September 27-28, 2000
Table of Contents
I. Record of Attendance
II. Call to Order and
III. Orientation for
- Travel Guidelines
- Federal Advisory
Procedure Act/Conflict of Interest
- History of Clinical
laboratory Improvement Amendments of 1988 (CLIA)
- CLIAC Process
IV. Call to Order -
Full Committee Introductions
V. Presentations and
Test Systems Not
Currently Regulated under CLIA
IV. The Addenda
Record of Attendance
Dr. Toby Merlin, Chair
Dr. George Birdsong
Dr. Joseph Campos
Dr. Patricia Charache
Dr. Brenta Davis
Dr. Andrea Ferreira-Gonzalez
Dr. Jaime Frias
Dr. Ronald Gagne
Dr. Barbara Goldsmith
Dr. Edward Hook
Ms. Cynthia Johns
Dr. Ronald Luff
Dr. Valerie Ng
Dr. Timothy O'Leary
Mr. Stewart Richardson
Dr. Lawrence Silverman
Dr. Lawrence Sturman
Dr. Roland Valdes
Dr. Alice Weissfeld
L. Baker, CDC
Ex Officio Members
Dr. Robert Martin, CDC
Ms. Judith Yost, HCFA
Ms. Kay Setzer, AdvaMed
Centers for Disease
Control and Prevention
Ms. Nancy Anderson
Dr. Rex Astles
Ms. Carol Bigelow
Dr. Joe Boone
Ms. Gail Bosley
Ms. Diane Bosse
Dr. Bin Chen
Ms. Judy Delany
Ms. Sharon Granade
Dr. Thomas Hearn
Dr. Adam Manasterski
Ms. Priscilla Patin
Mr. Darshan Singh
Dr. Barbara Slade
Dr. Steven Steindel
Mr. Eric Thompson
Ms. Rhonda Whalen
Improvement Advisory Committee
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
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.
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
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 regulations, the reader should not
infer that all of the advisory committee's recommendations will be
automatically accepted and acted upon by the Secretary.
INTRODUCTORY/ORIENTATION INFORMATION FOR NEW MEMBERS
Dr. Toby Merlin, CLIAC
Chair, began the orientation session for new CLIAC members by introducing
Dr. Robert Martin, Director, Division of Laboratory Systems (DLS), Public
Health Practice Program Office (PHPPO). Dr. Martin welcomed the CLIAC, and
stressed the value of the Committee's input to the Department of Health
and Human Services (HHS) and the agencies responsible for implementation
of the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Dr.
Martin also thanked DLS staff who support the CLIAC meetings, after which
the CLIAC members and CDC staff attending the meeting made
As part of the
orientation, Dr. Martin presented the organizational structures of CDC,
PHPPO, and DLS. He then described the major CDC initiatives for the year
2000, the DLS priorities, and summarized the projects and activities
conducted in DLS.
Dr. Merlin outlined the
framework for CLIAC operations, emphasizing that CLIAC is an HHS advisory
committee, and is not responsible for writing regulations. He added that
the meetings provide an opportunity for open discussion by Committee
members and input from the public.
ORIENTATION FOR NEW
Ms. Priscilla Patin,
Committee Management Specialist, DLS, reviewed the travel rules and
guidelines that apply to CLIAC members. She briefly outlined policies and
procedures for making airline reservations, and reimbursement of allowable
expenses, including hotel, meals, ground transportation, and other
Mr. Kevin Malone,
Senior Attorney, Office of General Counsel, Office of the Director, CDC,
described the Federal Advisory Committee Act (FACA) passed on October 6,
1972, explaining the role and purpose of federal advisory committees. He
said that more than 1000 federal advisory committees exist, and serve as a
means of public participation in the government decision-making process.
Members of the committees are appointed by relevant government agencies,
with committee membership balanced to represent varying points of view,
expertise, geographic distribution, gender, ethnic and minority groups.
Committee members are special government employees when they serve on
advisory committees, and are subject to the same rules as other government
employees when serving in this capacity. Most federal advisory committee
meetings are open to the public, except where there are issues of national
security, industry trade secrets, or other proprietary information being
discussed. However, even closed meetings are announced to the public by
publishing the notice of the meeting in the Federal Register.
Procedure Act / Conflict of Interest
Mr. Kevin Malone
briefly explained how federal laws are enacted and regulations developed,
with input from the public at several points in the process. He noted that
CLIAC was established in 1992 to provide a means for public input on the
CLIA regulations, which will continue to evolve as laboratory testing and
technology change over time. He then introduced a videotape on FACA and
ethical issues that pertain to special government employees.
videotape, Mr. Malone gave a brief overview of conflict of interest rules
that apply to CLIAC members. He stated when serving on the Committee as
federal employees, members should not have financial interests that would
compromise their participation. However, he explained, in as much as
financial conflicts of interest are inherent in certain instances of
advisory committee membership, waivers are granted if the need for service
outweighs the conflict.
CLIA History and
Overview (Addendum B)
Ms. Rhonda Whalen,
Chief, Laboratory Practice Standards Branch (LPSB), DLS, PHPPO, presented
a chronological overview of the CLIA law and its implementation,
emphasizing key features of the law, and revisions to the regulations
since publication of the final regulation in 1992. She explained that the
regulations are based on the complexity of laboratory testing, and
reviewed the CLIA technical standards, including proficiency testing (PT),
patient test management, quality control (QC), personnel, and quality
assurance. Ms. Whalen also outlined the roles and responsibilities of the
Health Care Financing Administration (HCFA), Food and Drug Administration
(FDA), and CDC in CLIA implementation, and showed the relationship of
CLIAC to the organizational structure of HHS.
