challenge, we do not expect a high analytes, using ALs based upon
biological variability would be percentage-based ALs): pH, potassium
unsuccessful rate based on the data and sodium.
simulations provided by the PT untenable because the current analytical
programs. We expect the rates of accuracy for such testing would not be b. Adding Fixed Concentration Units to
unsatisfactory events would be low expected to be able to meet such limits. Fixed Percentage Units
based on the simulation data, and that White blood cell differential is the only
remaining analyte that would have ALs A percentage-based criterion can be
the rates of unsuccessful events (two unnecessarily stringent at low
consecutive or two out of three testing in SD. In this case there were no
biological variability data available. concentrations—either because of
events being unsatisfactory) would be technical feasibility or because medical
even lower; therefore, we believe it is In general, fixed ALs, either in
percentages or concentration units, are needs at the low concentration do not
reasonable to propose tighter limits require such tight precision 15. Thus,
preferred to SDs for PT, for several
given current analytic accuracy. We when percentage-based fixed criteria are
important reasons: They can be tied
used all data available to us to minimize used for ALs, it may be necessary to
directly to objective goals for
the negative consequences of the place a minimum on the percentage as
performance, such as goals for analytical
proposed changes (for example, too currently occurs with the criterion for
accuracy and technical expectations;
many unsuccessful performances) to acceptable performance for glucose
they are constant in all PT events and
acceptance limits, including simulations (§ 493.931) for which the AL switches
do not vary because of statistical
provided by PT programs. from 10 percent to 6 mg/dL below a
randomness, masked outliers, or small
10. Changes to Percentage Acceptance sample size; they assure the same concentration of 60 mg/dL. The
Limits (ALs) evaluation criteria are used by all PT combined ALs direct PT programs to
programs and discourage opportunities score with whichever of the
a. Basis for Using Fixed Percentage PT
for participants to ‘‘shop’’ for PT specifications is more tolerant; at lower
ALs
programs with less stringent criteria for limits of the analytical range this will be
Currently, the CLIA regulations at which it is easier to achieve acceptable the fixed concentration limit. Therefore,
§§ 493.927(c)(2), 493.931(c)(2), performance; they do not unfairly result to allow for more fair and realistic ALs,
493.933(c)(2), 493.937(c)(2), and in tighter effective ALs for peer groups we propose to use combinations of
493.941(c)(2) prescribe a variety of ALs, that use analyzers that have tighter percentage and concentration limits as
including: A multiple of the standard analytical precision; they can combine a appropriate. These combination limits
deviation (SD) of results from the mean fixed percentage and a fixed absolute are similar to limits that already exist in
of other participants in the peer group; concentration to allow for more robust CLIA’88 regulations for glucose and
amozie on DSK3GDR082PROD with PROPOSALS2

fixed limit as a percentage of the evaluation while also fairly evaluating other analytes.
assigned value; fixed limit in low analyte concentrations; and they are Therefore, we are proposing to amend
concentration units; and a mixture of commonly used worldwide in other PT certain analytes in §§ 493.927, 493.931,
percentage and concentration units, and external quality assessment 493.933, 493.937, 493.941 and 493.959
depending on the concentration of the programs.
analyte. For all new and currently Our analysis of existing PT and 15 Thompson, Michael. Variation of precision
required non-microbiology analytes, we external quality assessment programs with concentration in an analytical system. Analyst,
propose to use fixed ALs, preferably as showed that ALs using two or three SDs 113, (1988), pp. 1579–1587.

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1545

to include percentage-based ALs with or monitoring progress, we believe the Howerton, et al.24 showed that for
without additional fixed ALs. most important factor is the ‘‘within almost all analytes examined, PT
individual’’ variability. It was not performance improved somewhat after
c. Establishing ALs Based on Analytical
possible for us to differentiate how CLIA’88 was implemented, but the
Accuracy Goals for Proposed New and
analytes are being used or will be used improvements were greater for
Several Current Analytes
clinically, with respect to diagnosis laboratories that were not previously
For the newly proposed analytes and versus monitoring. Therefore, we required to perform PT. The rates of
several current analytes for which accounted for both needs and used an unsatisfactory PT are now roughly the
current ALs are in units other than approach that accounted for both kinds same for analytes listed in subpart I,
percentages such as three SDs or of biological variability to estimate regardless of the laboratory type, and
concentration units, we are proposing to analytical accuracy goals as the basis for this is consistent with CLIA’s intent to
change the ALs to percentages. Over the our proposals for acceptance limits in ensure accurate clinical testing
years, there have been many proposed percentages.20 The advantage of using regardless of the setting where testing is
criteria for establishing goals for analytical accuracy goals that are performed. There are several factors
analytical performance.16 17 The various expressed in terms of percentages is that contributing to the improvements in PT
possible approaches were reviewed and they can be directly related to ALs in a performance, including improved
a hierarchy was established based upon mathematical way expressed as analytical methods being used in all
a 1999 consensus conference.18 These percentages. settings; technological advances
strategies were reconsidered in the 2014 We have assumed that a laboratory resulting in improved precision,
European Federation of Clinical that can meet the clinical needs for test sensitivity and specificity; and
Chemistry and Laboratory Medicine accuracy based upon biological increased familiarity with handling
Strategic Conference in Milan. variability should perform successfully preparation, and reporting of PT
Participants in both conferences on PT most or all of the time. Therefore, samples. Therefore, for the reasons
acknowledged that the ability of a test whenever possible, we have used above as well as supporting simulation
method to meet clinical needs is the publically available estimates of data date from the PT programs, we are
highest priority and the most defensible allowed total error based upon estimates proposing to make criteria for
approach would be clinical trials in of biological variability 21 to acceptable performance for existing
which patient outcomes could be approximate the proposed AL. CDC has analytes listed in subpart I tighter so
compared using different analytical shown in an a recent poster 22 that it is they are in closer agreement with
accuracy goals. This approach was not possible to design ALs based upon such analytical accuracy goals which are
feasible for many reasons. Although accuracy goals, and it is possible to based upon biological variability and
clinical outcomes studies would be the simulate the ability of a PT program to simulation data.
most rigorous basis for establishing identify laboratories that cannot meet Therefore, based on the simulation
analytical performance goals, these are such goals, while minimizing the data, we are proposing to tighten ALs
seldom possible, leaving the natural likelihood of misidentifying laboratories for certain current analytes in
dispersion of levels for each analyte that are meeting analytical accuracy §§ 493.927, 493.931, 493.933, 493.937,
(biological variability) as the next best goals based upon biological variability. 493.941 and 493.959.
scientifically defensible approach for Therefore, we are proposing to amend e. Simulating the Impact of New ALs on
establishing analytical accuracy goals.19 ALs for certain current analytes as well Unacceptable Scores for Challenges and
The less the biological variability, the as establish ALs for analytes proposed Unsatisfactory Rates for Events
more stringent the analytical accuracy for addition in §§ 493.927, 493.931,
needs to be. This approach makes sense We evaluated a very specific PT data
493.933, 493.937, 493.941 and 493.959 set to help CMS and CDC set
for two of the most important reasons to based on analytical accuracy goals.
conduct patient testing: Diagnosis of appropriate limits. The total simulations
disease, that is, differentiating an d. Tightening Existing Percentage ALs reproduced PT that covered 2 years,
abnormal result from a normal one, and as Needed representing 30 challenges (three events
monitoring a patient’s progress during per year; five challenges per event; 2
There have been significant years) of each proposed new analyte and
treatment. In the former case, we believe improvements in laboratories’
that the ‘‘within-group’’ biological for the analytes for which we propose to
performance in PT for the great majority modify ALs. We reviewed the
variability is the important limiting of analytes 23 and PT unsatisfactory
factor defining an appropriate error goal aggregated percentage of unacceptable
rates have dropped for all types of scores for each PT challenge using
for a test method. Furthermore, for laboratories. The improvements are retrospective data. We then reviewed
16 Tonks, David B. A study of the accuracy and
such that, for many analytes, the simulation data which applied two
precision of clinical chemistry determinations in
laboratories that began to use PT to or three new ALs for each of 84 analytes
170 Canadian laboratories. Clinical Chemistry 9, 2 comply with CLIA’88 now perform as (consisting of 27 new analytes and 57
(1963), pp. 217–233. well as the hospital and independent existing analytes). Based on the
17 Cotlove, Ernest, Eugene K. Harris, and George
laboratories which were previously simulation data, we were able to make
Z. Williams. Biological and analytic components of required to perform PT under CLIA’67.
variation in long-term studies of serum constituents informed decisions to help us create or
in normal subjects. Clinical Chemistry 16, 12
20 Burtis, Carl A., Edward R. Ashwood, David E.
adjust the ALs.
(1970), pp. 1028–1032. Based upon our analysis of the
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18 Fraser, Callum. The 1999 Stockholm consensus Bruns, Ed. Tietz textbook of clinical chemistry and
conference on quality specifications in laboratory molecular diagnostics. (Chapter 17 Preanalytic simulation results, we further refined
medicine. Clinical Chemistry and Laboratory variables and biological variation, pp. 470–471), the proposed ALs and added potential
Medicine 53, 6 (2015), pp. 837–840. Elsevier Saunders, Philadelphia, P.A., (2006).
19 Burtis, Carl A., Edward R. Ashwood, David E. 21 https://www.westgard.com/biodatabase1.htm. 24 Howerton D1, Krolak JM, Manasterski A,
22 Astles, Tholen, and Mitchell, 2016, https://
Bruns, Ed. Tietz textbook of clinical chemistry and Handsfield JH. Arch Pathol Lab Med. 2010
molecular diagnostics. (Chapter 2 Selection and www.aacc.org/science-and-practice/annual- May;134(5):751–8. Proficiency testing performance
analytical evaluation of methods with statistical meeting-abstracts-archive. in US laboratories: results reported to the Centers
techniques, pp. 17), Elsevier Saunders, 23 Howerton, Krolak, Manasterski, and for Medicare & Medicaid Services, 1994 through
Philadelphia, P.A., (2012). Handsfield, 2010. 2006.

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 1546 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

absolute concentrations in lieu of for acceptable performance for a single • Section 493.901(c)(6): We are
percentage ALs, as was described challenge or sample. proposing to add the requirement that
previously. We then requested narrowly • Peer group: We are proposing to PT programs limit the participants’
tailored data from PT programs as define this term as a group of online submission of PT data to one
described above using retrospective PT laboratories whose testing process submission or that a method be
data and peer group data for scoring, as utilizes similar instruments, provided to track changes made to
they ordinarily would do. We focused methodologies, and/or reagent systems electronically reported results. Many PT
on unsatisfactory scores with the data so and is not to be assigned using the programs currently allow laboratories an
that we could calculate the reagent lot number. PT programs should option to report PT results electronically
unsatisfactory rate per analyte among all assign peer groups based on their own while some other PT programs allow
participating laboratories that might policies and procedures and not based laboratories to only report PT results
occur with each proposed AL. The final on direction from any manufacturer. electronically with no other reporting
simulations were conducted by several We are also proposing the following option such as facsimile or mailed PT
of the PT programs and this set of data revisions to the regulation text at submission forms. However, at this
was used to determine the ALs subpart A: time, the PT programs who do
proposed in this rule. • Sections 493.20 and 493.25: We are participate in the online reporting have
We compared the unacceptable scores proposing to amend the regulations to no mechanism to review an audit trail
for each challenge and each proposed reflect that if moderate and high for the submitted result. In some cases
AL to determine at which complexity laboratories also perform of PT referral, it has been discovered
concentrations it would be necessary to waived tests, compliance with that laboratories have sent PT samples
switch to a fixed concentration AL. § 493.801(a) and (b)(7) are not to another CLIA certified laboratory for
Using this approach, we were able to applicable. However, we propose to testing, received results from the other
identify an AL for each analyte and, in continue to require compliance with laboratory, and then changed their
some cases, an additional concentration- § 493.801(b)(1) through (6) to align the online reported results to the PT
based AL. This approach enabled us to regulations with the CLIA statute (42 program since those results can be
identify an AL that would be sensitive U.S.C. 263a(i)(4)), which does not modified up until the PT event close
enough to identify poor performing exclude waived tests from the ban on date. In an effort to assist in PT referral
laboratories, yet not so sensitive that it improper PT referral. investigations and determinations, an
will incorrectly identify laboratories We are also proposing the following audit trail that includes all instances of
that are likely meeting requirements for revision to the regulation text at subpart reported results would aid in
accuracy. H: determining if a laboratory compared PT
results obtained from another laboratory
f. Limitation in Our Ability To Predict • Section 493.861: We are amending
and changed their previously submitted
the Number of New Unsatisfactory and the satisfactory performance criteria for
results.
Unsuccessful Scores failure to attain an overall testing event • Section 493.901(c)(8): We are
score for unexpected antibody detection proposing to add to the requirement
It is not possible for us to predict the from ‘‘at least 80 percent’’ to ‘‘100 previously found at § 493.901 that
precise effect of the proposed changes percent.’’ We are proposing this change contractors performing administrative
on the number of unsatisfactory and because it is critical for laboratories to responsibilities as described in
unsuccessful scores. The occurrence of identify any unexpected antibody when §§ 493.901 and 493.903 must be a
an unsatisfactory score for a PT event crossmatching blood to protect the private nonprofit organization or a
depends upon at least two of five public health and not impact patient federal or state agency or nonprofit
challenges being graded as unacceptable care. entity acting as a designated agent for
or outside the criteria for acceptable for We are also proposing the following the federal or state agency. Several PT
performance. PT programs select revisions to the regulation text at programs have divided their
different combinations of samples for subpart I: administrative and technical
each event and it is impossible to • Section 493.901(a): We are responsibilities into separate entities or
predict how their selection could be proposing to require that each HHS- have had the administrative
modelled statistically. Finally, the approved PT program have a minimum responsibilities performed by a
distribution of unsatisfactory and of ten laboratory participants before contractor. We were made aware that
unsuccessful PT scores is not randomly offering any PT analyte. We recognize administrative responsibilities were
distributed across all participants. that PT programs do not grade results being performed by a for-profit entity.
C. Additional Proposed Changes when there are fewer than ten laboratory Because the CLIA statute (42 U.S.C.
participants. This would require the 263a(f)(3)(C)) requires PT programs to be
We are proposing to amend § 493.2 to laboratory to perform additional steps to administered by a private nonprofit
modify the definition of an existing term verify the accuracy of their results. If at organization or a state, we are proposing
and define new terms as follows: any time a PT program does not meet to amend § 493.901 to state that all
• Target value: We are removing the the minimum requirement of 10 functions and activities related to
reference to NRSCL and NCCLS and participating laboratories for an analyte administering the PT program must be
retaining the other options for setting or module, HHS may withdraw performed by a private nonprofit
target values are retained in this approval for that analyte, specialty or organization or state.
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proposed rule. subspecialty. This change reduces some • Section 493.901(e): We are
• Acceptance Limit: We are proposing burden on laboratories that have proposing to add the requirement that
to define this term to mean the incurred the expense of enrolling in a HHS may perform on-site visits for all
symmetrical tolerance (plus and minus) PT program but do not receive a score initial PT program applications for HHS
around the target value. or receive an artificial score requiring approval and periodically for previously
• Unacceptable score: We are the laboratory to take additional steps to HHS-approved PT programs either
proposing to define this term to mean verify the accuracy of the analyte as during the reapproval process or as
PT results that are outside the criteria required by § 493.1236(b)(2). necessary to review and verify the

