[Federal Register Volume 84, Number 23 (Monday, February 4, 2019)]
[Proposed Rules]
[Pages 1536-1567]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-28363]



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Vol. 84

Monday,

No. 23

February 4, 2019

Part II





Department of Health and Human Services





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Centers for Medicare & Medicaid Services





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42 CFR Part 493





Clinical Laboratory Improvement Amendments of 1988 (CLIA) Proficiency 
Testing Regulations Related to Analytes and Acceptable Performance; 
Proposed Rules

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

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Medicare & Medicaid Services

42 CFR Part 493

[CMS-3355-P]
RIN 0938-AT55


Clinical Laboratory Improvement Amendments of 1988 (CLIA) 
Proficiency Testing Regulations Related to Analytes and Acceptable 
Performance

AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS; Centers 
for Disease Control and Prevention (CDC), HHS.

ACTION: Proposed rule.

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SUMMARY: This proposed rule would update proficiency testing (PT) 
regulations under the Clinical Laboratory Improvement Amendments of 
1988 (CLIA) to address current analytes (that is, substances or 
constituents for which the laboratory conducts testing) and newer 
technologies. This proposed rule would also make additional technical 
changes to PT referral regulations to more closely align them with the 
CLIA statute.

DATES: To be assured consideration, comments must be received at one of 
the addresses provided below, no later than 5 p.m. on April 5, 2019.

ADDRESSES: In commenting, please refer to file code CMS-3355-P. Because 
of staff and resource limitations, we cannot accept comments by 
facsimile (FAX) transmission.
    Comments, including mass comment submissions, must be submitted in 
one of the following three ways (please choose only one of the ways 
listed):
    1. Electronically. You may submit electronic comments on this 
regulation to http://www.regulations.gov. Follow the ``Submit a 
comment'' instructions.
    2. By regular mail. You may mail written comments to the following 
address ONLY: Centers for Medicare & Medicaid Services, Department of 
Health and Human Services, Attention: CMS-3355-P, P.O. Box 8016, 
Baltimore, MD 21244-8016.
    Please allow sufficient time for mailed comments to be received 
before the close of the comment period.
    3. By express or overnight mail. You may send written comments to 
the following address ONLY: Centers for Medicare & Medicaid Services, 
Department of Health and Human Services, Attention: CMS-3355-P, Mail 
Stop C4-26-05, 7500 Security Boulevard, Baltimore, MD 21244-1850.
    For information on viewing public comments, see the beginning of 
the SUPPLEMENTARY INFORMATION section.

FOR FURTHER INFORMATION CONTACT: Sarah Bennett, CMS, (410) 786-3531; 
Caecilia Blondiaux, CMS, (410) 786-2190; or Nancy Anderson, CDC, (404) 
498-2741

SUPPLEMENTARY INFORMATION: 
    Inspection of Public Comments: All comments received before the 
close of the comment period are available for viewing by the public, 
including any personally identifiable or confidential business 
information that is included in a comment. We post all comments 
received before the close of the comment period on the following 
website as soon as possible after they have been received: http://www.regulations.gov. Follow the search instructions on that website to 
view public comments.

Table of Contents

I. Background
II. Provisions of the Proposed Regulations
    A. Proposed Changes for Microbiology PT
    B. Proposed Changes to PT for Non-Microbiology Specialties and 
Subspecialties
    C. Additional Proposed Changes
III. Collection of Information Requirements
IV. Response to Comments
V. Regulatory Impact Analysis
    A. Statement of Need
    B. Overall Impact
    C. Anticipated Effects
    D. Alternatives Considered
    E. Accounting Statements and Table
    F. Regulatory Reform Analysis Under E.O. 13771
    G. Conclusion

I. Background

    On October 31, 1988, Congress enacted the Clinical Laboratory 
Improvement Amendments of 1988 (Pub. L. 100-578) (CLIA'88), codified at 
42 U.S.C. 263a, to ensure the accuracy and reliability of testing in 
all laboratories, including, but not limited to, those that participate 
in Medicare and Medicaid, that test human specimens for purpose of 
providing information for the diagnosis, prevention, or treatment of 
any disease or impairment, or the assessment of health, of human 
beings. The Secretary established the initial regulations implementing 
CLIA on February 28, 1992 at 42 CFR part 493 (57 FR 7002). Those 
regulations required, among other things, for laboratories conducting 
moderate or high-complexity testing to enroll in an approved 
proficiency testing (PT) program for each specialty, subspecialty, and 
analyte or test for which the laboratory is certified under CLIA. PT 
referral was further addressed by enactment of the Taking Essential 
Steps for Testing Act of 2012 (Pub. L. 112-202, December 4, 2012) (TEST 
Act) and our implementing regulations (79 FR 25435 and 79 FR 27105). As 
of January 2017, there were 246,143 CLIA-certified laboratories, of 
which 36,777 Certificate of Compliance and Certificate of Accreditation 
laboratories were required to enroll in a U.S. Department of Health and 
Human Services (HHS)-approved PT program and comply with the PT 
regulations.
    Testing has evolved significantly since 1992, and technology is now 
more accurate and precise than the methods in use at the time the PT 
regulations became effective for all laboratories in 1994. In addition, 
many tests for analytes for which PT was not initially required are now 
in routine clinical use. For example, tests for cardiac markers, such 
as troponins, and the hemoglobin A1c test commonly used to monitor 
glycemic control in persons with diabetes, were not routinely performed 
prior to 1992. Recognizing these changes, we are proposing revisions to 
our existing PT regulations in this proposed rule.
    As part of the process for developing our proposals to revise the 
PT regulations, HHS requested input from the Clinical Laboratory 
Improvement Advisory Committee (CLIAC) regarding appropriate revisions 
to the regulations. CLIAC is the official federal advisory committee 
charged with advising HHS regarding appropriate regulatory standards 
for ensuring accuracy, reliability and timeliness of laboratory 
testing. Questions posed to CLIAC at the September 2008 CLIAC meeting 
and their recommendations are documented in the meeting summary on the 
CLIAC website at https://ftp.cdc.gov/pub/CLIAC_meeting_presentations/pdf/CLIAC_Summary/cliac0908_summary.pdf.
    In response to our request for input, CLIAC established a PT 
Workgroup that included laboratory experts, representatives from 
accreditation organizations, state surveyors, and PT program officials. 
The CLIAC PT Workgroup provided information and data to CLIAC for their 
deliberation in making recommendations to HHS regarding appropriate 
revisions to subparts H and I of the CLIA regulations. These 
recommendations addressed updating the list of required PT analytes; 
revising the scoring criteria for acceptable performance for current 
and proposed analytes; changes to specialties or subspecialties, 
including microbiology, that do not have required

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PT analytes; and clarification of the PT referral requirements. The 
questions posed to CLIAC at the September 2010 CLIAC meeting and their 
recommendations are documented in the meeting summary on the CLIAC 
website at http://wwwn.cdc.gov/cliac/pdf/cliac0910.pdf.
    After the September 2010 CLIAC meeting, CMS and CDC met to review 
and consider the recommendations. Following this, the two agencies 
collaborated to develop a process to revise the list of required PT 
analytes. That is, CMS and CDC reviewed current analytes listed in 
subpart I to determine which analytes should be retained in the 
regulations and which should be deleted. In addition, CMS and CDC 
examined analytes not currently listed in subpart I to determine if any 
additional analytes should be added to subpart I.
    As discussed in section II of this proposed rule, a systematic 
approach was taken in order to update the required PT analytes, using 
various factors in selecting candidate analytes. A variety of PT-
related and test volume data were subsequently collected from HHS-
approved PT programs and various sources as described below, and 
analyzed by CMS and CDC.
    As discussed in section II.B.2. of this proposed rule, CMS and CDC 
used those data and applied the criteria in a step-wise approach to 
determine the analytes included in this proposed rule. Following 
selection of those candidate analytes, CMS and CDC sought feedback from 
PT programs on the following topics: Current PT program practices using 
``peer grouping'' to determine target values; the potential to include 
new analytes as required PT; mechanism for grading current of analytes; 
possible changes to the criteria for acceptable performance; and 
potential changes to microbiology subspecialties, including the 
replacement of the types of service as outlined currently at Sec. Sec.  
493.911(a), 493.913(a), 493.915(a), 493.917(a) and 493.919(a), with the 
candidate analytes and the replacement of the list of specific 
organisms for each microbiology subspecialty at the above citations 
with our proposal to adopt a general list of types of microorganisms 
for each microbiology subspecialty.
    Specifically, with CDC's expertise and assistance, we then 
developed an approach and rationale, as discussed in section II.B.10. 
of this proposed rule, for revising PT acceptance limits based upon 
empirical data, including clinical relevance. CMS and CDC worked to 
determine the acceptance limits, that is, the symmetrical tolerance 
(plus and minus) around the target value (as defined in Sec.  493.2), 
to propose for both new and existing required analytes. As a result of 
this work, we ultimately decided to propose stating acceptance limits 
as percentages whenever possible.
    We then again sought industry input. For each analyte, we requested 
that PT programs consider our potential new acceptance limits and 
provide data simulations using real PT data as a means of pilot testing 
our potential acceptance limits. We received simulation data from 
several PT programs, which facilitated the development of the 
acceptance limits proposed in this rule. We note that acceptance limits 
are intended to be used for scoring PT performance by PT programs and 
are not intended to be used by individual laboratories to satisfy the 
requirement at Sec.  493.1253(b) to establish performance 
specifications.

II. Provisions of the Proposed Regulations

    This section provides an overview of our proposed revisions to the 
CLIA definitions and PT requirements in subpart A--General Provisions, 
Sec.  493.2 Definitions; subpart H--Participation in Proficiency 
Testing for Laboratories Performing Nonwaived Testing; and subpart I--
Proficiency Testing Programs for Nonwaived Testing.

A. Proposed Changes to Microbiology PT

1. Categories of Testing
    Subpart I of the CLIA regulations includes PT requirements for each 
subspecialty of microbiology, Sec. Sec.  493.911 through 493.919, which 
describe ``Types of services offered by laboratories'' for each 
subspecialty. In addition, since the regulations do not specify 
required analytes for microbiology as they do for other specialties, 
they include descriptions of levels or extents (for example, 
identification to the genus level only, identification to the genus and 
species level) used to determine the type of laboratory for PT 
purposes. CLIAC discussed the usefulness and limitations of the types 
of services listed in subpart I in helping laboratories enroll properly 
or in helping surveyors conduct laboratory inspections. It was noted 
that the types of services listed in subpart I do not allow for 
reporting growth or no growth, presence or absence, or presumptive 
identification of microorganisms on PT samples, which are common ways 
that physician office laboratories report patient results. Based on 
input from the PT Workgroup, CLIAC suggested revision of the 
regulations to include broad categories for the types of PT required 
for each microbiology subspecialty to allow flexibility for inclusion 
of new technologies.
    After deliberation, CLIAC made the following recommendations:
     A system for categorizing types of service should be 
maintained in the regulations to help laboratories determine what PT 
they need to perform and assist surveyors in monitoring PT performance 
and patient testing.
     The regulations should include four categories of testing 
for each microbiology subspecialty, as applicable: Stain(s), 
susceptibility and resistance testing, antigen and/or toxin detection, 
and microbial identification or detection.
    Based on these recommendations, we conducted a review of the PT 
modules offered by HHS-approved PT programs and consulted with CDC 
microbiology subject matter experts who concurred that not all four 
recommended categories above are applicable to each microbiology 
subspecialty nor do PT programs have PT available for each category. If 
at some point in the future PT becomes available, we may propose to 
include additional categories of testing to microbiology subspecialties 
in future rulemaking. Based on these recommendations and our review, we 
are proposing to modify Sec. Sec.  493.911 through 493.919 to remove 
the types of services listed for each microbiology subspecialty and to 
add the recommended categories of testing for each microbiology 
subspecialty as described in the bullets below. We believe that the 
revised microbiology PT regulations would better reflect current 
practices in microbiology.
     Section 493.911(a): For bacteriology, we are proposing 
that the categories required include, as applicable: Gram stain 
including bacterial morphology; direct bacterial antigen detection; 
bacterial toxin detection; detection and identification of bacteria 
which includes one of the following: Detection of growth or no growth 
in culture media or identification of bacteria to the highest level 
that the laboratory reports results on patient specimens; and 
antimicrobial susceptibility or resistance testing on select bacteria.
     Section 493.913(a): For mycobacteriology, we are proposing 
that the categories for which PT is required include, as applicable: 
Acid-fast stain; detection and identification of mycobacteria which 
includes one of the following: Detection of growth or no growth in 
culture media or identification of mycobacteria; and

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

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

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susceptibility or resistance to common antiviral agents.
    In each of these subspecialties, we are also proposing to revise 
the requirements for evaluation of a laboratory's performance at 
Sec. Sec.  493.911(b), 493.913(b), 493.915(b), and 493.919(b) to 
account for the fact that PT would be required for susceptibility or 
resistance testing and that the scoring should be consistent with the 
testing performed.
7. Direct Antigen Testing
    PT for direct antigen testing is only required for bacteriology and 
virology under Sec. Sec.  493.911(a) and 493.919(a), respectively, not 
for the other microbiology subspecialties of mycobacteriology, 
mycology, and parasitology. Since this type of testing is commonly used 
for testing patient specimens especially in mycology and parasitology, 
CLIAC considered whether PT for direct antigen testing should be part 
of all of the microbiology subspecialty requirements. CLIAC indicated 
that direct antigen PT should be required in subspecialties where these 
methods are used and PT is available and made the following 
recommendation:
     PT for direct antigen testing should be required for all 
microbiology subspecialties.
    We reviewed the modules currently offered by PT programs and 
determined there are a number of modules that include direct antigen 
testing for all microbiology subspecialties except mycobacteriology, 
for which this technology is not commonly used for testing patient 
specimens. In addition, we recognized that in bacteriology, PT for 
direct antigen testing to detect toxins produced by organisms such as 
Clostridioides (formerly Clostridium) difficile is also commonly 
available. Based on the information collected from the PT programs, 
availability of the modules, and importance to the health and safety of 
the public, we are proposing:
     To retain the requirement for direct antigen detection 
for:
    ++ Section 493.911(a)(1)(ii): Bacteriology.
    ++ Section 493.919(a)(1)(i): Virology.
    And add the requirement for direct antigen testing detection for:
    ++ Section 493.915(a)(1)(i): Mycology.
    ++ Section 493.917(a)(1)(i): Parasitology.
     To require PT for bacterial toxin detection under Sec.  
493.911(a)(1)(iii). No changes are proposed for mycobacteriology.
     To add the evaluation criteria of a laboratory's 
performance for two of the affected subspecialties under Sec. Sec.  
493.911(b) and 493.917(b) to include performance and scoring criteria 
that address direct antigen and toxin detection. Evaluation of a 
laboratory's performance for direct antigen testing at Sec.  493.917(b) 
would align with the other microbiology subspecialties and reflect 
current microbiology practices in reporting patient results. Evaluation 
of a laboratory's performance for bacterial toxin detection at Sec.  
493.911(b) would reflect the current practice of reporting patient test 
results (that is, absence or presence of bacterial toxin).