Dr. Merlin concluded
the orientation session by describing the process usually followed at
CLIAC meetings. He read section 493.2001 of the CLIA regulations
describing the establishment and function of the CLIAC, and explained
that, in general, presentations are made to the CLIAC by HHS
representatives or technical experts on a specific topic, followed by
group discussions by the Committee. Since the meetings are public, there
is also opportunity for public comment. Although there may be consensus at
the end of a discussion, CLIAC may not vote on every issue. Dr. Martin
clarified that although the CLIAC is an advisory committee, some meetings
are primarily informative and not intended to solicit specific advice. Dr.
Merlin also explained that there may be instances where there is a need
for CLIAC Subcommittees or Workgroups to be formed to address certain
issues relevant to clinical laboratory testing.
CALL TO ORDER - FULL
Dr. Toby Merlin called
the CLIAC meeting to order, and reviewed the role of this Advisory
Committee. Dr. Robert Martin welcomed CLIAC members, who had not attended
the orientation session, and summarized the materials covered. He
introduced three new DLS branch chiefs:
Dr. Barbara Slade,
Chief of the Laboratory Practice Assessment Branch (LPAB); Ms. Judy Delany,
Chief of the Laboratory Practice Training Branch; and Ms. Rhonda Whalen,
Chief, LPSB. All CLIAC 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.
Centers for Disease
Control and Prevention (CDC)
Medicine Sentinel Monitoring Network (Addendum C)
Steindel, Supervisory Health Scientist, LPAB, DLS, PHPPO, presented a
brief history of the Laboratory Medicine Sentinel Monitoring Network (LMSMN)
and an update on current network activities. He envisions this network as
developing into a data source for information on laboratories, that could
be used to assess the impact of CLIA. He pointed out that many anecdotal
statements are made about the health system; the network is designed to
pose questions and collect data to prove or disprove these anecdotal
statements. The network serves as a mechanism to monitor the performance
of emerging tests and factors that impact the performance of these tests.
original LMSMN cooperative agreements to gather data on laboratory
operations were awarded to the State of Washington, New York City and the
University of Alabama, Birmingham. New York City and the University of
Alabama no longer participate in the program, however the University of
Alabama data is now being used for outcomes research. Washington has
remained in the program and monitors approximately 600 laboratories in
four states in the Pacific northwest. Half of the laboratories monitored
in this program are laboratories that perform moderate and/or high
complexity testing, with the remaining half comprised of waived
laboratories. There are currently 15 Washington reports available via the
DLS intranet site (http://www.phppo.cdc.gov/dls).
of areas examined by Washington State are the following:
patient reports. This has been the only prospective report conducted.
Dr. Steindel said that laboratory response to prospective reports is
poor, however there were no unique problems identified in this study.
sources. This study gathered data on the various sources of training
used by laboratories in the network and reported the preferred method
of training by laboratory type.
Testing (PT). This study found that most laboratories would continue
to participate in PT if it was not required, although many would
prefer fewer PT challenges per year.
CDC re-solicited proposals to expand the LMSMN project. Washington
continues to participate in the program, with the addition of Arkansas and
New York. Arkansas is monitoring more than100 laboratories, most of which
perform only waived testing. New York is primarily looking at the
laboratory practices of limited service laboratories and assessing the
accuracy of waived testing performed in these settings versus traditional
Care Financing Administration (HCFA)
Update and Discussion of Pilot Project (Addendum D)
Yost, Director, Division of Laboratories and Acute Care Services, Center
for Medicaid and State Operations, HCFA, presented an overview of the
number of laboratories registered, accrediting organizations approved and
deficiencies cited in inspections of certificate of compliance
laboratories. According to the data presented, the top four deficiencies
over the past three survey cycles were: 1) failure to follow the
manufacturer's instructions; 2) no quality assurance (QA) program; 3) no
QC testing; and 4) personnel deficiencies. She said HCFA is taking an
educational approach to address these problems. She noted that
laboratories are constantly changing and laboratory registration provides
a means to monitor trends. The laboratories self-select their application
type, with the majority registering as physician office laboratories
(POLs) and applying for a certificate of waiver. She pointed out that
laboratories issued a certificate of waiver have minimal regulatory
requirements, and 74% of the laboratories are in the
waiver/provider-performed microscopy (PPM) category with no oversight
complaints about waiver and PPM laboratories, HCFA initiated a pilot study
of a sample of those laboratories in Ohio and Colorado. The study
demonstrated that over 50% of the laboratories had problems, and the three
most common deficiencies were: 1) failure to follow the manufacturer's
instructions; 2) absence of QC testing; and 3) testing beyond the scope of
the certificate. The pilot study is being expanded to include laboratories
in eight additional states, with 2.5% of the laboratories in those states
evaluated through an announced survey. The surveyors will gather
information on waived and PPM testing and assist the laboratories in
correcting any problems identified during the survey. In addition,
surveyors from Ohio and Colorado will revisit laboratories that were
previously evaluated to determine whether identified problems have been
discussing the criteria FDA should use in determining waived status, Ms.
