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THE COMMITTEE ON HUMAN RESEARCH
UCSF GUIDANCE ON RESEARCH TOPICS AND ISSUES
LABORATORY TEST RESULTS:
CLIA COMPLIANCE
(Effective 11-21-03, Posted 12-18-03)
• Purpose
• Regulatory Background
• Ethical Concerns
• Guidelines
• Reporting Results to Individuals
• Withholding Results from Individuals
• Possible Exceptions
• HIPAA Considerations
• Consent Issues
• Ethical Justifications for Providing Results in the Absence of CLIA Certification
Purpose
To clarify the need for CLIA certification of laboratories testing human
specimens if results of the tests will be provided to individual subjects
in the course of research.
Regulatory Background
Laboratories performing testing on human specimens and
reporting patient-specific results must be certified under the provisions
of the Clinical Laboratory Improvement Amendments of 1988 (CLIA) (57 FR
7139, Sec. 493.1). CLIA makes an exception for “Research laboratories
that test human specimens but do not report patient specific results for
the diagnosis, prevention or treatment of any disease or impairment of,
or the assessment of the health of individual patients” (57 FR 7139,
Sec. 493.3(b)(2)). It follows that if researchers wish to provide diagnostic
results to subjects or use test results to alter care, they should have
laboratory tests performed under the auspices of a clinical laboratory that
has been certified in accord with CLIA. The extent to which CLIA applies
to a variety of tests used solely for research purposes is not clear (as
of May 2003), but caution requires complying with CLIA wherever possible.
Ethical Concerns
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Risk/Benefit Ratio: The benefits of providing
diagnostic results to individual subjects or their doctors—especially
possible improvements in individual treatment—must be weighed against
risks—including false diagnosis, diagnosis when no treatment is available,
and loss of insurability.
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Right to be Informed: Individuals
generally have a right to be fully informed about research in which
they participate, including receiving study results that may be useful
or interesting to them. However, some test results may be of unknown
value, and providing results may lead to misunderstanding, worry,
and unnecessary treatment. |
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Guidelines
Reporting Results to Individuals: If diagnostic tests
(such as STD screening) done in the course of research will be made available
to subjects or their physicians, the tests should be performed in compliance
with all CLIA requirements, which usually means they will need to be performed
by a clinical laboratory certified under CLIA. CLIA provides for “waivers” that
allow certain simple tests to be performed outside a clinical laboratory,
but the testing site must obtain a Certificate of Waiver and meet other
CLIA requirements. Applications for CHR review should assure the CHR that
the tests will be performed in compliance with CLIA requirements. Researchers
should consult with experts in the Clinical Laboratories for details of
the requirements (UCSF: 353-1723; SFGH: 476-1779, 206-8588; VAMC: 221-4810
x2260). Researchers should consider how the benefits of providing results
weigh against the risks and should try to minimize the risks.
Withholding Results from Individuals: If novel or experimental tests, including
genetic tests, will be performed outside of CLIA-certified auspices, one
option is to not report the results of those tests to research subjects
or their physicians and to not allow results to affect the subjects’ treatment.
When the meaning of results is uncertain, withholding individual results
may be the best option. In such cases, applications for CHR review should
indicate clearly that results will not be provided to subjects or their
physicians, and the study consent form should clearly state that subjects
will not be provided test results and explain why not.
Possible Exceptions: There may be situations where ethical considerations
(discussed in more detail below) require some use of results or reporting
of results to subjects or their physicians, but the tests cannot be done
under the auspices of a CLIA-certified lab. Researchers contemplating such
an exception should include all of the following in their CHR application:
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An explanation of why doing the
test under CLIA-certified auspices is not possible, preferably
with
supporting documentation reflecting unsuccessful attempts to arrange
for involvement of a CLIA-certified laboratory. The greater cost
of CLIA-certified testing generally is not a satisfactory explanation. |
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An explanation of the ethical reasons for using
and/or providing results. See below for an additional discussion
of possible ethical justifications. |
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A detailed plan for communicating results
to subjects or their physicians. In most cases, a process for
discussing the results with subjects should be described and a
written form for conveying results should be provided. Information
to be conveyed should include a description of the unproven nature
of the tests, explanation of the uncertified status of the laboratories,
and cautions against the use of the results for diagnosis, prevention,
or treatment of any disease or impairment, or the assessment of
health of individual patients. |
In determining whether to grant or refuse a request for
an exception the CHR may consult with a variety of resources, including
but not limited to clinical laboratory experts.
