D. Joe Boone, PhD
Assistant Director for Science
Division of Laboratory Systems
Public Health Practice Program Office
Centers for Disease Control and Prevention
4770 Buford Highway, NE
Atlanta, Georgia 30341

Dear Dr. Boone:

The American Association for Clinical Chemistry (AACC) welcomes the opportunity to comment on the Centers for Disease Control and Prevention's (CDC's) notice of intent, which outlines potential changes to the Clinical Laboratory Improvement Amendments of 1988 (CLIA'88) standards regarding genetic testing. AACC supports the objectives of this document, namely to ensure the accuracy and quality of genetic testing, while educating patients and providers about the strengths and weaknesses of such tests. We believe that most of the recommendations are reasonable and should be adopted. Our specific recommendations follow:

Are the categories of genetic testing appropriate?
AACC supports the creation of the two genetic subspecialties (molecular genetic and cytogenetic tests and biochemical tests) and the distinctions made between the two categories. We recommend, however, that the brackets be deleted within the Biochemical genetic test definition. The statement, "Tests that are used primarily for other purposes…." should be an integral part of the definition.

What is the role of a laboratory director in documenting the clinical validity of a genetic test their laboratory plans to offer? If there is a role, how should the laboratory director's documentation of the clinical validity of a genetic test be monitored?
CLIA'88 currently does not require that the Laboratory Director document the clinical validity of a test. For most non-genetic tests, this is not a problem since there is a plethora of data in peer-reviewed journals validating these tests. Unfortunately, for many new genetic tests, this information has not yet been collected. AACC agrees that this data must be gathered, but we do not believe it is feasible to place this burden on the laboratory director of a single institution. This is an industry issue and needs an industry-wide response.

There are two options for addressing this issue. One option, which the CDC has already identified, is to create a consortium of government agencies, professional associations, manufacturers and academics to gather the data needed to establish the clinical validity and utility of these tests. Another alternative, which may complement the consortium, is the creation of large multi-site studies, which can provide the definitive data needed to validate the test-similar to what the cardiology community has done. Such studies could be funded by the federal government or in a collaborative partnership with private industry.

Who should be authorized to order a genetic test?
AACC believes that the predictive nature of many genetic tests warrants federal limitations on who can order such testing. We recommend that CLIA'88 be amended to require that a physician or qualified genetics counselor order predictive genetic tests. The current CLIA requirements are sufficient for ordering diagnostic genetic tests.

Should the laboratory be required to document that informed consent has been obtained by an authorized person from the person being tested before performing certain genetic tests or types of tests (screening, diagnostic, carrier, presymptomatic, susceptibility)?
No. AACC recommends that the health care professional requesting the laboratory test obtain written informed consent from the patient, prior to ordering a genetic test for assessing predisposition to or risk of inherited disease (Tests for diagnostic purposes should not be subject to this requirement). The laboratory should be allowed to presume that the ordering provider has obtained patient consent.

Imposing this requirement on laboratories will not provide patients greater protection from inappropriate testing. It is the ordering provider, typically the physician, who interacts with the patient and orders the test, not the laboratory. Although the laboratory can counsel the physician on the appropriateness of a test request, it is the physician who ultimately orders the test and should be responsible for obtaining and maintaining informed consent.

We do agree, however, that the laboratory should assist the provider in developing an appropriate informed consent form for the tests it offers, if requested. AACC believes that the forms should fully inform patients of: (1) why the test is being done; (2) the strengths and limitations of the test; (3) the implications of the results for the individual and their family; and (4) available medical interventions. The burden for ensuring that an informed consent form meets CLIA standards should be the responsibility of the ordering provider, not the laboratory.

Should additional processes be in place to enhance the confidentiality of certain genetic test information and results?
The current CLIA requirements for protecting the confidentiality of laboratory test results, including genetic testing, are sufficient. Further, the Department of Health and Human Services (HHS) is currently working on its own comprehensive privacy standards and, therefore, any effort by CDC to develop separate confidentiality standards would be redundant. And, finally, there is no need to provide explicit protection for genetic testing. All laboratory testing results should remain confidential. Any limitations placed on the use of such data, such as barring health insurance and employment discrimination, are outside the scope of this regulation.