Yost provided the following HCFA recommendations:
level of accuracy of test system appropriate for untrained users.
previous performance (e.g., proficiency testing) data in review.
use of device (e.g., monitoring, screening) when developing threshold
for waiver decision.
criteria for re-evaluation if device fails in field.
pointed out the perception that waived tests don't have a negative impact
on patient care. They asked whether there is any data on the improper use
of waived devices or any data associating testing errors with patient
harm. Ms. Yost said no and noted that surveyors only cited deficiencies
that could have an impact on patient care and suggested further studies
may be possible after the expanded pilot study is completed. Dr. Steindel
pointed out that outcome studies are difficult to obtain because of the
limited amount of laboratory data on patient care.
asked about the type of deficiencies cited in the pilot studies. Ms. Yost
said the most frequent problem was obsolete instructions or the lack of
the appropriate instructions for the specific test kit being used by the
laboratory. She said there is no training requirement for personnel
performing waived tests. She emphasized that in many cases, personnel
performing waived testing are non-laboratory personnel.
expressed the following concerns:
between patient outcomes and test results is needed.
is a wide range of off-label use of test systems. Concerns were
expressed about preventing off-label use and regulatory authority for
the instructions for some rapid tests for group A streptococcus
indicate that a negative test should be confirmed by culture, cultures
are not performed.
do not have laboratory training. A mechanism is needed to disseminate
information on laboratory practices.
said the solution will need to be multifaceted. Education is important,
however there are costs associated with conducting the surveys, and waived
and PPM laboratories are not charged an inspection fee.
commented that anecdotes plus data leads to policy and requested that the
Committee members relate stories based on fact.
Drug Administration (FDA)
Waiver, Genetic Testing, FDA Reorganization (Addendum E)
Hackett, Division of Clinical Laboratory Devices (DCLD), Centers for
Devices and Radiological Health (CDRH), FDA, briefly discussed waived
tests, genetic testing and structural re-organization plans for the DCLD.
Dr. Hackett began with a discussion of waived tests. He referenced the
proposed regulation, published in September 1995, clarifying the statutory
criteria for a waived test. He reminded the Committee the FDA
Modernization Act of 1997 (FDAMA) changed the definition of a waived test.
He said industry believes the FDA processes for clearance (510(k) or
premarket approval (PMA)) should be used to establish the effectiveness of
a waived test and the waiver accuracy criterion should be defined as
untrained users obtaining the same result as trained professionals. Dr.
Hackett mentioned the FDA public workshop held in
the criteria and process for waiver, and noted that Ms. Clara Sliva would
report on that meeting. After the public meeting, FDA determined the next
steps with regard to waiver are:
the workshop comments.
an interim guidance document.
to follow the September 1995 proposed criteria.
information with CDC and HCFA.
topic of genetics, Dr. Hackett said the FDA does not currently regulate
"home brew" tests, although the Secretary's Advisory Committee
on Genetic Testing (SACGT) feels the FDA should have oversight of all
genetic tests, including "home brew" tests. He stated that FDA
genetics activities now include the FDA Genetics Advisory Panel, the CDC
Genetic Laboratory Forum, and SACGT.
Dr. Hackett discussed the DCLD proposed organizational changes. He said
currently DCLD consists of three branches and the proposal would create
six branches. He then listed the DCLD goals and five policy development
Discussion - Genetic Testing
asked about the proposal for classifying the 400 genetics tests currently
in use. Dr. Hackett replied the FDA will look at some of them, but is
primarily focusing on new tests. Another member expressed concern that
current genetic testing might be stopped while tests are under review by
the FDA. Dr. Hackett replied that there would be no interruption in
testing. One member asked where, in the new structure of the FDA, genetic
tests will be evaluated. Dr. Hackett stated that the evaluations will take
place throughout all of the branches, but primarily in the Immunology
Waiver Criteria Public Workshop (Addendum F)
Sliva, CLIA Coordinator (Acting), DCLD, Office of Device Evaluation, CDRH,
FDA, presented a report on the August 14 - 15, 2000, FDA CLIA Waiver
Criteria Public Workshop. She briefly reviewed the history of the FDA's
involvement in complexity categorization from the initial implementation
of CLIA to the present. She reviewed the role of CDRH and the Center for
Biologics Evaluation and Research in product review and categorization and
listed the benefits to manufacturers and laboratories of test
categorization performed by the FDA.
then reviewed the three paths to waiver: nine tests listed in the CLIA
regulations; waiver based on criteria in the proposed rule published
September 13, 1995; or automatic waiver when a product is cleared by the
FDA for over-the-counter (OTC) or prescription home use. She said an
increasing number of tests have been cleared by the FDA for OTC or
prescription use (e.g. prothrombin time) and briefly reviewed the FDA's
criteria for granting this status.
Sliva discussed the FDA Waiver Workshop meeting. She reviewed the comments
made by individuals representing professional organizations, industry,
medical associations, inspection agencies and clinicians. She said the FDA
is currently drafting a Level 1 Guidance Document on criteria for waiver
and may ask CLIAC for advice.
