Neil A. Holtzman, MD, MPH
Genetics and Public Policy Studies
The Johns Hopkins Medical Institutions
550 N. Broadway, Suite 511
Baltimore, Maryland 21205-0241
Dear Dr. Holtzman:
The American Association for Clinical Chemistry (AACC) welcomes the opportunity to comment on the National Institutes of Health (NIH) and Department of Energy (DOE) Task Force on Genetic Testing’s recommendations to improve the safety, quality and effectiveness of genetic testing. AACC shares your concerns regarding the potential misuse and misinterpretation of genetic information. We also agree that health care providers should adopt appropriate safeguards necessary to ensure the confidentiality of genetic test results. We are not convinced, however, that the recommendations set forth in this notice achieve these ends.
Our principal concern with the Task Force’s recommendations is the artificial distinction it makes between genetic testing for assessing a predisposition for an inherited disease and laboratory testing used for diagnostic purposes. Both types of testing use analytical techniques that isolate, characterize and/or quantify molecular species. All analytical techniques, whether measuring nucleic acids or any other analyte, can be subject to errors of imprecision and inaccuracy. Errors of this type are best addressed by the safeguards created by the Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88). The Task Force’s proposals, however, do not take account of these existing protections, and instead focus on recommendations for heightened oversight, such as creating additional federal advisory committees and expanding government regulation of the testing process—neither of which address the confidentiality-related concerns, nor the potential misuse of the results.
AACC believes the best mechanism for regulating laboratory testing is implementing quality control systems; inspecting external bodies; and requiring laboratories to participate in proficiency testing, maintain adequate personnel standards and meet process control requirements. Although the CLIA ’88 regulations implementing the law are not perfect, they provide a framework to achieve quality genetic testing, as they do for other testing. If the Task Force has testing-related issues that need to be discussed, we recommend that they present them to the Clinical Laboratory Improvement Advisory Committee (CLIAC), the advisory panel to the Health Care Financing Administration (HCFA) and Centers for Disease Control and Prevention (CDC), for consideration. Our specific comments follow:
AACC agrees that patients have a right to be informed of the reasons for, and the possible implications of, the laboratory tests being performed. This information should be provided by the physician or health care professional ordering the test. We also believe that the health care professional requesting the laboratory test should obtain written informed consent from the patient when ordering genetic testing for assessing predisposition to or risk of inherited disease. AACC does not believe, however, that investigators should be required to obtain informed consent in order to conduct genetic research using archived, anonymous samples (for retrospective study).
Creation of new advisory panels
We agree that federal agencies and advisory panels should make greater use of geneticists’ expertise when making policy decisions affecting genetic testing. However, creating new advisory panels, such as the Genetics Advisory Committee and Food and Drug Administration (FDA) advisory panel is not the best course of action. Instead, we recommend that the agencies and existing federal panels work more closely with the associations that have demonstrated expertise in this area, such as the American College of Medical Genetics (ACMG), the Association for Molecular Pathology (AMP), and College of American Pathologists (CAP), among others. AACC and its Molecular Pathology Division are also ready to assist in this endeavor.
The Task recommends that the FDA use its authority under the Medical Device Amendments of 1976 to "ensure that all organizations developing new, predictive genetic tests submit protocols to an institutional review board." AACC does not support this approach. In the past, the FDA has expressed concerns about regulating genetic testing beyond its proposed Analyte Specific Reagents (ASRs) classification. The Agency has suggested that regulating the end user, which is already accomplished by CLIA '88, is a more appropriate, more effective and a more comprehensive guarantee that testing is performed correctly and competently. AACC supports the FDA’s position on this matter.
The Task Force also suggests that HCFA limit reimbursement for genetic tests to those laboratories that can demonstrate that: (a) the tests have been clinically validated or that the laboratory is participating in a systemic validation plan; and (b) the laboratory is "qualified" to perform such tests. AACC objects to this recommendation because:
it fails to recognize that CLIA ’88 requires clinical laboratories to complete an extensive validation phase before offering new tests; and
it would duplicate the provisions of CLIA ’88 by creating parallel standards and processes.