B. Proposed Changes to PT for Non-Microbiology Specialties and 
Subspecialties

1. Analytes Proposed for Addition to Subpart I
    The CLIA statute requires the PT standards established by the 
Secretary to require PT for each examination and procedure for which 
the laboratory is certified ``except for examinations and procedures 
for which the Secretary has determined that a proficiency test cannot 
reasonably be developed'' (42 U.S.C. 263a(f)(3)(A)). In determining 
whether PT can reasonably be developed for a given analyte, we 
considered whether the estimated cost of PT is reasonable in comparison 
to the expected benefit. Considering CLIAC's recommendations regarding 
possible changes to the analytes for which PT is required, we attempted 
to maximize improvements to the effectiveness of PT to improve 
accuracy, reliability and timeliness of testing while minimizing costs 
to the laboratories. In addition, we recognize that it is not necessary 
to require PT for every analyte to derive benefits generalizable to all 
test methods. For example, systematic analytical problems on a 
multichannel analyzer might be detected by participation in PT for any 
of the analytes tested. Further, laboratories are already required 
under Sec.  493.1236(c)(1) to verify the accuracy of any test or 
procedure they perform that is not included in subpart I at least twice 
annually. Also, based on the results of the national PT survey \1\ 
conducted by CDC and the Association of Public Health Laboratories 
(APHL) in 2013, a large number of laboratories voluntarily purchased PT 
materials for many nonrequired analytes.\2\ Keeping this in mind, as 
discussed in section II.B.2. of this proposed rule, we are proposing to 
add the most crucial analytes based upon the following criteria:
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    \1\ Office of Management and Budget control number 0920-0961. 
Expiration date 4/30/2015.
    \2\ Earley, Marie C., J. Rex Astles, and Karen Breckenridge. 
Practices and Perceived Value of Proficiency Testing in Clinical 
Laboratories. Journal of Applied Laboratory Medicine 1, 4 (2017), 
pp. 415-420.
---------------------------------------------------------------------------

    (1) Current availability of PT materials and the number of PT 
programs offering PT.
    (2) Volume of patient testing performed nationwide.
    (3) Impact on patient health and/or public health.
    (4) Cost and feasibility of implementation.
2. Process for Ranking Analytes Proposed for Addition to Subpart I
    We used a sequential process to narrow the list of eligible 
analytes for addition based on each of the four criteria listed above.
a. Current Availability of PT Materials and the Number of PT Programs 
Already Offering PT
    We believe that the availability of these PT samples for a 
particular analyte is an appropriate criterion for narrowing the list 
of eligible analytes and that scaling up a program would be relatively 
less difficult than creating a PT sample for a particular analyte that 
had not previously been offered. For the reasons noted below, we 
believe that at least three PT programs offering PT samples for a 
particular analyte under consideration would provide a sufficient 
number of programs to offer immediate access to PT by laboratories and 
a reasonable starting point for the analytes under consideration. CMS 
and CDC want to ensure that the laboratories could choose the best PT 
program for the services that their laboratories offered as well as not 
create a market advantage for a small number of PT programs. To 
evaluate the current availability of PT materials and PT programs 
offering PT samples for a particular analyte, we analyzed the 
distribution of available PT programs for analytes for which PT is 
currently not required by subpart I of the CLIA regulations. The 
supporting data were collected from available sources, including data 
from PT program catalogs, and data routinely reported by PT programs, 
including enrollment data. We examined the number of PT programs 
offering these analytes at any number of events per year and any number 
of challenges per event. We initially determined the number of analytes 
under consideration for which PT was offered by at least two, three, or 
four of the eleven existing PT programs. We determined that limiting 
the

[[Page 1541]]

analytes under consideration to those for which PT was offered by at 
least three PT programs allowed a sufficient number of programs to 
offer immediate access to PT by laboratories and provided a reasonable 
starting point of 199 for the number of analytes under consideration 
(96 in routine chemistry, 27 in endocrinology, 28 in toxicology, 25 in 
general immunology, 21 in hematology, two for antibody identification). 
Expected impact on laboratories and PT programs was also taken into 
account (for example, minimizing the cost of purchasing and providing 
samples) when determining the minimum number of PT programs. Decreasing 
the minimum PT programs to two rather than three would increase the 
number of analytes under consideration to 303, but presumably decrease 
PT program availability and access for a given analyte. Conversely, 
increasing the minimum number of PT programs to four, while presumably 
increasing PT program availability and access for a given analyte, 
decreased the number of analytes under consideration to 164. This was 
the first cut, based upon available PT modules.
b. Volume of Patient Testing Being Performed Nationwide
    For the second cut, we prioritized the remaining 199 analytes under 
consideration based upon estimated national testing volumes. We decided 
that an estimated national test volume of 500,000 per analyte annually 
was an appropriate threshold as it was based upon testing volumes of 
the majority (68 out of 81) of analytes currently listed in subpart I. 
For comparison, of the analytes that are currently required under 
subpart I, 63 had a total national test volume above 1,000,000; five 
had national test volumes between 500,000 and 1,000,000; and 13 had 
national test volumes below 500,000. We used 500,000 annual tests as a 
preliminary cut-off for retention on the list of analytes under 
consideration. We also retained analytes that were below the 500,000 
threshold that we determined to be clinically important based on 
literature already footnoted in section II.B.2.b. of this proposed rule 
and consultation with CDC health experts. The following analytes with 
test volumes less than 500,000 that were retained are: Carbamazepine, 
alpha-1-antitrypsin, phenobarbital, hepatitis Be antigen, antibody 
identification, theophylline, gentamicin, and tobramycin.
    In estimating national testing volumes to rank the remaining 199 
analytes under consideration in this proposed rule, we were unable to 
identify a single source of available data for all patient testing 
being performed nationwide. We had complete data for Medicare 
reimbursements, as well as the most current MarketScan Commercial 
Claims and Encounters (CCAE) and MarketScan Medicaid Multi-state data 
sets (2009 Truven Health MarketScan[supreg] data, https://truvenhealth.com/your-healthcare-focus/life-sciences/data_databases_and_online_toolsMarkets/Life-Sciences/Products/Data-Tools/MarketScan-Databases) and extrapolated accordingly. We used data 
provided by an HHS-approved accreditation organization, specifically a 
list of the number of their accredited laboratories offering each tests 
we considered for addition to, or deletion from, subpart I in order to 
determine how many laboratories were performing testing for the 
proposed analytes. We also considered smaller representative data sets, 
including data sets obtained from a large healthcare network, a large 
reference laboratory, and a university hospital network in order to 
evaluate the trends in performing testing for the proposed analytes. We 
analyzed national trends in testing based upon Medicare Part B 
reimbursement data (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698806/) to determine the analytes in each specialty that are 
increasingly used for patient diagnosis and/or management. We concluded 
that the trends revealed in the data could continue to show increases 
in reimbursement for the proposed analytes.
    We estimated the 2009 national test volumes based upon two data 
sets: (1) Medicare Part B reimbursement statistics (excluding waived 
testing); and (2) CCAE. For all analytes under consideration for the 
addition to subpart I, we used Current Procedural Terminology (CPT) 
codes from claims data. We identified all possible occurrences of a 
particular analyte and combined them into one count. For example, if 
bicarbonate could be performed in a panel and by itself, we included 
all possible occurrences.
    A complete count was available for the Medicare Part B data, and 
for this sector no estimation of total counts was necessary. MarketScan 
data, which is a sample of approximately 40 million covered 
individuals, was necessary to estimate CCAE data and approximately 6.5 
million covered individuals for Medicaid data. Therefore, we estimated 
the total number of tests in both of these categories for the entire 
United States. The Agency for Healthcare Research and Quality (AHRQ) 
\3\ data showed that an estimated total of 181.5 million covered 
individuals enrolled in CCAE healthcare insurance; from this we derived 
a factor of 4.5 (181.5 million individuals/40 million individuals) by 
which to multiply the MarketScan CCAE estimates to extrapolate 
estimates for the entire U.S. Similarly, for the Medicaid estimates, we 
knew from CMS data that there were approximately 52.5 million 
individuals covered by Medicaid, so we derived a factor of 8.0 (52.5 
million individuals/6.5 million individuals) by which to multiply the 
MarketScan Medicaid estimates to extrapolate estimates for the entire 
United States.
---------------------------------------------------------------------------

    \3\ https://meps.ahrq.gov/mepstrends/hc_ins/.
---------------------------------------------------------------------------

    We note that these estimates did not account for some inpatient 
testing that was paid through capitation arrangements for inpatient 
testing. Testing paid directly by patients was also not counted 
because, in these cases, CPT codes would not be captured in the data 
because there was no request for reimbursement. Even with this 
limitation, we believe that these estimates provide a relative sense of 
the numbers of tests being performed annually per analyte. No other 
accurate data were available to us.
    As noted above, for the second cut, based upon our estimates of 
national testing volumes, we decided that an estimated national test 
volume of 500,000 per analyte annually was an appropriate threshold as 
most of the analytes listed in subpart I had national testing volumes 
above this threshold. Together with the above-described analytes that 
were below the 500,000 threshold that we determined to be clinically 
important, this narrowed our list of potential analytes under 
consideration for addition to subpart I to 73, representing analytes in 
five specialties or subspecialties
c. Impact on Patient and/or Public Health
    For the third cut, we considered the evidence available as to 
patient and public impact for each analyte. There was no standardized, 
generally accepted way available to us to assess the relative impact of 
testing for particular analytes on clinical care and public health. 
Therefore, we used the following parameters to get a relative sense of 
the importance of the analytes under consideration: A review of 
published laboratory practice guidelines (LPGs); a review of critical 
values; and a review of the analyte's classification by the Food and 
Drug Administration (FDA) (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfClia/Search.cfm). We accessed several data sources, including 
tests listed in the CDC Guide to Community Preventive Services

[[Page 1542]]

(https://www.thecommunityguide.org); National Healthcare Priorities/
Disparities reports (https://www.ahrq.gov/research/findings/nhqrdr/index.html); clinical practice guidelines including the National 
Guideline Clearinghouse (NGC) database available from AHRQ (https://www.guideline.gov/); \4\ critical values available in publications; \5\ 
and (CAP) Q-Probes.\6\
---------------------------------------------------------------------------

    \4\ AHRQ's National Guideline Clearinghouse website accessed for 
this proposed rule, however, no longer exists on the internet 
effective July 16, 2018.
    \5\ Burtis, C. A., Ashwood, E. R., & Bruns, D. E. (2012). Tietz 
Textbook of Clinical Chemistry and Molecular Diagnostics. London: 
Elsevier Health Sciences.
    \6\ Laboratory critical values policies and procedures: a 
college of American Pathologists Q-Probes Study in 623 institutions. 
Howanitz PJ, Steindel SJ, Heard NV. Arch Pathol Lab Med. 2002 
Jun;126(6):663-9.
---------------------------------------------------------------------------

    In order to assess patient and public impact for each analyte, we 
considered the evidence available related to each analyte under 
consideration. To do so, our first parameter was a review of published 
LPGs. We hypothesized that if there was a relatively large number of 
LPGs available for a particular analyte, that analyte would be 
important for health testing. To estimate the number of LPGs, we used 
the AHRQ's NGC database. For example, there were 60 LPGs listed in the 
NGC for LDL cholesterol, 31 for hemoglobin A1c, and 27 for troponin, 
all of which are proposed for addition in Table 1. However, this 
approach did not differentiate analytes for which there were 
conflicting recommendations. For example, there are controversies about 
the value of screening men with prostate specific antigen (PSA) 
testing, and there is an ongoing debate about the prudence of testing 
vitamin D in asymptomatic adults (Kopes-Kerr, 2013).7 8 9
---------------------------------------------------------------------------

    \7\ Barry, Micheael J. Screening for Prostate Cancer--The 
Controversy That Refuses to Die. New England Journal of Medicine 
360;13 (March 2009).
    \8\ Eck, Leigh M. Should family physicians screen for vitamin D 
deficiency? yes: targeted screening in at-risk populations is 
prudent. American Family Physician 87, 8 (2013), pp. 541b.Fr.
    \9\ Kopes-Kerr, Colin. Should family physicians screen for 
vitamin D deficiency? no: screening is unnecessary, and routine 
supplementation makes more sense. American Family Physician 87, 8 
(2013), pp. 540b.
---------------------------------------------------------------------------

    Our second parameter was a review of critical values. Critical 
values are pre-determined limits for specific analytes that when 
exceeded may suggest that immediate clinical intervention is required. 
We assessed analytes included on ``critical values'' lists to determine 
the analyte's relative importance in helping clinicians to make rapid 
life-altering decisions. This approach allowed us to gauge how 
important an accurate result could be because an incorrect result could 
lead to a life-threatening intervention or a failure to intervene. We 
reviewed published literature \10\ and critical values posted online 
from 16 institutions including small hospitals, university hospitals, 
and reference laboratories.\11\
---------------------------------------------------------------------------

    \10\ Wagar, Friedberg, Souers, and Stankovic, 2007, https://www.ncbi.nlm.nih.gov/pubmed/18081434.
    \11\ www.mayomedicallaboratories.com/test-catalog/appendix/criticalvalues/index.html.
---------------------------------------------------------------------------

    Our final parameter for assessing the clinical impact of an analyte 
was reviewing its medical device classification (Class I, II, or III) 
as categorized by the Food and Drug Administration's risk 
classification list. In a similar way, we assessed the public health 
importance of the eligible analytes by counting the number of 
recommendations for testing the analytes from CDC's Morbidity and 
Mortality Weekly Report, the Infectious Disease Society of America, and 
the Council of State and Territorial Epidemiologists for surveillance 
of health conditions related to the particular analyte under 
consideration. We found supporting evidence for national prioritization 
in some of the following: the U.S. Preventive Services Task Force 
(https://www.uspreventiveservicestaskforce.org/Page/Name/recommendations), the National Healthcare Quality and Disparities 
Report (https://www.ahrq.gov/research/findings/nhqrdr/index.html), the 
CDC Hormone Standardization Program (https://www.cdc.gov/labstandards/hs.html). For some analytes that have important public health impact, 
such as blood lead, we consulted with subject matter experts in the CDC 
National Center for Environmental Health, which promotes national 
testing and/or has standardization programs for some priority analytes, 
specifically estradiol and testosterone. CMS and CDC used this 
information to help determine which analytes should be included in this 
proposed rule.
    Therefore, we used those parameters in an attempt to get a relative 
sense of the patient and public health impact of the analytes under 
consideration, but, using the data available to us, we found no 
standardized, generally accepted way to assess the relative impact of 
testing for particular analytes on clinical care and public health. 
After assessing patient and public health impact on a case-by-case 
basis for the third cut, we narrowed the analytes down to 34 for 
consideration of addition to the proposed list of analytes in subpart 
I.
d. Cost and Feasibility of Implementation
    For the final analysis to determine whether an analyte would be 
proposed for inclusion in subpart I of the CLIA regulations, we focused 
upon feasibility and costs of conducting PT for each of the remaining 
34 analytes under consideration. We provided each of the HHS-approved 
PT programs the opportunity to submit comments in writing related to: 
inclusion/deletion of analytes, grading schemes, method(s) for 
determining target values, evaluating data using peer groups, cost of 
including new analytes, and structure of microbiology PT. Analytes for 
which it would be difficult for the PT programs to scale up production 
to meet the CLIA required frequency of three events per year with five 
challenges per event were eliminated from consideration because we 
believe that the costs passed down to laboratories to purchase the PT 
would be overly burdensome. In other cases, the decisions were based on 
the difficulty of finding any suitable PT materials. Some potential 
analytes were eliminated because they were too unstable for product 
development or shipping or because the testing methodology was not 
sufficiently standardized to support PT, such as vitamin D testing. 
After assessing cost and feasibility of implementing PT on a case-by-
case basis, we made the final cut, narrowing the analytes down to 29 
potential analytes for the proposed list of analytes in subpart I.
3. Specific Analytes Proposed for Addition to Subpart I
    Based upon the sequential process described above, information 
received from the PT programs and consultation between CDC and CMS, we 
narrowed the list down to 29 analytes that we are proposing to add to 
subpart I of the CLIA regulations (Table 1).

          Table 1--Analytes Proposed for Addition to Subpart I
------------------------------------------------------------------------
            CLIA  Regulation                         Analytes
------------------------------------------------------------------------
General Immunology, Sec.   493.927.....  Anti-HBs, Anti-HCV, C-reactive
                                          protein (high sensitivity).