Discussion - Waiver
raised a number of issues regarding the criteria and process for waiver
currently being developed and used by the FDA. Their concerns centered
around: the interpretation of the CLIA and FDAMA statutes regarding
waiver; definitions for accuracy, precision, and risk of harm; intended
use of waived tests; studies required for waiver determinations versus
requirements for FDA 510(k) or PMA clearance/approval; the off-label use
of waived tests; waiver based on OTC or prescription home use;
post-analytic concerns; post-market surveillance; the absence of required
standards for laboratories performing waived testing; and potential waiver
of new technology, including genetic tests. A summary of the pertinent
comments and the CLIAC plans for addressing waiver issues follows.
of Accuracy vs. Precision (trained versus untrained users)
inquired whether accuracy is being considered for waiver determinations.
Another member pointed out that making waiver determinations based on
comparing the performance of untrained users to laboratory professionals
(as recommended by industry) is defined as precision, not accuracy.
Using this approach, manufacturers only need to show that the same test
result can be obtained by trained and untrained users.
members emphasized the need to define accuracy, with one member
suggesting accuracy be defined for medical decision making. Ms. Sliva
said there are two interpretations of the definition of accuracy, the
laboratory definition (scientific) and the legal interpretation of the
law (FDAMA). For waiver determinations, she said the FDA is considering
using the definition of accuracy that is based on legal interpretation
(i.e. data demonstrating that untrained users obtain the same result as
trained professionals) rather than comparing waived test performance to
the reference method.
member stressed that accuracy should be defined the same by everyone.
Another CLIAC member recommended accuracy be documented using clinical
and analytical sensitivity and precision.
member asked if the term accuracy should be removed from the law.
suggested the FDA evaluate studies comparing trained versus untrained
Sliva said the FDA is considering this approach.
asked who should define risk of harm, and another member responded that
perhaps CLIAC should define this.
member suggested that the terms "risk of harm" and
"erroneous result" need to be better defined and explored
further. Another member agreed this is important and an explicit
explanation of "harm" is needed.
noted that accuracy and risk of harm are all context specific. Another
member said laboratory tests only provide information and harm only
occurs when action is taken.
noted that risk is a subjective term.
Martin agreed that risk of harm is a subjective term, and for this
reason, the CDC evaluated accuracy as part of their waiver
determinations to minimize risk of harm.
member said that the "OR" in the statute - "employ
methodologies that are so simple and accurate as to render the
likelihood of erroneous results by the user negligible, or
(emphasis added) the Secretary has determined pose no reasonable risk of
harm to the patient if performed incorrectly." - should be changed
to an "AND".
/ Premarket Approval Clearance Processes
Steindel commented that the FDA uses substantial equivalence to clear
instruments/tests under the 510(k) process, and accuracy may not be
evaluated in this process.
Setzer, Manufacturer Liaision, stated the process for 510(k) or PMA
clearance, as defined under the Federal Food, Drug, and Cosmetic Act,
assesses accuracy through comparison with a reference method,
calibration, linearity and reportable range. She added if the product
has no value to the public, then it doesn't get cleared. She said CLIA
was meant to focus on the user of the products, and the laws (FDA and
CLIA) should not be redundant.
asked if studies are included in the FDA 510(k) or PMA process to show
that a lay user can perform the test as well as a laboratory worker. Ms.
Sliva responded that these studies are included if this is part of the
manufacturer's claims for the product.
Martin said the FDA product reviews focus on the manufacturer's claims.
Dr. Hackett clarified that, under the premarket clearance/approval
process, the FDA looks at accuracy, precision, and positive and negative
said the FDA evaluation clears or approves a test for market use. The
waiver process should be a separate determination using parameters such
as user competency and how well a user can perform and interpret the
Use of Waived Tests
suggested intended use be used for waiver evaluations.
member said intended use studies are more optimistic than in real
practice because the user always performs better when observed.
member asked whether tests could be waived on the basis of how they are
used, rather than the accuracy of the test. Dr. Thomas Hearn, Deputy
Director, DLS, replied that the CLIA construct does not address test use
and that is the reason CDC tried to limit risk associated with waived
tests by requiring these tests be highly accurate.
Use of Waived Tests
member asked if the FDA could cite off-label use of waived tests. Dr.
Hackett said that the FDA could do so if the manufacturer promoted that
Setzer said the manufacturer tries to provide accurate labeling for use
of a test, but users don't always read the labeling. She added that the
manufacturers also provide education.
Steindel pointed out that off-label use of a waived test would result in
the laboratory performing a high-complexity procedure, because
performing off-label testing would not be categorized, and as such,
would be considered high complexity. However, a member pointed out that
if it was a waived laboratory, probably no one would know that the
laboratory was performing a high complexity procedure.
member asked whether the FDA considers the consequences of off-label use
when it clears a product for home use. Dr. Hackett said no, the FDA must
assume the user is following the manufacturer's labeling.
Based on OTC or Prescription Home Use
member commented on the difficulty of reconciling the different
philosophies of the FDA and CDC for determining waiver status. For
example, FDA's criteria for clearing a prothrombin time test for OTC
prescription use differs from the CDC process for waiver approval. Ms.
Sliva responded that a different set of criteria (as opposed to waiver
criteria) were used for the determination of OTC prescription use for
the ITC prothrombin time test. By law, any test system approved for home
use or cleared for OTC use by the FDA is also approved for waiver. Ms.