Assuming that a genetic specialty under CLIA is defined and recognized, should a laboratory covered under this specialty be required to provide genetic counseling to their clients (including medical care providers and patients) for the tests they offer?
AACC agrees that laboratories offering genetic services must employ someone who can assist in ordering the tests and interpreting the results. We also support CLIAC's recommendation that the Clinical Consultant qualifications be modified (for the genetic testing subspecialty) to require that individuals have experience in genetic testing and to permit qualified Genetic Counselors to serve in that position.

However, we are seeking clarification about the recommendation (implicit in the question) that laboratories must provide genetic counseling services. If the intent is to ensure that laboratories have qualified personnel available to assist physicians and other practitioners in choosing the most appropriate genetic tests and understand the results, then we support the recommendation.

We do believe, however, that laboratories providing genetic testing should not be required to provide comprehensive medical counseling, nor should the Clinical Consultant be required to assist clients in ordering tests, even if the physician or other practitioner declines the laboratories assistance. The primary objective of the laboratory is to provide accurate, quality testing to assist practitioners in medical decision-making. The laboratory should not intrude in the patient-health care practitioner relationship, unless requested to do so or it has reason to question the appropriateness of a test.

Should the following requirements be added under a specialty of genetics to CLIA to address unique aspects of laboratory responsibility for genetic testing?

Pre-analytic Phase

Test Requisition and ordering additional tests
AACC agrees that appropriate clinical information must be provided on the request form. Often ethnicity or family history is needed for the proper test interpretation. Requiring ordering providers to submit such information will streamline the process, while improving the laboratories ability to provide timely, accurate and understandable results. AACC also agrees that the laboratory should assist physicians and other ordering providers in selecting the most appropriate tests, including suggesting follow-up tests. It should be noted, however, that the ultimate responsibility for ordering the test is the ordering provider, not the laboratory.

Re-use of tested specimens
AACC supports the continuation of the longstanding clinical practice that permits laboratories to maintain a specimen for clinical research once the requested test is performed, as long as patient identifiers are removed. We do not believe that investigators should be required to obtain informed consent in order to conduct genetic research using archived, anonymous samples. The use of anonymous samples is vital to ensuring the quality of laboratory testing. Further, such a restriction could limit scientists' ability to conduct research into new and improved test development. We believe that the use of patient samples is already adequately regulated by HHS under Title 45, part 46.101 (b) of the Code of the Federal Register, Protection of Human Subjects.

Analytic Phase

Personnel Qualifications and Responsibilities
AACC supports the personnel changes for Laboratory Director, Technical Supervisor, General Supervisor and Clinical Consultant. We support the grandfathering provisions outlined in this document. We do not believe, however, that it is appropriate to "require" the Clinical Consultant to assist clients in ordering appropriate tests (see previous comments).

Quality Control and Patient Test Management
AACC supports most of the recommendations outlined in this section. However, the section on contamination control indicates RNA work areas must be separated from DNA work areas. We are requesting further information on the rationale for this recommendation.

Validation of Tests
AACC agrees with a number of recommendations under this section, such as: laboratories must verify or establish reproducibility for each method within and between runs and among technologists; the methodology must be appropriate for conditions being evaluated; quality control parameters must be applicable; and reagents must be validated. Further, we agree that laboratories should provide information on the positive predictive value of a test. This requirement can be met by using data from published studies, a laboratory's own experience or other statistically valid methods. See our earlier comments for additional information on how to address this issue.

Proficiency Testing
AACC recommends that proficiency testing be extended to genetic tests, where available. The College of American Pathologists and American College of Medical Genetics already have existing programs in place to assist in this endeavor.

Post-Analytic Phase: Special Reporting Requirements & Record/Specimen Retention
AACC agrees that the laboratory should interpret the test results and suggest further tests, if necessary, as well as provide the ordering provider with a summary of the test method and its limitations. The Association accepts the ten-year retention policy for genetic testing results.

By way of background, AACC is the principal association of professional laboratory scientists--including MDs, PhDs and medical technologists. AACC's members develop and use chemical concepts, procedures, techniques and instrumentation in health-related investigations and work in hospitals, independent laboratories and the diagnostics industry nationwide. The AACC's objectives are to further the public interest and educational activities and to help maintain high professional standards.

If you have any questions or we may be of any assistance, please call me at (919) 684-8724 or Vince Stine, Director, Government Affairs, at (202) 835-8721.



Frank A. Sedor, PhD President

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