[[Page 1543]]

 
Routine Chemistry, Sec.   493.931......  B-natriuretic peptide (BNP),
                                          ProBNP, Cancer antigen (CA)
                                          125, Carbon dioxide,
                                          Carcinoembryonic antigen,
                                          Cholesterol, low density
                                          lipoprotein, Ferritin, Gamma
                                          glutamyl transferase,
                                          Hemoglobin A1c, Phosphorus,
                                          Prostate specific antigen,
                                          total, Total iron binding
                                          capacity, Troponin I, Troponin
                                          T.
Endocrinology, Sec.   493.933..........  Estradiol, Folate, serum,
                                          Follicle stimulating hormone,
                                          Luteinizing hormone,
                                          Progesterone, Prolactin,
                                          Parathyroid hormone,
                                          Testosterone, Vitamin B12.
Toxicology, Sec.   493.937.............  Acetaminophen, serum,
                                          Salicylate, Vancomycin.
------------------------------------------------------------------------

4. Analytes Proposed for Removal From Subpart I
    Recognizing that changes in the practice of clinical medicine have 
resulted in less frequent use of certain analytes, we used the same 
process to review the existing list of analytes in subpart I to 
determine which should be retained. In addition to requesting CLIAC's 
recommendations, we generally used the same criteria for retention of 
an analyte in subpart I as those used for determining which PT analytes 
to propose adding, however, as such PT testing was already available on 
the market, we did not consider the availability of PT material or the 
feasibility of implementation; therefore, we believe that PT programs 
already have the mechanism(s) in place to manufacture and ship PT for 
these analytes.
5. Process for Ranking and Assessing Existing Analytes and Proposals 
for Removal From Subpart I
a. Estimating Nationwide Testing Volume
    We generally used the same rationale to select currently required 
analytes to propose for deletion. Specifically, we used the same 
threshold of 500,000 tests performed annually as an initial criterion 
for considering PT analytes. Those estimated to be lower than this 
threshold were considered for deletion from required PT. In particular, 
we focused on PT for several of the therapeutic drugs (ethosuximide, 
quinidine, primidone, and procainamide and its metabolite, N-acetyl 
procainamide). New drugs that are more effective or safer have entered 
the market since 1992, and may have replaced use of the therapeutic 
drugs that were included in the 1992 regulations. If so, we would 
expect to see a continued decline in the volume of testing for the use 
of such drugs. In addition to identifying decreases in testing for 
these drugs, we looked for probable causes of those decreases. These 
decreases in testing could be a result of new and emerging tests, 
including methodologies, replacing older tests, new technology, and 
changes to the way that the medical community orders laboratory 
testing. For example, the decrease in testing for LDH isoenzymes could 
be explained by the increased reliance on better alternative cardiac 
markers, especially troponin.\12\ For some of the anticonvulsant drugs, 
there may have been changes in medical practice, including alternative 
drugs and other treatments, possibly decreasing the need to measure 
them.\13\ We identified 13 currently required analytes with national 
test volumes that were less than our 500,000 annual test volume 
threshold.
---------------------------------------------------------------------------

    \12\ Shahangian, Alspach, Astles, Yesupriya, and Dettwyler, 
2014, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698806/.
    \13\ Krumholz, et al, 2015) (NICE, 2012, https://www.nice.org.uk/guidance/cg137).
---------------------------------------------------------------------------

b. Estimated Impact on Patient and Public Health
    For any analyte still under consideration for removal, we performed 
literature reviews to determine if testing for alternative analytes or 
other diagnostic strategies had begun to supplant testing for the 
considered analyte. We took into account testing trends over the past 
10 years \14\ and we attempted to project expected testing trends. We 
then assessed the critical importance of candidates for deletion from 
subpart I based upon the number of guidelines available in the AHRQ NGC 
and the same sources used for considering inclusion in subpart I, 
bearing in mind that for all analytes and tests that are not listed in 
subpart I, laboratories must demonstrate accuracy twice per year as 
specified at Sec.  493.1236(c)(1). We also considered the potential 
impact on clinical medicine and public health of deleting these 
analytes. Based on our literature review and consultation with CDC 
health experts, we decided not to propose the elimination of eight 
analytes based upon their critical importance for patient testing: 
carbamazepine, alpha-1-antitrypsin, phenobarbital, hepatitis Be antigen 
(HBeAg), antibody identification, theophylline, gentamicin and 
tobramycin. These are used for making important health decisions, for 
example, diagnosing hepatitis B (HBeAg), performing crossmatching for 
blood transfusions (antibody identification), or assessing compliance 
with medication for critically ill asthmatic patients (theophylline).
---------------------------------------------------------------------------

    \14\ Shahangian, Alspach, Astles, Yesupriya, and Dettwyler, 2014 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698806/.
---------------------------------------------------------------------------

6. Analytes Proposed for Deletion From Subpart I
    Based upon the sequential process described above, we propose that 
the following analytes be deleted from subpart I: At Sec.  493.931 LDH 
isoenzymes and at Sec.  493.937 ethosuximide, quinidine, primidone, and 
procainamide (and its metabolite, N-acetyl procainamide).
7. Determining Criteria for Acceptable Performance
    ``Criteria for Acceptable Performance'', as that term is used in 
Sec. Sec.  493.923, 493.927, 493.931, 493.933, 493.937, 493.941, and 
493.959, is defined by the target value and acceptance limits. Criteria 
for acceptable performance is meant for PT scoring only and not 
intended to be used to set acceptability criteria for a laboratory's 
verification or establishment of performance specifications.
8. Setting Target Values
    Under Sec.  493.2, ``target value'' for quantitative tests are 
currently generally defined as either the mean of all participant 
responses after removal of outliers (those responses greater than 3 
standard deviations from the original mean) or the mean established by 
definitive or reference methods acceptable for use in the National 
Reference System for the Clinical Laboratory (NRSCL) by the National 
Committee for the Clinical Laboratory Standards (NCCLS). However, in 
instances where definitive or reference methods are not available or a 
specific method's results demonstrate bias that is not observed with 
actual patient specimens, as determined by a defensible scientific 
protocol, a comparative method or a method group (``peer'' group) may 
be used. If the method group is less than 10 participants ``target 
value'' means the overall mean after outlier removal (as defined above) 
unless acceptable scientific reasons are available to indicate that 
such an evaluation is not appropriate.
    We recognize, based on input from PT programs, that peer grouping 
is generally the way that target values are

[[Page 1544]]

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

    \15\ Thompson, Michael. Variation of precision with 
concentration in an analytical system. Analyst, 113, (1988), pp. 
1579-1587.
---------------------------------------------------------------------------

    Therefore, we are proposing to amend certain analytes in Sec. Sec.  
493.927, 493.931, 493.933, 493.937, 493.941 and 493.959

[[Page 1545]]

to include percentage-based ALs with or without additional fixed ALs.
c. Establishing ALs Based on Analytical Accuracy Goals for Proposed New 
and Several Current Analytes
    For the newly proposed analytes and several current analytes for 
which current ALs are in units other than percentages such as three SDs 
or concentration units, we are proposing to change the ALs to 
percentages. Over the years, there have been many proposed criteria for 
establishing goals for analytical performance.16 17 The 
various possible approaches were reviewed and a hierarchy was 
established based upon a 1999 consensus conference.\18\ These 
strategies were reconsidered in the 2014 European Federation of 
Clinical Chemistry and Laboratory Medicine Strategic Conference in 
Milan. Participants in both conferences acknowledged that the ability 
of a test method to meet clinical needs is the highest priority and the 
most defensible approach would be clinical trials in which patient 
outcomes could be compared using different analytical accuracy goals. 
This approach was not feasible for many reasons. Although clinical 
outcomes studies would be the most rigorous basis for establishing 
analytical performance goals, these are seldom possible, leaving the 
natural dispersion of levels for each analyte (biological variability) 
as the next best scientifically defensible approach for establishing 
analytical accuracy goals.\19\ The less the biological variability, the 
more stringent the analytical accuracy needs to be. This approach makes 
sense for two of the most important reasons to conduct patient testing: 
Diagnosis of disease, that is, differentiating an abnormal result from 
a normal one, and monitoring a patient's progress during treatment. In 
the former case, we believe that the ``within-group'' biological 
variability is the important limiting factor defining an appropriate 
error goal for a test method. Furthermore, for monitoring progress, we 
believe the most important factor is the ``within individual'' 
variability. It was not possible for us to differentiate how analytes 
are being used or will be used clinically, with respect to diagnosis 
versus monitoring. Therefore, we accounted for both needs and used an 
approach that accounted for both kinds of biological variability to 
estimate analytical accuracy goals as the basis for our proposals for 
acceptance limits in percentages.\20\ The advantage of using analytical 
accuracy goals that are expressed in terms of percentages is that they 
can be directly related to ALs in a mathematical way expressed as 
percentages.
---------------------------------------------------------------------------

    \16\ Tonks, David B. A study of the accuracy and precision of 
clinical chemistry determinations in 170 Canadian laboratories. 
Clinical Chemistry 9, 2 (1963), pp. 217-233.
    \17\ Cotlove, Ernest, Eugene K. Harris, and George Z. Williams. 
Biological and analytic components of variation in long-term studies 
of serum constituents in normal subjects. Clinical Chemistry 16, 12 
(1970), pp. 1028-1032.
    \18\ Fraser, Callum. The 1999 Stockholm consensus conference on 
quality specifications in laboratory medicine. Clinical Chemistry 
and Laboratory Medicine 53, 6 (2015), pp. 837-840.
    \19\ Burtis, Carl A., Edward R. Ashwood, David E. Bruns, Ed. 
Tietz textbook of clinical chemistry and molecular diagnostics. 
(Chapter 2 Selection and analytical evaluation of methods with 
statistical techniques, pp. 17), Elsevier Saunders, Philadelphia, 
P.A., (2012).
    \20\ Burtis, Carl A., Edward R. Ashwood, David E. Bruns, Ed. 
Tietz textbook of clinical chemistry and molecular diagnostics. 
(Chapter 17 Preanalytic variables and biological variation, pp. 470-
471), Elsevier Saunders, Philadelphia, P.A., (2006).
---------------------------------------------------------------------------

    We have assumed that a laboratory that can meet the clinical needs 
for test accuracy based upon biological variability should perform 
successfully on PT most or all of the time. Therefore, whenever 
possible, we have used publically available estimates of allowed total 
error based upon estimates of biological variability \21\ to 
approximate the proposed AL. CDC has shown in an a recent poster \22\ 
that it is possible to design ALs based upon such accuracy goals, and 
it is possible to simulate the ability of a PT program to identify 
laboratories that cannot meet such goals, while minimizing the 
likelihood of misidentifying laboratories that are meeting analytical 
accuracy goals based upon biological variability.
---------------------------------------------------------------------------

    \21\ https://www.westgard.com/biodatabase1.htm.
    \22\ Astles, Tholen, and Mitchell, 2016, https://www.aacc.org/science-and-practice/annual-meeting-abstracts-archive.
---------------------------------------------------------------------------

    Therefore, we are proposing to amend ALs for certain current 
analytes as well as establish ALs for analytes proposed for addition in 
Sec. Sec.  493.927, 493.931, 493.933, 493.937, 493.941 and 493.959 
based on analytical accuracy goals.
d. Tightening Existing Percentage ALs as Needed
    There have been significant improvements in laboratories' 
performance in PT for the great majority of analytes \23\ and PT 
unsatisfactory rates have dropped for all types of laboratories. The 
improvements are such that, for many analytes, laboratories that began 
to use PT to comply with CLIA'88 now perform as well as the hospital 
and independent laboratories which were previously required to perform 
PT under CLIA'67. Howerton, et al.\24\ showed that for almost all 
analytes examined, PT performance improved somewhat after CLIA'88 was 
implemented, but the improvements were greater for laboratories that 
were not previously required to perform PT. The rates of unsatisfactory 
PT are now roughly the same for analytes listed in subpart I, 
regardless of the laboratory type, and this is consistent with CLIA's 
intent to ensure accurate clinical testing regardless of the setting 
where testing is performed. There are several factors contributing to 
the improvements in PT performance, including improved analytical 
methods being used in all settings; technological advances resulting in 
improved precision, sensitivity and specificity; and increased 
familiarity with handling preparation, and reporting of PT samples. 
Therefore, for the reasons above as well as supporting simulation data 
date from the PT programs, we are proposing to make criteria for 
acceptable performance for existing analytes listed in subpart I 
tighter so they are in closer agreement with analytical accuracy goals 
which are based upon biological variability and simulation data.
---------------------------------------------------------------------------

    \23\ Howerton, Krolak, Manasterski, and Handsfield, 2010.
    \24\ Howerton D1, Krolak JM, Manasterski A, Handsfield JH. Arch 
Pathol Lab Med. 2010 May;134(5):751-8. Proficiency testing 
performance in US laboratories: results reported to the Centers for 
Medicare & Medicaid Services, 1994 through 2006.
---------------------------------------------------------------------------

    Therefore, based on the simulation data, we are proposing to 
tighten ALs for certain current analytes in Sec. Sec.  493.927, 
493.931, 493.933, 493.937, 493.941 and 493.959.
e. Simulating the Impact of New ALs on Unacceptable Scores for 
Challenges and Unsatisfactory Rates for Events
    We evaluated a very specific PT data set to help CMS and CDC set 
appropriate limits. The total simulations reproduced PT that covered 2 
years, representing 30 challenges (three events per year; five 
challenges per event; 2 years) of each proposed new analyte and for the 
analytes for which we propose to modify ALs. We reviewed the aggregated 
percentage of unacceptable scores for each PT challenge using 
retrospective data. We then reviewed the simulation data which applied 
two or three new ALs for each of 84 analytes (consisting of 27 new 
analytes and 57 existing analytes). Based on the simulation data, we 
were able to make informed decisions to help us create or adjust the 
ALs.
    Based upon our analysis of the simulation results, we further 
refined the proposed ALs and added potential

[[Page 1546]]

absolute concentrations in lieu of percentage ALs, as was described 
previously. We then requested narrowly tailored data from PT programs 
as described above using retrospective PT data and peer group data for 
scoring, as they ordinarily would do. We focused on unsatisfactory 
scores with the data so that we could calculate the unsatisfactory rate 
per analyte among all participating laboratories that might occur with 
each proposed AL. The final simulations were conducted by several of 
the PT programs and this set of data was used to determine the ALs 
proposed in this rule.
    We compared the unacceptable scores for each challenge and each 
proposed AL to determine at which concentrations it would be necessary 
to switch to a fixed concentration AL. Using this approach, we were 
able to identify an AL for each analyte and, in some cases, an 
additional concentration-based AL. This approach enabled us to identify 
an AL that would be sensitive enough to identify poor performing 
laboratories, yet not so sensitive that it will incorrectly identify 
laboratories that are likely meeting requirements for accuracy.
f. Limitation in Our Ability To Predict the Number of New 
Unsatisfactory and Unsuccessful Scores
    It is not possible for us to predict the precise effect of the 
proposed changes on the number of unsatisfactory and unsuccessful 
scores. The occurrence of an unsatisfactory score for a PT event 
depends upon at least two of five challenges being graded as 
unacceptable or outside the criteria for acceptable for performance. PT 
programs select different combinations of samples for each event and it 
is impossible to predict how their selection could be modelled 
statistically. Finally, the distribution of unsatisfactory and 
unsuccessful PT scores is not randomly distributed across all 
participants.