Whalen said that since the prothrombin test was cleared through the home
use process, and automatically approved for waiver, the comparability
between the test system instructions for the professional product versus
home use product was evaluated to determine waiver status of the
professional product. The accuracy of the ITC prothrombin test was not
evaluated by CDC. Another member commented on the difficulty in dosage
regulation if the home use prothrombin time result differs from the
result obtained in a laboratory.
said it seemed unreasonable to be able to market a test for OTC use and
not be able to use it in a POL as a waived test. It was noted that FDAMA
clarified the waiver provisions by requiring that any test approved for
home use is approved for waiver under CLIA.
suggested that since FDAMA changed the CLIA law to waive any test system
approved/cleared for home use, changes to the home use process might
need to be considered.
Setzer commented that industry develops test systems users want, and
users want simple tests that will provide faster results, allowing the
physician to treat the patient more rapidly. A CLIAC member said a home
test may get people into the physician's office sooner, however, the
patient expects the physician to perform tests that are higher quality
than those that could be performed at home.
stated the post-analytic phase of testing needs to be considered in
evaluating test systems for waiver.
inquired about post-market surveillance of waived tests. Ms. Sliva said
that if the product doesn't work in laboratory settings, it is an FDA
member suggested there are some areas that could be monitored by the FDA
after waiver approval, such as comparing performance of waived tests in
different test settings. Ms. Sliva said the FDA is studying this issue.
Tests Exempt from Standards
members requested a clarification of waived status. Ms. Whalen said
waived tests are exempt from the CLIA regulations. A Committee member
pointed out that waived tests are not subject to quality assurance,
proficiency testing or personnel regulations, so moving more tests to
waived status may have the effect of circumventing the intent of CLIA
(quality testing). The member expressed concern that the waiver category
may be a mechanism to undermine CLIA.
member asked whether genetic testing is included in the waiver process.
A Committee member responded that most genetic tests are high complexity
Carolyn Jones, representing the Advanced Medical Technology Association,
expressed the opinion that CLIA is stagnant and does not fit all
situations; it does not address new technology.
suggested that the Committee focus on the criteria that should be used to
determine waiver status. He said the principles need to be clarified and
the issues that drive policy practices need to be defined. To summarize
the CLIAC concerns, Dr. Merlin suggested that the Committee try to frame a
statement such as "the committee urges the FDA to exercise caution in
determining the waiver criteria."
member summed up the discussion by saying waived tests must be simple to
perform and pose no risk of harm; the FDA needs to define accuracy more
substantively; guidance on the definition of accuracy should be addressed
with the FDA evaluating accuracy and the positive and negative predictive
values; the place where testing is to be performed and the type of users
performing testing needs to be evaluated; the implementation of the CLIA
regulations is the responsibility of the laboratory director and includes
a determination of which methodologies are appropriate for patient
Committee agreed the waiver criteria of simple and accurate should be
maintained. It was pointed out that since CLIAC last addressed the waiver
issue, there have been changes in both testing technologies and in the
statute. Dr. Baker suggested the formation of a CLIAC workgroup to
evaluate the waiver criteria and noted the definition of accuracy is
central to the discussion. Dr. Merlin asked the Committee to: 1) frame the
question; 2) appoint members to the Waiver Workgroup; 3) clarify points
for the Workgroup and; 4) identify issues of concern. He said the charge
to CLIAC was to provide consultation to HHS concerning the recommended
criteria to be used for determining waiver status.
Committee identified 23 areas of concern for the Waiver Workgroup to
of lack of compliance with manufacturers directions.
use of waived tests.
developing faster than policy. Waiver reviews need to consider the way
a test will be used.
of "accuracy"; technical and clinical aspects.
of waived does not reflect discipline specific need. (e.g. simple
"Or" as used in the law.
of data relating to adverse outcomes to waived status.
testing and internet-based testing.
waived testing that is not cleared/approved by the FDA for
over-the-counter use, testing personnel should have some sort of
responsibility of manufacturer/vendor to assure that the purchaser
knows how to use a waived test.
of post-analytic phase of testing. Where are post testing resources?
risk of harm? Psychological?
versus untrained person.
test versus CLIA-user venue.
advisory panel members should participate in the Waiver Workgroup.
of personnel standards for waived laboratories.
FDA on criteria for "home use" approval.
previous CLIAC waiver recommendations.
for withdrawal of waiver.
resolve interagency differences.
venue for waived test used off-label. Multiple venues.
nominated the following members to serve on the Waiver Workgroup: Dr.
Joseph Campos, Dr. Barbara Goldsmith, Dr. Roland Valdes, Dr. Ronald Gagne,
Ms. Cynthia Johns,
Patricia Charache, Ms. Kay Setzer, and HHS representatives (ex officio
Dr. Hearn asked if CLIAC had a recommendation concerning the waiver
process FDA should use while it is determining the criteria and process
for waiver reviews. The Committee recommended maintaining the current
guidelines published in the September 1995 Federal Register notice, and
using these guidelines in evaluating waiver applications. The Committee
unanimously agreed to send a letter to Donna Shalala, Secretary of HHS,
expressing concerns about the waiver process, and requesting an
opportunity to comment and provide advice on the criteria for waiver
determinations. The letter was drafted and approved by CLIAC (see Addendum
Systems Not Currently Regulated Under CLIA (Addendum H)
Hook, Division of Infectious Diseases, University of Alabama at
Birmingham, presented a summary of the CLIAC Workgroup meeting on test
systems not currently regulated by CLIA. He said the Workgroup agreed that
the phrase "materials derived from the human body" should be
interpreted broadly and concurred that exhaled gas meets the CLIA
definition of a specimen under certain conditions. The Workgroup concluded
there are possible criteria that could be used to determine CLIA
applicability (i.e. testing site and use of test results) to breath tests
and other tests not currently regulated, and agreed there are unique
testing contexts for which CLIA would not be appropriate. They said most
testing should be regulated with personnel, QC, and test reliability
standards being applicable. They also said CLIA is broad enough that
specimen type or manner of collection did not have to be limited. Finally,
the Workgroup agreed some testing should possibly be excluded from CLIA
regulation, and further discussion is needed on the topic of unregulated
commented that there will be a broad expansion of breath testing
technology and asked about future Workgroup deliberations. Dr. Hook
answered that future deliberations had not been planned, and a decision
must be made as to whether the Workgroup would continue. Another member
said CLIA should regulate these tests and also consider new technologies.