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1547

policies and procedures represented in susceptibility or resistance testing on 493.931(c)(1), 493.933(c)(1),

its application and other information, select bacteria. 493.937(c)(1), 493.941(c)(1), and
including, but not limited to, review • Section 493.911(a)(3): We are 493.959(d)(1): We are proposing to
and examination of documents and proposing that the bacteriology annual amend these provisions to clarify that
interviews of staff. PT program content described must for the purpose of achieving consensus,
• Section 493.901(f): We are include representatives of the following PT programs must attempt to grade
proposing to add an additional major groups of medically important using both participant and referee
requirement to the regulation that aerobic and anaerobic bacteria if laboratories before determining that the
specifies CMS may require a PT appropriate for the sample sources: sample is ungradable. We believe that
program to reapply for approval using Gram-negative bacilli; gram-positive this change will enhance consistency
the process for initial applications if bacilli; gram-negative cocci; and gram- among the PT programs when grading
widespread or systemic problems are positive cocci. samples. The current regulations noted
encountered during the reapproval • Section 493.913(a): We are above allow for scoring either with
process. The initial application for the proposing to include required PT for participants or with referees before
approval as an HHS PT program acid-fast stain; detection and calling a sample ungradable.
requires more documentation in the identification of mycobacteria; and • Sections 493.923(a), 493.927(a),
application process than that which is antimycobacterial susceptibility or 493.931(a), 493.933(a), 493.937(a),
required of PT programs seeking HHS resistance testing. 493.941(a), and 493.959(b): We are
reapproval. • Section 493.913(a)(3): For proposing to amend these provisions to
• Section 493.903(a)(3): It has come to mycobacteriology, we are proposing that remove the option that PT samples, ‘‘at
our attention that PT programs may the annual program content must HHS’ option, may be provided to HHS
have on occasion modified a include Mycobacterium tuberculosis or its designee for on-site testing’’.
laboratory’s PT result submission by complex and Mycobacterium other than • Section 493.927: We are proposing
adding information such as the testing tuberculosis (MOTT), if appropriate for to amend, as discussed in sections II.B.8
methodology which was inadvertently the sample sources. through II.B.10. of this proposed rule,
omitted by the laboratory. Therefore, we • Section 493.915(a): For mycology, the criteria for acceptable PT
are proposing to add the requirement we are proposing to require PT for direct performance to permit scoring of
that PT programs must not change or fungal antigen detection; detection and quantitative test results for the following
add any information on the PT result identification of fungi and aerobic immunology analytes: Antinuclear
submission for any reason including, actinomycetes; and antifungal antibody; antistreptolysin O;
but not limited to, the testing susceptibility or resistance testing. rheumatoid factor; and rubella. For
methodology, results, data, or units. • Section 915(a)(3): We are we are these analytes, we have determined that
• Section 493.905: We are proposing proposing that annual program content there are one or more test systems that
to add that HHS may withdraw the must include the following major currently report results in quantitative
approval of a PT program at any point groups of medically important fungi and units; therefore, we are adding ALs
in the calendar year if the PT program aerobic actinomycetes if appropriate for based on percentages or target values in
provides false or misleading information the sample sources: Yeast or yeast like addition to retaining the qualitative
that is necessary to meet a requirement organisms; molds that include target values. We propose to make this
for program approval or if the PT dematiaceous fungi, dermatophytes, allowance in CLIA for reporting PT
program has failed to correct issues dimorphic fungi, hyaline which reflects current practice.
identified by HHS related to PT program hyphomycetes, and mucormycetes; and • Section 493.931(b): We are making
requirements. We are also proposing to aerobic actinomycetes. a technical change to the description for
add a requirement that the PT program • Section 493.917(a): For creatine kinase isoenzymes to be CK–
may request reconsideration should parasitology, we are proposing to MB isoenzymes, which may be
CMS determine that false or misleading require PT for direct parasite antigen measured either by electrophoresis or by
information was provided of if the PT detection and detection and direct mass determination, for example
program has failed to correct issues identification of parasites. using an immunoassay.
identified by HHS related to PT program • Section 493.917(a)(3): We are • Section 493.933: We propose to add
requirements. proposing that the annual program the following analytes: Estradiol, folate
• Sections 493.911 through 493.919: content must include intestinal (serum), follicle stimulating hormone,
We are proposing, as discussed in parasites and blood and tissue parasites, luteinizing hormone, progesterone,
section II.A.1. of this proposed rule, to if appropriate for the sample source. prolactin, parathyroid hormone,
modify the regulation by removing the • Section 493.919(a): For virology, we testosterone, and vitamin B12.
types of services listed for each are proposing to require PT for viral • Section 493.937(a): We are
microbiology subspecialty. We are also antigen detection; detection and proposing to revise this provision by
proposing to remove specific lists of identification of viruses to the highest including the requirement that annual
example organisms from each level that the laboratory reports results PT programs must provide samples that
microbiology subspecialty and replace on patient specimens; and antiviral cover the full range of values that could
the list with broader categories of susceptibility or resistance testing. occur in patient specimens. We are
organisms. • Section 493.919(a)(3): We are proposing this amendment so that PT
• Section 493.911(a): For proposing that the annual program programs must provide samples across a
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bacteriology, as discussed in sections content must include respiratory toxicology sample’s entire reportable
II.A.1. and V.C. of this proposed rule, viruses, herpes viruses, enterovirus, and range rather than just provide samples
we are proposing that the categories intestinal viruses, if appropriate for the within a sample’s therapeutic range.
required include Gram stain including sample source. • Section 493.941: We are
bacterial morphology; direct bacterial • Sections 493.911(b)(1), differentiating the criteria for units of
antigen detection; bacterial toxin 493.913(b)(1), 493.915(b)(1), reporting of the analyte prothrombin
detection; detection and identification 493.917(b)(1), 493.919(b)(1), time. Currently the analyte prothrombin
of bacteria; and antimicrobial 493.923(b)(1), 493.927(c)(1), time can be reported in seconds and/or

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 1548 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

INR (international normalized ratio), so we solicit comment on the following benefits. The total cost would be
we are proposing to amend the criteria issues: $18,834 (368 hours × $51.18).
for acceptable performance to reflect • The need for the information
collection and its usefulness in carrying B. Submission of PT Data by
both units of reporting and proposing to
out the proper functions of our agency. Laboratories
add the requirement that laboratories
must report prothrombin time for PT the • The accuracy of our burden At § 493.901(c)(6), we are proposing
same way they report it for patient estimates. to add the requirement that PT programs
results; if patient results are reported in • The quality, utility, and clarity of limit the participants’ online
seconds or as INR results, they should the information to be collected. submission of PT data to one
report the same way to PT programs. If • Our effort to minimize the submission or that a method be
the laboratory reports patient results information collection burden on the provided to track changes made to
both in seconds and as INR, they should affected public, including the use of electronically reported results. In an
be reported the same way to the PT automated collection techniques. effort to assist in PT referral
programs. We are also proposing to add We are soliciting public comment on investigations and determinations, an
criteria for acceptable performance for each of the section 3506(c)(2)(A)- audit trail that includes all instances of
directly measured INR for prothrombin required issues for the following reported results would aid in
time. In addition, we propose to require information collection requirements determining if a laboratory compared PT
laboratories that perform both cell (ICRs). results obtained from another laboratory
counts and differentials to conduct PT The requirements and burden will be and changed their previously submitted
for both (that is, the ‘‘or’’ would be submitted to OMB under (OMB control results. In accordance with the
changed to an ‘‘and’’). Finally, we are number 0938-New). implementing regulations of the PRA at
proposing to change the criteria for A. Clarification for Reporting of 5 CFR 1320.3(b)(2), we believe the
acceptable performance for ‘‘cell Microbiology Organism Identification ability for the PT programs to track this
identification’’ from 90 percent to 80 data already exists in their software;
We are proposing to clarify a however, they may need to make minor
percent. We are proposing this change requirement at §§ 493.801(b),
as the requirement of five samples per modifications to their software in order
493.911(b), 493.913(b), 493.915(b), to meet this requirement. If a PT
event does not allow for a score of 90
493.917(b), and 493.919(b), to program would need to update their
percent (that is, five samples would
emphasize the point that, as currently software, we would estimate that the
allow for scores of 0 percent, 20 percent,
required, laboratories must report PT cost would be 15 hours for software
40 percent, 60 percent, 80 percent, or
results for microbiology organism modification. The total burden is 135
100 percent). PT for cell identification is
identification to the highest level that hours (9 PT programs × 15 hours).
currently required in § 493.941. Further,
they report results on patient However, this would not be an annual
§ 493.851(a) states that ‘‘failure to attain
specimens. In accordance with the burden, rather it would only occur once
a score of at least 80 percent of
implementing regulations of the PRA at when the requirement is implemented.
acceptable responses for each analyte in
5 CFR 1320.3(b)(2), we believe the A Software Developer, System Software
each testing event is unsatisfactory
performance for the testing event.’’ If the reporting of microbiology organism would perform this task at an hourly
requirement for acceptable performance identification is a usual and customary wage of $107.48 as published in 2017 by
remains at 90 percent, a laboratory can practice when reporting PT results to PT the Bureau of Labor Statistics (https://
only have satisfactory performance if programs. We are able to determine how www.bls.gov/oes/current/oes_nat.htm).
they receive 100 percent; however, many laboratories provide services in The wage rate would be $107.48 to
§ 493.851(a) allows satisfactory microbiology; however, we are unable to include overhead and fringe benefits.
performance for both 80 percent and determine if the laboratories are The total high estimated cost would be
100 percent. enrolled in the appropriate PT outside $14,510 (135 hours × $107.48). For those
• Section 493.959: We are proposing of the survey process, or if the PT programs who already have this
to change the criteria for acceptable microbiology PT samples for which the mechanism in place, there would be no
performance for unexpected antibody laboratory is enrolled are required under additional burden or cost to meet this
detection from 80 percent accuracy to subpart I. There are no data systems that requirement.
100 percent accuracy. We are proposing capture this information. We estimate
the number of laboratories that are not C. Optional On-Site Visits to PT
this change because it is critical for Programs
laboratories to identify any unexpected currently reporting microbiology
antibody when crossmatching blood in organisms to the highest level that they At § 493.901(e), we propose to add the
order to protect the public health and report results on patient specimens to be requirement that HHS may require on-
not impact patient care. about 10 percent of 36,777 laboratories site visits for all initial PT program
which is 368 laboratories. We estimate applications for HHS approval and
III. Collection of Information it would take 20 minutes for a periodically for previously HHS-
Requirements laboratory to fill this information on the approved PT programs either during the
Under the Paperwork Reduction Act PT submission form. Each laboratory reapproval process or as necessary to
of 1995 (PRA), we are required to would report this information 3 times a review and verify the policies and
publish a 60-day notice in the Federal year which would take approximately 1 procedures represented in its
Register and solicit public comment hour. The total annual burden is 368 application and other information,
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before a collection of information hours (368 laboratories × 1 hour). A including, but not limited to, review
requirement is submitted to the Office of Clinical Laboratory Technologists/ and examination of documents and
Management and Budget (OMB) for Technicians would perform this task at interviews of staff. There is no
review and approval. an hourly wage of $25.59 as published collection of information requirements
To fairly evaluate whether an in 2017 by the Bureau of Labor Statistics associated with this proposed
information collection should be (https://www.bls.gov/oes/current/oes_ requirement because the documentation
approved by OMB, PRA section nat.htm). The wage rate would be is already being collected and
3506(c)(2)(A) of the PRA requires that $51.18 to include overhead and fringe maintained by the PT program as

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normal course of business and is a usual clinical laboratories under CLIA’67. another agency; (3) materially altering
and customary practice in accordance When CLIA’88 was enacted, and its the budgetary impacts of entitlement
with implementing regulations at 42 implementing regulations were finalized grants, user fees, or loan programs or the
CFR 493, subpart I. in 1992, all clinical laboratories that rights and obligations of recipients
perform nonwaived testing became thereof; or (4) raising novel legal or
D. PT Program Reapproval
subject to the CLIA PT requirements. policy issues arising out of legal
At § 493.901(f), we propose to specify Since that time, there have been many mandates, the President’s priorities, or
that we may require a PT program to changes in the practice of laboratory the principles set forth in the Executive
reapply for approval using the process medicine and improvements in the Order. A regulatory impact analysis
for initial applications if widespread or analytical accuracy of test methods, (RIA) is required for economically-
systemic problems are encountered such that HHS decided to assess the significant regulatory actions that are
during the reapproval process. If a PT need to revise the PT regulations. For likely to impose costs or benefits of
program would need to reapply for example, a number of analytes and tests $100 million or more in any given year.
approval using the initial application now used for making clinical decisions This proposed regulation is
process, we would estimate that the cost were not recognized or commonly used economically significant within the
would be 10 hours for document at the time the CLIA PT requirements meaning of section 3(f)(1) of the
collection. The total burden is 90 hours were published on February 28, 1992 at Executive Order since the estimated cost
(9 PT programs × 10 hour). However, 42 CFR part 493 (57 FR 7002). alone is likely to exceed the $150
this would not be an annual burden, Improvements in analytical accuracy million annual threshold. However, our
rather it would only occur under the required revisions to the criteria for upper limit of estimated impact is under
circumstances outlined above, and we acceptable performance to reflect the the threshold of $150 million for the
believe that these would only occur current practices. We based our decision year of 2018 under Unfunded Mandates
rarely. An Office/Administrative to update the regulations and Reform Act (UMRA). The proposed rule,
Support Worker would perform this task incorporate the changes proposed in if finalized, would revise the CLIA PT
at an hourly wage of $17.96 as this rule upon advice from the CLIAC. requirements and would affect
published in 2017 by the Bureau of approximately 36,777 clinical
Labor Statistics (https://www.bls.gov/ B. Overall Impact laboratories now subject to participation
oes/current/oes_nat.htm). The wage rate We have examined the impacts of this in PT, resulting in some financial
would be $35.92 to include overhead rule as required by Executive Order implications. In addition, this proposed
and fringe benefits. The total cost would 12866 on Regulatory Planning and rule, if finalized, would cause the seven
be $3,233 (90 hours × $35.92). Review (September 30, 1993), Executive existing CLIA-approved PT programs to
Order 13563 on Improving Regulation incur some costs as they modify their
E. Withdrawal of Approval of a PT
and Regulatory Review (January 18, programs to meet the requirements
Program
2011), the Regulatory Flexibility Act specified in this proposed rule. It may
At § 493.905, we propose to add that (RFA) (September 19, 1980, Pub. L. 96– also have an effect on some state PT
HHS may withdraw the approval of a PT 354), section 1102(b) of the Social requirements. We prepared the RIA and
program at any point in the calendar Security Act, section 202 of the found that it did not meet the UMRA
year if the PT program provides false or Unfunded Mandates Reform Act of 1995 threshold for a significant regulatory
misleading information that is necessary (March 22, 1995; Pub. L. 104–4), action.
to meet a requirement for program Executive Order 13132 on Federalism The RFA requires agencies to analyze
approval or if the PT program has failed (August 4, 1999) and the Congressional options for regulatory relief of small
to correct issues identified by HHS Review Act (5 U.S.C. 804(2)), and entities if a rule has a significant impact
related to PT program requirements. We Executive Order 13771 on Reducing on a substantial number of small
are also proposing to add a requirement Regulation and Controlling Regulatory entities. For purposes of the RFA, we
that the PT program may request Costs (January 30, 2017). assume that the great majority of clinical
reconsideration. We believe this is Executive Orders 12866 and 13563 laboratories and PT programs are small
excepted because of it being an direct agencies to assess all costs and entities, either by virtue of being
administrative action per 5 CFR benefits of available regulatory nonprofit organizations or by meeting
1320.4(a)(2). alternatives and, if regulation is the Small Business Administration
IV. Response to Comments necessary, to select regulatory definition of a small business by having
approaches that maximize net benefits revenues of less than $7.5 million to
Because of the large number of public (including potential economic, $38.5 million in any one year. For
comments we normally receive on environmental, public health and safety purposes of the RFA, we believe that
Federal Register documents, we are not effects, distributive impacts, and approximately 82 percent of clinical
able to acknowledge or respond to them equity). Section 3(f) of Executive Order laboratories qualify as small entities
individually. We will consider all 12866 defines a ‘‘significant regulatory based on their nonprofit status as
comments we receive by the date and action’’ as an action that is likely to reported in the American Hospital
time specified in the DATES section of result in a rule: (1) Having an annual Association Fast Fact Sheet, updated
this preamble, and, when we proceed effect on the economy of $100 million January 2017 (https://www.aha.org/
with a subsequent document, we will or more in any one year, or adversely system/files/2018-01/fast-facts-us-
respond to the comments in the and materially affecting a sector of the hospitals-2017_0.pdf) and 100 percent
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preamble to that document. economy, productivity, competition, of PT programs are nonprofit

V. Regulatory Impact Analysis jobs, the environment, public health or organizations. Individuals and states are
safety, or state, local or tribal not included in the definition of a small
A. Statement of Need governments or communities (also entity. We are voluntarily preparing a
Proficiency testing (PT) has long been referred to as ‘‘economically Regulatory Impact Analysis and are
recognized as a critical component of a significant’’); (2) creating a serious requesting public comments in this area
quality management system. It was first inconsistency or otherwise interfering to assist us in making this determination
required at a national level for some with an action taken or planned by in the final rule.

