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Clinical Laboratory Improvement Advisory Committee
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The Secretary of Health and Human Services is authorized
under Section 353 of the Public Health Service Act, as amended, to establish standards to
assure consistent, accurate, and reliable test results by all clinical laboratories in the
United States. The Secretary is authorized under Section 222 to establish advisory
committees.
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The Clinical Laboratory Improvement Advisory Committee
(CLIAC) was chartered in February 1992 to provide scientific and technical advice and
guidance to the Secretary and the Assistant Secretary for Health regarding the need for,
and the nature of, revisions to the standards under which clinical laboratories are
regulated; the impact on medical and laboratory practice of proposed revisions to the
standards; and the modification of the standards to accommodate technological advances.
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The Committee consists of 20 members, including the
Chair. Members are selected by the Secretary from authorities knowledgeable in the fields
of microbiology, immunology, chemistry, hematology, pathology, and representatives of
medical technology, public health, clinical practice, and consumers. In addition, CLIAC
includes three ex officio members, or designees: the Director, Centers for Disease Control
and Prevention; the Commissioner, Food and Drug Administration; the Administrator, Health
Care Financing Administration; and such additional officers of the U.S. Government that
the Secretary deems are necessary for the Committee to effectively carry out its
functions. CLIAC will also include a non-voting liaison representative who is a member of
the Health Industry Manufacturers Association and such other non-voting liaison
representatives that the Secretary deems are necessary for the Committee to effectively
carry out its functions.
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Due to the diversity of its membership, CLIAC is at times
divided in the guidance and advice it offers to the Secretary. Even when all CLIAC members
agree on a specific recommendation, the Secretary may not follow their advice due to other
overriding concerns. Thus, while some of the actions recommended by CLIAC may eventually
result in changes to the law, the reader should not infer that all of the advisory
committee's recommendations will be automatically accepted and acted upon by the
Secretary.
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Welcome and Introductory Information
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The meeting was called to order by CLIAC Chairman Dr.
Morton Schwartz. The committee members made self-introductions and disclosure statements
of their relevant financial interests as they relate to the topics to be discussed during
the CLIAC meeting. Dr. Edward L. Baker, Director of the Public Health Practice Program
Office (PHPPO) at the Centers for Disease Control and Prevention, thanked the Genetic
Testing Subcommittee, that met on January 27 - 28.
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Presentations and Committee Discussion
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CLINICAL LABORATORY IMPROVEMENT AMENDMENTS
OF 1988 (CLIA) UPDATE
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Centers for Disease Control and Prevention (CDC)
Addendum C-1
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Dr. Carlyn Collins, Director of the Division of
Laboratory Systems (DLS), PHPPO, reported that guidelines for the public health response
to the regulatory closure of cervical cytology laboratories were published in the CDC
Morbidity and Mortality Weekly Report on December 19, 1997. She also said that two
articles on proficiency testing performance (one authored by DLS staff) would be published
in the Journal of the American Medical Association on February 11, 1998. Dr. Collins
announced that the CLIAC minutes from the September, 1997 meeting are posted on the
Division of Laboratory Systems homepage on the Internet (http://www.cdc.gov/phppo/dls);
and that since future minutes will also be posted, the CDC is considering eliminating the
distribution of hardcopy minutes to the public. The CLIAC would still receive the hardcopy
reports. Dr. Collins concluded by noting that the final waiver regulation is still
undergoing work for final clearance, and describing recent changes in the CLIA statute to
clarify that procedures cleared by the Food and Drug Administration (FDA) for home use are
waived regardless of whether or not a prescription is required.
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Committee Discussion:
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A CLIAC member asked for clarification regarding the
waiver process for tests approved by the FDA for home use. Mr. Kevin Malone stated that a
request for waiver must still be submitted to the CDC for registration purposes, and Dr.