C. Additional Proposed Changes

    We are proposing to amend Sec.  493.2 to modify the definition of 
an existing term and define new terms as follows:
     Target value: We are removing the reference to NRSCL and 
NCCLS and retaining the other options for setting target values are 
retained in this proposed rule.
     Acceptance Limit: We are proposing to define this term to 
mean the symmetrical tolerance (plus and minus) around the target 
value.
     Unacceptable score: We are proposing to define this term 
to mean PT results that are outside the criteria for acceptable 
performance for a single challenge or sample.
     Peer group: We are proposing to define this term as a 
group of laboratories whose testing process utilizes similar 
instruments, methodologies, and/or reagent systems and is not to be 
assigned using the reagent lot number. PT programs should assign peer 
groups based on their own policies and procedures and not based on 
direction from any manufacturer.
    We are also proposing the following revisions to the regulation 
text at subpart A:
     Sections 493.20 and 493.25: We are proposing to amend the 
regulations to reflect that if moderate and high complexity 
laboratories also perform waived tests, compliance with Sec.  
493.801(a) and (b)(7) are not applicable. However, we propose to 
continue to require compliance with Sec.  493.801(b)(1) through (6) to 
align the regulations with the CLIA statute (42 U.S.C. 263a(i)(4)), 
which does not exclude waived tests from the ban on improper PT 
referral.
    We are also proposing the following revision to the regulation text 
at subpart H:
     Section 493.861: We are amending the satisfactory 
performance criteria for failure to attain an overall testing event 
score for unexpected antibody detection from ``at least 80 percent'' to 
``100 percent.'' We are proposing this change because it is critical 
for laboratories to identify any unexpected antibody when crossmatching 
blood to protect the public health and not impact patient care.
    We are also proposing the following revisions to the regulation 
text at subpart I:
     Section 493.901(a): We are proposing to require that each 
HHS-approved PT program have a minimum of ten laboratory participants 
before offering any PT analyte. We recognize that PT programs do not 
grade results when there are fewer than ten laboratory participants. 
This would require the laboratory to perform additional steps to verify 
the accuracy of their results. If at any time a PT program does not 
meet the minimum requirement of 10 participating laboratories for an 
analyte or module, HHS may withdraw approval for that analyte, 
specialty or subspecialty. This change reduces some burden on 
laboratories that have incurred the expense of enrolling in a PT 
program but do not receive a score or receive an artificial score 
requiring the laboratory to take additional steps to verify the 
accuracy of the analyte as required by Sec.  493.1236(b)(2).
     Section 493.901(c)(6): We are proposing to add the 
requirement that PT programs limit the participants' online submission 
of PT data to one submission or that a method be provided to track 
changes made to electronically reported results. Many PT programs 
currently allow laboratories an option to report PT results 
electronically while some other PT programs allow laboratories to only 
report PT results electronically with no other reporting option such as 
facsimile or mailed PT submission forms. However, at this time, the PT 
programs who do participate in the online reporting have no mechanism 
to review an audit trail for the submitted result. In some cases of PT 
referral, it has been discovered that laboratories have sent PT samples 
to another CLIA certified laboratory for testing, received results from 
the other laboratory, and then changed their online reported results to 
the PT program since those results can be modified up until the PT 
event close date. In an effort to assist in PT referral investigations 
and determinations, an audit trail that includes all instances of 
reported results would aid in determining if a laboratory compared PT 
results obtained from another laboratory and changed their previously 
submitted results.
     Section 493.901(c)(8): We are proposing to add to the 
requirement previously found at Sec.  493.901 that contractors 
performing administrative responsibilities as described in Sec. Sec.  
493.901 and 493.903 must be a private nonprofit organization or a 
federal or state agency or nonprofit entity acting as a designated 
agent for the federal or state agency. Several PT programs have divided 
their administrative and technical responsibilities into separate 
entities or have had the administrative responsibilities performed by a 
contractor. We were made aware that administrative responsibilities 
were being performed by a for-profit entity. Because the CLIA statute 
(42 U.S.C. 263a(f)(3)(C)) requires PT programs to be administered by a 
private nonprofit organization or a state, we are proposing to amend 
Sec.  493.901 to state that all functions and activities related to 
administering the PT program must be performed by a private nonprofit 
organization or state.
     Section 493.901(e): We are proposing to add the 
requirement that HHS may perform on-site visits for all initial PT 
program applications for HHS approval and periodically for previously 
HHS-approved PT programs either during the reapproval process or as 
necessary to review and verify the

[[Page 1547]]

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

[[Page 1548]]

INR (international normalized ratio), so we are proposing to amend the 
criteria for acceptable performance to reflect both units of reporting 
and proposing to add the requirement that laboratories must report 
prothrombin time for PT the same way they report it for patient 
results; if patient results are reported in seconds or as INR results, 
they should report the same way to PT programs. If the laboratory 
reports patient results both in seconds and as INR, they should be 
reported the same way to the PT programs. We are also proposing to add 
criteria for acceptable performance for directly measured INR for 
prothrombin time. In addition, we propose to require laboratories that 
perform both cell counts and differentials to conduct PT for both (that 
is, the ``or'' would be changed to an ``and''). Finally, we are 
proposing to change the criteria for acceptable performance for ``cell 
identification'' from 90 percent to 80 percent. We are proposing this 
change as the requirement of five samples per event does not allow for 
a score of 90 percent (that is, five samples would allow for scores of 
0 percent, 20 percent, 40 percent, 60 percent, 80 percent, or 100 
percent). PT for cell identification is currently required in Sec.  
493.941. Further, Sec.  493.851(a) states that ``failure to attain a 
score of at least 80 percent of acceptable responses for each analyte 
in each testing event is unsatisfactory performance for the testing 
event.'' If the requirement for acceptable performance remains at 90 
percent, a laboratory can only have satisfactory performance if they 
receive 100 percent; however, Sec.  493.851(a) allows satisfactory 
performance for both 80 percent and 100 percent.
     Section 493.959: We are proposing to change the criteria 
for acceptable performance for unexpected antibody detection from 80 
percent accuracy to 100 percent accuracy. We are proposing this change 
because it is critical for laboratories to identify any unexpected 
antibody when crossmatching blood in order to protect the public health 
and not impact patient care.

III. Collection of Information Requirements

    Under the Paperwork Reduction Act of 1995 (PRA), we are required to 
publish a 60-day notice in the Federal Register and solicit public 
comment before a collection of information requirement is submitted to 
the Office of Management and Budget (OMB) for review and approval.
    To fairly evaluate whether an information collection should be 
approved by OMB, PRA section 3506(c)(2)(A) of the PRA requires that we 
solicit comment on the following issues:
     The need for the information collection and its usefulness 
in carrying out the proper functions of our agency.
     The accuracy of our burden estimates.
     The quality, utility, and clarity of the information to be 
collected.
     Our effort to minimize the information collection burden 
on the affected public, including the use of automated collection 
techniques.
    We are soliciting public comment on each of the section 
3506(c)(2)(A)-required issues for the following information collection 
requirements (ICRs).
    The requirements and burden will be submitted to OMB under (OMB 
control number 0938-New).

A. Clarification for Reporting of Microbiology Organism Identification

    We are proposing to clarify a requirement at Sec. Sec.  493.801(b), 
493.911(b), 493.913(b), 493.915(b), 493.917(b), and 493.919(b), to 
emphasize the point that, as currently required, laboratories must 
report PT results for microbiology organism identification to the 
highest level that they report results on patient specimens. In 
accordance with the implementing regulations of the PRA at 5 CFR 
1320.3(b)(2), we believe the reporting of microbiology organism 
identification is a usual and customary practice when reporting PT 
results to PT programs. We are able to determine how many laboratories 
provide services in microbiology; however, we are unable to determine 
if the laboratories are enrolled in the appropriate PT outside of the 
survey process, or if the microbiology PT samples for which the 
laboratory is enrolled are required under subpart I. There are no data 
systems that capture this information. We estimate the number of 
laboratories that are not currently reporting microbiology organisms to 
the highest level that they report results on patient specimens to be 
about 10 percent of 36,777 laboratories which is 368 laboratories. We 
estimate it would take 20 minutes for a laboratory to fill this 
information on the PT submission form. Each laboratory would report 
this information 3 times a year which would take approximately 1 hour. 
The total annual burden is 368 hours (368 laboratories x 1 hour). A 
Clinical Laboratory Technologists/Technicians would perform this task 
at an hourly wage of $25.59 as published in 2017 by the Bureau of Labor 
Statistics (https://www.bls.gov/oes/current/oes_nat.htm). The wage rate 
would be $51.18 to include overhead and fringe benefits. The total cost 
would be $18,834 (368 hours x $51.18).

B. Submission of PT Data by Laboratories

    At Sec.  493.901(c)(6), we are proposing to add the requirement 
that PT programs limit the participants' online submission of PT data 
to one submission or that a method be provided to track changes made to 
electronically reported results. In an effort to assist in PT referral 
investigations and determinations, an audit trail that includes all 
instances of reported results would aid in determining if a laboratory 
compared PT results obtained from another laboratory and changed their 
previously submitted results. In accordance with the implementing 
regulations of the PRA at 5 CFR 1320.3(b)(2), we believe the ability 
for the PT programs to track this data already exists in their 
software; however, they may need to make minor modifications to their 
software in order to meet this requirement. If a PT program would need 
to update their software, we would estimate that the cost would be 15 
hours for software modification. The total burden is 135 hours (9 PT 
programs x 15 hours). However, this would not be an annual burden, 
rather it would only occur once when the requirement is implemented. A 
Software Developer, System Software would perform this task at an 
hourly wage of $107.48 as published in 2017 by the Bureau of Labor 
Statistics (https://www.bls.gov/oes/current/oes_nat.htm). The wage rate 
would be $107.48 to include overhead and fringe benefits. The total 
high estimated cost would be $14,510 (135 hours x $107.48). For those 
PT programs who already have this mechanism in place, there would be no 
additional burden or cost to meet this requirement.

C. Optional On-Site Visits to PT Programs

    At Sec.  493.901(e), we propose to add the requirement that HHS may 
require on-site visits for all initial PT program applications for HHS 
approval and periodically for previously HHS-approved PT programs 
either during the reapproval process or as necessary to review and 
verify the policies and procedures represented in its application and 
other information, including, but not limited to, review and 
examination of documents and interviews of staff. There is no 
collection of information requirements associated with this proposed 
requirement because the documentation is already being collected and 
maintained by the PT program as

[[Page 1549]]

normal course of business and is a usual and customary practice in 
accordance with implementing regulations at 42 CFR 493, subpart I.

D. PT Program Reapproval

    At Sec.  493.901(f), we propose to specify that we may require a PT 
program to reapply for approval using the process for initial 
applications if widespread or systemic problems are encountered during 
the reapproval process. If a PT program would need to reapply for 
approval using the initial application process, we would estimate that 
the cost would be 10 hours for document collection. The total burden is 
90 hours (9 PT programs x 10 hour). However, this would not be an 
annual burden, rather it would only occur under the circumstances 
outlined above, and we believe that these would only occur rarely. An 
Office/Administrative Support Worker would perform this task at an 
hourly wage of $17.96 as published in 2017 by the Bureau of Labor 
Statistics (https://www.bls.gov/oes/current/oes_nat.htm). The wage rate 
would be $35.92 to include overhead and fringe benefits. The total cost 
would be $3,233 (90 hours x $35.92).

E. Withdrawal of Approval of a PT Program

    At Sec.  493.905, we propose to add that HHS may withdraw the 
approval of a PT program at any point in the calendar year if the PT 
program provides false or misleading information that is necessary to 
meet a requirement for program approval or if the PT program has failed 
to correct issues identified by HHS related to PT program requirements. 
We are also proposing to add a requirement that the PT program may 
request reconsideration. We believe this is excepted because of it 
being an administrative action per 5 CFR 1320.4(a)(2).

IV. Response to Comments

    Because of the large number of public comments we normally receive 
on Federal Register documents, we are not able to acknowledge or 
respond to them individually. We will consider all comments we receive 
by the date and time specified in the DATES section of this preamble, 
and, when we proceed with a subsequent document, we will respond to the 
comments in the preamble to that document.

V. Regulatory Impact Analysis

A. Statement of Need

    Proficiency testing (PT) has long been recognized as a critical 
component of a quality management system. It was first required at a 
national level for some clinical laboratories under CLIA'67. When 
CLIA'88 was enacted, and its implementing regulations were finalized in 
1992, all clinical laboratories that perform nonwaived testing became 
subject to the CLIA PT requirements. Since that time, there have been 
many changes in the practice of laboratory medicine and improvements in 
the analytical accuracy of test methods, such that HHS decided to 
assess the need to revise the PT regulations. For example, a number of 
analytes and tests now used for making clinical decisions were not 
recognized or commonly used at the time the CLIA PT requirements were 
published on February 28, 1992 at 42 CFR part 493 (57 FR 7002). 
Improvements in analytical accuracy required revisions to the criteria 
for acceptable performance to reflect the current practices. We based 
our decision to update the regulations and incorporate the changes 
proposed in this rule upon advice from the CLIAC.

B. Overall Impact

    We have examined the impacts of this rule as required by Executive 
Order 12866 on Regulatory Planning and Review (September 30, 1993), 
Executive Order 13563 on Improving Regulation and Regulatory Review 
(January 18, 2011), the Regulatory Flexibility Act (RFA) (September 19, 
1980, Pub. L. 96-354), section 1102(b) of the Social Security Act, 
section 202 of the Unfunded Mandates Reform Act of 1995 (March 22, 
1995; Pub. L. 104-4), Executive Order 13132 on Federalism (August 4, 
1999) and the Congressional Review Act (5 U.S.C. 804(2)), and Executive 
Order 13771 on Reducing Regulation and Controlling Regulatory Costs 
(January 30, 2017).
    Executive Orders 12866 and 13563 direct agencies to assess all 
costs and benefits of available regulatory alternatives and, if 
regulation is necessary, to select regulatory approaches that maximize 
net benefits (including potential economic, environmental, public 
health and safety effects, distributive impacts, and equity). Section 
3(f) of Executive Order 12866 defines a ``significant regulatory 
action'' as an action that is likely to result in a rule: (1) Having an 
annual effect on the economy of $100 million or more in any one year, 
or adversely and materially affecting a sector of the economy, 
productivity, competition, jobs, the environment, public health or 
safety, or state, local or tribal governments or communities (also 
referred to as ``economically significant''); (2) creating a serious 
inconsistency or otherwise interfering with an action taken or planned 
by another agency; (3) materially altering the budgetary impacts of 
entitlement grants, user fees, or loan programs or the rights and 
obligations of recipients thereof; or (4) raising novel legal or policy 
issues arising out of legal mandates, the President's priorities, or 
the principles set forth in the Executive Order. A regulatory impact 
analysis (RIA) is required for economically-significant regulatory 
actions that are likely to impose costs or benefits of $100 million or 
more in any given year.
    This proposed regulation is economically significant within the 
meaning of section 3(f)(1) of the Executive Order since the estimated 
cost alone is likely to exceed the $150 million annual threshold. 
However, our upper limit of estimated impact is under the threshold of 
$150 million for the year of 2018 under Unfunded Mandates Reform Act 
(UMRA). The proposed rule, if finalized, would revise the CLIA PT 
requirements and would affect approximately 36,777 clinical 
laboratories now subject to participation in PT, resulting in some 
financial implications. In addition, this proposed rule, if finalized, 
would cause the seven existing CLIA-approved PT programs to incur some 
costs as they modify their programs to meet the requirements specified 
in this proposed rule. It may also have an effect on some state PT 
requirements. We prepared the RIA and found that it did not meet the 
UMRA threshold for a significant regulatory action.
    The RFA requires agencies to analyze options for regulatory relief 
of small entities if a rule has a significant impact on a substantial 
number of small entities. For purposes of the RFA, we assume that the 
great majority of clinical laboratories and PT programs are small 
entities, either by virtue of being nonprofit organizations or by 
meeting the Small Business Administration definition of a small 
business by having revenues of less than $7.5 million to $38.5 million 
in any one year. For purposes of the RFA, we believe that approximately 
82 percent of clinical laboratories qualify as small entities based on 
their nonprofit status as reported in the American Hospital Association 
Fast Fact Sheet, updated January 2017 (https://www.aha.org/system/files/2018-01/fast-facts-us-hospitals-2017_0.pdf) and 100 percent of PT 
programs are nonprofit organizations. Individuals and states are not 
included in the definition of a small entity. We are voluntarily 
preparing a Regulatory Impact Analysis and are requesting public 
comments in this area to assist us in making this determination in the 
final rule.

[[Page 1550]]

    In addition, section 1102(b) of the Social Security Act (the Act) 
requires us to prepare a regulatory impact analysis if a rule may have 
a significant impact on the operations of a substantial number of small 
rural hospitals. This analysis must conform to the provisions of 
section 603 of the RFA. For purposes of section 1102(b) of the Act, we 
define a small rural hospital as a hospital that is located outside of 
a metropolitan statistical area and has fewer than 100 beds. We do not 
expect this proposed rule, if finalized, would have a significant 
impact on small rural hospitals. Such hospitals often provide very 
limited laboratory services and may refer testing for the analytes we 
propose to add, to larger laboratories. For the small rural hospitals 
that have laboratories and perform testing for the analytes, we expect 
that our proposals will add minimal effort since they should already 
have PT policies and procedures in place. We are unable to estimate the 
number of laboratories that support small rural hospitals. We are 
requesting public comments in this area to assist us in making this 
determination in the final rule.
    Section 202 of the Unfunded Mandates Reform Act of 1995 (UMRA) also 
requires that agencies assess anticipated costs and benefits before 
issuing any rule whose mandates require spending in any one year of 
$100 million in 1995 dollars, updated annually for inflation. In 2018, 
that threshold is approximately $150 million.\25\ We do not anticipate 
this proposed rule would impose an unfunded mandate on states, tribal 
governments, or the private sector of more than $150 million annually. 
We request comments from states, tribal governments, and the private 
sector on this assumption.
---------------------------------------------------------------------------

    \25\ Bush, Laina. HHS Memo on Annual Update to the Unfunded 
Mandate Reform Act Threshold for 2017, March 24, 2017.
---------------------------------------------------------------------------

    Executive Order 13132 establishes certain requirements that an 
agency must meet when it promulgates a proposed rule (and subsequent 
final rule) that imposes substantial direct requirement costs on state 
and local governments, preempts state law, or otherwise has federalism 
implications. The proposed changes would not have a substantial direct 
effect on state and local governments, preempt state law, or otherwise 
have a federalism implication and there is no change in the 
distribution of power and responsibilities among the various levels of 
government. We do not believe that this rule would impose substantial 
direct compliance costs on state and local governments that are not 
required by statute. We do not believe that a significant number of 
laboratories affected by these proposals are operated by state or local 
governments. Therefore, the proposed modifications in these areas would 
not cause additional costs to state and local governments.
    We are proposing to require that each HHS-approved PT program have 
a minimum of ten laboratory participants before offering any PT 
analyte. This change reduces some burden on laboratories that have 
incurred the expense of enrolling in a PT program but do not receive a 
score or receive an artificial score requiring the laboratory to take 
additional steps to verify the accuracy of the analyte as required by 
Sec.  493.1236(b)(2). PT programs will determine if it is economically 
feasible to offer those analytes or if they should market their 
products to laboratories. Both of these activities are outside the 
scope of our authority.