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 1550 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

In addition, section 1102(b) of the local governments that are not required types of services offered by a laboratory
Social Security Act (the Act) requires us by statute. We do not believe that a and an overall score is given per that
to prepare a regulatory impact analysis significant number of laboratories subspecialty. In the other specialties
if a rule may have a significant impact affected by these proposals are operated and subspecialties, PT participation is
on the operations of a substantial by state or local governments. Therefore, required and scores are given based on
number of small rural hospitals. This the proposed modifications in these specific required analytes listed in the
analysis must conform to the provisions areas would not cause additional costs regulations.
of section 603 of the RFA. For purposes to state and local governments. For both the microbiology PT changes
of section 1102(b) of the Act, we define We are proposing to require that each and addition of proposed analytes to
a small rural hospital as a hospital that HHS-approved PT program have a subpart I, we anticipate minimal burden
is located outside of a metropolitan minimum of ten laboratory participants to laboratories as CLIA already requires
statistical area and has fewer than 100 before offering any PT analyte. This that laboratories must verify the
beds. We do not expect this proposed change reduces some burden on accuracy of tests not currently listed in
rule, if finalized, would have a laboratories that have incurred the subpart I at least twice annually. We
significant impact on small rural expense of enrolling in a PT program believe many laboratories meet this
hospitals. Such hospitals often provide but do not receive a score or receive an requirement by participating in
very limited laboratory services and artificial score requiring the laboratory proficiency testing voluntarily.
may refer testing for the analytes we to take additional steps to verify the However, we do not have a way of
propose to add, to larger laboratories. accuracy of the analyte as required by estimating how many of these
For the small rural hospitals that have § 493.1236(b)(2). PT programs will participating laboratories actually meet
laboratories and perform testing for the determine if it is economically feasible the requirement through additional
analytes, we expect that our proposals to offer those analytes or if they should verification. Information on the costs of
will add minimal effort since they market their products to laboratories. voluntary participation is also not
should already have PT policies and Both of these activities are outside the reported. Although we cannot precisely
procedures in place. We are unable to scope of our authority. predict how the proposed changes may
estimate the number of laboratories that qualitatively affect clinical laboratories,
C. Anticipated Effects
support small rural hospitals. We are we do not expect there to be major
requesting public comments in this area This proposed rule, if finalized, changes in how they function. We have
to assist us in making this determination would impact approximately 36,777 quantified the costs we expect
in the final rule. clinical laboratories (total of Certificate laboratories to incur but there may be
Section 202 of the Unfunded of Compliance and Certificate of costs associated with other
Mandates Reform Act of 1995 (UMRA) Accreditation laboratories, as of January administrative functions related to PT
also requires that agencies assess 2017) required to participate in PT ordering, result reporting, and record
anticipated costs and benefits before under the CLIA regulations keeping that we are not able to estimate.
issuing any rule whose mandates implemented by the February 28, 1992 As stated above, we are unable to
require spending in any one year of final rule, seven current HHS-approved estimate the number of laboratories
$100 million in 1995 dollars, updated PT programs, and to a lesser extent, in voluntarily enrolled in PT which is not
annually for inflation. In 2018, that vitro diagnostics (IVD) manufacturers, currently required in subpart I. Cost of
threshold is approximately $150 healthcare providers, laboratory adding a new analyte would range from
million.25 We do not anticipate this surveyors, and patients. Although $0.39 to $86.50; however, the majority
proposed rule would impose an complete data are not available to of the costs/analyte are less than $5.00
unfunded mandate on states, tribal calculate all estimated costs and per analyte.
governments, or the private sector of benefits that would result from the
changes proposed in this rule, we are 1. Quantifiable Impacts for Laboratories
more than $150 million annually. We
request comments from states, tribal providing an analysis of the potential CDC receives catalogs from all CLIA-
governments, and the private sector on impact based on available information approved PT programs annually. We
this assumption. and certain assumptions. estimated material costs for purchasing
Executive Order 13132 establishes Implementation of these proposed PT based on the range of 2017 catalog
certain requirements that an agency requirements in a final rule would result prices from the seven CLIA-approved
must meet when it promulgates a in changes that are anticipated to have PT programs. In estimating the costs for
proposed rule (and subsequent final quantifiable impacts on laboratories and performing PT for all laboratory
rule) that imposes substantial direct non-quantifiable impacts on specialties that would be affected by
requirement costs on state and local laboratories, PT programs, and others this regulatory change, we assumed that
governments, preempts state law, or mentioned above. In estimating the the average national CMS
otherwise has federalism implications. quantifiable impacts, we separated the reimbursement rate for Part B Medicare
The proposed changes would not have laboratory specialties into two broad (CMS Virtual Research Data Center:
categories that include: (1) Proposed PT https://www.resdac.org/cms-data/
a substantial direct effect on state and
changes to the microbiology specialty; request/cms-virtual-research-data-
local governments, preempt state law, or
and (2) proposed PT changes to non- center) was a reasonable estimate of the
otherwise have a federalism implication
microbiology specialties. This was done cost the laboratory incurs when testing
and there is no change in the
because the PT requirements for each sample (or challenge) because this
distribution of power and
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microbiology differ from those than for amount represents the average
responsibilities among the various
other laboratory specialties, and reimbursement to laboratories
levels of government. We do not believe
laboratories that are certified to perform performing patient testing for that
that this rule would impose substantial
microbiology testing may be impacted analyte or test. We also assume the cost
direct compliance costs on state and
differently than those that perform non- for testing patient samples is the same
25 Bush, Laina. HHS Memo on Annual Update to microbiology clinical testing. In each as the cost for testing PT samples.
the Unfunded Mandate Reform Act Threshold for microbiology subspecialty PT We calculate that, on average, the
2017, March 24, 2017. participation is required based on the impact would be between $721 and

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1551

$3,218 per laboratory, with laboratories result for a single type of test. Many Category M1: Laboratories Already
having fewer analytes bearing a smaller microbiology modules include Participating in Required Microbiology
burden. challenges that address different types PT
a. Impacts of Proposed PT Changes to of testing. These modules, such as urine For proposed changes or additions to
the Microbiology Specialty culture, may include individual PT required microbiology PT, we used data
challenges for Gram stain, bacterial from the PT program event summaries
Proposed changes to the microbiology identification, and antimicrobial
specialty include changes in each of the provided to CDC by the PT programs to
susceptibility testing. In many cases, estimate the total number of laboratories
subspecialties (bacteriology, estimating the challenge cost was
mycobacteriology, mycology, performing the already required PT. We
difficult because PT programs’ pricing then used that number to estimate how
parasitology, and virology) that would
varies and in some cases the PT many laboratories would be affected by
replace the types of services offered and
challenge cost per microbiology test proposed changes or additions to the
the examples of organisms to be
depends upon whether the test is required PT.
included over time with a proposed list
of categories of tests and groups of offered as an individual module or as
part of a collection of multiple types of Category M2: Laboratories not
microorganisms for which PT is Participating in a PT Program for
required. In addition, changes are being PT challenges in a module. In addition,
to accurately estimate the challenge Proposed Microbiology PT
proposed for each individual
subspecialty that would require specific cost, we had to account for differences As stated, we used Certificate of
PT for certain microbiology tests and in the frequency at which the PT Accreditation data to facilitate the
procedures. These changes, if finalized, programs currently offer their modules estimation of the number of laboratories
could have a cost impact on and challenges. For example, one PT that would be subject to proposed
laboratories. However, as stated in program may offer an antigen detection microbiology PT and are not already
§ 493.801(a)(2)(ii) and § 493.1236(c)(1), module at a frequency of two events per participating in a PT program. Of the
for tests or procedures performed by the year, and three samples per event (six seven CLIA-approved accreditation
laboratory that are not listed in the CLIA total samples per year); while another organizations, data were provided by
regulations subpart I, Proficiency offers a similar module at three events COLA showing how many of the 7,414
Testing Programs for Nonwaived per year, and five samples per event (15 COLA-accredited laboratories offer
Testing, a laboratory must verify the total samples per year). Based upon the testing for four of the new microbiology
accuracy of that test or procedure at module type and frequency, we tests we are proposing to add to the list
least twice annually. Although we can estimated the total low and high for required PT. We used these data to
estimate how many microbiology challenge cost for PT material using the estimate the percentage of COLA-
laboratories voluntarily enroll in PT range of 2017 catalog prices from the accredited laboratories that provide
with HHS-approved PT programs to seven CLIA-approved PT programs. testing for these microbiology tests. We
meet this requirement, we cannot Details are explained under each assumed that COLA-accredited
estimate how many laboratories meet subsection. We acknowledge that these laboratories are similar to CoC
this requirement through other accuracy estimated ranges may be higher than the laboratories and laboratories accredited
verification methods. The numbers of actual costs of requiring additional PT by accreditation organizations other
laboratories reported in Table 2 and since laboratories may already than the College of American
Table 3 represent those laboratories the voluntarily purchase PT to meet the Pathologists (CAP). Therefore, we
CDC was able to verify as voluntarily biannual CLIA requirement for verifying assumed that the percentage of COLA-
enrolled in PT for those types of the accuracy of testing. accredited laboratories that perform a
microbiology tests not currently specific microbiology test could be used
included in subpart I. The number of In estimating the number of to approximate the total number of
laboratories affected by this change as microbiology laboratories that would be laboratories that perform the test using
well as the cost can be estimated by impacted by each of the proposed the OSCAR/QIES data. For the proposed
adding the M1 (that is, laboratories changes, we determined the numbers of microbiology PT changes, the number of
already participating in required Certificate of Compliance (CoC) and CAP-accredited laboratories was
microbiology PT) and M2 (that is, Certificate of Accreditation (CoA) considered negligible because they are
laboratories not participating in a PT laboratories for each microbiology already required to purchase PT for all
program for proposed microbiology PT) subspecialty using the CMS Online testing performed and were not
number in Table 2 and Table 3. For the Survey Certification & Reporting System included in the total. We analyzed each
7,160 affected microbiology laboratories, (OSCAR)/Quality Improvement and proposed change for the microbiology
the estimated cost of the proposed Evaluation System (QIES) database. To specialty for each category and added
quantifiable changes to required PT for categorize the laboratories as described our estimates to obtain the total
each microbiology subspecialty follows. below, the OSCAR/QIES database was projected impact to all affected
To estimate the costs that would be used to determine the accreditation laboratories.
incurred by laboratories to purchase PT organization for each CoA laboratory.
materials for the proposed changes to (1) Effects of the Proposed PT Changes
For the analysis of the impact on in the Bacteriology Subspecialty
the microbiology specialty, if finalized, laboratories by the proposed
we compiled a range of PT material cost microbiology PT changes, we used two In the bacteriology subspecialty, the
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estimates per each challenge using 2017 laboratory categories: proposed changes that may have a cost
catalog pricing for each PT program. For impact include the determination of
this analysis we refer to the PT catalog • Laboratories participating in a PT bacterial morphology as part of the
offerings as ‘‘modules’’. In microbiology, program for already required Gram stain module, the addition of
PT programs offer different types of microbiology PT (Category M1). bacterial toxin detection as required PT,
modules. Independent modules such as • Laboratories not participating in a and the addition of a second
stain(s), antigen detection, or toxin PT program for proposed microbiology antimicrobial susceptibility or
detection are intended for reporting a PT (Category M2). resistance testing challenge per year.

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 1552 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

Gram stain reaction is currently antimicrobial susceptibility testing in already meeting the proposed PT
required in the PT regulations and all bacteriology. To evaluate the proposed requirements. Since CAP-accredited
PT programs that offer a Gram stain PT impact of increasing the required laboratories are already required to
module also offer the determination of antimicrobial susceptibility or perform PT if they perform direct fungal
bacterial morphology as part of the same resistance testing from currently antigen detection, we assumed they are
module. We know the numbers of total required one challenge per year to a already meeting the proposed PT
laboratories enrolled in the PT program proposed two challenges per year, we requirements and did not include them
modules that require Gram stain calculated the total number of category in our estimate. The range of estimated
reporting from the PT program event M1 laboratories already participating in costs was determined by using the
summaries. To determine the number of PT for antimicrobial susceptibility number of category M2 impacted
laboratories that would be impacted by testing. The range of estimated costs was laboratories that perform direct fungal
this proposed change, if finalized, we determined by using the number of antigen detection; the estimate of the
calculated the number enrolled in Gram category M1 laboratories that currently cost the laboratory incurs when testing
stain PT who do not report the bacterial perform antimicrobial susceptibility each challenge, using the average
morphology PT portion of the Gram testing; the estimate of the cost the national CMS reimbursement rate for
stain module. Since this change would laboratory incurs when testing each Part B Medicare; the low price and high
require that laboratories already challenge, using the average national price per challenge for PT (based on PT
performing PT report bacterial CMS reimbursement rate for Part B program catalog variations); and the
morphology in addition to Gram stain Medicare; the low price and high price number of challenges required per year
reaction on each challenge, we estimate per challenge for PT (based on PT using one challenge for the low estimate
the cost impact would be minimal. program catalog variations); and the and 15 challenges for the high estimate
Since laboratories are already number of challenges required per year (Tables 2 and 3).
participating in Gram stain PT and we using one challenge for the low estimate The proposal to add detection of
know the numbers of laboratories not (Tables 2 and 3). Considering all of the growth or no growth in culture media to
currently participating in the potential cost impacts, the range of the mycology PT identification would
determination of bacterial morphology, estimated impact for the proposed impact laboratories that are currently
the range of estimated costs was bacteriology subspecialty changes for performing dermatophyte identification
determined by using the number of the first year would be $101,785 to using dermatophyte test medium to
category M1 laboratories that perform $2,599,552. determine the presence or absence of
Gram stain; the estimate of the cost the dermatophytes in a patient specimen.
(2) Effects of the Proposed PT Changes We calculated the impact of this
laboratory incurs when testing each
in the Mycobacteriology Subspecialty proposal using the same methodology as
challenge, using the average national
CMS reimbursement rate for Part B In the mycobacteriology subspecialty, was performed to determine the impact
Medicare; the low price and high price the proposed changes that may have a of the proposal to include direct fungal
per challenge for PT (based on PT cost impact include the addition of a antigen detection (Tables 2 and 3).
program catalog variations); and the second antimycobacterial susceptibility Because COLA did not indicate that
number of challenges required per year or resistance testing challenge per year. any of their accredited laboratories
using one challenge for the low estimate The same type of analysis that was participate in antifungal susceptibility
and 15 challenges for the high estimate performed to evaluate the proposed or resistance testing, we assumed that
(Tables 2 and 3). impact of increasing the required no CoC or CoA laboratories other than
To evaluate the impact of requiring bacterial antimicrobial susceptibility or those accredited by CAP would be
PT for bacterial toxin detection, we resistance testing from one challenge to required to participate in PT for
determined the total number of category two challenges per year was performed antifungal susceptibility or resistance
M2 laboratories for bacteriology. to evaluate the proposed impact of testing. Therefore, the cost impact of the
Laboratories performing voluntary PT increasing the required proposed change to include two
for bacterial toxin detection are already antimycobacterial susceptibility or antifungal susceptibility or resistance
meeting the proposed PT requirements. resistance testing from one challenge to testing challenges per year was
Since CAP-accredited laboratories are two challenges per year (Tables 2 and calculated using the total number of
already required to perform PT if they 3). The range of estimated impact for the category M1 laboratories that participate
perform bacterial toxin detection, we proposed mycobacteriology subspecialty in CAP PT for antifungal susceptibility
assumed they are already meeting the changes for the first year would be testing, the only program that offers
proposed PT requirements and did not $12,558 to $39,420. challenges, as the number of impacted
include them in our estimate. The range laboratories. The range of estimated
(3) Effects of the Proposed PT Changes costs was determined by using the
of estimated costs was determined by
in the Mycology Subspecialty number of CAP category M1 impacted
using the number of category M2
impacted laboratories that perform In the mycology subspecialty, the laboratories that perform antifungal
bacterial toxin detection; the estimate of proposed changes that may have a cost susceptibility or resistance testing; the
the cost the laboratory incurs when impact include the addition of required estimate of the cost the laboratory incurs
testing each challenge, using the average PT for direct fungal antigen detection, when testing each challenge; based on
national CMS reimbursement rate for detection of growth or no growth in the average national CMS
Part B Medicare; the low price and high culture media, and the addition of two reimbursement rate for Part B Medicare;
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price per challenge for PT (based on PT antifungal susceptibility or resistance the low price and high price per
program catalog variations); and the testing challenges per year. To evaluate challenge for PT (based on PT program
number of challenges required per year the impact of the proposed regulated PT catalog variations); and the number of
using one challenge for the low estimate for direct fungal antigen detection, we challenges required per year using one
and 15 challenges for the high estimate determined the total number of category challenge for the low estimate (Tables 2
(Tables 2 and 3). M2 laboratories for mycology. and 3). Considering all of the potential
Currently, one sample or challenge Laboratories performing voluntary PT cost impacts, the range of estimated
per testing event is required for for direct fungal antigen detection are impact for the proposed mycology