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HIPAA
Considerations
If test results will be recorded in our medical records,
the results are Protected Health Information under the Health Information
Portability and Accountability Act (HIPAA). An Authorization for Release
of Personal Health Information for Research must be obtained from each research
subject and must specify to whom the results may be released.
Consent
Issues
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Consent forms should discuss the
treatment implications of diagnostic tests, especially when the
test is experimental or there is no clear course of recommended
treatment. |
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If test results may reveal a condition that
is not already documented in a patient’s medical records,
the consent form should discuss the possible loss of insurability
if test results become known to insurers. |
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Researchers should consider allowing subjects
to choose which specific test results will be reported to the
subject or placed in the medical record. |
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Ethical
Justifications for Providing Results in the Absence of CLIA Certification
There are situations in which it is unethical to withhold
all results. However, citing one or more of the following ethical justifications
for providing results is not in itself sufficient to ensure CHR approval.
The CHR must consider the overall context of the study and will make decisions
on a case-by-case basis. The following are meant only as examples of ethical
justifications that the CHR may consider:
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Research subjects may desire
and have a right to learn individual results of unproven tests
to satisfy intellectual curiosity, to gain a greater sense of
control of their own condition, or for a variety of other personal
reasons. The Belmont Report:
Ethical Principles for the Protection
of Human Subjects of Research cites basic ethical principles which may be seen as supporting
research subjects’ right to have access to information about
themselves. The principle of Respect for Persons establishes the
right of individuals to be fully informed about research in which
they participate. The principle of Beneficence requires that benefits
to the subjects be maximized while risks are minimized. Providing
subjects with experimental test results may provide them with
benefit, even if it is only the intellectual satisfaction and
feeling of control of learning difficult-to-interpret information
about themselves. Because individual interests may vary, studies
may need provisions that allow individual subjects to decide whether
or not to receive results. |
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The results of the experimental test or
regimen of tests may point toward additional testing that could
in turn lead to an improvement in the subject’s care. For
example, the Department of Health and Human Services recently
placed a rapid screening test for HIV in a CLIA “waived” category
because the test could reasonably be presumed to lead the individual
to a confirmatory test for clinical diagnosis and linkage to care.
CLIA waivers generally require formal certification and adherence
to specified procedures. |
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There are some studies in which subjects
may refuse to participate unless they have access to the perceived
benefit of test results. If the study is well designed and could
provide important scientific results, the benefits of completing
the study may outweigh the risks of providing individual test
results. This justification is stronger if refusals based on withholding
results are documented for the same or a similar study. |
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In the absence of proven tests, an experimental
test or regimen of tests may provide the best available guide
to future action, and in certain circumstances it could be unethical
to withhold such results. For example, although CLIA certification
attempts to address reliability within assays and between labs,
it cannot address validity in the realm of genetic testing of
complex disease where the knowledge base is still incomplete.
Non-CLIA labs may have demonstrable high reliability within their
own system, yet be unable to satisfy CLIA requirements that were
based on a different set of expectations regarding the existence
of standard methods or other already approved labs. |
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The design for an ethical and important
study may require determining whether it is effective to change
subjects’ care based on the results of a clinical test that
for some unavoidable reason cannot be conducted by a CLIA certified
laboratory (for example, tests of viral fitness that determine
whether changes in an antiviral treatment are effective; or early-stage
pharmacogenomic studies). |
Even when providing results seems ethically justified,
the possible negative consequences of doing so must be considered
and minimized.
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