C. Anticipated Effects

    This proposed rule, if finalized, would impact approximately 36,777 
clinical laboratories (total of Certificate of Compliance and 
Certificate of Accreditation laboratories, as of January 2017) required 
to participate in PT under the CLIA regulations implemented by the 
February 28, 1992 final rule, seven current HHS-approved PT programs, 
and to a lesser extent, in vitro diagnostics (IVD) manufacturers, 
healthcare providers, laboratory surveyors, and patients. Although 
complete data are not available to calculate all estimated costs and 
benefits that would result from the changes proposed in this rule, we 
are providing an analysis of the potential impact based on available 
information and certain assumptions. Implementation of these proposed 
requirements in a final rule would result in changes that are 
anticipated to have quantifiable impacts on laboratories and non-
quantifiable impacts on laboratories, PT programs, and others mentioned 
above. In estimating the quantifiable impacts, we separated the 
laboratory specialties into two broad categories that include: (1) 
Proposed PT changes to the microbiology specialty; and (2) proposed PT 
changes to non-microbiology specialties. This was done because the PT 
requirements for microbiology differ from those than for other 
laboratory specialties, and laboratories that are certified to perform 
microbiology testing may be impacted differently than those that 
perform non-microbiology clinical testing. In each microbiology 
subspecialty PT participation is required based on the types of 
services offered by a laboratory and an overall score is given per that 
subspecialty. In the other specialties and subspecialties, PT 
participation is required and scores are given based on specific 
required analytes listed in the regulations.
    For both the microbiology PT changes and addition of proposed 
analytes to subpart I, we anticipate minimal burden to laboratories as 
CLIA already requires that laboratories must verify the accuracy of 
tests not currently listed in subpart I at least twice annually. We 
believe many laboratories meet this requirement by participating in 
proficiency testing voluntarily. However, we do not have a way of 
estimating how many of these participating laboratories actually meet 
the requirement through additional verification. Information on the 
costs of voluntary participation is also not reported. Although we 
cannot precisely predict how the proposed changes may qualitatively 
affect clinical laboratories, we do not expect there to be major 
changes in how they function. We have quantified the costs we expect 
laboratories to incur but there may be costs associated with other 
administrative functions related to PT ordering, result reporting, and 
record keeping that we are not able to estimate. As stated above, we 
are unable to estimate the number of laboratories voluntarily enrolled 
in PT which is not currently required in subpart I. Cost of adding a 
new analyte would range from $0.39 to $86.50; however, the majority of 
the costs/analyte are less than $5.00 per analyte.
1. Quantifiable Impacts for Laboratories
    CDC receives catalogs from all CLIA-approved PT programs annually. 
We estimated material costs for purchasing PT based on the range of 
2017 catalog prices from the seven CLIA-approved PT programs. In 
estimating the costs for performing PT for all laboratory specialties 
that would be affected by this regulatory change, we assumed that the 
average national CMS reimbursement rate for Part B Medicare (CMS 
Virtual Research Data Center: https://www.resdac.org/cms-data/request/cms-virtual-research-data-center) was a reasonable estimate of the cost 
the laboratory incurs when testing each sample (or challenge) because 
this amount represents the average reimbursement to laboratories 
performing patient testing for that analyte or test. We also assume the 
cost for testing patient samples is the same as the cost for testing PT 
samples.
    We calculate that, on average, the impact would be between $721 and

[[Page 1551]]

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

[[Page 1552]]

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

[[Page 1553]]

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

                                          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 cost  impact for one   microbiology
                                                           laboratories    laboratories                         **           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--                    0             527            8.16           16.00       12,732.32
 dermatophytes (DTM)....................................
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-research-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                       Supply/       Total high      Total high      impact for
      Proposed PT regulation change       of affected M1  of affected M2     Labor \1\     material cost  impact/for one   impact/for 15   microbiology
                                           laboratories    laboratories                         \2\          challenge      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                3,281               0            9.89           34.80      146,627.89             N/A
 resistance testing.....................
Antimycobacterial susceptibility or                  454               0            4.33           82.50       39,420.82             N/A
 resistance testing.....................
Direct fungal antigen detection.........               0              96           14.22           31.80        4,417.92       66,268.80
Detection of growth or no growth in                    0             527            8.16           33.00       21,691.32      325,369.80
 culture media--dermatophytes (DTM).....
Antifungal susceptibility or resistance                0             369            9.89           31.80   \3\ 15,383.61             N/A
 testing................................
Direct parasite antigen detection.......               0             533           14.22           70.67       45,246.37      678,695.55
Antiviral susceptibility or resistance               332               0          230.11          243.00  \3\ 157,072.52             N/A
 testing................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Average national CMS reimbursement rate for Part B Medicare (CMS Virtual Research Data Center: https://www.resdac.org/cms-data/request/cms-virtual-research-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.


[[Page 1554]]

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

[[Page 1555]]

accredited by the CAP that might provide testing for each analyte.
    COLA provided us with the percentages of the approximately 7,414 
COLA-accredited laboratories that perform testing for each proposed 
analyte. We determined that COLA-accredited laboratories are similar to 
CoC laboratories in terms of their annual test volumes. Therefore, we 
assumed that the percentage of COLA-accredited laboratories that test 
each proposed analyte could be used to estimate the number of CoC and 
CoA (other than CAP- or COLA-accredited) laboratories that test each 
analyte.
    We used the percentage of CAP-accredited laboratories that 
participate in PT for each proposed analyte to estimate the maximum 
number of CoC and CoA (other than CAP and COLA) laboratories that test 
each analyte. This percentage was much higher for many of the analytes 
when compared to the laboratories accredited by organizations other 
than the CAP. Since CAP-accredited laboratories are often either 
hospital-based or commercial laboratories that already participate in 
PT for the additional analytes, approximations for high estimates may 
substantially overestimate the number of laboratories impacted.
    Using the above information, we calculated low and high estimates 
for the total number of non-CAP-accredited, CoC and CoA laboratories 
that may provide testing for each proposed analyte.
    For each proposed analyte, we calculated the number of CAP-
accredited laboratories that buy from non-CAP PT programs by 
subtracting the CAP-accredited laboratories enrolled in CAP PT from the 
total number of CAP-accredited laboratories.
    We derived a low estimate of the total number of laboratories not 
accredited by the CAP and not enrolled in one of the non-CAP PT 
programs for each analyte. Negative estimates were taken as ``0''. This 
represents our low estimate of the number of laboratories that will 
need to purchase PT for each analyte.
    To obtain the high estimate for the number of laboratories not 
accredited by the CAP and not enrolled in one of the non-CAP PT 
programs, we took the high estimate of CoA laboratories not accredited 
by the CAP and CoC laboratories and subtracted the number of this 
subset of CoA laboratories already known to be enrolled in PT. For the 
high estimate of the number of laboratories not accredited by CAP and 
not enrolled in one of the non-CAP PT programs, we also used an 
additional criterion of the number of laboratories in the respective 
specialty from OSCAR/QIES to limit the estimate at the number of 
laboratories in the specialty. If this number was less than the high 
estimate of CoC laboratories and CoA laboratories accredited by a 
program other than the CAP, then the high estimate was calculated by 
subtracting the number of laboratories not accredited by CAP and not 
enrolled in one of the non-CAP PT programs from the total number of 
laboratories in the specialty.
    The cost increase in this category was calculated on a per analyte 
basis. The minimum cost per sample that was the lowest across all eight 
non-CAP PT programs and the maximum cost per sample that was the 
highest across all eight non-CAP PT programs were used for these 
calculations. The minimum cost increase was calculated by multiplying 
the minimum cost per sample, including the CMS reimbursement amount, by 
the number of laboratories that are not purchasing PT from any PT 
program. The same calculation was made using the maximum cost per 
sample for the maximum cost increase.
     Category 4: Laboratories not accredited by the CAP and 
enrolled in PT programs other than the CAP PT program: We obtained the 
number of laboratories enrolled in PT programs other than the CAP PT 
program and subtracted the number of CAP-accredited laboratories 
enrolled in a non-CAP PT program per analyte for this category. The 
cost increase in this category was calculated on a per analyte basis. 
The estimated cost increases were calculated for each of the non-CAP PT 
programs for which information was available. The minimum increase was 
calculated for each of the PT programs by multiplying the cost per 
sample, including the CMS reimbursement amount, by the increase in 
frequency of samples and the number of laboratories that purchase PT 
from that individual program. To determine the maximum increase, the 
same calculation was made using the highest cost per analyte including 
the CMS reimbursement amount.
c. Results
    We estimate that the overall impact of adding requirements for the 
proposed analytes in the specialties and subspecialties other than 
microbiology will range from $26 to $114 million for the first year 
(Table 4), if these proposed changed are finalized. Because of their 
larger number, and the fact that non-CAP accredited laboratories tend 
not to enroll in non-required PT as frequently as CAP-accredited 
laboratories do, we estimate that non-CAP accredited laboratories that 
are not enrolled in any PT program will have an impact between $16 and 
$100 million for the first year. We also estimate that laboratories 
that are enrolled in PT programs other than CAP will have a relatively 
minor impact, $5.4 million for 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     4,516,673.........  4,516,673.
 CAP that purchase material from
 the CAP PT program.
2. Laboratories accredited by     Included in         Included in
 CAP that purchase PT materials    Category 4.         Category 4.
 from other PT programs.
3. Laboratories not accredited    16,248,746........  100,303,499.
 by CAP that not already
 enrolled in other PT programs.
4. Laboratories not accredited    5,351,565.........  4,103,686.
 by CAP enrolled in other PT
 programs (category 2 and 4
 combined).
                                 ---------------------
    Total increased cost........  $26,116,984.......  $114,275,423.
------------------------------------------------------------------------

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

[[Page 1556]]



                                                                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
    If the changes proposed in this rule are finalized, a number of 
non-quantifiable impacts will also result for PT programs and 
laboratories. We solicit comments and data to facilitate the 
determination of quantifiable estimates in the final rule.
    As with any currently required PT, if finalized, the proposed 
regulation would not require approved PT programs to offer additional 
analytes. Several programs already offer the analytes or tests that 
would be required by laboratories, and in these cases, we expect 
minimal impact on the PT programs. If the proposed changes outlined in 
this rule are finalized, we expect there will initially be some 
increased expenditures for PT programs to implement the changes, even 
if they are only scaling up currently offered PT. At the same time, PT 
programs will also increase revenue received if they increase the PT 
analytes or tests they offer. We have no way to estimate how many 
programs may choose to offer additional PT analytes or tests, but we 
assume that most will implement the changes included in the final rule. 
For some programs, this would mean offering an analyte or test for the 
first time, while for others it would mean increasing the yearly number 
of events and/or challenges per event. The costs would be relatively 
less for the programs that are already offering the PT analytes or 
tests, including those currently offering challenges at less than the 
PT frequency required under CLIA. There are also differences in what 
the PT programs charge laboratories for PT which would change the 
impact of the final rule. In part, these differences depend upon the 
total number of samples distributed per year and how the PT is 
packaged; some PT is sold as modules that group several related 
analytes together. Because CLIA-approved PT programs are required to 
maintain non-profit status, any increased revenue that results from an 
expanded PT menu will not be turned into profit. We have attempted to 
account for the quantifiable impacts in our estimates for laboratories.
    If the proposed analyte deletions are finalized, some PT programs 
may cease offering the deleted analytes, others may continue to offer 
them at a frequency less than that required under CLIA, and still 
others may continue to offer them at the PT frequency required under 
CLIA. For these reasons, we are unable to estimate the cost impact to 
PT programs for this change. We solicit comments and data that would 
help us estimate the impact of the PT changes on PT programs in the 
final rule.
    Although we cannot precisely predict how the proposed changes may 
affect clinical laboratories, we do not expect there to be major 
changes in how they function. We have quantified the costs we expect 
laboratories to incur but there may be costs associated with other 
administrative functions related to PT ordering, result reporting, and 
record keeping that we are not able to estimate. For those laboratories 
that currently purchase PT for the five analytes we propose to delete, 
we cannot estimate the lowered expenditure for laboratories that stop 
buying PT materials and must begin doing something else to verify 
accuracy. Based upon our focus groups and surveys, we know there are a 
variety of things laboratories may do to externally verify accuracy, 
ranging from splitting samples with other laboratories to purchasing PT 
materials voluntarily. Also, we do not know the extent to which split 
samples are tested, or how many patient samples might be tested in this 
way; there is no stated minimum number of specimens that must be tested 
semi-annually to verify accuracy. Therefore, we have not attempted to 
estimate the costs for alternative approaches that may be adopted to 
verify accuracy for the deleted analytes. Regardless of how 
laboratories might be impacted, we expect that they will not spend more 
than they currently spend on PT for the analytes we propose to delete, 
but we cannot estimate this. By not attempting to estimate the number 
of laboratories that may stop buying PT material for the deleted 
analytes, we may be slightly overestimating the net impact.
3. Benefits
    While we cannot quantify the benefits that the proposed changes 
will bring, if finalized, we believe that the changes will facilitate 
more rapid identification of unacceptable practices in laboratories, 
especially for those laboratories that have not previously participated 
in PT. There are very few published reports that have investigated the 
impact of PT performance on testing accuracy or patient outcomes. In 
part this is because performing PT is now a standard practice for most 
analytes we are considering to add, so it is not possible to separate 
cohorts of PT users from non-users.\26\ \27\ \28\ \29\ In addition, 
remediation after identification of problems should also occur more 
quickly and clinical test results of marginal or inferior quality are 
less likely to be used as analytical systems will improve. All of these 
things will serve to minimize the potential adverse impact to patients 
and benefiting physicians and healthcare providers that could occur 
with inaccurate testing.
---------------------------------------------------------------------------

    \26\ Reilly AA Salkin IF McGinnis MR et al. Evaluation of 
mycology laboratory proficiency testing. J Clin Microbiol. 
1999;37:2297-2305.
    \27\ Parsons PJ Reilly AA Esernio-Jenssen D et al. Evaluation of 
blood lead proficiency testing: comparison of open and blind 
paradigms. Clin Chem. 2001;47:322-330.
    \28\ Shahangian S and Snyder SR. Laboratory Medicine Quality 
Indicators: A Review of the Literature. American Journal of Clinical 
Pathology, 2009; 131: 418-431.
    \29\ Jenny RW and Jackson KY. PT performance as a predictor of 
accuracy of routine patient testing for theophylline. Clin Chem 
1993; 39:76-81.
---------------------------------------------------------------------------

    PT performance partially reflects daily clinical laboratory 
performance (Stull, Hearn, Hancock, Handsfield, and Collins, 1998). 
Updating acceptance limits will benefit laboratories by helping to 
ensure the accuracy and reliability of testing and providing a 
mechanism for laboratories to be held accountable for clinically 
appropriate patient test results, which directly affects the public's 
health (Astles, Tholen, and Mitchell, 2016). Both

[[Page 1557]]

clinical laboratories and patients can benefit from continued 
monitoring of PT to help assess the success of intervention efforts to 
improve the overall quality of clinical laboratory testing.\30\
---------------------------------------------------------------------------

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

    Another benefit that may result from adding new PT analytes and 
tests and updating the limits for acceptable PT performance under CLIA 
includes the generation of additional information on test performance 
and sources of errors that PT programs can share with laboratories 
(Howerton, Krolak, Manasterski, and Handsfield, 2010). Such information 
can also be used as a source of training and can help to maintain the 
competency of testing personnel (Garcia, et al., 2014).
    Last, while we do not anticipate that the changes being proposed in 
this rule would incur any costs on the IVD industry, we expect the IVD 
industry to potentially benefit by the changes made in this proposed 
rule when finalized. Having the ability to track PT results for the 
added analytes will enable better and faster detection of problems with 
product manufacturing, including reagent problems. We are aware that 
some IVD manufacturers enroll in PT and are able to track the 
performance of the peer groups using their instruments in summary 
reports issued by the PT programs.
    Ultimately, we believe that laboratories, healthcare providers, 
patients, and the IVD industry will benefit from improved analytical 
performance (Howerton, Krolak, Manasterski, and Handsfield, 2010) that 
is expected to occur when this rule becomes finalized.