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1553

subspecialty changes for the first year rate for Part B Medicare; the low price include two antiviral susceptibility or
would be $41,235 to $422,406. and high price per challenge for PT resistance testing challenges per year
(based on PT program catalog was calculated using the total number of
(4) Effects of the Proposed PT Changes
variations); and the number of category M1 laboratories that participate
in the Parasitology Subspecialty
challenges required per year using one in CAP PT for antiviral susceptibility or
In the parasitology subspecialty, the challenge for the low estimate and 15 resistance testing, the only program that
proposed change that may have a cost challenges for the high estimate (Tables had subscribers to a PT module, as the
impact is the addition of required PT for 2 and 3). Considering all of the potential number of impacted laboratories. The
direct parasite antigen detection. To cost impacts, the range of estimated
evaluate the potential impact of this range of estimated costs was determined
impact for the proposed parasitology
addition, we determined the total by using the number of CAP category
subspecialty changes for the first year
number of category M2 laboratories for M1 impacted laboratories that perform
would be $14,151 to $678,696.
parasitology. Laboratories performing antiviral susceptibility or resistance
voluntary PT for direct parasite antigen (5) Effects of the Proposed PT Changes testing; the estimate of the cost the
detection are already meeting the in the Virology Subspecialty laboratory incurs when testing each
proposed PT requirements. Since CAP- In the virology subspecialty, the challenge, using the average national
accredited laboratories are already proposed change that may have a cost CMS reimbursement rate for Part B
required to perform PT if they perform impact includes the addition of two Medicare; the low price and high price
direct parasite antigen detection, we antiviral susceptibility or resistance per challenge for PT (based on PT
assumed they are already meeting the testing challenges per year. Because program catalog variations); and the
proposed PT requirements and did not COLA did not indicate that any of their number of challenges required per year
include them in our estimate. The range accredited laboratories participate in using one challenge for the low estimate
of estimated costs was determined by antiviral susceptibility or resistance (Tables 2 and 3). Considering all of the
using the number of category M2 testing, we assumed that no CoC or CoA potential cost impacts, the range of
impacted laboratories that perform laboratories other than those accredited estimated impact for the proposed
direct parasite antigen detection; the by CAP would be required to participate virology subspecialty changes for the
estimate of the cost the laboratory incurs in PT for antiviral susceptibility or first year would be $216,318 to
when testing each challenge, using the resistance testing. Therefore, the cost $314,145.
average national CMS reimbursement impact of the proposed change to
TABLE 2—LOW ESTIMATE FOR PROPOSED MICROBIOLOGY PT REGULATORY CHANGES
Total low
Total number Total number Supply/ Total low impact for
Proposed PT regulation change of affected M1 of affected M2 Labor * material impact for microbiology
laboratories laboratories cost ** one challenge regulation
changes

Gram Stain including Morphology ............................................. 26 0 $4.54 $4.67 $239.46 $386,047

Bacterial Toxin Detection .......................................................... 0 1,542 14.22 11.44 39,567.72
Antimicrobial susceptibility and/or resistance testing ............... 3,281 0 9.89 9.00 61,978.09
Antimycobacterial susceptibility or resistance testing ............... 454 0 4.33 23.33 12,557.64
Direct fungal antigen detection ................................................. 0 96 14.22 16.00 2,901.12
Detection of growth or no growth in culture media—
dermatophytes (DTM) ............................................................ 0 527 8.16 16.00 12,732.32
Antifungal susceptibility or resistance testing ........................... 0 369 9.89 24.80 *** 12,800.61
Direct parasite antigen detection .............................................. 0 533 14.22 12.33 14,151.15
Antiviral susceptibility or resistance testing .............................. 332 0 230.11 95.67 3 108,158.96

* Average national CMS reimbursement rate for Part B Medicare (CMS Virtual Research Data Center: https://www.resdac.org/cms-data/request/cms-virtual-re-
search-data-center).
** Low 2017 PT catalog price per challenge.
*** Total low impact is multiplied by two for the proposal to add two new susceptibility or resistance testing challenges.

TABLE 3—HIGH IMPACT FOR PROPOSED MICROBIOLOGY PT REGULATIONS

Total high
Total number Total number Total high Total high impact for
Supply/
Proposed PT regulation change of affected M1 of affected M2 Labor 1 impact/for impact/for microbiology
material cost 2
laboratories laboratories one challenge 15 challenges regulation
changes

Gram Stain including Morphology ................. 26 0 $4.54 $15.00 $508.04 $7,620.60 $4,054,219
Bacterial Toxin Detection .............................. 0 1,542 14.22 91.50 163,020.24 2,445,303.60
Antimicrobial susceptibility and/or resistance
testing ........................................................ 3,281 0 9.89 34.80 146,627.89 N/A
Antimycobacterial susceptibility or resistance
testing ........................................................ 454 0 4.33 82.50 39,420.82 N/A
Direct fungal antigen detection ..................... 0 96 14.22 31.80 4,417.92 66,268.80
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Detection of growth or no growth in culture

media—dermatophytes (DTM) .................. 0 527 8.16 33.00 21,691.32 325,369.80
Antifungal susceptibility or resistance testing 0 369 9.89 31.80 3 15,383.61 N/A
Direct parasite antigen detection .................. 0 533 14.22 70.67 45,246.37 678,695.55
Antiviral susceptibility or resistance testing .. 332 0 230.11 243.00 3 157,072.52 N/A
1 Average national CMS reimbursement rate for Part B Medicare (CMS Virtual Research Data Center: https://www.resdac.org/cms-data/request/cms-virtual-re-
search-data-center).
2 High 2017 PT catalog price per challenge.
3 Total low impact is multiplied by two for the proposal to add two new susceptibility or resistance testing challenges.

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 1554 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

b. Impacts of Proposed PT Changes to a frequency other than the CLIA- program. Therefore, we have designated
the Non-Microbiology Specialties/ required frequency (3 × 5 = 15 samples four categories to estimate the cost
Subspecialties per year); and the extent to which impact, if the proposed changes are
The proposed changes in specialties laboratories already use PT varies—that finalized:
and subspecialties other than is, laboratories accredited by the CAP • Category 1: Laboratories accredited
microbiology include adding 29 new are required to enroll in PT for each test by the CAP that purchase material from
analytes at the frequency of three events they perform. For all these reasons, the CAP PT program: The CAP provided
per year and five challenges per event. laboratories enrolled in different PT us with the number of their accredited
According to CLIA, laboratories with programs will be impacted differently. laboratories that are enrolled in their PT
Certificates of Compliance and Based on this observation and our program for each proposed analyte. The
Certificates of Accreditation are inability to make estimates at the level cost increase was calculated on a per
required to perform PT. There are of individual laboratories, we accounted analyte basis by multiplying the cost per
36,777 clinical laboratories that will be for each of these variations when sample (PT material + CMS
affected (19,287 Certificate of calculating the costs incurred. reimbursement amount) by the increase
To account for the different prices in frequency of samples and the number
Compliance and 17,490 Certificate of
each PT program charges for different of laboratories that purchase PT from
Accreditation laboratories). This will be
analytes, either alone or in different the CAP PT program.
a new burden for some laboratories, but
combinations, we used a range of • Category 2: CAP-accredited
many laboratories are already paying for
estimates based upon the programs’ unit laboratories that purchase PT materials
PT of these analytes. As previously
costs for PT currently offered. We used from other PT programs: For the
mentioned, in §§ 493.801(a)(2)(ii) and two approaches to estimate the cost of
493.1236(c)(1), for tests or procedures analytes we considered adding, CAP-
individual PT analytes. If the analyte accredited laboratories are already
performed by the laboratory that are not was offered individually by the PT
listed in the CLIA regulations subpart I, required by CAP to enroll in a CAP-
program, we used that price. However, approved PT program. Ordinarily CAP-
the laboratory must verify the accuracy if the analyte was not offered
of that test or procedure at least twice accredited laboratories enroll in the
individually, we divided the panel price
annually. Since laboratories may CAP PT program but they are permitted
by the total number of analytes in the
voluntarily enroll in PT as one way to to enroll in PT from other CAP-
panel to estimate the cost per analyte,
meet this requirement, we assume the approved PT programs. Using the data
which is used as individual analyte
added burden would be minimal. We the CAP provided, we calculated the
price. For the lower cost estimate, we
have evidence from laboratories that total number of CAP-accredited
selected the lowest individual analyte
responded to our national PT survey laboratories enrolled in one of the other
price among all PT programs. For the
(Earley, Astles, and Breckenridge, 2017) PT programs provided through PT
higher cost estimate, we used the
that of those who were not already Program A, PT Program D, PT Program
highest individual analyte price. In
required by the CAP to perform PT on E, or PT Program G. The cost increase
some cases, PT programs offer PT for the
more than the CLIA-required analytes, proposed analytes at different in this category was calculated on a per
39 percent purchased PT for 1 to 5 frequencies, that is, different numbers of analyte basis. We were able to obtain the
analytes, 17 percent for 6 to 10 analytes, events per year and different numbers of enrollment distribution of the CAP-
10 percent for 11 to 20 analytes, and 10 challenges per event. Therefore, to accredited laboratories in each of the
percent for more than 20 analytes. We accurately estimate the future unit costs, non-CAP PT programs. The enrollment
estimated the costs for proposed we had to calculate the increased of laboratories not accredited by the
analytes by grouping all affected frequency for each analyte in order to CAP in each of the non-CAP PT
laboratories into four categories, achieve three events/year with five programs (Category 4) was also
calculating the number of laboratories in challenges per event. available. Because the methodology to
each category and calculated the costs The proposed rule will have different calculate Category 2 is the same as
using the analyte price and test impacts on CoA laboratories mainly Category 4, we combine these two
reimbursement rate. We also propose to because the CAP has strict requirements categories by using the enrollment of all
tighten acceptance limits of several for PT participation that exceed CLIA laboratories (CAP-accredited
currently-required analytes, which may minimal requirements, while other laboratories and laboratories not
have an impact on laboratories, but the accreditation organizations may not. accredited by the CAP) in each of the
cost impact is not included in our Therefore, our analysis starts with CAP- non-CAP PT program in the calculation.
estimate. In addition, we are proposing accredited laboratories as CAP is not • Category 3: Laboratories not already
to delete five currently-required only a large accreditation organization enrolled in a PT program: To derive the
analytes (ethosuximide, LDH but also the largest PT program. In minimum and maximum number of
isoenzymes, primidone, procainamide/ estimating the number of affected laboratories not already enrolled in a PT
NAPA, and quinidine) that are laboratories resulting from the proposed program that may provide testing for the
infrequently performed. As such, we do PT changes, if finalized, we proposed analytes, we began by
not anticipate this being a substantial acknowledged that any CAP-accredited estimating that there are 29,927
cost savings since laboratories may laboratory that offers patient testing for laboratories that perform nonwaived
continue to use PT voluntarily as a way one of the CAP PT program analytes testing and are not accredited by the
of meeting the biannual accuracy must enroll in the relevant program for CAP in the United States. To facilitate
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verification requirement. that analyte. However, CAP-accredited the calculations, we presumed that
Three issues had to be considered to laboratories are permitted to enroll in laboratories not accredited by the CAP
estimate the costs for PT materials for PT from other CAP-approved PT will not purchase CAP PT. From the
proposed analytes: PT programs may programs for certain analytes and only OSCAR/QIES database, we derived the
offer analytes as an individual analyte for specific programs. Laboratories not number of laboratories not accredited by
or as part of a module that combines accredited by the CAP may purchase PT the CAP that provide testing in each
multiple analytes; some of the proposed materials from any CMS-approved PT specialty and reasoned that this was the
analytes may already be offered but at program, including the CAP PT maximum number of laboratories not