However, certain concepts should be followed: 1) identify a concrete
problem; 2) define the problem, including the magnitude and consequences;
3) propose a remedy; 4) ensure the resources are available to solve the
problem; 5) implement the remedy and; 6) monitor the effectiveness of the
remedy. Dr. Hook said he agreed with all of the steps, except the need to
identify a concrete problem. He said potential problems should be
anticipated, as they are easier to deal with before they become concrete.
The member explained that experience is needed to develop standards to
address problems that are well defined.
summarized Committee consensus that the Workgroup on unregulated testing
should continue its activities and asked what else was needed from CLIAC.
Dr. Martin responded that although the primary issue was breath testing,
what other tests would CLIAC suggest be considered for CLIA regulation and
what other issues did CLIAC believe necessitate the continuation of
Workgroup activity? Ms. Whalen commented that data is needed. She said the
Workgroup discussed the data needs and suggested that broader
representation was needed on the Workgroup. She also said that issues need
to be prioritized. Ms. Setzer commented that the NCCLS has standards for
point-of-care testing devices based on risk analysis of the devices and
the unique aspect of QC testing. Dr. Merlin asked about the Workgroup
recommendation that HHS proceed with rule-making for unregulated testing
devices but cautiously. One member responded that a problem must first be
identified before regulations could be developed. The member said that
only specific test systems should be considered for regulation because the
technologies available to monitor patients are different from those used
in the laboratory. Dr. Martin said that CDC and HCFA would not proceed
with rule-making at this time, additional consultation is needed.
Frazier representing the American Association for Anesthesiologists
emphasized the contrast in testing equipment used at the bedside versus
instruments used in the laboratory. He said in the operating room, the
only requirement is to show that the devices don't shock the patient, and
calibration of most devices is not performed even yearly. He emphasized
resources are needed to assure that the devices are working correctly.
Update: Laboratory Workforce Shortages (Addendum I)
Anderson, Senior Health Scientist, LPSB, DLS, PHPPO, reviewed the past
CLIAC discussions on clinical laboratory workforce shortages, during which
it had been suggested that more data and current data are needed to
accurately assess the scope of the problem. She said the Health Resources
Services Administration (HRSA) was contacted to determine whether
additional data were available. HRSA has taken steps to address clinical
laboratory workforce shortages, including awarding allied health training
grants to academic institutions. HRSA also has two projects underway to
provide additional data; development of state health workforce profiles
and development of a comprehensive analysis of national trends and issues
affecting approximately 16 health care professions. Ms. Anderson informed
CLIAC that the letter to the Secretary of HHS alerting her of the
workforce shortage was sent on May 16, 2000. Also, in response to the
CLIAC concerns about the laboratory workforce, two DLS staff members
attended the Summit on the Shortage of Clinical Laboratory Personnel (SSCLP)
hosted by the American Society for Clinical Laboratory Science (ASCLS) in
June 2000. She said that based on the progress made at the ASCLS Summit
and ongoing activities of this working group, it is believed that the
Summit participants will complete the development of a strategic plan,
which will address both long- and short- term CLIAC concerns relative to
laboratory workforce shortages.
Summit on the Shortage of Clinical Laboratory Personnel (Addendum J)
Griffith, president, ASCLS, summarized the SSCLP held on June 16, 2000. He
said the Summit was seeking to identify the components of the workforce
shortage problem, categorize these components and identify solutions
through development of a strategic plan. Nineteen professional
organizations were represented at the Summit. Some components considered
by Summit attendees included test settings, growth rate of the field,
vacancy rates by geographic location, and fiscal impact of these shortages
on the laboratory profession. He pointed out that the laboratory workforce
is decreasing as a result of both losing people to industry and the
retirement of long-term laboratory employees. He said the current training
programs are not getting adequate numbers of qualified applicants and are
producing only half of the personnel needed in this field. In addition,
over the last 25 years, approximately half of the medical technology
training programs have been discontinued. He reviewed the factors
influencing people not to enter this profession. He said there is a
playing field shift and, in the future, the healthcare arena may be
characterized by quality-oriented issues rather than fiscally-oriented
issues. He said there are five components affecting the workforce:
education; transition (combined) healthcare; financial resources; human
resources; and technology. He reviewed the draft of the Summit strategic
plan consisting of data collection, marketing, recruitment, financing of
education, profession in transition, and co-operation. He said the next
phase will occur after the strategic plan is fully developed and announced
that ASCLS will be sponsoring another Summit meeting in the near future to
continue the work begun at the June 2000, Summit.