D. Alternatives Considered

    In proposing these changes, several alternatives were considered. 
We considered the possibility of changing either the required frequency 
of PT events per year or changing the number of required PT challenges 
per event. Responses from our national survey did not support changing 
either parameter, nor did CLIAC recommend any changes to the required 
PT frequency or number of challenges per event. We did not perceive a 
benefit from either reducing or increasing the number of events per 
year. Reducing the number of events to two per year and keeping all 
other factors the same would cost less compared to the proposed rule, 
but it would delay the potential time it takes to identify a poor 
performing laboratory as ``unsuccessful'' to at least 12 months, 
instead of the current 8 months. Increasing the number of events might 
help to identify a laboratory with testing issues slightly earlier, but 
increasing the number of events would increase costs. We are proposing 
to continue to require five challenges per event, with a passing score 
generally defined as a minimum of four challenges falling within the 
criteria for acceptable performance. A minimum of five challenges per 
event are necessary to follow the approach taken in the final 
regulation implementing CLIA '88 which states that a minimum event 
score should be 80 percent to be successful allowing for one missed 
result per event.
    For the microbiology specialty, we considered the possibility of 
including required PT analytes in each subspecialty at a frequency of 
three events per year with five challenges per event. We determined 
that the increase in required PT would result in an additional impact 
of over $5.3 million to laboratories that would be required to perform 
susceptibility or resistance testing for 15 challenges per year. For 
the non-microbiology specialties and subspecialties, we could have 
opted not to add any new PT analytes, but testing of the analytes we 
are proposing to add is widespread and is important in clinical 
decision making and public health testing. We also considered adding 
all analytes for which there was at least one existing PT program, but 
we believed this alternative would have been excessively burdensome as 
it would mean adding hundreds of new required analytes which may not be 
necessary to identify problematic laboratory performance. We could have 
left the acceptance limits as they were established in CLIA '88, but we 
believe those are outdated given advancements in technology. We 
considered retaining the definition of peer group established in CLIA 
'88, but we decided this would be too expensive and ultimately 
unworkable because it would require PT programs to perform 
commutability testing using analyzers from multiple peer groups every 
time a new batch of PT materials was created. We are requesting public 
comments related to alternative changes to be considered to assist us 
in finalizing this rule.

E. Accounting Statement and Table

    We have prepared the following accounting statement showing the 
classification of expenditures associated with the provisions of this 
proposed rule.

                                                                Table 6--Accounting Table
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                   Units
                                             Primary       Minimum       Maximum   ------------------------------------
                Category                    estimate      estimate      estimate       Year      Discount     Period             Source citation
                                                                                      dollars     rate %      covered
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                        Benefits
--------------------------------------------------------------------------------------------------------------------------------------------------------
Qualitative.............................   More effective detection of laboratories that provide inaccurate     Preamble and Impact Analysis.
                                          laboratory test results.
                                           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  ................................
                                            67,678,819    24,769,188   110,588,450        2017           7   2019-2028  ................................
--------------------------------------------------------------------------------------------------------------------------------------------------------


[[Page 1558]]

F. Regulatory Reform Analysis Under E.O. 13771

    Executive Order 13771, titled Reducing Regulation and Controlling 
Regulatory Costs, was issued on January 30, 2017 and requires that the 
costs associated with significant new regulations ``shall, to the 
extent permitted by law, be offset by the elimination of existing costs 
associated with at least two prior regulations.'' This proposed rule, 
if finalized, is considered an E.O. 13771 regulatory action. We 
estimate that this rule would generate $58.0 million in annualized 
costs in 2016 dollars, discounted at 7 percent relative to year 2016 
over a perpetual time horizon. Details on the estimated costs of this 
rule can be found in the preceding analyses.

G. Conclusion

    We estimate that the cost to laboratories to participate in PT for 
the analytes and tests proposed in this rule would cost between 
$26,503,031 and $118,329,642 in 2017 dollars. Although the effect of 
the changes proposed will increase laboratory costs, implementation of 
these changes in a final rule will increase the confidence of 
laboratory professionals and the end-users of test results, including 
physicians and other healthcare providers, patients, and the public, in 
the reliability and accuracy of test results.
    We have determined that this rule would not have a significant 
economic impact on a substantial number of small entities or a 
significant impact in the operations of a substantial number of small 
rural hospitals and for these reasons, we are not preparing analyses 
for either the RFA or section 1102(b) of the Act.
    In accordance with the provisions of Executive Order 12866, this 
proposed regulation was reviewed by the Office of Management and 
Budget.

List of Subjects in 42 CFR Part 493

    Administrative practice and procedure, Grant programs--health, 
Health facilities, Laboratories, Medicaid, Medicare, Penalties, 
Reporting and recordkeeping requirements.

    For the reasons set forth in the preamble, the Centers for Medicare 
& Medicaid Services proposes to amend 42 CFR part 493 as set forth 
below:

PART 493--LABORATORY REQUIRMENTS

0
1. The authority citation for part 493 is revised to read as follows:

    Authority: 42 U.S.C. 263a, 1302, 1395x(e), the sentence 
following 1395x(s)(11) through 1395x(s)(16).

0
2. Section 493.2 is amended by--
0
a. Adding the definitions of ``Acceptance limit'' and ``Peer group'' in 
alphabetical order;
0
b. Revising the definition of ``Target value''; and
0
c. Adding the definition of ``Unacceptable score'' in alphabetical 
order.
    The additions and revision read as follows:


Sec.  493.2  Definitions.

* * * * *
    Acceptance limit is the symmetrical tolerance (plus and minus) 
around the target value.
* * * * *
    Peer group is a group of laboratories whose testing process 
utilizes similar instruments, methodologies, and/or reagent systems and 
is not to be assigned using the reagent lot number level.
* * * * *
    Target value for quantitative tests is:
    (1) If the peer group consists of 10 participants or greater:
    (i) The mean of all participant responses after removal of outliers 
(that is, those responses greater than three standard deviations from 
the original mean, as applicable); or
    (ii) The mean established by a definitive method or reference 
methods; or
    (iii) The mean of a peer group, in instances when a definitive 
method or reference methods are not available; or
    (iv) If the peer group consists of fewer than 10 participants, 
``target value'' means the overall mean after outlier removal (as 
defined in paragraph (1) of this definition) unless acceptable 
scientific reasons are available to indicate that such an evaluation is 
not appropriate.
    (2) [Reserved]
* * * * *
    Unacceptable score is a PT result that is outside of the criteria 
for acceptable performance for a single challenge or sample.
* * * * *
0
3. Section 493.20 is amended by revising paragraph (c) to read as 
follows:


Sec.  493.20  Laboratories performing tests of moderate complexity.

* * * * *
    (c) If the laboratory also performs waived tests, compliance with 
Sec.  493.801(a) and (b)(7) and subparts J, K, and M of this part is 
not applicable to the waived tests. However, the laboratory must comply 
with the requirements in Sec.  493.15(e), Sec. Sec.  493.801(b)(1) 
through (6), 493.1771, 493.1773, and 493.1775.
0
4. Section 493.25 is amended by revising paragraph (d) to read as 
follows:


Sec.  493.25  Laboratories performing tests of high complexity.

* * * * *
    (d) If the laboratory also performs waived tests, compliance with 
Sec. Sec.  493.801(a) and 493.801(b)(7) and subparts J, K, and M of 
this part are not applicable to the waived tests. However, the 
laboratory must comply with the requirements in Sec. Sec.  493.15(e), 
493.801(b)(1) through (6), 493.1771, 493.1773, and 493.1775.
0
5. Section 493.801 is amended by--
0
a. Redesignating paragraphs (b)(3) through (6) as paragraphs (b)(4) 
through (7), respectively; and
0
b. Adding new paragraph (b)(3).
    The addition reads as follows:


Sec.  493.801   Condition: Enrollment and testing of samples.

* * * * *
    (b) * * *
    (3) The laboratory must report PT results for microbiology organism 
identification to the highest level that it reports results on patient 
specimens.
* * * * *
0
6. Section 493.861 is amended by revising paragraph (a) to read as 
follows:


Sec.  493.861  Standard; Unexpected antibody detection.

    (a) Failure to attain an overall testing event score of at least 
100 percent is unsatisfactory performance.
* * * * *
0
7. Section 493.901 is amended by--
0
a. Redesignating paragraphs (a), (b), (c), and (d) as paragraphs (b), 
(c), (d), and (e), respectively;
0
b. Adding new paragraph (a);
0
c. Redesignating newly redesignated paragraphs (c)(6) and (7) as 
paragraphs (c)(7) and (8), respectively;
0
d. Adding new paragraph (c)(6);
0
e. Revising newly redesignated paragraph (c)(8);
0
f. Adding paragraph (c)(9);
0
g. Revising newly redesignated paragraph (e); and
0
h. Adding paragraph (f).
    The additions and revisions read as follows:


Sec.  493.901  Approval of proficiency testing programs.

* * * * *
    (a) Require a minimum of ten laboratory participants before 
offering a proficiency testing analyte;
* * * * *

[[Page 1559]]

    (c) * * *
    (6) For those results submitted electronically, a mechanism to 
track changes to any result reported to the proficiency testing program 
and the reason for the change;
* * * * *
    (8) A process to resolve technical, administrative, and scientific 
problems about program operations; and
    (9) A contractor performing administrative responsibilities as 
described in this section and Sec.  493.903 must be a private nonprofit 
organization or a Federal or State agency, or an entity acting as a 
designated agent for the Federal or State agency.
* * * * *
    (e) HHS may require on-site visits for all initial proficiency 
testing program applications for CMS approval and periodically or when 
problems are encountered for previously HHS-approved proficiency 
testing programs either during the reapproval process or as necessary 
to review and verify the policies and procedures represented in its 
application and other information, including, but not limited to, 
review and examination of documents and interviews of staff.
    (f) HHS may require a proficiency testing program to reapply for 
approval using the process for initial applications if significant 
problems are encountered during the reapproval process.
0
8. Section 493.903 is amended--
0
a. In paragraph (a)(1) by removing the period and adding ``;'';
0
b. In paragraph (a)(2) by removing ``;'' and adding in its place ``; 
and''; and
0
c. By adding paragraph (a)(3).
    The addition reads as follows:


Sec.  493.903  Administrative responsibilities.

* * * * *
    (a) * * *
    (3) Not change submitted laboratory data and results for any 
proficiency testing event;
* * * * *
0
9. Section 493.905 is revised to read as follows:


Sec.  493.905  Nonapproved proficiency testing programs.

    (a) If a proficiency testing program is determined by HHS to fail 
to meet any criteria contained in Sec. Sec.  493.901 through 493.959 
for approval of the proficiency testing program, CMS will notify the 
program and the program must notify all laboratories enrolled of the 
nonapproval and the reasons for nonapproval within 30 days of the 
notification. CMS may disapprove any proficiency testing program that 
provides false or misleading information with respect to any 
information that is necessary to meet any criteria contained in 
Sec. Sec.  493.901 through 493.959 for approval of the proficiency 
testing program.
    (b) Request for reconsideration. Any PT program that is 
dissatisfied with a determination to disapprove the program, as 
applicable, may request that CMS reconsider the determination, in 
accordance with subpart D of part 488 of this chapter.
0
10. Section 493.911 is revised to read as follows:


Sec.  493.911  Bacteriology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for bacteriology, the annual program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events provided to the laboratory at approximately equal 
intervals per year. The samples may be provided to the laboratory 
through mailed shipments. The specific organisms included in the 
samples may vary from year to year.
    (1) The annual program must include, as applicable, samples for:
    (i) Gram stain including bacterial morphology;
    (ii) Direct bacterial antigen detection;
    (iii) Bacterial toxin detection; and,
    (iv) Detection and identification of bacteria which includes one of 
the following:
    (A) Detection of growth or no growth in culture media;
    (B) Identification of bacteria; and
    (v) Antimicrobial susceptibility or resistance testing.
    (2) An approved program must furnish HHS and its agents with a 
description of samples that it plans to include in its annual program 
no later than 6 months before each calendar year. The program must 
include bacteria commonly occurring in patient specimens and other 
important emerging pathogens. The program determines the reportable 
isolates and correct responses for antimicrobial susceptibility or 
resistance for any designated isolate. At least 25 percent of the 
samples must be mixtures of the principal organism and appropriate 
normal flora. Mixed cultures are samples that require reporting of one 
or more principal pathogens. Mixed cultures are not ``negative'' 
samples such as when two commensal organisms are provided in a PT 
sample with the intended response of ``negative'' or ``no pathogen 
present.'' The program must include the following two types of samples 
to meet the 25 percent mixed culture criterion:
    (i) Samples that require laboratories to report only organisms that 
the testing laboratory considers to be a principal pathogen that is 
clearly responsible for a described illness (excluding immuno-
compromised patients). The program determines the reportable isolates, 
including antimicrobial susceptibility or resistance for any designated 
isolate; and
    (ii) Samples that require laboratories to report all organisms 
present. Samples must contain multiple organisms frequently found in 
specimens where multiple isolates are clearly significant or where 
specimens are derived from immuno-compromised patients. The program 
determines the reportable isolates.
    (3) The content of an approved program must vary over time, as 
appropriate. The types of bacteria included annually must be 
representative of the following major groups of medically important 
aerobic and anaerobic bacteria, if appropriate for the sample sources:
    (i) Gram-negative bacilli.
    (ii) Gram-positive bacilli.
    (iii) Gram-negative cocci.
    (iv) Gram-positive cocci.
    (4) For antimicrobial susceptibility or resistance testing, the 
program must provide at least two samples per testing event that 
include one Gram-positive and one Gram-negative organism that have a 
predetermined pattern of susceptibility or resistance to the common 
antimicrobial agents.
    (b) Evaluation of a laboratory's performance. HHS approves only 
those programs that assess the accuracy of a laboratory's responses in 
accordance with paragraphs (b)(1) through (9) of this section.
    (1) The program determines the reportable bacterial staining and 
morphological characteristics to be interpreted by Gram stain. The 
program determines the bacteria to be reported by direct bacterial 
antigen detection, bacterial toxin detection, detection of growth or no 
growth in culture media, identification of bacteria, and antimicrobial 
susceptibility or resistance testing. To determine the accuracy of each 
of the laboratory's responses, the program must compare each response 
with the response which reflects agreement of either 80 percent or more 
of ten or more referee laboratories or 80 percent or more of all 
participating laboratories. Both methods must be attempted before the 
program can choose to not grade a PT sample.
    (2) A laboratory must identify the organisms to highest level that 
it performs these procedures on patient specimens.
    (3) A laboratory's performance will be evaluated on the basis of 
the average of