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1555

accredited by the CAP that might non-CAP PT programs for each analyte. • Category 4: Laboratories not
provide testing for each analyte. Negative estimates were taken as ‘‘0’’. accredited by the CAP and enrolled in
COLA provided us with the This represents our low estimate of the PT programs other than the CAP PT
percentages of the approximately 7,414 number of laboratories that will need to program: We obtained the number of
COLA-accredited laboratories that purchase PT for each analyte. laboratories enrolled in PT programs
perform testing for each proposed To obtain the high estimate for the other than the CAP PT program and
analyte. We determined that COLA- number of laboratories not accredited by subtracted the number of CAP-
accredited laboratories are similar to the CAP and not enrolled in one of the accredited laboratories enrolled in a
CoC laboratories in terms of their annual non-CAP PT programs, we took the high non-CAP PT program per analyte for
test volumes. Therefore, we assumed estimate of CoA laboratories not this category. The cost increase in this
that the percentage of COLA-accredited accredited by the CAP and CoC category was calculated on a per analyte
laboratories that test each proposed laboratories and subtracted the number basis. The estimated cost increases were
analyte could be used to estimate the of this subset of CoA laboratories calculated for each of the non-CAP PT
number of CoC and CoA (other than already known to be enrolled in PT. For programs for which information was
CAP- or COLA-accredited) laboratories the high estimate of the number of available. The minimum increase was
that test each analyte. laboratories not accredited by CAP and calculated for each of the PT programs
We used the percentage of CAP- not enrolled in one of the non-CAP PT by multiplying the cost per sample,
accredited laboratories that participate including the CMS reimbursement
programs, we also used an additional
in PT for each proposed analyte to amount, by the increase in frequency of
criterion of the number of laboratories
estimate the maximum number of CoC samples and the number of laboratories
in the respective specialty from OSCAR/
and CoA (other than CAP and COLA) that purchase PT from that individual
QIES to limit the estimate at the number
laboratories that test each analyte. This program. To determine the maximum
of laboratories in the specialty. If this
percentage was much higher for many of increase, the same calculation was made
number was less than the high estimate
the analytes when compared to the using the highest cost per analyte
of CoC laboratories and CoA laboratories
laboratories accredited by organizations including the CMS reimbursement
accredited by a program other than the
other than the CAP. Since CAP- amount.
CAP, then the high estimate was
accredited laboratories are often either
hospital-based or commercial calculated by subtracting the number of c. Results
laboratories that already participate in laboratories not accredited by CAP and
PT for the additional analytes, not enrolled in one of the non-CAP PT We estimate that the overall impact of
approximations for high estimates may programs from the total number of adding requirements for the proposed
substantially overestimate the number laboratories in the specialty. analytes in the specialties and
of laboratories impacted. The cost increase in this category was subspecialties other than microbiology
Using the above information, we calculated on a per analyte basis. The will range from $26 to $114 million for
calculated low and high estimates for minimum cost per sample that was the the first year (Table 4), if these proposed
the total number of non-CAP-accredited, lowest across all eight non-CAP PT changed are finalized. Because of their
CoC and CoA laboratories that may programs and the maximum cost per larger number, and the fact that non-
provide testing for each proposed sample that was the highest across all CAP accredited laboratories tend not to
analyte. eight non-CAP PT programs were used enroll in non-required PT as frequently
For each proposed analyte, we for these calculations. The minimum as CAP-accredited laboratories do, we
calculated the number of CAP- cost increase was calculated by estimate that non-CAP accredited
accredited laboratories that buy from multiplying the minimum cost per laboratories that are not enrolled in any
non-CAP PT programs by subtracting sample, including the CMS PT program will have an impact
the CAP-accredited laboratories enrolled reimbursement amount, by the number between $16 and $100 million for the
in CAP PT from the total number of of laboratories that are not purchasing first year. We also estimate that
CAP-accredited laboratories. PT from any PT program. The same laboratories that are enrolled in PT
We derived a low estimate of the total calculation was made using the programs other than CAP will have a
number of laboratories not accredited by maximum cost per sample for the relatively minor impact, $5.4 million for
the CAP and not enrolled in one of the maximum cost increase. the first year (Table 4).

TABLE 4—ESTIMATED IMPACT FOR PROPOSED NON-MICROBIOLOGY PT REGULATIONS FOR THE FIRST YEAR IN 2017
DOLLARS
Category Low estimate High estimate

1. Laboratories accredited by CAP that purchase material from the CAP PT program .............. 4,516,673 .................... 4,516,673.
2. Laboratories accredited by CAP that purchase PT materials from other PT programs .......... Included in Category 4 Included in Category 4.
3. Laboratories not accredited by CAP that not already enrolled in other PT programs ............ 16,248,746 .................. 100,303,499.
4. Laboratories not accredited by CAP enrolled in other PT programs (category 2 and 4 com- 5,351,565 .................... 4,103,686.
bined).

Total increased cost .............................................................................................................. $26,116,984 ................ $114,275,423.

amozie on DSK3GDR082PROD with PROPOSALS2

For each of the four categories of microbiology and non-microbiology) in The base year is 2017 for the
affected laboratories previously undiscounted 2017 dollars and calculations displayed in Table 5 and
described, Table 5 shows the total discounted at 3 percent and 7 percent to we assume inflation-adjusted costs in
estimated range of annual cost for the translate expected costs in any given future years to be the same as costs in
proposed changes (including both future years into present value terms. the base year.

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 1556 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

TABLE 5—TOTAL ESTIMATED ANNUAL COSTS FOR PROPOSED PT REGULATIONS

[All specialties in both microbiology and non-microbiology]

Undiscounted (2017 $) Discounted at 3 percent Discounted at 7 percent

Primary Low # High & Primary Low High Primary Low High

2019 .................. $72,416,336 $26,503,031 $118,329,642 $68,259,342 $24,981,649 $111,537,036 $63,251,232 $23,148,774 $103,353,692
2020 .................. 72,416,336 26,503,031 118,329,642 66,271,206 24,254,028 108,288,385 59,113,301 21,634,368 96,592,236
2021 .................. 72,416,336 26,503,031 118,329,642 64,340,977 23,547,600 105,134,354 55,246,076 20,219,035 90,273,117
2022 .................. 72,416,336 26,503,031 118,329,642 62,466,968 22,861,748 102,072,188 51,631,847 18,896,294 84,367,399
2023 .................. 72,416,336 26,503,031 118,329,642 60,647,542 22,195,871 99,099,212 48,254,062 17,660,088 78,848,037
# Total low cost is the sum of Table 2 (microbiology) and Table 4 (non-microbiology).
& Total high cost is the sum of Table 3 (microbiology) and Table 4 (non-microbiology).

2. Non-Quantifiable Impacts account for the quantifiable impacts in may be slightly overestimating the net
our estimates for laboratories. impact.
If the changes proposed in this rule If the proposed analyte deletions are
are finalized, a number of non- finalized, some PT programs may cease 3. Benefits
quantifiable impacts will also result for offering the deleted analytes, others may While we cannot quantify the benefits
PT programs and laboratories. We solicit continue to offer them at a frequency that the proposed changes will bring, if
comments and data to facilitate the less than that required under CLIA, and finalized, we believe that the changes
determination of quantifiable estimates still others may continue to offer them will facilitate more rapid identification
in the final rule. at the PT frequency required under of unacceptable practices in
As with any currently required PT, if CLIA. For these reasons, we are unable laboratories, especially for those
finalized, the proposed regulation to estimate the cost impact to PT laboratories that have not previously
would not require approved PT programs for this change. We solicit participated in PT. There are very few
programs to offer additional analytes. comments and data that would help us published reports that have investigated
Several programs already offer the estimate the impact of the PT changes the impact of PT performance on testing
analytes or tests that would be required on PT programs in the final rule. accuracy or patient outcomes. In part
by laboratories, and in these cases, we Although we cannot precisely predict this is because performing PT is now a
expect minimal impact on the PT how the proposed changes may affect standard practice for most analytes we
programs. If the proposed changes clinical laboratories, we do not expect are considering to add, so it is not
outlined in this rule are finalized, we there to be major changes in how they possible to separate cohorts of PT users
expect there will initially be some function. We have quantified the costs from non-users.26 27 28 29 In addition,
increased expenditures for PT programs we expect laboratories to incur but there remediation after identification of
to implement the changes, even if they may be costs associated with other problems should also occur more
are only scaling up currently offered PT. administrative functions related to PT quickly and clinical test results of
At the same time, PT programs will also ordering, result reporting, and record marginal or inferior quality are less
increase revenue received if they keeping that we are not able to estimate. likely to be used as analytical systems
increase the PT analytes or tests they For those laboratories that currently will improve. All of these things will
offer. We have no way to estimate how purchase PT for the five analytes we serve to minimize the potential adverse
many programs may choose to offer propose to delete, we cannot estimate impact to patients and benefiting
additional PT analytes or tests, but we the lowered expenditure for laboratories physicians and healthcare providers
assume that most will implement the that stop buying PT materials and must that could occur with inaccurate testing.
changes included in the final rule. For begin doing something else to verify PT performance partially reflects
some programs, this would mean accuracy. Based upon our focus groups daily clinical laboratory performance
offering an analyte or test for the first and surveys, we know there are a (Stull, Hearn, Hancock, Handsfield, and
time, while for others it would mean variety of things laboratories may do to Collins, 1998). Updating acceptance
increasing the yearly number of events externally verify accuracy, ranging from limits will benefit laboratories by
and/or challenges per event. The costs splitting samples with other laboratories helping to ensure the accuracy and
would be relatively less for the to purchasing PT materials voluntarily. reliability of testing and providing a
programs that are already offering the Also, we do not know the extent to mechanism for laboratories to be held
PT analytes or tests, including those which split samples are tested, or how accountable for clinically appropriate
currently offering challenges at less than many patient samples might be tested in patient test results, which directly
the PT frequency required under CLIA. this way; there is no stated minimum affects the public’s health (Astles,
There are also differences in what the number of specimens that must be Tholen, and Mitchell, 2016). Both
PT programs charge laboratories for PT tested semi-annually to verify accuracy.
which would change the impact of the Therefore, we have not attempted to 26 Reilly AA Salkin IF McGinnis MR et al.
final rule. In part, these differences estimate the costs for alternative Evaluation of mycology laboratory proficiency
depend upon the total number of approaches that may be adopted to testing. J Clin Microbiol. 1999;37:2297–2305.
27 Parsons PJ Reilly AA Esernio-Jenssen D et al.
samples distributed per year and how verify accuracy for the deleted analytes.
amozie on DSK3GDR082PROD with PROPOSALS2

Evaluation of blood lead proficiency testing:

the PT is packaged; some PT is sold as Regardless of how laboratories might be comparison of open and blind paradigms. Clin
modules that group several related impacted, we expect that they will not Chem. 2001;47:322–330.
analytes together. Because CLIA- spend more than they currently spend 28 Shahangian S and Snyder SR. Laboratory

approved PT programs are required to on PT for the analytes we propose to Medicine Quality Indicators: A Review of the
maintain non-profit status, any delete, but we cannot estimate this. By Literature. American Journal of Clinical Pathology,
2009; 131: 418–431.
increased revenue that results from an not attempting to estimate the number 29 Jenny RW and Jackson KY. PT performance as
expanded PT menu will not be turned of laboratories that may stop buying PT a predictor of accuracy of routine patient testing for
into profit. We have attempted to material for the deleted analytes, we theophylline. Clin Chem 1993; 39:76–81.

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1557

clinical laboratories and patients can D. Alternatives Considered event. We determined that the increase
benefit from continued monitoring of PT In proposing these changes, several in required PT would result in an
to help assess the success of alternatives were considered. We additional impact of over $5.3 million to
intervention efforts to improve the considered the possibility of changing laboratories that would be required to
overall quality of clinical laboratory either the required frequency of PT perform susceptibility or resistance
testing.30 events per year or changing the number testing for 15 challenges per year. For
Another benefit that may result from of required PT challenges per event. the non-microbiology specialties and
adding new PT analytes and tests and Responses from our national survey did subspecialties, we could have opted not
updating the limits for acceptable PT not support changing either parameter, to add any new PT analytes, but testing
performance under CLIA includes the nor did CLIAC recommend any changes of the analytes we are proposing to add
generation of additional information on to the required PT frequency or number is widespread and is important in
test performance and sources of errors of challenges per event. We did not clinical decision making and public
that PT programs can share with perceive a benefit from either reducing health testing. We also considered
laboratories (Howerton, Krolak, or increasing the number of events per adding all analytes for which there was
Manasterski, and Handsfield, 2010). year. Reducing the number of events to at least one existing PT program, but we
Such information can also be used as a two per year and keeping all other believed this alternative would have
source of training and can help to factors the same would cost less been excessively burdensome as it
maintain the competency of testing compared to the proposed rule, but it would mean adding hundreds of new
personnel (Garcia, et al., 2014). would delay the potential time it takes required analytes which may not be
Last, while we do not anticipate that to identify a poor performing laboratory necessary to identify problematic
the changes being proposed in this rule as ‘‘unsuccessful’’ to at least 12 months, laboratory performance. We could have
would incur any costs on the IVD instead of the current 8 months. left the acceptance limits as they were
industry, we expect the IVD industry to Increasing the number of events might established in CLIA ’88, but we believe
potentially benefit by the changes made help to identify a laboratory with testing those are outdated given advancements
in this proposed rule when finalized. issues slightly earlier, but increasing the in technology. We considered retaining
Having the ability to track PT results for number of events would increase costs. the definition of peer group established
the added analytes will enable better We are proposing to continue to require in CLIA ’88, but we decided this would
and faster detection of problems with five challenges per event, with a passing be too expensive and ultimately
product manufacturing, including score generally defined as a minimum of unworkable because it would require PT
reagent problems. We are aware that four challenges falling within the programs to perform commutability
some IVD manufacturers enroll in PT criteria for acceptable performance. A testing using analyzers from multiple
and are able to track the performance of minimum of five challenges per event peer groups every time a new batch of
the peer groups using their instruments are necessary to follow the approach PT materials was created. We are
in summary reports issued by the PT taken in the final regulation requesting public comments related to
programs. implementing CLIA ’88 which states alternative changes to be considered to
Ultimately, we believe that that a minimum event score should be assist us in finalizing this rule.
laboratories, healthcare providers, 80 percent to be successful allowing for E. Accounting Statement and Table
patients, and the IVD industry will one missed result per event.
benefit from improved analytical For the microbiology specialty, we We have prepared the following
performance (Howerton, Krolak, considered the possibility of including accounting statement showing the
Manasterski, and Handsfield, 2010) that required PT analytes in each classification of expenditures associated
is expected to occur when this rule subspecialty at a frequency of three with the provisions of this proposed
becomes finalized. events per year with five challenges per rule.

TABLE 6—ACCOUNTING TABLE

Units
Primary Minimum Maximum Source
Category Discount
estimate estimate estimate Year Period citation
rate
dollars covered
%

Benefits

Qualitative ....................................... • More effective detection of laboratories that provide inaccurate laboratory test Preamble and Im-
results. pact Analysis.
• Increased confidence in laboratory test results.