Baker added that the CDC continues to have a process for requesting waiver for tests not
approved by the FDA for home use. Several CLIAC members expressed concern regarding
recently published FDA final rules pertaining to exemption of certain medical devices from
the premarket review process, and questioned whether home use tests would fall into this
category. Dr. Steve Gutman explained that the FDA is currently assembling a list of
products that will not be exempt from review, and that he believes that tests for
near-patient and home use will most likely be in this group of products. Dr. Schwartz
asked that this issue be addressed at a future CLIAC meeting, with input from the CDC and
the FDA.
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Health Care Financing Administration (HCFA) Addendum
C-2
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Ms. Judy Yost, Director of Outcomes and Improvement,
HCFA, presented a status report on CLIA implementation. She indicated that approximately
70% of laboratories currently hold either a certificate of waiver or provider-performed
microscopy, and are not subject to routine inspections. Applications for State exemption
for Florida, Georgia, and California are now under review by HCFA and CDC. Reapproval of
deemed organizations is ongoing, and validation inspections of laboratories accredited by
these organizations have all demonstrated that the organizations are performing
satisfactorily. Ms Yost stated that HCFA is reviewing proficiency testing (PT) enrollment
and performance data for 1995 - 1996 as a mechanism to evaluate CLIA implementation under
the Government Performance Review Act. HCFA has noted that some laboratories fail to
enroll in PT in alternate years when they are not being inspected. The CLIA fee schedule
increases for certificate fees were effective as of January 1, 1998. Seventy-one comments
were received in response to the Federal Register notice announcing the revised fee
schedules. HCFA will monitor the fee increases and review the fees based on comments to
the Federal Register notice and the impact on laboratories. Ms. Yost next noted
that Medicare/Medicaid reimbursement for laboratory tests is being denied for laboratories
that are not appropriately certified to perform the services. She ended her update by
indicating that outcome oriented surveys have been implemented, and are being well
received in the field.
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Committee Discussion:
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Committee members asked for clarification of several
points made by Ms. Yost, including the fee increases and Medicare/Medicaid issues, and one
member asked about laboratory fraud and abuse investigations. Ms. Yost explained that HCFA
has pilot projects in several states to investigate billing practices. The member
expressed concerns about integrating billing audits with CLIA inspections, to which Ms.
Yost responded that fraud and abuse investigations are not part of the laboratory surveys
to determine compliance with CLIA requirements.
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GENETIC TESTING
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Genetic Testing Subcommittee Report Addendum C-3
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Dr. Wendell O'Neal summarized the activities of the
January 27-28 meeting of the Genetic Testing Subcommittee. He emphasized the charge to the
Subcommittee and the Subcommittee's relationship to the CLIAC. He noted that presentations
were made to the Subcommittee by: Dr. Margaret McGovern (Mount Sinai School of Medicine);
Dr. Michael Watson (American College of Medical Genetics); and Dr. William Raub (Office of
the Secretary, Department of Health and Human Services - HHS). The presentations included,
respectively, the results of a survey on quality assurance practices in molecular genetics
testing laboratories in the United States; a summary of the issues addressed and
recommendations made by the National Institutes of Health - Department of Energy (NIH/DOE)
Task Force on Genetic Testing; and a report on the activities of an HHS workgroup created
to address regulatory and advisory issues related to genetic testing. Dr. O'Neal then
presented to the CLIAC for consideration a summary of the issues discussed by the
Subcommittee pertaining to the definition of genetic testing; unique aspects of genetic
tests; and issues specific to the pre-analytic, analytic, and post-analytic phases of
genetic testing. The Subcommittee suggested to the CLIAC that these topics be considered
by workgroups, which will bring recommendations to future Subcommittee and CLIAC meetings.
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Committee Discussion:
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Definition of Genetic Testing
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The Genetic Testing Subcommittee recommended that the
CLIAC consider the definition of genetic testing developed by the Subcommittee as a
proposed working definition, which may be revised. Dr. Schwartz added that in developing
this definition, the Subcommittee suggested beginning with a broad definition, which could
be more narrowly defined later. However, he indicated that the Subcommittee had agreed
that the definition should clearly exclude microbial genetic material, and thus the word
"human" was used twice in describing what is being tested. Some CLIAC members
shared their thoughts about terms in the definition that are flagged as being subject to
further discussion, and the Committee agreed that the proposed working definition as
written is sufficient at this point (phrases in italics are subject to further discussion
and potential revision).