[[Page 1560]]

its scores for paragraph (b)(4) through (8) of this section as 
determined in paragraph (b)(9) of this section.
    (4) The performance criteria for Gram stain including bacterial 
morphology is staining reaction, that is, Gram positive or Gram 
negative and morphological description for each sample. The score is 
the number of correct responses for Gram stain reaction plus the number 
of correct responses for morphological description divided by 2 then 
divided by the number of samples to be tested, multiplied by 100.
    (5) The performance criterion for direct bacterial antigen 
detection is the presence or absence of the bacterial antigen. The 
score is the number of correct responses divided by the number of 
samples to be tested, multiplied by 100.
    (6) The performance criterion for bacterial toxin detection is the 
presence or absence of the bacterial toxin. The score is the number of 
correct responses divided by the number of samples to be tested 
multiplied by 100.
    (7) The performance criterion for the detection and identification 
of bacteria includes one of the following:
    (i) The performance criterion for the detection of growth or no 
growth in culture media is the presence or absence of bacteria or 
growth. The score is the number of correct responses divided by the 
number of samples to be tested multiplied by 100.
    (ii) The performance criterion for the identification of bacteria 
is the total number of correct responses for bacterial identification 
submitted by the laboratory divided by the number of organisms present 
plus the number of incorrect organisms reported by the laboratory 
multiplied by 100 to establish a score for each sample in each testing 
event. Since laboratories may incorrectly report the presence of 
organisms in addition to the correctly identified principal 
organism(s), the scoring system must provide a means of deducting 
credit for additional erroneous organisms that are reported. For 
example, if a sample contained one principal organism and the 
laboratory reported it correctly but reported the presence of an 
additional organism, which was not considered reportable, the sample 
grade would be 1/(1 + 1) x 100 = 50 percent.
    (8) For antimicrobial susceptibility or resistance testing, a 
laboratory must indicate which drugs are routinely included in its test 
panel when testing patient samples. A laboratory's performance will be 
evaluated for only those antimicrobials for which susceptibility or 
resistance testing is routinely performed on patient specimens. A 
correct response for each antimicrobial will be determined as described 
in paragraph (b)(1) of this section. Scoring for each sample is based 
on the number of correct susceptibility or resistance responses 
reported by the laboratory divided by the actual number of correct 
susceptibility or resistance responses determined by the program, 
multiplied by 100. For example, if a laboratory offers susceptibility 
or resistance testing using three antimicrobial agents, and the 
laboratory reports correct responses for two of the three antimicrobial 
agents, the laboratory's grade would be 2/3 x 100 = 67 percent.
    (9) The score for a testing event in bacteriology is the average of 
the scores determined under paragraphs (b)(4) through (8) of this 
section based on the type of service offered by the laboratory.
0
11. Section 493.913 is revised to read as follows:


Sec.  493.913  Mycobacteriology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for mycobacteriology, the annual program must 
provide a minimum of five samples per testing event. There must be at 
least two testing events provided to the laboratory at approximately 
equal intervals per year. The samples may be provided through mailed 
shipments. The specific organisms included in the samples may vary from 
year to year.
    (1) The annual program must include, as applicable, samples for:
    (i) Acid-fast stain;
    (ii) Detection and identification of mycobacteria which includes 
one of the following:
    (A) Detection of growth or no growth in culture media; or
    (B) Identification of mycobacteria; and
    (iii) Antimycobacterial susceptibility or resistance testing.
    (2) An approved program must furnish HHS and its agents with a 
description of the samples it plans to include in its annual program no 
later than 6 months before each calendar year. At least 25 percent of 
the samples must be mixtures of the principal mycobacteria and 
appropriate normal flora. The program must include mycobacteria 
commonly occurring in patient specimens and other important emerging 
mycobacteria. The program determines the reportable isolates and 
correct responses for antimycobacterial susceptibility or resistance 
for any designated isolate.
    (3) The content of an approved program may vary over time, as 
appropriate. The mycobacteria included annually must contain species 
representative of the following major groups of medically important 
mycobacteria, if appropriate for the sample sources:
    (i) Mycobacterium tuberculosis complex; and
    (ii) Mycobacterium other than tuberculosis (MOTT).
    (4) The program must provide at least five samples per testing 
event that include challenges that are acid-fast and challenges which 
do not contain acid-fast organisms.
    (5) For antimycobacterial susceptibility or resistance testing, the 
program must provide at least two samples per testing event that have a 
predetermined pattern of susceptibility or resistance to the common 
antimycobacterial agents.
    (b) Evaluation of a laboratory's performance. HHS approves only 
those programs that assess the accuracy of a laboratory's response in 
accordance with paragraphs (b)(1) through (7) of this section.
    (1) The program determines the reportable mycobacteria to be 
detected by acid-fast stain. The program determines the mycobacteria to 
be reported by detection of growth or no growth in culture media, 
identification of mycobacteria, and for antimycobacterial 
susceptibility or resistance testing. To determine the accuracy of each 
of the laboratory's responses, the program must compare each response 
with the response that reflects agreement of either 80 percent or more 
of ten or more referee laboratories or 80 percent or more of all 
participating laboratories. Both methods must be attempted before the 
program can choose to not grade a PT sample.
    (2) A laboratory must detect and identify the organism to the 
highest level that it performs these procedures on patient specimens.
    (3) A laboratory's performance will be evaluated on the basis of 
the average of its scores for paragraph (b)(4) through (6) of this 
section as determined in paragraph (b)(7) of this section.
    (4) The performance criterion for acid-fast stains is positive or 
negative or the presence or absence of acid-fast organisms. The score 
is the number of correct responses divided by the number of samples to 
be tested, multiplied by 100.
    (5) The performance criterion for the detection and identification 
of mycobacteria includes one of the following:
    (i) The performance criterion for the detection of growth or no 
growth in culture media is the presence or absence of bacteria or 
growth. The score is the number of correct responses divided by

[[Page 1561]]

the number of samples to be tested multiplied by 100.
    (ii) The performance criterion for the identification of 
mycobacteria is the total number of correct responses for mycobacterial 
identification submitted by the laboratory divided by the number of 
organisms present plus the number of incorrect organisms reported by 
the laboratory multiplied by 100 to establish a score for each sample 
in each testing event. Since laboratories may incorrectly report the 
presence of mycobacteria in addition to the correctly identified 
principal organism(s), the scoring system must provide a means of 
deducting credit for additional erroneous organisms reported. For 
example, if a sample contained one principal organism and the 
laboratory reported it correctly but reported the presence of an 
additional organism, which was not considered reportable, the sample 
grade would be 1/(1 + 1) x 100 = 50 percent.
    (6) For antimycobacterial susceptibility or resistance testing, a 
laboratory must indicate which drugs are routinely included in its test 
panel when testing patient samples. A laboratory's performance will be 
evaluated for only those antimycobacterial agents for which 
susceptibility or resistance testing is routinely performed patient 
specimens. A correct response for each antimycobacterial agent will be 
determined as described in paragraph (b)(1) of this section. Scoring 
for each sample is based on the number of correct susceptibility or 
resistance responses reported by the laboratory divided by the actual 
number of correct susceptibility or resistance responses as determined 
by the program, multiplied by 100. For example, if a laboratory offers 
susceptibility or resistance testing using three antimycobacterial 
agents and the laboratory reports correct responses for two of the 
three antimycobacterial agents, the laboratory's grade would be 2/3 x 
100 = 67 percent.
    (7) The score for a testing event in mycobacteriology is the 
average of the scores determined under paragraphs (b)(4) through (6) of 
this section based on the type of service offered by the laboratory.
0
12. Section 493.915 is revised to read as follows:


Sec.  493.915  Mycology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for mycology, the annual program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events provided to the laboratory at approximately equal 
intervals per year. The samples may be provided through mailed 
shipments. The specific organisms included in the samples may vary from 
year to year.
    (1) The annual program must include, as applicable, samples for:
    (i) Direct fungal antigen detection;
    (ii) Detection and identification of fungi and aerobic 
actinomycetes which includes one of the following:
    (A) Detection of growth or no growth in culture media; or
    (B) Identification of fungi and aerobic actinomycetes; and
    (iii) Antifungal susceptibility or resistance testing.
    (2) An approved program must furnish HHS and its agents with a 
description of the samples it plans to include in its annual program no 
later than 6 months before each calendar year. At least 25 percent of 
the samples must be mixtures of the principal organism and appropriate 
normal background flora. The program must include fungi and aerobic 
actinomycetes commonly occurring in patient specimens and other 
important emerging fungi. The program determines the reportable 
isolates and correct responses for antifungal susceptibility or 
resistance for any designated isolate.
    (3) The content of an approved program must vary over time, as 
appropriate. The fungi included annually must contain species 
representative of the following major groups of medically important 
fungi and aerobic actinomycetes, if appropriate for the sample sources:
    (i) Yeast or yeast-like organisms;
    (ii) Molds that include;
    (A) Dematiaceous fungi;
    (B) Dermatophytes;
    (C) Dimorphic fungi;
    (D) Hyaline hyphomycetes;
    (E) Mucormycetes; and
    (iii) Aerobic actinomycetes.
    (4) For antifungal susceptibility or resistance testing, the 
program must provide at least two challenges per testing event that 
include fungi that have a predetermined pattern of susceptibility or 
resistance to the common antifungal agents.
    (b) Evaluation of a laboratory's performance. HHS approves only 
those programs that assess the accuracy of a laboratory's response, in 
accordance with paragraphs (b)(1) through (8) of this section.
    (1) The program determines the reportable fungi to be reported by 
direct fungal antigen detection, detection of growth or no growth in 
culture media, identification of fungi and aerobic actinomycetes, and 
antifungal susceptibility or resistance testing. To determine the 
accuracy of a laboratory's responses, the program must compare each 
response with the response reflects agreement of either 80 percent or 
more of ten or more referee laboratories or 80 percent or more of all 
participating laboratories. Both methods must be attempted before the 
program can choose to not grade a PT sample.
    (2) A laboratory must detect and identify the organisms to highest 
level that it performs these procedures on patient specimens.
    (3) A laboratory's performance will be evaluated on the basis of 
the average of its scores for paragraphs (b)(4) through (6) of this 
section as determined in paragraph (b)(7) of this section.
    (4) The performance criterion for direct fungal antigen detection 
is the presence or absence of the fungal antigen. The score is the 
number of correct responses divided by the number of samples to be 
tested, multiplied by 100.
    (5) The performance criterion for the detection and identification 
of fungi and aerobic actinomycetes includes one of the following:
    (i) The performance criterion for the detection of growth or no 
growth in culture media is the presence or absence of fungi or growth. 
The score is the number of correct responses divided by the number of 
samples to be tested multiplied by 100.
    (ii) The performance criterion for the identification of fungi and 
aerobic actinomycetes is the total number of correct responses for 
fungal and aerobic actinomycetes identification submitted by the 
laboratory divided by the number of organisms present plus the number 
of incorrect organisms reported by the laboratory multiplied by 100 to 
establish a score for each sample in each testing event. Since 
laboratories may incorrectly report the presence of fungi and aerobic 
actinomycetes in addition to the correctly identified principal 
organism(s), the scoring system must provide a means of deducting 
credit for additional erroneous organisms that are reported. For 
example, if a sample contained one principal organism and the 
laboratory reported it correctly but reported the presence of an 
additional organism, which was not considered reportable, the sample 
grade would be 1/(1 + 1) x 100 = 50 percent.
    (6) For antifungal susceptibility or resistance testing, a 
laboratory must indicate which drugs are routinely included in its test 
panel when testing patient samples. A laboratory's performance will be 
evaluated for only those antifungal agents for which

[[Page 1562]]

susceptibility or resistance testing is routinely performed on patient 
specimens. A correct response for each antifungal agent will be 
determined as described in paragraph (b)(1) of this section. Scoring 
for each sample is based on the number of correct susceptibility or 
resistance responses reported by the laboratory divided by the actual 
number of correct susceptibility or resistance responses as determined 
by the program, multiplied by 100. For example, if a laboratory offers 
susceptibility or resistance testing using three antifungal agents and 
the laboratory reports correct responses for two of the three 
antifungal agents, the laboratory's grade would be 2/3 x 100 = 67 
percent.
    (7) The score for a testing event is the average of the sample 
scores as determined under paragraphs (b)(4) through (6) of this 
section.
0
13. Section 493.917 is revised to read as follows:


Sec.  493.917  Parasitology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing in parasitology, the annual program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events provided to the laboratory at approximately equal 
intervals per year. The samples may be provided through mailed 
shipments. The specific organisms included in the samples may vary from 
year to year.
    (1) The annual program must include, as applicable, samples for:
    (i) Direct parasite antigen detection; and
    (ii) Detection and identification of parasites which includes one 
of the following:
    (A) Detection of presence or absence of parasites; or
    (B) Identification of parasites.
    (2) An approved program must furnish HHS and its agents with a 
description of the samples it plans to include in its annual program no 
later than 6 months before each calendar year. Samples must include 
both formalinized specimens and PVA (polyvinyl alcohol) fixed specimens 
as well as blood smears, as appropriate for a particular parasite and 
stage of the parasite. The majority of samples must contain protozoa or 
helminths or a combination of parasites. Some samples must be devoid of 
parasites.
    (3) The content of an approved program must vary over time, as 
appropriate. The types of parasites included annually must be 
representative of the following major groups of medically important 
parasites, if appropriate for the sample sources:
    (i) Intestinal parasites; and
    (ii) Blood and tissue parasites.
    (4) The program must provide at least five samples per testing 
event that include challenges which contain parasites and challenges 
that are devoid of parasites.
    (b) Evaluation of a laboratory's performance. HHS approves only 
those programs that assess the accuracy of a laboratory's responses in 
accordance with paragraphs (b)(1) through (6) of this section.
    (1) The program determines the reportable parasites to be detected 
by direct parasite antigen detection, detection of presence or absence 
of parasites, and identification of parasites. It may elect to 
establish a minimum number of parasites to be identified in samples 
before they are reported. Parasites found in rare numbers by referee 
laboratories are not considered in a laboratory's performance; such 
findings are neutral. To determine the accuracy of a laboratory's 
response, the program must compare each response with the response 
which reflects agreement of either 80 percent or more of ten or more 
referee laboratories or 80 percent or more of all participating 
laboratories. Both methods must be attempted before the program can 
choose to not grade a PT sample.
    (2) A laboratory must detect and identify or concentrate and 
identify the parasites to the highest level that it performs these 
procedures on patient specimens.
    (3) A laboratory's performance will be evaluated on the basis of 
the average of its scores for paragraphs (b)(4) through (5) of this 
section as determined in paragraph (b)(6) of this section.
    (4) The performance criterion for direct parasite antigen detection 
is the presence or absence of the parasite antigen. The score is the 
number of correct responses divided by the number of samples to be 
tested, multiplied by 100.
    (5) The performance criterion for the detection and identification 
of parasites includes one of the following:
    (i) The performance criterion for the detection of presence or 
absence of parasites is the presence or absence of parasites. The score 
is the number of correct responses divided by the number of samples to 
be tested, multiplied by 100.
    (ii) The performance criterion for the identification of parasites 
is the total number of correct responses for parasite identification 
submitted by the laboratory divided by the number of parasites present 
plus the number of incorrect parasites reported by the laboratory 
multiplied by 100 to establish a score for each sample in each testing 
event. Since laboratories may incorrectly report the presence of 
parasites in addition to the correctly identified principal 
organism(s), the scoring system must provide a means of deducting 
credit for additional erroneous organisms that are reported and not 
found in rare numbers by the program's referencing process. For 
example, if a sample contained one principal organism and the 
laboratory reported it correctly but reported the presence of an 
additional organism, which was not considered reportable, the sample 
grade would be 1/(1 + 1) x 100 = 50 percent.
    (6) The score for a testing event is the average of the sample 
scores as determined under paragraphs (b)(4) through (5) of this 
section.
0
14. Section 493.919 is revised to read as follows:


Sec.  493.919  Virology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing in virology, a program must provide a minimum of 
five samples per testing event. There must be at least three testing 
events at approximately equal intervals per year. The samples may be 
provided to the laboratory through mailed shipments. The specific 
organisms included in the samples may vary from year to year.
    (1) The annual program must include, as applicable, samples for:
    (i) Viral antigen detection;
    (ii) Detection and identification of viruses; and
    (iii) Antiviral susceptibility or resistance testing.
    (2) An approved program must furnish HHS and its agents with a 
description of the samples it plans to include in its annual program no 
later than 6 months before each calendar year. The program must include 
other important emerging viruses and viruses commonly occurring in 
patient specimens. The program determines the reportable isolates and 
correct responses for antiviral susceptibility or resistance for any 
designated isolate.
    (3) The content of an approved program must vary over time, as 
appropriate. If appropriate for the sample sources, the types of 
viruses included annually must be representative of the following major 
groups of medically important viruses:
    (i) Respiratory viruses;
    (ii) Herpes viruses;
    (iii) Enterovirus; and
    (iv) Intestinal viruses.
    (4) For antiviral susceptibility or resistance testing, the program 
must