Costs

Annualized Monetized $/year .......... $72,416,336 $26,503,031 $118,329,642 2017 0 2019–2028 Impact Analysis.
70,307,122 25,731,098 114,883,148 2017 3 2019–2028
amozie on DSK3GDR082PROD with PROPOSALS2

67,678,819 24,769,188 110,588,450 2017 7 2019–2028

30 Bainbridge, J., C.L. Wilkening, W. Rountree, R. Testing Program for CD3+4+ and CD3+8+ longitudinal mixed effects modeling. NIH Public
Louzao, J. Wong, N. Perza, A. Garcia, T.N. Denny Lymphocyte Subsets: A ten year review via Access Author Manuscript (July 2014).
The Immunology Quality Assessment Proficiency

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 1558 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

F. Regulatory Reform Analysis Under Authority: 42 U.S.C. 263a, 1302, 1395x(e), laboratory must comply with the
E.O. 13771 the sentence following 1395x(s)(11) through requirements in § 493.15(e),
1395x(s)(16). §§ 493.801(b)(1) through (6), 493.1771,
Executive Order 13771, titled 493.1773, and 493.1775.
■ 2. Section 493.2 is amended by—
Reducing Regulation and Controlling ■ 4. Section 493.25 is amended by
■ a. Adding the definitions of
Regulatory Costs, was issued on January revising paragraph (d) to read as
‘‘Acceptance limit’’ and ‘‘Peer group’’ in
30, 2017 and requires that the costs follows:
alphabetical order;
associated with significant new
■ b. Revising the definition of ‘‘Target
regulations ‘‘shall, to the extent § 493.25 Laboratories performing tests of
value’’; and high complexity.
permitted by law, be offset by the
■ c. Adding the definition of
elimination of existing costs associated * * * * *
‘‘Unacceptable score’’ in alphabetical
with at least two prior regulations.’’ (d) If the laboratory also performs
order.
This proposed rule, if finalized, is The additions and revision read as waived tests, compliance with
considered an E.O. 13771 regulatory follows: §§ 493.801(a) and 493.801(b)(7) and
action. We estimate that this rule would subparts J, K, and M of this part are not
generate $58.0 million in annualized § 493.2 Definitions. applicable to the waived tests. However,
costs in 2016 dollars, discounted at 7 * * * * * the laboratory must comply with the
percent relative to year 2016 over a Acceptance limit is the symmetrical requirements in §§ 493.15(e),
perpetual time horizon. Details on the tolerance (plus and minus) around the 493.801(b)(1) through (6), 493.1771,
estimated costs of this rule can be found target value. 493.1773, and 493.1775.
in the preceding analyses. ■ 5. Section 493.801 is amended by—
* * * * *
■ a. Redesignating paragraphs (b)(3)
G. Conclusion Peer group is a group of laboratories
through (6) as paragraphs (b)(4) through
whose testing process utilizes similar
We estimate that the cost to (7), respectively; and
instruments, methodologies, and/or ■ b. Adding new paragraph (b)(3).
laboratories to participate in PT for the reagent systems and is not to be
analytes and tests proposed in this rule The addition reads as follows:
assigned using the reagent lot number
would cost between $26,503,031 and level. § 493.801 Condition: Enrollment and
$118,329,642 in 2017 dollars. Although testing of samples.
the effect of the changes proposed will * * * * *
Target value for quantitative tests is: * * * * *
increase laboratory costs, (b) * * *
(1) If the peer group consists of 10
implementation of these changes in a (3) The laboratory must report PT
participants or greater:
final rule will increase the confidence of results for microbiology organism
(i) The mean of all participant
laboratory professionals and the end- identification to the highest level that it
responses after removal of outliers (that
users of test results, including reports results on patient specimens.
is, those responses greater than three
physicians and other healthcare
standard deviations from the original * * * * *
providers, patients, and the public, in ■ 6. Section 493.861 is amended by
mean, as applicable); or
the reliability and accuracy of test revising paragraph (a) to read as follows:
(ii) The mean established by a
results.
definitive method or reference methods;
We have determined that this rule § 493.861 Standard; Unexpected antibody
or detection.
would not have a significant economic (iii) The mean of a peer group, in
impact on a substantial number of small instances when a definitive method or (a) Failure to attain an overall testing
entities or a significant impact in the reference methods are not available; or event score of at least 100 percent is
operations of a substantial number of (iv) If the peer group consists of fewer unsatisfactory performance.
small rural hospitals and for these than 10 participants, ‘‘target value’’ * * * * *
reasons, we are not preparing analyses means the overall mean after outlier ■ 7. Section 493.901 is amended by—
for either the RFA or section 1102(b) of ■ a. Redesignating paragraphs (a), (b),
removal (as defined in paragraph (1) of
the Act. this definition) unless acceptable (c), and (d) as paragraphs (b), (c), (d),
In accordance with the provisions of scientific reasons are available to and (e), respectively;
Executive Order 12866, this proposed ■ b. Adding new paragraph (a);
indicate that such an evaluation is not
regulation was reviewed by the Office of ■ c. Redesignating newly redesignated
appropriate.
Management and Budget. paragraphs (c)(6) and (7) as paragraphs
(2) [Reserved]
(c)(7) and (8), respectively;
List of Subjects in 42 CFR Part 493 * * * * * ■ d. Adding new paragraph (c)(6);
Unacceptable score is a PT result that ■ e. Revising newly redesignated
Administrative practice and is outside of the criteria for acceptable paragraph (c)(8);
procedure, Grant programs—health, performance for a single challenge or ■ f. Adding paragraph (c)(9);
Health facilities, Laboratories, Medicaid, sample. ■ g. Revising newly redesignated
Medicare, Penalties, Reporting and paragraph (e); and
* * * * *
recordkeeping requirements. ■ h. Adding paragraph (f).
■ 3. Section 493.20 is amended by
For the reasons set forth in the revising paragraph (c) to read as follows: The additions and revisions read as
preamble, the Centers for Medicare & follows:
amozie on DSK3GDR082PROD with PROPOSALS2

Medicaid Services proposes to amend § 493.20 Laboratories performing tests of

moderate complexity. § 493.901 Approval of proficiency testing
42 CFR part 493 as set forth below: programs.
* * * * *
PART 493—LABORATORY (c) If the laboratory also performs * * * * *
REQUIRMENTS waived tests, compliance with (a) Require a minimum of ten
§ 493.801(a) and (b)(7) and subparts J, K, laboratory participants before offering a
■ 1. The authority citation for part 493 and M of this part is not applicable to proficiency testing analyte;
is revised to read as follows: the waived tests. However, the * * * * *

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1559

(c) * * * meet any criteria contained in laboratory considers to be a principal

(6) For those results submitted §§ 493.901 through 493.959 for approval pathogen that is clearly responsible for
electronically, a mechanism to track of the proficiency testing program. a described illness (excluding immuno-
changes to any result reported to the (b) Request for reconsideration. Any compromised patients). The program
proficiency testing program and the PT program that is dissatisfied with a determines the reportable isolates,
reason for the change; determination to disapprove the including antimicrobial susceptibility or
* * * * * program, as applicable, may request that resistance for any designated isolate;
(8) A process to resolve technical, CMS reconsider the determination, in and
administrative, and scientific problems accordance with subpart D of part 488 (ii) Samples that require laboratories
about program operations; and of this chapter. to report all organisms present. Samples
(9) A contractor performing ■ 10. Section 493.911 is revised to read must contain multiple organisms
administrative responsibilities as as follows: frequently found in specimens where
described in this section and § 493.903 multiple isolates are clearly significant
§ 493.911 Bacteriology.
must be a private nonprofit organization or where specimens are derived from
or a Federal or State agency, or an entity (a) Program content and frequency of immuno-compromised patients. The
acting as a designated agent for the challenge. To be approved for program determines the reportable
Federal or State agency. proficiency testing for bacteriology, the isolates.
annual program must provide a (3) The content of an approved
* * * * *
minimum of five samples per testing program must vary over time, as
(e) HHS may require on-site visits for
event. There must be at least three appropriate. The types of bacteria
all initial proficiency testing program
testing events provided to the laboratory included annually must be
applications for CMS approval and
at approximately equal intervals per representative of the following major
periodically or when problems are
year. The samples may be provided to groups of medically important aerobic
encountered for previously HHS-
the laboratory through mailed and anaerobic bacteria, if appropriate
approved proficiency testing programs
shipments. The specific organisms for the sample sources:
either during the reapproval process or
included in the samples may vary from (i) Gram-negative bacilli.
as necessary to review and verify the
year to year. (ii) Gram-positive bacilli.
policies and procedures represented in
(1) The annual program must include, (iii) Gram-negative cocci.
its application and other information, (iv) Gram-positive cocci.
as applicable, samples for:
including, but not limited to, review (i) Gram stain including bacterial (4) For antimicrobial susceptibility or
and examination of documents and morphology; resistance testing, the program must
interviews of staff. (ii) Direct bacterial antigen detection; provide at least two samples per testing
(f) HHS may require a proficiency (iii) Bacterial toxin detection; and, event that include one Gram-positive
testing program to reapply for approval (iv) Detection and identification of and one Gram-negative organism that
using the process for initial applications bacteria which includes one of the have a predetermined pattern of
if significant problems are encountered following: susceptibility or resistance to the
during the reapproval process. (A) Detection of growth or no growth common antimicrobial agents.
■ 8. Section 493.903 is amended—
in culture media; (b) Evaluation of a laboratory’s
■ a. In paragraph (a)(1) by removing the
(B) Identification of bacteria; and performance. HHS approves only those
period and adding ‘‘;’’; (v) Antimicrobial susceptibility or programs that assess the accuracy of a
■ b. In paragraph (a)(2) by removing ‘‘;’’
resistance testing. laboratory’s responses in accordance
and adding in its place ‘‘; and’’; and (2) An approved program must
■ c. By adding paragraph (a)(3).
with paragraphs (b)(1) through (9) of
furnish HHS and its agents with a this section.
The addition reads as follows:
description of samples that it plans to (1) The program determines the
§ 493.903 Administrative responsibilities. include in its annual program no later reportable bacterial staining and
* * * * * than 6 months before each calendar morphological characteristics to be
(a) * * * year. The program must include bacteria interpreted by Gram stain. The program
(3) Not change submitted laboratory commonly occurring in patient determines the bacteria to be reported
data and results for any proficiency specimens and other important by direct bacterial antigen detection,
testing event; emerging pathogens. The program bacterial toxin detection, detection of
* * * * * determines the reportable isolates and growth or no growth in culture media,
■ 9. Section 493.905 is revised to read correct responses for antimicrobial identification of bacteria, and
as follows: susceptibility or resistance for any antimicrobial susceptibility or
designated isolate. At least 25 percent of resistance testing. To determine the
§ 493.905 Nonapproved proficiency testing the samples must be mixtures of the accuracy of each of the laboratory’s
programs. principal organism and appropriate responses, the program must compare
(a) If a proficiency testing program is normal flora. Mixed cultures are each response with the response which
determined by HHS to fail to meet any samples that require reporting of one or reflects agreement of either 80 percent
criteria contained in §§ 493.901 through more principal pathogens. Mixed or more of ten or more referee
493.959 for approval of the proficiency cultures are not ‘‘negative’’ samples laboratories or 80 percent or more of all
testing program, CMS will notify the such as when two commensal organisms participating laboratories. Both methods
amozie on DSK3GDR082PROD with PROPOSALS2

program and the program must notify all are provided in a PT sample with the must be attempted before the program
laboratories enrolled of the nonapproval intended response of ‘‘negative’’ or ‘‘no can choose to not grade a PT sample.
and the reasons for nonapproval within pathogen present.’’ The program must (2) A laboratory must identify the
30 days of the notification. CMS may include the following two types of organisms to highest level that it
disapprove any proficiency testing samples to meet the 25 percent mixed performs these procedures on patient
program that provides false or culture criterion: specimens.
misleading information with respect to (i) Samples that require laboratories to (3) A laboratory’s performance will be
any information that is necessary to report only organisms that the testing evaluated on the basis of the average of

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 1560 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

its scores for paragraph (b)(4) through specimens. A correct response for each representative of the following major
(8) of this section as determined in antimicrobial will be determined as groups of medically important
paragraph (b)(9) of this section. described in paragraph (b)(1) of this mycobacteria, if appropriate for the
(4) The performance criteria for Gram section. Scoring for each sample is sample sources:
stain including bacterial morphology is based on the number of correct (i) Mycobacterium tuberculosis
staining reaction, that is, Gram positive susceptibility or resistance responses complex; and
or Gram negative and morphological reported by the laboratory divided by (ii) Mycobacterium other than
description for each sample. The score the actual number of correct tuberculosis (MOTT).
is the number of correct responses for susceptibility or resistance responses (4) The program must provide at least
Gram stain reaction plus the number of determined by the program, multiplied five samples per testing event that
correct responses for morphological by 100. For example, if a laboratory include challenges that are acid-fast and
description divided by 2 then divided offers susceptibility or resistance testing challenges which do not contain acid-
by the number of samples to be tested, using three antimicrobial agents, and fast organisms.
multiplied by 100. the laboratory reports correct responses (5) For antimycobacterial
(5) The performance criterion for for two of the three antimicrobial agents, susceptibility or resistance testing, the
direct bacterial antigen detection is the the laboratory’s grade would be 2/3 × program must provide at least two
presence or absence of the bacterial 100 = 67 percent. samples per testing event that have a
antigen. The score is the number of (9) The score for a testing event in predetermined pattern of susceptibility
correct responses divided by the bacteriology is the average of the scores or resistance to the common
number of samples to be tested, determined under paragraphs (b)(4) antimycobacterial agents.
multiplied by 100. through (8) of this section based on the (b) Evaluation of a laboratory’s
(6) The performance criterion for type of service offered by the laboratory. performance. HHS approves only those
bacterial toxin detection is the presence ■ 11. Section 493.913 is revised to read programs that assess the accuracy of a
or absence of the bacterial toxin. The as follows: laboratory’s response in accordance
score is the number of correct responses with paragraphs (b)(1) through (7) of
divided by the number of samples to be § 493.913 Mycobacteriology. this section.
tested multiplied by 100. (a) Program content and frequency of (1) The program determines the
(7) The performance criterion for the challenge. To be approved for reportable mycobacteria to be detected
detection and identification of bacteria proficiency testing for by acid-fast stain. The program
includes one of the following: mycobacteriology, the annual program determines the mycobacteria to be
(i) The performance criterion for the must provide a minimum of five reported by detection of growth or no
detection of growth or no growth in samples per testing event. There must growth in culture media, identification
culture media is the presence or absence be at least two testing events provided of mycobacteria, and for
of bacteria or growth. The score is the to the laboratory at approximately equal antimycobacterial susceptibility or
number of correct responses divided by intervals per year. The samples may be resistance testing. To determine the
the number of samples to be tested provided through mailed shipments. accuracy of each of the laboratory’s
multiplied by 100. The specific organisms included in the responses, the program must compare
(ii) The performance criterion for the samples may vary from year to year. each response with the response that
identification of bacteria is the total (1) The annual program must include, reflects agreement of either 80 percent
number of correct responses for as applicable, samples for: or more of ten or more referee
bacterial identification submitted by the (i) Acid-fast stain; laboratories or 80 percent or more of all
laboratory divided by the number of (ii) Detection and identification of participating laboratories. Both methods
organisms present plus the number of mycobacteria which includes one of the must be attempted before the program
incorrect organisms reported by the following: can choose to not grade a PT sample.
laboratory multiplied by 100 to establish (A) Detection of growth or no growth (2) A laboratory must detect and
a score for each sample in each testing in culture media; or identify the organism to the highest
event. Since laboratories may (B) Identification of mycobacteria; and level that it performs these procedures
incorrectly report the presence of (iii) Antimycobacterial susceptibility on patient specimens.
organisms in addition to the correctly or resistance testing. (3) A laboratory’s performance will be
identified principal organism(s), the (2) An approved program must evaluated on the basis of the average of
scoring system must provide a means of furnish HHS and its agents with a its scores for paragraph (b)(4) through
deducting credit for additional description of the samples it plans to (6) of this section as determined in
erroneous organisms that are reported. include in its annual program no later paragraph (b)(7) of this section.
For example, if a sample contained one than 6 months before each calendar (4) The performance criterion for acid-
principal organism and the laboratory year. At least 25 percent of the samples fast stains is positive or negative or the
reported it correctly but reported the must be mixtures of the principal presence or absence of acid-fast
presence of an additional organism, mycobacteria and appropriate normal organisms. The score is the number of
which was not considered reportable, flora. The program must include correct responses divided by the
the sample grade would be 1/(1 + 1) × mycobacteria commonly occurring in number of samples to be tested,
100 = 50 percent. patient specimens and other important multiplied by 100.
(8) For antimicrobial susceptibility or emerging mycobacteria. The program (5) The performance criterion for the
amozie on DSK3GDR082PROD with PROPOSALS2

resistance testing, a laboratory must determines the reportable isolates and detection and identification of
indicate which drugs are routinely correct responses for antimycobacterial mycobacteria includes one of the
included in its test panel when testing susceptibility or resistance for any following:
patient samples. A laboratory’s designated isolate. (i) The performance criterion for the
performance will be evaluated for only (3) The content of an approved detection of growth or no growth in
those antimicrobials for which program may vary over time, as culture media is the presence or absence
susceptibility or resistance testing is appropriate. The mycobacteria included of bacteria or growth. The score is the
routinely performed on patient annually must contain species number of correct responses divided by