said that the methods of data collection are partially obscuring the
problem. If the individual laboratory disciplines are examined, it will be
apparent that some areas have greater shortages. Different points of time
need to be examined, and competitors for the new workforce must be
considered. Further, pay scales are dismal and financial data must be
examined carefully, excluding supervisors and managers. The member also
pointed out that the academic institutions have lost teachers. Another
member commented that opening new training programs won't solve the
problem; students must be attracted to the programs. One member asked
whether the pool of trained people, who have left the profession, has been
examined to determine their reasons for leaving. Dr. Griffith answered
that this will be addressed at the next Summit. Another member said that
the largest drain on the workforce is coming from the professions outside
of medicine. Money is really the issue, employee pay and training in these
non-clinical professions are more attractive. Healthcare is competing with
a free market economy; therefore, the healthcare economy must be
restructured. Another member agreed and said that workforce projections to
2020 indicate a low healthcare workforce overall. In general, money
attracts people, but the quality of the workplace retains them. The member
said that attrition is a huge factor in the shortages and retirement
trends are important; older people may be retained with job sharing.
Another factor is the impact of future technologies in which technical
oversight may not be necessary. There will be different demands on the
workforce, formulas will be altered. The Committee nominated Dr. Brenta
Davis to represent CLIAC at the next ASCLS Summit meeting.
Genetic Test Survey (Addendum K)
Margaret McGovern, Mount Sinai Medical Center, spoke about the results of
the survey she conducted on biochemical genetic testing and reporting
practices. She said that biochemical genetic testing has some unique
concerns, such as very few reference methods or reference materials for
biochemical tests. She said the survey respondents consisted of greater
than 1000 laboratory directors, 61% certified by the American Board of
Medical Genetics (ABMG), with the majority of these clinical biochemical
geneticists. The majority of the responses were from hospital
laboratories. Some laboratories had two directors, each responding to a
portion of the survey.
showed that 92% of the laboratory supervisors had at least a Bachelor of
Science degree, while 95% of the on-site supervision and 40% of the
clinical consultation was provided by the laboratory director. However,
the survey also showed that clinical consultation was unavailable in 32%
of the laboratories.
respondents indicated that their laboratories offered four types of tests:
amino acids; substrates; enzymes; and organic acids. The majority of the
laboratories offered both screening and diagnostic testing.
McGovern said the survey showed that 97% of the laboratories had CLIA
certification, 95% participated in proficiency testing, and 98% provided
interpretation for the non-geneticist physician. The interpretation was
generally provided by the laboratory director. According to the survey,
only 19% of the laboratories required informed consent and only 12% had a
McGovern said the overall QA score of the participating laboratories was
77% based on the American College of Medical Genetics(ACMG)/College of
American Pathologists(CAP) standards. Laboratories with a New York state
permit had higher QA scores. The survey showed there were four factors
associated with the QA score: 1) laboratory setting; 2) enrollment in a PT
program; 3) director's academic degree; and 4) whether the director was
summarized by saying the following:
degree and ABMG certification were associated with higher QA scores
substantial number of laboratories did not have a clinical consultant
in PT was associated with higher scores
for many different analytes may make the development of additional PT
use of in-house methods and reagents was common
and research laboratories had higher QA scores and were more likely to
employ ABMG professionals
laboratories required informed consent
identified two areas for further study: 1) The impact of substandard QA
practices on mis-diagnoses; 2) The effect of deficiencies in reporting
practices on the clinical use of testing results.
asked whether there was any correlation between the CAP PT scores and the
study scores. Dr. McGovern replied that the survey did not collect
information to answer this question. Another member asked about the
distribution curve. Dr. McGovern replied that it was bell shaped. One
member asked which individual provided test interpretation in the majority
of the laboratories. Dr. McGovern said that the laboratories were not
providing test interpretation and, in many cases, laboratories did not
provide the test method. Another member asked if there was a relationship
between the volume of testing and the QA scores. Dr. McGovern answered
that data was not gathered to answer that question. One member commented
on the fact that many laboratories have more than one individual who
qualifies as laboratory director. Dr. McGovern replied that this was a
complicated issue, and many laboratories provided information indicating
there were different directors for different testing areas. Another member
asked if there are reference materials for molecular genetic tests. Dr.
McGovern responded for most molecular genetic tests, there are no
reference materials. Another member asked whether research laboratories
are CAP-approved. Dr. McGovern responded most research laboratories
conducting diagnostic tests had CLIA certification. One member asked if
the survey results of laboratories performing biochemical testing differed
from those of laboratories performing molecular testing. Dr. McGovern said
in molecular testing, the QA is methodology driven and that independent
and hospital laboratories had better QA scores in this study. One member
asked if Dr. McGovern could identify the non-respondents in the survey.
Dr. McGovern said that information was yet to be captured. Another member
asked about the high percentage of laboratories that did not have a
clinical consultant. Another member responded it could be due to a
misunderstanding concerning the functions of a clinical consultant.