[[Page 1563]]

provide at least two challenges per testing event that include viruses 
that have a predetermined pattern of susceptibility or resistance to 
the common antiviral agents.
    (b) Evaluation of laboratory's performance. HHS approves only those 
programs that assess the accuracy of a laboratory's response in 
accordance with paragraphs (b)(1) through (7) of this section.
    (1) The program determines the viruses to be reported by direct 
viral antigen detection, detection and identification of viruses, and 
antiviral susceptibility or resistance testing. To determine the 
accuracy of a laboratory's response, the program must compare each 
response with the response which reflects agreement of either 80 
percent or more of ten or more referee laboratories or 80 percent or 
more of all participating laboratories. Both methods must be attempted 
before the program can choose to not grade a PT sample.
    (2) A laboratory must detect and identify the viruses to the 
highest level that it performs these procedures on patient specimens.
    (3) A laboratory's performance will be evaluated on the basis of 
the average of its scores for paragraphs (b)(4) through (6) of this 
section as determined in paragraph (b)(7) of this section.
    (4) The performance criterion viral antigen detection is the 
presence or absence of the viral antigen. The score is the number of 
correct responses divided by the number of samples to be tested, 
multiplied by 100.
    (5) The performance criterion for the detection and identification 
of viruses is the total number of correct responses for viral detection 
and identification submitted by the laboratory divided by the number of 
viruses present plus the number of incorrect virus reported by the 
laboratory multiplied by 100 to establish a score for each sample in 
each testing event. Since laboratories may incorrectly report the 
presence of viruses in addition to the correctly identified principal 
organism(s), the scoring system must provide a means of deducting 
credit for additional erroneous organisms that are reported. For 
example, if a sample contained one principal organism and the 
laboratory reported it correctly but reported the presence of an 
additional organism, which was not considered reportable, the sample 
grade would be 1/(1 + 1) x 100 = 50 percent.
    (6) For antiviral susceptibility or resistance testing, a 
laboratory must indicate which drugs are routinely included in its test 
panel when testing patient samples. A laboratory's performance will be 
evaluated for only those antiviral agents for which susceptibility or 
resistance testing is routinely performed patient specimens. A correct 
response for each antiviral agent will be determined as described in 
paragraph (b)(1) of this section. Scoring for each sample is based on 
the number of correct susceptibility or resistance responses reported 
by the laboratory divided by the actual number of correct 
susceptibility or resistance responses as determined by the program, 
multiplied by 100. For example, if a laboratory offers susceptibility 
or resistance testing using three antiviral agents and the laboratory 
reports correct responses for two of the three antiviral agents, the 
laboratory's grade would be 2/3 x 100 = 67 percent.
    (7) The score for a testing event is the average of the sample 
scores as determined under paragraphs (b)(4) and (6) of this section.
0
15. Section 493.923 is amended by revising paragraphs (a) and (b)(1) to 
read as follows:


Sec.  493.923  Syphilis serology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing in syphilis serology, a program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events at approximately equal intervals per year. The samples 
may be provided through mailed shipments. An annual program must 
include samples that cover the full range of reactivity from highly 
reactive to non-reactive.
    (b) * * *
    (1) To determine the accuracy of a laboratory's response for 
qualitative and quantitative syphilis tests, the program must compare 
the laboratory's response with the response that reflects agreement of 
either 80 percent or more of ten or more referee laboratories or 80 
percent or more of all participating laboratories. Both methods must be 
attempted before the program can choose to not grade a PT sample.
* * * * *
0
16. Section 493.927 is amended by revising paragraphs (a), (b), and 
(c)(1) and (2) to read as follows:


Sec.  493.927  General immunology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for immunology, the annual program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events at approximately equal intervals per year. The annual 
program must provide samples that cover the full range of reactivity 
from highly reactive to nonreactive. The samples may be provided 
through mailed shipments.
    (b) Challenges per testing event. The minimum number of challenges 
per testing event the program must provide for each analyte or test 
procedure is five. Analytes or tests for which laboratory performance 
is to be evaluated include:
    Alpha-l antitrypsin.
    Alpha-fetoprotein (tumor marker).
    Antinuclear antibody.
    Antistreptolysin O.
    Anti-human immunodeficiency virus (HIV).
    Complement C3.
    Complement C4.
    C-reactive protein (high sensitivity).
    HBsAg.
    Anti-HBc.
    HBeAg.
    Anti-HBs.
    Anti-HCV.
    IgA.
    IgG.
    IgE.
    IgM.
    Infectious mononucleosis.
    Rheumatoid factor.
    Rubella.
    (c) * * *
    (1) To determine the accuracy of a laboratory's response for 
quantitative and qualitative immunology tests or analytes, the program 
must compare the laboratory's response for each analyte with the 
response that reflects agreement of either 80 percent or more of ten or 
more referee laboratories or 80 percent or more of all participating 
laboratories. The proficiency testing program must indicate the minimum 
concentration that will be considered as indicating a positive 
response. Both methods must be attempted before the program can choose 
to not grade a PT sample.
    (2)(i) For quantitative immunology analytes or tests, the program 
must determine the correct response for each analyte by the distance of 
the response from the target value. After the target value has been 
established for each response, the appropriateness of the response must 
be determined by using either fixed criteria or the number of standard 
deviations (SDs) the response differs from the target value.

Criteria for Acceptable Performance

    The criteria for acceptable performance are--

[[Page 1564]]



------------------------------------------------------------------------
                                             Criteria for acceptable
            Analyte or test                        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.
------------------------------------------------------------------------

* * * * *
0
17. Section 493.931 is amended by revising paragraphs (a), (b), and 
(c)(1) and (2) to read as follows:


Sec.  493.931  Routine chemistry.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for routine chemistry, a program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events at approximately equal intervals per year. The annual 
program must provide samples that cover the clinically relevant range 
of values that would be expected in patient specimens. The specimens 
may be provided through mailed.
    (b) Challenges per testing event. The minimum number of challenges 
per testing event a program must provide for each of the following 
analyte or test procedure is five serum, plasma or blood samples.

Analyte or Test Procedure

Alanine aminotransferase (ALT/SGPT)
Albumin
Alkaline phosphatase
Amylase
Aspartate aminotransferase (AST/SGOT)
Bilirubin, total
Blood gas (pH, pO2, and pCO2)
B-natriuretic peptide (BNP)
proBNP
Calcium, total
Carbon dioxide
Chloride
Cholesterol, total
Cholesterol, high density lipoprotein
Cholesterol, low density lipoprotein
Creatine kinase (CK)
CK-MB isoenzymes
Creatinine
Ferritin
Gamma glutamyl transferase
Glucose (Excluding measurements on devices cleared by FDA for home use)
Hemoglobin A1c
Iron, total
Lactate dehydrogenase (LDH)
Magnesium
Phosphorus
Potassium
Prostate specific antigen, total
Sodium
Total iron binding capacity
Total Protein
Triglycerides
Troponin I
Troponin T
Urea Nitrogen
Uric Acid

    (c) * * *
    (1) To determine the accuracy of a laboratory's response for 
qualitative and quantitative chemistry tests or analytes, the program 
must compare the laboratory's response for each analyte with the 
response that reflects agreement of either 80 percent or more of ten or 
more referee laboratories or 80 percent or more of all participating 
laboratories. Both methods must be attempted before the program can 
choose to not grade a PT sample.
    (2) For quantitative chemistry tests or analytes, the program must 
determine the correct response for each analyte by the distance of the 
response from the target value. After the target value has been 
established for each response, the appropriateness of the response must 
be determined by using either fixed criteria based on the percentage 
difference from the target value or the number of standard deviations 
(SD) the response differs from the target value.

Criteria for Acceptable Performance

    The criteria for acceptable performance are--

------------------------------------------------------------------------
                                             Criteria for acceptable
            Analyte or test                        performance
------------------------------------------------------------------------
Alanine aminotransferase (ALT/SGPT)....  Target value 15%.
Albumin................................  Target value 8%.
Alkaline phosphatase...................  Target value 20%.
Amylase................................  Target value 10%.
Aspartate aminotransferase (AST/SGOT)..  Target value 15%.
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%.

[[Page 1565]]

 
Chloride...............................  Target value 5%.
Cholesterol, total.....................  Target value 10%.
Cholesterol, high density lipoprotein..  Target value 20%.
Cholesterol, low density lipoprotein     Target value 20%.
 (direct measurement).
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  Target value 8%
 cleared by FDA for home use.).           (greater).
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      Target value 20%.
 measurement).
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%.
------------------------------------------------------------------------

* * * * *
0
18. Section 493.933 is amended by revising paragraphs (a), (b), and 
(c)(1) and (2) to read as follows:


Sec.  493.933  Endocrinology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for endocrinology, a program must provide a minimum 
of five samples per testing event. There must be at least three testing 
events at approximately equal intervals per year. The annual program 
must provide samples that cover the clinically relevant range of values 
that would be expected in patient specimens. The samples may be 
provided through mailed shipments.
    (b) Challenges per testing event. The minimum number of challenges 
per testing event a program must provide for each analyte or test 
procedure is five serum, plasma, blood, or urine samples.

Analyte or Test

Cancer antigen (CA) 125
Carcinoembryonic antigen (CEA)
Cortisol
Estradiol
Folate, serum
Follicle stimulating hormone
Free thyroxine
Human chorionic gonadotropin (excluding urine pregnancy tests done by 
visual color
comparison categorized as waived tests)
Luteinizing hormone
Parathyroid hormone
Progesterone
Prolactin
Testosterone
T3 Uptake
Triiodothyronine
Thyroid-stimulating hormone
Thyroxine
Vitamin B12
    (c) * * *
    (1) To determine the accuracy of a laboratory's response for 
qualitative and quantitative endocrinology tests or analytes, a program 
must compare the laboratory's response for each analyte with the 
response that reflects agreement of either 80 percent or more of ten or 
more referee laboratories or 80 percent or more of all participating 
laboratories. Both methods must be attempted before the program can 
choose to not grade a PT sample.
    (2) For quantitative endocrinology tests or analytes, the program 
must determine the correct response for each analyte by the distance of 
the response from the Target value. After the Target value has been 
established for each response, the appropriateness of the response must 
be determined by using either fixed criteria based on the percentage 
difference from the Target value or the number of standard deviations 
(SDs) the response differs from the Target value.

Criteria for Acceptable Performance

    The criteria for acceptable performance are--

------------------------------------------------------------------------
                                              Criteria for acceptable
            Analyte or test                        performance
------------------------------------------------------------------------
Cancer antigen (CA) 125................  Target value 20%.
Carcinoembryonic antigen (CEA).........  Target value 15%.
Cortisol...............................  Target value 20%.
Estradiol..............................  Target value 30%.
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%.

[[Page 1566]]

 
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%.
------------------------------------------------------------------------

* * * * *
0
19. Section 493.937 is amended by revising paragraphs (a), (b), and 
(c)(1) and (2) to read as follows:


Sec.  493.937  Toxicology.

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for toxicology, the annual program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events at approximately equal intervals per year. The annual 
program must provide samples that cover the full range of values that 
could occur in patient specimens and that cover the level of clinical 
significance for the particular drug. The samples may be provided 
through mailed shipments.
    (b) Challenges per testing event. The minimum number of challenges 
per testing event a program must provide for each analyte or test 
procedure is five serum, plasma, or blood samples.

Analyte or Test Procedure

Acetaminophen, serum
Alcohol (blood)
Blood lead
Carbamazepine
Digoxin
Gentamicin
Lithium
Phenobarbital
Phenytoin
Salicylate
Theophylline
Tobramycin
Valproic Acid
Vancomycin

    (c) * * *
    (1) To determine the accuracy of a laboratory's responses for 
quantitative toxicology tests or analytes, the program must compare the 
laboratory's response for each analyte with the response that reflects 
agreement of either 80 percent or more of ten or more referee 
laboratories or 80 percent or more of all participating laboratories. 
Both methods must be attempted before the program can choose to not 
grade a PT sample.
    (2) For quantitative toxicology tests or analytes, the program must 
determine the correct response for each analyte by the distance of the 
response from the target value. After the target value has been 
established for each response, the appropriateness of the response must 
be determined by using fixed criteria based on the percentage 
difference from the target value.

Criteria for Acceptable Performance

    The criteria for acceptable performance are:

------------------------------------------------------------------------
                                             Criteria for acceptable
            Analyte or test                        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).
------------------------------------------------------------------------

* * * * *
0
20. Section 493.941 is amended by revising paragraphs (a), (b), and 
(c)(1) and (2) to read as follows:


Sec.  493.941  Hematology (including routine hematology and 
coagulation).

    (a) Program content and frequency of challenge. To be approved for 
proficiency testing for hematology, a program must provide a minimum of 
five samples per testing event. There must be at least three testing 
events at approximately equal intervals per year. The annual program 
must provide samples that cover the full range of values that would be 
expected in patient specimens. The samples may be provided through 
mailed shipments.
    (b) Challenges per testing event. The minimum number of challenges 
per testing event a program must provide for each analyte or test 
procedure is five.

Analyte or Test Procedure

Cell identification
White blood cell differential
Erythrocyte count
Hematocrit (excluding spun microhematocrit)
Hemoglobin
Leukocyte count
Platelet count
Fibrinogen
Partial thromboplastin time
Prothrombin time (seconds or INR)

    (c) * * *
    (1) To determine the accuracy of a laboratory's responses for 
qualitative and quantitative hematology tests or analytes, the program 
must compare the laboratory's response for each analyte with the 
response that reflects agreement of either 80 percent or more of ten or 
more referee laboratories or 80 percent or more of all participating 
laboratories. Both methods must be attempted before the program can 
choose to not grade a PT sample.
    (2) For quantitative hematology tests or analytes, the program must 
determine the correct response for each analyte by

[[Page 1567]]

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

Criteria for Acceptable Performance

    The criteria for acceptable performance are:

------------------------------------------------------------------------
                                             Criteria for acceptable
            Analyte or test                        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%.
------------------------------------------------------------------------

* * * * *
0
21. Section 493.959 is amended by revising paragraphs (b) and (d)(1) 
and (2) to read as follows:


Sec.  493.959   Immunohematology.

* * * * *
    (b) Program content and frequency of challenge. To be approved for 
proficiency testing for immunohematology, a program must provide a 
minimum of five samples per testing event. There must be at least three 
testing events at approximately equal intervals per year. The annual 
program must provide samples that cover the full range of 
interpretation that would be expected in patient specimens. The samples 
may be provided through mailed shipments.
    (d) * * *
    (1) To determine the accuracy of a laboratory's response, a program 
must compare the laboratory's response for each analyte with the 
response that reflects agreement of either 100 percent of ten or more 
referee laboratories or 95 percent or more of all participating 
laboratories except for antibody identification. To determine the 
accuracy of a laboratory's response for antibody identification, a 
program must compare the laboratory's response for each analyte with 
the response that reflects agreement of either 95 percent or more of 
ten or more referee laboratories or 95 percent or more of all 
participating laboratories. Both methods must be attempted before the 
program can choose to not grade a PT sample.
    (2) Criteria for acceptable performance.
    The criteria for acceptable performance are--

------------------------------------------------------------------------
                                              Criteria for  acceptable
             Analyte  or test                        performance
------------------------------------------------------------------------
ABO group.................................  100% accuracy.
D (Rho) typing............................  100% accuracy.
Unexpected antibody detection.............  100% accuracy.
Compatibility testing.....................  100% accuracy.
Antibody identification...................  80% + accuracy.
------------------------------------------------------------------------

* * * * *

    Dated: June 25, 2018.
Seema Verma,
Administrator, Centers for Medicare & Medicaid Services.
    Dated: December 17, 2018.
Robert Redfield, MD
Director, Centers for Disease Control and Prevention and Administrator, 
Agency for Toxic Substances and Disease Registry
    Dated: December 18, 2018.
Alex M. Azar II,
Secretary, Department of Health and Human Services.
[FR Doc. 2018-28363 Filed 2-1-19; 8:45 am]
 BILLING CODE 4120-01-P