AACC believes that trying to regulate the quality of laboratory testing by limiting payment is the wrong approach; there are more appropriate means, such as the adoption of a quality assurance system, proficiency surveys and other mechanisms embodied in the CLIA regulations.
The need for stringent scrutiny of certain predictive genetic tests.
AACC objects to the rationale set forth in this section. The section suggests that laboratorians should institute differing levels of care and scrutiny for different laboratory tests. It is the laboratorians’ responsibility to ensure that all tests are done carefully and under the appropriate regulatory framework. In-house assays, including all genetic tests, are rigorously controlled at each step from specimen extraction to final result. CLIA ’88 also requires that laboratories confirm the clinical accuracy and precision of these test results before implementing them. Thus, we do not believe that genetic tests need increased scrutiny from laboratorians.
Moreover, the proposed requirement ignores the reality that many tests for genetic diseases have been done for years, and continue without any of the additional proposed controls. Tests for phenylalanine (PKU), sweat chloride (CF), hemoglobin electrophoresis (Sickle Cell Anemia and thalassemias), and many other carbohydrate and amino acid metabolites are accurately performed and competently interpreted, without the additional scrutiny being proposed.
National Genetics Board
AACC supports the creation of a National Genetics Board (NGB), which is based on the model three approach set forth in the notice (on FR 4544). We agree that the NGB should focus on generic policy issues and set general guidelines for review, but have no mandatory review function. Further, such a Board should work with existing private-sector organizations that are already active in this field. ACMG has already published performance guidelines for clinical laboratories performing genetic testing, such as their policy statement on Fragile X syndrome--these guidelines could be of assistance to such a Board. In addition, other organizations, such as AMP are currently drafting clinical guidelines to assist laboratories.
National Accreditation Program
We oppose the creation of a separate accreditation program for genetic testing under CLIA’88. As the notice says, there are already private-sector accrediting organizations, such as CAP (in cooperation with ACMG), that administer proficiency surveys and accrediting programs for genetic testing. A new federal accreditation program would only duplicate what is currently being done by the private sector.
AACC believes that a better approach would be for HCFA to review the existing genetic testing PT programs and, if they are acceptable, add them to the list of approved analytes requiring PT. We think this would be a better approach for effective oversight of genetic testing rather than creating a new program or a separate "deeming" authority for genetic testing under CLIA.
CLIAC Advisory Panel
We support CDC’s decision to create a CLIAC subcommittee of genetic testing experts to advise the agency. AACC agrees that the CLIAC is the appropriate body to provide this advice because it has access to experts that can assist the Secretary on issues of quality in genetic testing and their relationship to the CLIA ’88 standards.
Publication of CAP/ACMG Laboratories
The Task Force recommends that the CAP/ACMG publish a list of laboratories performing genetic testing satisfactorily under its voluntary accreditation program. AACC supports the voluntary publication of this list by CAP and ACMG. However, we strongly object to any efforts to link performance in a voluntary program to reimbursement. There is already a mechanism for penalizing a laboratory for poor performance—revoking its CLIA certificate or certificate of accreditation. All laboratories, including those performing genetic testing, must have a CLIA license to operate. And, under CLIA, laboratories performing such tests must have a system "for verifying the accuracy and reliability of its test results at least twice a year (section 493.1707)." We strongly recommend that reimbursement be contingent upon CLIA accreditation alone.
By way of background, AACC is the principal association of clinical chemists--professional laboratory scientists--including MDs, PhDs and medical technologists. Clinical chemists develop and use chemical concepts, procedures, techniques and instrumentation in health-related investigations. The AACC represents clinical chemists working in hospitals, independent laboratories and industries nationwide. The AACC's objectives are to further the public interest and educational activities and help maintain high professional standards.
If we may be of any assistance, or if you have any questions about our comments, please call me at (717) 531-8316 or Vince Stine, Manager, Government Affairs at (202) 835-8721.
Laurence M. Demers, PhD, DABCC