Another member said the need for clinical consultation differs with
respect to laboratory setting (independent laboratory, hospital laboratory
or reference laboratory). Dr. McGovern responded by stating there is a
need for clinical consultants in all laboratories because requests come
from all types of physicians who have different levels of knowledge about
CLIA on the SACGT (Addendum L)
Patricia Charache, Johns Hopkins Medical Institutions, reviewed the
history behind the creation of the SACGT. She emphasized there is a
growing public concern about genetic testing and its social, as well as
medical risks. She summarized the recommendations made by the SACGT at its
last meeting on August 4, 2000. The SACGT identified four levels of
genetic testing and correlated those levels to the amount of oversight
necessary through Institutional Review Board (IRB), CLIA or FDA. The
Committee identified a triage plan for the FDA review of genetic tests.
Teams were established and working groups created to report on specific
topics, and SACGT identified additional areas of concern to be discussed
at future meetings. Finally, she discussed how CLIA and the SACGT
interface, pointing out that CLIA has special expertise in laboratories,
while SACGT has special expertise in the medical/social area of genetic
commented that a major concern in genetic testing is patents. At present,
there is no information available when a patent application is being
developed. If another company or laboratory begins testing, it is possible
that it will be precluded from testing, if there is a patent on the
method. The member said there will be a shift to well-funded laboratories
due to the effects of patents. Another member proposed FDA oversight, and
Dr. Charache noted the concern associated with the FDA oversight burden.
She said the IRBs need appropriate oversight and institutions can provide
guidance and documentation. Dr. Charache said if the IRB is set up with
institutional support, oversight could be provided. One member said that
accessability is also an important issue. Another member commented that
small laboratories have difficulty providing training because of the
overlay of bureaucracy. A member said there is also the matter of research
in practice sites, solely to obtain specimens for controls. In these cases
reports should not be provided to the patients or to the clinicians.
Anonymity is necessary to exempt these studies from CLIA and IRB
oversight. Dr. Charache noted the CLIA regulations specify the laboratory
director is responsible for tests being conducted, and this includes the
appropriateness of the test methodology.
Genetics Laboratory Forum (Addendum M)
Michael Watson, Washington School of Medicine, reported on the CDC
Genetics Laboratory Forum meeting in Atlanta on September 8, 2000. The
Forum had representatives from 12 professional groups. Dr. Watson
commented there are many technologies with many uses in healthcare, and
most of these don't raise the concerns expressed by the SACGT. He pointed
out the goal to include or integrate testing into the practice of
medicine. He emphasized genetic testing and associated technology is
evolving and changing rapidly and used the discovery of the cystic
fibrosis gene as an example, pointing out it took only 15 years from the
discovery of the gene to develop testing which currently is available for
60 mutations. In addition some 500 mutations are known. He said at the
beginning of this discovery, testing was family-based but, as the test
evolved, the target population changed to individuals at risk, although
the initial use was diagnostic and to identify carriers. Now, as testing
for known mutations increases, the significance of each mutation becomes
important. He said we now evaluate populations to determine the incidence
of mutations, and the sensitivity changes based on the population.
discussed the proposed SACGT genetic test oversight algorithm and reported
that when the participants at the Forum evaluated the model using six
genetic tests, the model was unable to address the concerns identified in
the algorithm. He discussed the Notice of Intent (NOI) and commented that,
under CLIA, all genetic tests would have the same requirements. He said
the laboratory director's responsibility of documenting clinical validity
is important. Dr. Watson said tests should be ordered by qualified
personnel, and all medical procedures should require informal consent, but
neither consent requirements nor the need for clinical information should
compromise specimen integrity. Laboratories should not be required to
provide counseling to patients but should work with providers to ensure
appropriate use of test services. Finally, pre-analytical and
post-analytical concerns should be focused on constitutional testing and
PT should be required.
Testing Notice of Intent (NOI) Comments (Addendum N)
Boone, Assistant Director for Science, DLS, PHPPO, CDC, presented an
overview of the comments received concerning the NOI. He noted that 818
total comments were received, with specific comments addressing 152
issues. In general, the comments were somewhat negative, with commenters
expressing concern that genetic testing was singled out for regulation.
The following seven issues received the most comments:
documentation of informed consent
of genetic testing specialty
person ordering a genetic test
reviewed the time-line for implementing the CLIAC genetic testing
recommendations and suggested that CLIAC form a Genetic Testing Workgroup
to evaluate the NOI comments.
appointed the following members to the Genetic Testing Workgroup: Dr.
Timothy O'Leary, Dr. Patricia Charache, Dr. Lawrence Silverman, Dr. Ronald
Luff, Dr. Andrea Ferreira-Gonzalez, Mr. Stewart Richardson, and Dr. Jaime
Frias. The Committee also suggested that Dr. Margaret McGovern
participate, as well as others with experience and expertise in genetic
Comment (Addendum O)
Deborah Leonard, representing the Association of Molecular Pathology
(AMP), spoke on the impact of implementing the proposed revisions to the
CLIA requirements published in the NOI. She said the AMP's concerns focus
on three issues: the definition of genetic testing; regulations that are
important for all laboratory testing, without singling out genetic
testing; and requirements that will increase the cost of testing and delay
the time required to report results. She urged that some of the proposed
regulations be reconsidered, and suggested that the proposed regulations
be confined to testing for inherited conditions.
the next CLIAC meeting: February 7-8, 2001.
that this summary report of the September 27-28, 2000, meeting of the
Clinical Laboratory Improvement Advisory Committee is an accurate and
correct representation of the meeting.
/S/ Toby L.