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1561

the number of samples to be tested testing events provided to the laboratory actinomycetes, and antifungal
multiplied by 100. at approximately equal intervals per susceptibility or resistance testing. To
(ii) The performance criterion for the year. The samples may be provided determine the accuracy of a laboratory’s
identification of mycobacteria is the through mailed shipments. The specific responses, the program must compare
total number of correct responses for organisms included in the samples may each response with the response reflects
mycobacterial identification submitted vary from year to year. agreement of either 80 percent or more
by the laboratory divided by the number (1) The annual program must include, of ten or more referee laboratories or 80
of organisms present plus the number of as applicable, samples for: percent or more of all participating
incorrect organisms reported by the (i) Direct fungal antigen detection; laboratories. Both methods must be
laboratory multiplied by 100 to establish (ii) Detection and identification of attempted before the program can
a score for each sample in each testing fungi and aerobic actinomycetes which choose to not grade a PT sample.
event. Since laboratories may includes one of the following: (2) A laboratory must detect and
incorrectly report the presence of (A) Detection of growth or no growth identify the organisms to highest level
mycobacteria in addition to the in culture media; or that it performs these procedures on
correctly identified principal (B) Identification of fungi and aerobic patient specimens.
organism(s), the scoring system must actinomycetes; and (3) A laboratory’s performance will be
provide a means of deducting credit for (iii) Antifungal susceptibility or evaluated on the basis of the average of
additional erroneous organisms resistance testing. its scores for paragraphs (b)(4) through
reported. For example, if a sample (2) An approved program must (6) of this section as determined in
contained one principal organism and furnish HHS and its agents with a paragraph (b)(7) of this section.
the laboratory reported it correctly but description of the samples it plans to (4) The performance criterion for
reported the presence of an additional include in its annual program no later direct fungal antigen detection is the
organism, which was not considered than 6 months before each calendar presence or absence of the fungal
reportable, the sample grade would be year. At least 25 percent of the samples antigen. The score is the number of
1/(1 + 1) × 100 = 50 percent. must be mixtures of the principal correct responses divided by the
(6) For antimycobacterial organism and appropriate normal number of samples to be tested,
susceptibility or resistance testing, a background flora. The program must multiplied by 100.
laboratory must indicate which drugs include fungi and aerobic actinomycetes (5) The performance criterion for the
are routinely included in its test panel commonly occurring in patient detection and identification of fungi and
when testing patient samples. A specimens and other important aerobic actinomycetes includes one of
laboratory’s performance will be emerging fungi. The program the following:
evaluated for only those determines the reportable isolates and (i) The performance criterion for the
antimycobacterial agents for which correct responses for antifungal detection of growth or no growth in
susceptibility or resistance testing is susceptibility or resistance for any culture media is the presence or absence
routinely performed patient specimens. designated isolate. of fungi or growth. The score is the
A correct response for each (3) The content of an approved number of correct responses divided by
antimycobacterial agent will be program must vary over time, as the number of samples to be tested
determined as described in paragraph appropriate. The fungi included multiplied by 100.
(b)(1) of this section. Scoring for each annually must contain species (ii) The performance criterion for the
sample is based on the number of representative of the following major identification of fungi and aerobic
correct susceptibility or resistance groups of medically important fungi and actinomycetes is the total number of
responses reported by the laboratory aerobic actinomycetes, if appropriate for correct responses for fungal and aerobic
divided by the actual number of correct the sample sources: actinomycetes identification submitted
susceptibility or resistance responses as (i) Yeast or yeast-like organisms; by the laboratory divided by the number
determined by the program, multiplied (ii) Molds that include; of organisms present plus the number of
by 100. For example, if a laboratory (A) Dematiaceous fungi; incorrect organisms reported by the
offers susceptibility or resistance testing (B) Dermatophytes; laboratory multiplied by 100 to establish
using three antimycobacterial agents (C) Dimorphic fungi; a score for each sample in each testing
and the laboratory reports correct (D) Hyaline hyphomycetes; event. Since laboratories may
responses for two of the three (E) Mucormycetes; and incorrectly report the presence of fungi
antimycobacterial agents, the (iii) Aerobic actinomycetes. and aerobic actinomycetes in addition
laboratory’s grade would be 2/3 × 100 = (4) For antifungal susceptibility or to the correctly identified principal
67 percent. resistance testing, the program must organism(s), the scoring system must
(7) The score for a testing event in provide at least two challenges per provide a means of deducting credit for
mycobacteriology is the average of the testing event that include fungi that additional erroneous organisms that are
scores determined under paragraphs have a predetermined pattern of reported. For example, if a sample
(b)(4) through (6) of this section based susceptibility or resistance to the contained one principal organism and
on the type of service offered by the common antifungal agents. the laboratory reported it correctly but
laboratory. (b) Evaluation of a laboratory’s reported the presence of an additional
■ 12. Section 493.915 is revised to read performance. HHS approves only those organism, which was not considered
as follows: programs that assess the accuracy of a reportable, the sample grade would be
amozie on DSK3GDR082PROD with PROPOSALS2

laboratory’s response, in accordance 1/(1 + 1) × 100 = 50 percent.

§ 493.915 Mycology. with paragraphs (b)(1) through (8) of (6) For antifungal susceptibility or
(a) Program content and frequency of this section. resistance testing, a laboratory must
challenge. To be approved for (1) The program determines the indicate which drugs are routinely
proficiency testing for mycology, the reportable fungi to be reported by direct included in its test panel when testing
annual program must provide a fungal antigen detection, detection of patient samples. A laboratory’s
minimum of five samples per testing growth or no growth in culture media, performance will be evaluated for only
event. There must be at least three identification of fungi and aerobic those antifungal agents for which

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 1562 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

susceptibility or resistance testing is groups of medically important parasites, incorrect parasites reported by the
routinely performed on patient if appropriate for the sample sources: laboratory multiplied by 100 to establish
specimens. A correct response for each (i) Intestinal parasites; and a score for each sample in each testing
antifungal agent will be determined as (ii) Blood and tissue parasites. event. Since laboratories may
described in paragraph (b)(1) of this (4) The program must provide at least incorrectly report the presence of
section. Scoring for each sample is five samples per testing event that parasites in addition to the correctly
based on the number of correct include challenges which contain identified principal organism(s), the
susceptibility or resistance responses parasites and challenges that are devoid scoring system must provide a means of
reported by the laboratory divided by of parasites. deducting credit for additional
the actual number of correct (b) Evaluation of a laboratory’s erroneous organisms that are reported
susceptibility or resistance responses as performance. HHS approves only those and not found in rare numbers by the
determined by the program, multiplied programs that assess the accuracy of a program’s referencing process. For
by 100. For example, if a laboratory laboratory’s responses in accordance example, if a sample contained one
offers susceptibility or resistance testing with paragraphs (b)(1) through (6) of principal organism and the laboratory
using three antifungal agents and the this section. reported it correctly but reported the
laboratory reports correct responses for (1) The program determines the presence of an additional organism,
two of the three antifungal agents, the reportable parasites to be detected by which was not considered reportable,
laboratory’s grade would be 2/3 × 100 = direct parasite antigen detection, the sample grade would be 1/(1 + 1) ×
67 percent. detection of presence or absence of 100 = 50 percent.
(7) The score for a testing event is the parasites, and identification of parasites. (6) The score for a testing event is the
average of the sample scores as It may elect to establish a minimum average of the sample scores as
determined under paragraphs (b)(4) number of parasites to be identified in determined under paragraphs (b)(4)
through (6) of this section. samples before they are reported. through (5) of this section.
Parasites found in rare numbers by ■ 14. Section 493.919 is revised to read
■ 13. Section 493.917 is revised to read
referee laboratories are not considered as follows:
as follows:
in a laboratory’s performance; such
§ 493.919 Virology.
§ 493.917 Parasitology. findings are neutral. To determine the
accuracy of a laboratory’s response, the (a) Program content and frequency of
(a) Program content and frequency of challenge. To be approved for
challenge. To be approved for program must compare each response
with the response which reflects proficiency testing in virology, a
proficiency testing in parasitology, the program must provide a minimum of
annual program must provide a agreement of either 80 percent or more
of ten or more referee laboratories or 80 five samples per testing event. There
minimum of five samples per testing must be at least three testing events at
event. There must be at least three percent or more of all participating
laboratories. Both methods must be approximately equal intervals per year.
testing events provided to the laboratory The samples may be provided to the
at approximately equal intervals per attempted before the program can
choose to not grade a PT sample. laboratory through mailed shipments.
year. The samples may be provided The specific organisms included in the
through mailed shipments. The specific (2) A laboratory must detect and
identify or concentrate and identify the samples may vary from year to year.
organisms included in the samples may (1) The annual program must include,
vary from year to year. parasites to the highest level that it
performs these procedures on patient as applicable, samples for:
(1) The annual program must include, (i) Viral antigen detection;
as applicable, samples for: specimens. (ii) Detection and identification of
(3) A laboratory’s performance will be
(i) Direct parasite antigen detection; viruses; and
evaluated on the basis of the average of (iii) Antiviral susceptibility or
and
its scores for paragraphs (b)(4) through resistance testing.
(ii) Detection and identification of (5) of this section as determined in
parasites which includes one of the (2) An approved program must
paragraph (b)(6) of this section. furnish HHS and its agents with a
following: (4) The performance criterion for
(A) Detection of presence or absence description of the samples it plans to
direct parasite antigen detection is the include in its annual program no later
of parasites; or presence or absence of the parasite
(B) Identification of parasites. than 6 months before each calendar
antigen. The score is the number of year. The program must include other
(2) An approved program must correct responses divided by the
furnish HHS and its agents with a important emerging viruses and viruses
number of samples to be tested, commonly occurring in patient
description of the samples it plans to multiplied by 100. specimens. The program determines the
include in its annual program no later (5) The performance criterion for the reportable isolates and correct responses
than 6 months before each calendar detection and identification of parasites for antiviral susceptibility or resistance
year. Samples must include both includes one of the following: for any designated isolate.
formalinized specimens and PVA (i) The performance criterion for the (3) The content of an approved
(polyvinyl alcohol) fixed specimens as detection of presence or absence of program must vary over time, as
well as blood smears, as appropriate for parasites is the presence or absence of appropriate. If appropriate for the
a particular parasite and stage of the parasites. The score is the number of sample sources, the types of viruses
parasite. The majority of samples must correct responses divided by the included annually must be
amozie on DSK3GDR082PROD with PROPOSALS2

contain protozoa or helminths or a number of samples to be tested, representative of the following major
combination of parasites. Some samples multiplied by 100. groups of medically important viruses:
must be devoid of parasites. (ii) The performance criterion for the (i) Respiratory viruses;
(3) The content of an approved identification of parasites is the total (ii) Herpes viruses;
program must vary over time, as number of correct responses for parasite (iii) Enterovirus; and
appropriate. The types of parasites identification submitted by the (iv) Intestinal viruses.
included annually must be laboratory divided by the number of (4) For antiviral susceptibility or
representative of the following major parasites present plus the number of resistance testing, the program must

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1563

provide at least two challenges per included in its test panel when testing testing events at approximately equal
testing event that include viruses that patient samples. A laboratory’s intervals per year. The annual program
have a predetermined pattern of performance will be evaluated for only must provide samples that cover the full
susceptibility or resistance to the those antiviral agents for which range of reactivity from highly reactive
common antiviral agents. susceptibility or resistance testing is to nonreactive. The samples may be
(b) Evaluation of laboratory’s routinely performed patient specimens. provided through mailed shipments.
performance. HHS approves only those A correct response for each antiviral (b) Challenges per testing event. The
programs that assess the accuracy of a agent will be determined as described in minimum number of challenges per
laboratory’s response in accordance paragraph (b)(1) of this section. Scoring testing event the program must provide
with paragraphs (b)(1) through (7) of for each sample is based on the number for each analyte or test procedure is five.
this section. of correct susceptibility or resistance Analytes or tests for which laboratory
(1) The program determines the responses reported by the laboratory performance is to be evaluated include:
viruses to be reported by direct viral divided by the actual number of correct Alpha-l antitrypsin.
antigen detection, detection and susceptibility or resistance responses as Alpha-fetoprotein (tumor marker).
identification of viruses, and antiviral determined by the program, multiplied Antinuclear antibody.
susceptibility or resistance testing. To by 100. For example, if a laboratory Antistreptolysin O.
determine the accuracy of a laboratory’s offers susceptibility or resistance testing Anti-human immunodeficiency virus
response, the program must compare using three antiviral agents and the (HIV).
each response with the response which laboratory reports correct responses for
Complement C3.
reflects agreement of either 80 percent two of the three antiviral agents, the
Complement C4.
or more of ten or more referee laboratory’s grade would be 2/3 × 100 =
67 percent. C-reactive protein (high sensitivity).
laboratories or 80 percent or more of all HBsAg.
participating laboratories. Both methods (7) The score for a testing event is the
average of the sample scores as Anti-HBc.
must be attempted before the program
determined under paragraphs (b)(4) and HBeAg.
can choose to not grade a PT sample.
(2) A laboratory must detect and (6) of this section. Anti-HBs.
identify the viruses to the highest level ■ 15. Section 493.923 is amended by Anti-HCV.
that it performs these procedures on revising paragraphs (a) and (b)(1) to read IgA.
patient specimens. as follows: IgG.
(3) A laboratory’s performance will be IgE.
§ 493.923 Syphilis serology.
evaluated on the basis of the average of IgM.
(a) Program content and frequency of
its scores for paragraphs (b)(4) through Infectious mononucleosis.
challenge. To be approved for
(6) of this section as determined in Rheumatoid factor.
proficiency testing in syphilis serology,
paragraph (b)(7) of this section. a program must provide a minimum of Rubella.
(4) The performance criterion viral five samples per testing event. There (c) * * *
antigen detection is the presence or must be at least three testing events at (1) To determine the accuracy of a
absence of the viral antigen. The score approximately equal intervals per year. laboratory’s response for quantitative
is the number of correct responses The samples may be provided through and qualitative immunology tests or
divided by the number of samples to be mailed shipments. An annual program analytes, the program must compare the
tested, multiplied by 100. must include samples that cover the full laboratory’s response for each analyte
(5) The performance criterion for the range of reactivity from highly reactive with the response that reflects
detection and identification of viruses is to non-reactive. agreement of either 80 percent or more
the total number of correct responses for (b) * * * of ten or more referee laboratories or 80
viral detection and identification (1) To determine the accuracy of a percent or more of all participating
submitted by the laboratory divided by laboratory’s response for qualitative and laboratories. The proficiency testing
the number of viruses present plus the quantitative syphilis tests, the program program must indicate the minimum
number of incorrect virus reported by must compare the laboratory’s response concentration that will be considered as
the laboratory multiplied by 100 to with the response that reflects indicating a positive response. Both
establish a score for each sample in each agreement of either 80 percent or more methods must be attempted before the
testing event. Since laboratories may of ten or more referee laboratories or 80 program can choose to not grade a PT
incorrectly report the presence of percent or more of all participating sample.
viruses in addition to the correctly laboratories. Both methods must be (2)(i) For quantitative immunology
identified principal organism(s), the attempted before the program can analytes or tests, the program must
scoring system must provide a means of choose to not grade a PT sample. determine the correct response for each
deducting credit for additional * * * * * analyte by the distance of the response
erroneous organisms that are reported. ■ 16. Section 493.927 is amended by from the target value. After the target
For example, if a sample contained one revising paragraphs (a), (b), and (c)(1) value has been established for each
principal organism and the laboratory and (2) to read as follows: response, the appropriateness of the
reported it correctly but reported the response must be determined by using
presence of an additional organism, § 493.927 General immunology. either fixed criteria or the number of
amozie on DSK3GDR082PROD with PROPOSALS2

which was not considered reportable, (a) Program content and frequency of standard deviations (SDs) the response
the sample grade would be 1/(1 + 1) × challenge. To be approved for differs from the target value.
100 = 50 percent. proficiency testing for immunology, the
(6) For antiviral susceptibility or annual program must provide a Criteria for Acceptable Performance
resistance testing, a laboratory must minimum of five samples per testing The criteria for acceptable
indicate which drugs are routinely event. There must be at least three performance are—

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 1564 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

Analyte or test Criteria for acceptable performance

Alpha-1 antitrypsin .................................................................................... Target value ±20% or positive or negative.