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Genetic Test - The analysis of materials derived from the
human body, including human DNA, RNA, chromosomes, proteins, and certain metabolites
in order to detect heritable or acquired disease-related genotypes, mutations,
phenotypes, or karyotypes for clinical purposes. Such purposes include predicting risk of
disease, identifying carriers, and establishing prenatal or clinical diagnoses or
prognoses in individuals, families, or populations.
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Pre-analytic Genetic Testing Issues
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Dr. Pat Charache reviewed the list of work topics for all
phases of genetic testing. She began with the pre-analytic phase of genetic testing,
explaining that each workgroup will address these issues to make recommendations to the
CLIAC regarding the applicability and appropriateness of CLIA. Several CLIAC members
questioned whether the pre-analytic issues are beyond the scope of CLIA and "quality
laboratory testing". One member noted that additional expertise would be required to
address the issues sufficiently. Dr. O'Neal and other Subcommittee members agreed that
some of the areas of concern may go beyond what CLIA can or should address, but that they
need to be considered from a broad policy point of view. The workgroup should consider
where the line of responsibility for the laboratory should be drawn, especially for the
issues of providing consultation to physicians and appropriateness of testing, genetic
counseling, and specimen preparation and handling. From a regulatory (CLIA) standpoint,
the workgroup may determine that some of the issues are already adequately addressed. When
asked if any additional items should be included for consideration, suggestions were made
to add the following: communication between the laboratory and the healthcare provider
community; and ordering of tests by a laboratory, patient (self-ordering) or public health
agency.
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Analytic Genetic Testing Issues
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In discussing the work topics for the analytic phase of
genetic testing, members stated that many of the current CLIA standards for high
complexity testing (especially chemistry, cytogenetics, and histocompatibility) are most
likely adequate and appropriate. The two biggest areas of concern were personnel
requirements and proficiency testing. Dr. Collins raised the issue of validation for
"home-brew" genetic tests, and noted that while CLIA has a requirement for
laboratories to establish performance characteristics for "in house" methods,
there is a gap between FDA/CLIA oversight. CLIAC members added the issues of control of
contamination, workflow, and the laboratory environment to the list of concerns to be
addressed by the workgroup for the analytic phase of testing.
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Post-analytic Genetic Testing Issues
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No additions were made to the work topics for the
post-analytic phase of genetic testing. One CLIAC member asked for clarification as to the
term "non-geneticist care givers". It was explained that these are professional
healthcare providers with no expertise in genetics. Two members stressed that it is
important that genetic test results not be reported directly to patients, but that these
be given to a provider who can appropriately explain the results and counsel the patient
(or family) if needed. Genetic test results were compared to surgical pathology reports,
which always go through a physician, who explains them to the patient.
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Public Comments on Genetic Testing
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There were no public comments on genetic testing.
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PROFICIENCY TESTING
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Overview of CLIA Proficiency Testing Addendum C-4
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Dr. Joe Boone, Assistant Director for Science for DLS,
PHPPO, presented a brief overview of the Federal PT program, including a historical
perspective, the current CLIA program, and goals for PT in the year 2000 and beyond. In
looking towards the future, Dr. Boone stated that goals include updating and clarifying PT
requirements; bringing the CLIA requirements into alignment with international standards
to the extent possible; and making the program relevant by expanding the required PT menu.
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International Guidelines for Proficiency Testing
Addendum C-5
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Mr. Dan Tholen, a statistical consultant with extensive
expertise in PT, described national and international standards and guidelines for PT
providers and compared the CLIA standards with these guidelines. He indicated that
international standards emphasize the educational value of PT. Several areas in which
international standards for PT providers are more stringent than CLIA are in requirements
for an advisory group with technical knowledge and expertise; methods of determining
traceability of assigned values; procedures to establish accuracy of consensus values;
standardization of participant reports, to include information regarding target values and
summary results; and methods of ensuring the homogeneity of samples. International PT
standards also require an oversight body with knowledge of the guidelines to monitor
compliance with PT programs by performing on-site audits and statistical reviews of the
data.
