Although Congress was quite clear in the purpose and requirements of CLIA, HHS's implementation of CLIA for genetic testing has been inadequate. Genetic tests are considered high-complexity tests, but no specialty or subspecialty for molecular or biochemical genetics has been established. Thus, there are no specific personnel, quality control, or proficiency-testing requirements for the vast majority of genetic tests. The regulations do include a subspecialty of clinical cytogenetics under the cytology specialty, and establish requirements related to cytogenetics-testing quality control. However, clinical cytogenetics is limited to chromosomal analysis and does not include molecular or biochemical genetic testing. A limited number of proficiency-testing programs exist for molecular and biochemical tests, but enrollment in these programs is not mandated under CLIA. Nor is information about an individual genetic testing laboratory's performance on proficiency testing accessible to the public.
Thus in significant ways genetic testing has been left out of CLIA implementation. This situation persists despite the fact that several federal advisory groups have recommended that CMS establish a genetic testing specialty under CLIA (9-11, 53). In 1997, the National Institutes of Health - Department of Energy Task Force on Genetic Testing determined that, in the absence of a genetic testing specialty, "there is no assurance that every laboratory performing genetic tests for clinical purposes meets high standards"(9). In addition to recommending that a specialty be established, the Task Force also recommended that proficiency testing be mandated for all laboratories doing genetic testing and that a list of laboratories performing genetic tests satisfactorily be made public. In 2000, the Secretary's Advisory Committee on Genetic Testing (SACGT), which succeeded the Task Force, similarly recommended that CLIA regulations be augmented with specific provisions for laboratories conducting genetic tests (10).
In 2000, HHS published a "Notice of Intent" in the Federal Register, announcing the government's intent to issue a proposed rule for a genetic testing specialty under CLIA (13). The Notice included the recommendations of the Clinical Laboratory Improvement Advisory Committee (CLIAC), an advisory group within the CDC. In the Notice HHS explained that, along with the "tremendous potential for improving health and preventing disease, genetic testing can also do great harm" if errors occur in test selection, performance, or interpretation. The Notice cited literature pointing to errors or substandard practice in each of these categories.
The Notice requested public comments on the CLIAC's recommendations. Fifty-seven comments were submitted to the government. The overwhelming majority of respondents supported the recommendation to create a genetic testing specialty for molecular and biochemical genetic tests as a means to promote their reliability, accuracy, and quality.
Moreover, there was little opposition to the recommendations for proficiency testing, personnel standards, or quality control — those elements considered to be the "core" of CLIA. However, some commenters were concerned that requiring laboratories to obtain patient consent and provide genetic counseling "overreached" CLIA's mandate by requiring the laboratory to assume functions more appropriately handled by healthcare providers (24).
The CLIAC modified its recommendations in response to the comments received, and continued to recommend that HHS develop a proposed rule to create a genetic testing specialty under CLIA. For the next five years, CMS periodically reported to the CLIAC that development of a proposed rule for a genetic testing specialty was in progress (12).
In a September 2005 letter responding to an inquiry from the Genetics and Public Policy Center, CMS stated that "[u]nder a Notice of Proposed Rulemaking ... we will propose to add a specialty category for genetic testing"(25, 26). Similarly, in a January 2006 response to a Genetics and Public Policy Center inquiry (27), CMS averred that "we intend to publish a Notice for Proposed Rule Making for genetic testing as quickly as feasible"(28). Consistent with this intent, in April 2006 HHS placed the issuance of a proposed rule on its semiannual regulatory agenda, with a target release date of November 2006 (14). CMS's intent to move forward with the proposed rule was confirmed by the testimony of a CMS official before the SACGHS in June 2006. She stated that "we do have a notice of proposed rule making in CMS clearance at this time"(29).
But one month later, at a hearing of the Senate Special Committee on Aging, CMS signaled it had abruptly shifted course and abandoned its six-year effort. The hearing was held to consider a report by the Government Accountability Office (GAO) indicating serious deficiencies on the part of companies providing direct-to-consumer "nutrigenetic" testing (30).
According to the GAO report, some of the laboratories performing the genetic testing were not CLIA certified and had returned incorrect test results to consumers. In his testimony, the director of CMS's Survey and Certification Group made no mention of the proposed rule (2). Moreover, he testified that genetic testing already is adequately covered under existing regulations (2). Even more surprisingly, he testified that because genetic tests are highly complex, laboratories must "participate in an approved proficiency-testing program" three times a year (2). This statement is at odds with current regulations. In fact, there currently are no regulations mandating that genetic testing laboratories enroll in available proficiency-testing programs. Data obtained by the Genetics and Public Policy Center show that many genetic testing laboratories do not enroll in available voluntary proficiency-testing programs or perform any type of proficiency testing for the genetic tests they offer (23).
The director further testified that "[t]ests for genetic markers are dispersed throughout various laboratory specialties and the requirements for those tests are encompassed by the current quality standards"(2). However, as discussed below, a number of genetic testing laboratories are not certified in any specialty. Additionally, the relevance to genetic testing of certification in a specialty such as pathology or chemistry is unclear.