Alpha-fetoprotein (tumor marker) ............................................................. Target value ±20% or positive or negative.
Antinuclear antibody ................................................................................. Target value ±3 SD or positive or negative.
Antistreptolysin O ..................................................................................... Target value ±3 SD or positive or negative.
Anti-Human Immunodeficiency virus (HIV) .............................................. Reactive (positive) or nonreactive (negative).
Complement C3 ........................................................................................ Target value ±15% or positive or negative.
Complement C4 ........................................................................................ Target value ±5 mg/dL or 20% (greater) or positive or negative.
C-reactive protein (HS) ............................................................................. Target value ±1 mg/dL or 30% (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 ±15%.
IgE ............................................................................................................ Target value ±20%.
IgG ............................................................................................................ Target value ±20%.
IgM ............................................................................................................ Target value ±20%.
Infectious mononucleosis ......................................................................... Positive or negative.
Rheumatoid factor .................................................................................... Target value ±3 SD or positive or negative.
Rubella ...................................................................................................... Target value ±3 SD or positive or negative or immune or nonimmune.

* * * * * Bilirubin, total Uric Acid

■ 17. Section 493.931 is amended by Blood gas (pH, pO2, and pCO2) (c) * * *
revising paragraphs (a), (b), and (c)(1) B-natriuretic peptide (BNP)
and (2) to read as follows: proBNP (1) To determine the accuracy of a
Calcium, total laboratory’s response for qualitative and
§ 493.931 Routine chemistry. quantitative chemistry tests or analytes,
Carbon dioxide
(a) Program content and frequency of Chloride the program must compare the
challenge. To be approved for Cholesterol, total laboratory’s response for each analyte
proficiency testing for routine Cholesterol, high density lipoprotein with the response that reflects
chemistry, a program must provide a Cholesterol, low density lipoprotein agreement of either 80 percent or more
minimum of five samples per testing Creatine kinase (CK) of ten or more referee laboratories or 80
event. There must be at least three CK–MB isoenzymes percent or more of all participating
testing events at approximately equal Creatinine laboratories. Both methods must be
intervals per year. The annual program Ferritin attempted before the program can
must provide samples that cover the Gamma glutamyl transferase choose to not grade a PT sample.
clinically relevant range of values that Glucose (Excluding measurements on (2) For quantitative chemistry tests or
would be expected in patient devices cleared by FDA for home use) analytes, the program must determine
specimens. The specimens may be Hemoglobin A1c the correct response for each analyte by
provided through mailed. Iron, total the distance of the response from the
(b) Challenges per testing event. The target value. After the target value has
Lactate dehydrogenase (LDH)
minimum number of challenges per been established for each response, the
Magnesium
testing event a program must provide for appropriateness of the response must be
Phosphorus
each of the following analyte or test determined by using either fixed criteria
Potassium
procedure is five serum, plasma or based on the percentage difference from
Prostate specific antigen, total
blood samples. the target value or the number of
Sodium
Analyte or Test Procedure Total iron binding capacity standard deviations (SD) the response
Alanine aminotransferase (ALT/SGPT) Total Protein differs from the target value.
Albumin Triglycerides Criteria for Acceptable Performance
Alkaline phosphatase Troponin I
Amylase Troponin T The criteria for acceptable
Aspartate aminotransferase (AST/SGOT) Urea Nitrogen performance are—

Analyte or test Criteria for acceptable performance

Alanine aminotransferase (ALT/SGPT) .................................................... Target value ±15%.

Albumin ..................................................................................................... Target value ±8%.
Alkaline phosphatase ............................................................................... Target value ±20%.
Amylase .................................................................................................... Target value ±10%.
±15%.
amozie on DSK3GDR082PROD with PROPOSALS2

Aspartate aminotransferase (AST/SGOT) ................................................ Target value

Bilirubin, total ............................................................................................ Target value ±20%.
Blood gas pCO2 ....................................................................................... Target value ±5 mm Hg or ±8% (greater).
Blood gas pO2 .......................................................................................... Target value ±15 mmHg or 15% (greater).
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%.

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1565

Analyte or test Criteria for acceptable performance

Chloride .................................................................................................... Target value ±5%.

Cholesterol, total ....................................................................................... Target value ±10%.
Cholesterol, high density lipoprotein ........................................................ Target value ±20%.
Cholesterol, low density lipoprotein (direct measurement) ...................... Target value ±20%.
Creatine kinase (CK) ................................................................................ Target value ±20%.
CK–MB isoenzymes ................................................................................. MB elevated (presence or absence) or Target value ±25% (greater).
Creatinine ................................................................................................. Target value ±0.2 mg/dL or ±10% (greater).
Ferritin ....................................................................................................... Target value ±20%.
Gamma glutamyl transferase ................................................................... Target value ±5 U/L or ±15% (greater).
Glucose (excluding measurements devices cleared by FDA for home Target value ±8% (greater).
use.).
Hemoglobin A1c ....................................................................................... Target value ±10%.
Iron, total ................................................................................................... Target value ±15%.
Lactate dehydrogenase (LDH) ................................................................. Target value ±15%.
Magnesium ............................................................................................... Target value ±15%.
Phosphorus ............................................................................................... Target value ±0.3 mg/dL or ±10% (greater).
Potassium ................................................................................................. Target value ±0.3 mmol/L.
Prostate Specific Antigen, total ................................................................ Target value ±0.2 ng/dL or 20% (greater).
Sodium ...................................................................................................... Target value ±4 mmol/L.
Total Iron Binding Capacity (direct measurement) .................................. Target value ±20%.
Total Protein ............................................................................................. Target value ±8%.
Triglycerides ............................................................................................. Target value ±15%.
Troponin I ................................................................................................. Target value ±0.9 ng/mL or 30% (greater).
Troponin T ................................................................................................ Target value ±0.2 ng/mL or 30% (greater).
Urea nitrogen ............................................................................................ Target value ±2 mg/dL or ±9% (greater).
Uric acid .................................................................................................... Target value ±10%.

* * * * * Analyte or Test analytes, a program must compare the

■ 18. Section 493.933 is amended by Cancer antigen (CA) 125 laboratory’s response for each analyte
revising paragraphs (a), (b), and (c)(1) Carcinoembryonic antigen (CEA) with the response that reflects
and (2) to read as follows: Cortisol agreement of either 80 percent or more
Estradiol of ten or more referee laboratories or 80
§ 493.933 Endocrinology. Folate, serum percent or more of all participating
Follicle stimulating hormone laboratories. Both methods must be
(a) Program content and frequency of attempted before the program can
challenge. To be approved for Free thyroxine
Human chorionic gonadotropin choose to not grade a PT sample.
proficiency testing for endocrinology, a (2) For quantitative endocrinology
(excluding urine pregnancy tests done
program must provide a minimum of tests or analytes, the program must
by visual color
five samples per testing event. There comparison categorized as waived tests) determine the correct response for each
must be at least three testing events at Luteinizing hormone analyte by the distance of the response
approximately equal intervals per year. Parathyroid hormone from the Target value. After the Target
The annual program must provide Progesterone value has been established for each
samples that cover the clinically Prolactin response, the appropriateness of the
relevant range of values that would be Testosterone response must be determined by using
expected in patient specimens. The T3 Uptake either fixed criteria based on the
samples may be provided through Triiodothyronine percentage difference from the Target
mailed shipments. Thyroid-stimulating hormone value or the number of standard
(b) Challenges per testing event. The Thyroxine deviations (SDs) the response differs
minimum number of challenges per Vitamin B12 from the Target value.
(c) * * *
testing event a program must provide for Criteria for Acceptable Performance
(1) To determine the accuracy of a
each analyte or test procedure is five laboratory’s response for qualitative and The criteria for acceptable
serum, plasma, blood, or urine samples. quantitative endocrinology tests or performance are—

Analyte or test Criteria for acceptable performance

Cancer antigen (CA) 125 ......................................................................... Target value ±20%.

Carcinoembryonic antigen (CEA) ............................................................. Target value ±15%.
Cortisol ...................................................................................................... Target value ±20%.
Estradiol .................................................................................................... Target value ±30%.
amozie on DSK3GDR082PROD with PROPOSALS2

Folate, serum ............................................................................................ Target value ±1 ng/mL or ±30% (greater).

Follicle stimulating hormone ..................................................................... Target value ±2 IU/L or ±18% (greater).
Free thyroxine ........................................................................................... Target value ±0.3 ng/dL or ±15% (greater).
Human chorionic ....................................................................................... Target value ±18% or positive or negative.
Gonadotropin (excluding urine pregnancy tests done by visual color
comparison categorized as waived tests).
Luteinizing hormone ................................................................................. Target value ±20%.
Parathyroid hormone ................................................................................ Target value ±30%.
Progesterone ............................................................................................ Target value ±25%.

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 1566 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules

Analyte or test Criteria for acceptable performance

Prolactin .................................................................................................... Target value ±20%.

Testosterone ............................................................................................. Target value ±20 ng/dL or ±30% (greater).
T3 uptake .................................................................................................. Target value ±18%.
Triiodothyronine ........................................................................................ Target value ±30%.
Thyroid-stimulating hormone .................................................................... Target value ±20% or 0.2 mIU/L (greater).
Thyroxine (greater) ................................................................................... Target value ±20% or 1.0 mcg/dL.
Vitamin B12 .............................................................................................. Target value ±25%.

* * * * * testing event a program must provide for must compare the laboratory’s response
■ 19. Section 493.937 is amended by each analyte or test procedure is five for each analyte with the response that
revising paragraphs (a), (b), and (c)(1) serum, plasma, or blood samples. reflects agreement of either 80 percent
and (2) to read as follows: or more of ten or more referee
Analyte or Test Procedure
laboratories or 80 percent or more of all
§ 493.937 Toxicology. Acetaminophen, serum participating laboratories. Both methods
(a) Program content and frequency of Alcohol (blood) must be attempted before the program
challenge. To be approved for Blood lead can choose to not grade a PT sample.
proficiency testing for toxicology, the Carbamazepine
Digoxin (2) For quantitative toxicology tests or
annual program must provide a analytes, the program must determine
Gentamicin
minimum of five samples per testing Lithium the correct response for each analyte by
event. There must be at least three Phenobarbital the distance of the response from the
testing events at approximately equal Phenytoin target value. After the target value has
intervals per year. The annual program Salicylate been established for each response, the
must provide samples that cover the full Theophylline appropriateness of the response must be
range of values that could occur in Tobramycin determined by using fixed criteria based
patient specimens and that cover the Valproic Acid on the percentage difference from the
level of clinical significance for the Vancomycin target value.
particular drug. The samples may be (c) * * *
provided through mailed shipments. Criteria for Acceptable Performance
(1) To determine the accuracy of a
(b) Challenges per testing event. The laboratory’s responses for quantitative The criteria for acceptable
minimum number of challenges per toxicology tests or analytes, the program performance are:

Analyte or test Criteria for acceptable performance

Acetaminophen ......................................................................................... Target value ±15%.

Alcohol, blood ........................................................................................... Target Value ±20%.
Blood lead ................................................................................................. Target Value ±10% or 2 mcg/dL (greater).
Carbamazepine ........................................................................................ Target Value ±20%.
Digoxin ...................................................................................................... Target Value ±15% or ±0.2 ng/mL (greater).
Gentamicin ................................................................................................ Target Value ±25%.
Lithium ...................................................................................................... Target Value ±15%.
Phenobarbital ............................................................................................ Target Value ±15%.
Phenytoin .................................................................................................. Target Value ±15% or ±2 mcg/dL (greater).
Salicylate .................................................................................................. Target Value ±15%.
Theophylline ............................................................................................. Target Value ±20%.
Tobramycin ............................................................................................... Target Value ±20%.
Valproic Acid ............................................................................................. Target Value ±20%.
Vancomycin .............................................................................................. Target Value ±15% or ±2 mcg/dL (greater).

* * * * * specimens. The samples may be Prothrombin time (seconds or INR)

■ 20. Section 493.941 is amended by provided through mailed shipments. (c) * * *
revising paragraphs (a), (b), and (c)(1) (b) Challenges per testing event. The
(1) To determine the accuracy of a
and (2) to read as follows: minimum number of challenges per
laboratory’s responses for qualitative
testing event a program must provide for
and quantitative hematology tests or
§ 493.941 Hematology (including routine each analyte or test procedure is five.
analytes, the program must compare the
hematology and coagulation).
Analyte or Test Procedure laboratory’s response for each analyte
(a) Program content and frequency of Cell identification with the response that reflects
challenge. To be approved for White blood cell differential agreement of either 80 percent or more
amozie on DSK3GDR082PROD with PROPOSALS2

proficiency testing for hematology, a Erythrocyte count of ten or more referee laboratories or 80
program must provide a minimum of Hematocrit (excluding spun percent or more of all participating
five samples per testing event. There microhematocrit) laboratories. Both methods must be
must be at least three testing events at Hemoglobin attempted before the program can
approximately equal intervals per year. Leukocyte count choose to not grade a PT sample.
The annual program must provide Platelet count (2) For quantitative hematology tests
samples that cover the full range of Fibrinogen or analytes, the program must determine
values that would be expected in patient Partial thromboplastin time the correct response for each analyte by

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 Federal Register / Vol. 84, No. 23 / Monday, February 4, 2019 / Proposed Rules 1567

the distance of the response from the based on the percentage difference from Criteria for Acceptable Performance
target value. After the target value has the target value or the number of
been established for each response, the standard deviations (SD) the response The criteria for acceptable
appropriateness of the response is differs from the target value. performance are:
determined using either fixed criteria

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 hematocrit) .................................................. Target ±4%.
Hemoglobin ............................................................................................... Target ±4%.
Leukocyte count ....................................................................................... Target ±5%.
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.

Prothrombin time (seconds or INR) ......................................................... Target ±15%.

* * * * * of ten or more referee laboratories or 95 Criteria for

Analyte
■ 21. Section 493.959 is amended by percent or more of all participating or test acceptable
revising paragraphs (b) and (d)(1) and laboratories except for antibody performance
(2) to read as follows: identification. To determine the
Compatibility testing .. 100% accuracy.
accuracy of a laboratory’s response for
§ 493.959 Immunohematology. Antibody identification 80% + accuracy.
antibody identification, a program must
* * * * * compare the laboratory’s response for
(b) Program content and frequency of * * * * *
each analyte with the response that
challenge. To be approved for reflects agreement of either 95 percent Dated: June 25, 2018.
proficiency testing for or more of ten or more referee Seema Verma,
immunohematology, a program must laboratories or 95 percent or more of all Administrator, Centers for Medicare &
provide a minimum of five samples per participating laboratories. Both methods Medicaid Services.
testing event. There must be at least must be attempted before the program
three testing events at approximately Dated: December 17, 2018.
can choose to not grade a PT sample.
equal intervals per year. The annual Robert Redfield, MD
(2) Criteria for acceptable
program must provide samples that performance. Director, Centers for Disease Control and
cover the full range of interpretation The criteria for acceptable Prevention and Administrator, Agency for
that would be expected in patient performance are— Toxic Substances and Disease Registry
specimens. The samples may be Dated: December 18, 2018.
provided through mailed shipments. Criteria for Alex M. Azar II,
Analyte
(d) * * * acceptable
or test Secretary, Department of Health and Human
(1) To determine the accuracy of a performance
Services.
laboratory’s response, a program must ABO group ................. 100% accuracy. [FR Doc. 2018–28363 Filed 2–1–19; 8:45 am]
compare the laboratory’s response for D (Rho) typing ........... 100% accuracy. BILLING CODE 4120–01–P
each analyte with the response that Unexpected antibody 100% accuracy.
reflects agreement of either 100 percent detection.
amozie on DSK3GDR082PROD with PROPOSALS2

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