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Committee Discussion:
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The industry liaison commented on manufacturers' concerns
about the increased costs of PT that would result from compliance with more stringent
standards. He questioned the need for higher PT standards, in light of the fact that
United States manufacturers are operating under the FDA Good Manufacturing Practices
requirements. A CLIAC member noted that there are reasons for higher stringency in PT for
environmental testing, or when operating in the global economy, for which the
international standards are intended. Several Committee members raised the issue of the
numbers of ungradable PT samples determined by various providers under CLIA, and
emphasized the need for standardization of the PT programs. Dr. Schwartz ended the
discussion by asking for comments from any of the CLIA-approved PT providers in the
audience. The following providers responded:
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Bill Donohue (Accutest) - Mr. Donohue commented on the
ungradable PT samples, noting that Accutest is a small PT program. He stated that Accutest
attempts to grade small peer groups by using comparable methods, and provides reason codes
for ungraded samples to HCFA and the CDC. He felt that Accutest could comply with
international PT standards.
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Diedre Astin (New York State - NYS, Clinical Laboratory
Evaluation program) - Ms. Astin reported that although NYS is a CLIA-exempt program,
physician offices are not regulated under New York law. NYS gathers PT data for physician
office laboratories. She was concerned about the numbers of ungraded samples, and
nonparticipation in PT. She added that NYS could probably comply with international PT
standards.
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Nick Serafy, Jr. (American Association of Bioanalysts) -
Mr. Serafy commented on the international PT standards, and indicated his concern that
compliance with these standards would increase the costs of PT significantly. He did not
see a need for increased stringency to improve sample quality, and noted that PT for
clinical laboratory testing is not required globally at this time.
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Criteria for Adding Analytes to CLIA PT Addendum C-6
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Ms. Nancy Anderson, a Health Scientist in DLS, PHPPO,
discussed the current PT requirements under CLIA, and asked the CLIAC for recommendations
regarding expanding the PT program content and options for implementation of changes to
PT. She explained that when the 1992 final CLIA regulations were published, the PT program
requirements were gradually phased-in. In addition, the number of analytes or tests for
which PT is currently required is limited compared to the number of analytes for which PT
is available on a voluntary basis. Ms. Anderson asked the Committee for input on criteria
to be used if additional analytes are to be included in the required PT program, and for
suggestions as to whether an expanded program should be implemented in a single step or
through a phase-in process.
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Committee Discussion:
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Several CLIAC members asked for clarification as to which
analytes are "regulated", and one member referenced the CLIA statute which says
that PT is required for all analytes for which it can be developed. Members asked if
required PT analytes could be removed from the list, and
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whether the law states that analytes must be added. Dr.
Collins agreed that the law does require PT for all analytes (except when HHS has
determined that a PT program can not reasonably be developed), and noted that the preamble
to the 1992 final regulations explained that although required PT was limited at that
time, analytes would be added to those that are required. She indicated that the law may
not allow removal of regulated analytes. Although there was disagreement among Committee
members as to which criteria for adding analytes be given the highest priority, they did
suggest that all of the criteria mentioned by Ms. Anderson are important to consider. The
Committee also recommended that a PT Subcommittee be re-established to look at the issues
presented by Ms. Anderson.
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Public Comments
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There were no public comments for the CLIAC.
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Concluding Remarks
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Dr. Schwartz announced that the date for the next CLIAC
meeting would be May 29, 1998, preceded by a meeting of the Genetic Testing Subcommittee
on May 27 - 28. Dr. Schwartz then adjourned the CLIAC meeting.
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I certify that this summary report of the January 29 - 30,
1998, meeting of the Clinical Laboratory Improvement Advisory Committee is an accurate and
correct representation of the meeting.
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/S/ Morton K. Schwartz, Ph.D.
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Chairman
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