Finally, the director testified that a July 2003 quality control regulation promulgated by CMS incorporated some CLIAC recommendations for genetic testing, specifically, "confidentiality requirements, facility workflow requirements to minimize contamination, and quality control requirements for the genetic test method of polymerase chain reaction (PCR)"(2, 31). Notably missing from this list was any mention of proficiency testing. Additionally, PCR is only one of many methods used by genetic testing laboratories, and contamination is only one of the potential causes of laboratory error. Only 18% of laboratories surveyed by the Genetics and Public Policy Center indicated they had encountered contamination during specimen testing in the past two years, compared with 27% that had experienced sample switches in the laboratory, 52% that had experienced equipment failure, and 44% that had encountered human error in data analysis (32). The contention that the 2003 regulation adequately addresses genetic testing quality is incorrect.
The proposal to create a genetic testing specialty was never mentioned in CMS's testimony. Its omission, together with the assertion that existing regulations are sufficient, revealed that CMS had reversed course. A July 2006 CMS letter to the Genetic Alliance, which represents 600 advocacy organizations, also indicated the agency's policy reversal. In response to a request that CMS issue a proposed rule for a genetic testing specialty (33), CMS replied that genetic testing laboratories already are adequately covered under CLIA, making no mention of the proposed rule (34).
Representatives of the Genetics and Public Policy Center met with CMS officials in August 2006 (15). During that meeting, officials confirmed that CMS no longer intended to issue a proposed rule, stating that the regulation lacked sufficient "criticality" to warrant moving forward and that CMS believed a regulation for a genetic testing specialty was unnecessary to ensure genetic testing quality. Additionally, CMS officials expressed concern about creating a specialty given the limited number of formal proficiency-testing programs currently available for genetic testing.
Thus, a decade-long saga has returned to where it began, having consumed substantial taxpayer dollars and produced no meaningful changes to ensure the quality of laboratories performing genetic testing.
Oversight of Genetic Testing Laboratory Quality: A Timeline
1988 — The Clinical Laboratory Improvement Amendments of 1988 (CLIA) is enacted (1) to "strengthen federal oversight of clinical laboratories to assure that the test results are accurate and reliable"(17).
1997 — The National Institutes of Health-Department of Energy (NIH-DOE) Task Force on Genetic Testing issues recommendations to improve the quality of genetic testing. Their report, "Promoting Safe and Effective Genetic Testing in the United States," contains recommendations for enhanced regulation of genetic testing laboratories, including requiring clinical validity to be established for genetic tests, creating a genetic testing specialty under CLIA, establishing a national accreditation program for laboratories performing genetic tests, making public the names of laboratories performing satisfactorily, and requiring post-market surveillance to assess clinical validity and clinical utility (9).
1998 — The Genetic Testing Working Group formed by the Clinical Laboratories Improvement Advisory Committee (CLIAC) in 1997 meets repeatedly to consider the applicability of CLIA to genetic testing and recommends that CLIA be amended to include a genetic testing specialty (53).
2000 — The Secretary's Advisory Committee on Genetic Testing (SACGT) states that "CLIA regulations should be augmented to provide more specific provisions ensuring the quality of laboratories conducting genetic tests"(10).
2000 — The Department of Health and Human Services (HHS) issues a Notice of Intent for public comment indicating that HHS is considering preparing a Notice of Proposed Rule Making (NPRM) to create a specialty area for molecular and biochemical genetic tests under CLIA (13).
2001 January — Secretary Shalala indicates the HHS intends to implement an enhanced system of oversight for genetic tests (54).
2001 February — Based on comments on the Notice of Intent, the CLIAC Genetic Testing Working Group presents revised recommendations to the full CLIAC. The CLIAC recommends that HHS proceed with the development of a proposed rule for a genetic testing specialty under CLIA (12).
2003 January — The Centers for Medicare and Medicaid Services (CMS) issues a final rule, Laboratory Requirements Relating to Quality Systems and Certain Personnel Qualifications (31). The rule introduces two requirements specific to genetic testing: a unidirectional workflow requirement for molecular amplification procedures that are not contained in closed systems, in order to reduce contamination, and a requirement that each molecular amplification procedure include two control materials, and if necessary, a control material capable of detecting false negative results.
2005 September — In response to an inquiry from the Genetics and Public Policy Center regarding the status of the proposed rule for a genetic testing specialty, CMS responds that "we will propose to add a specialty category for Genetic Testing," and that the "publication date for the NPRM is expected to be sometime next year." The letter adds that the "revised CLIA regulations contain sufficient generic and fail-safe language in the preanalytic, analytic, and postanalytic systems to accommodate the oversight of genetic testing until we establish specific requirements"(26).
2005 November — The Genetics and Public Policy Center releases a White Paper, "Creating a Genetic Testing Specialty Under CLIA: What Are We Waiting For?" that reviews all of the comments submitted in response to the Notice of Intent and details widespread support for the creation of a genetic testing specialty (24).
2005 November — In a letter, the Genetics and Public Policy Center calls upon Mark McClellan, administrator of CMS, to end years of delay in issuing the proposed rule to create a genetic testing specialty under CLIA (27).
2006 January — In a written response, Thomas Hamilton, director, Center for Medicaid and State Operations/Survey Certification Group at CMS, states "[w]e [CMS] intend to publish a Notice of Proposed Rule Making for genetic testing as quickly as feasible" (28).
2006 February — The Genetic Alliance board of directors sends a letter to Administrator McClellan urging CMS to issue the proposed regulations for a genetic testing specialty under CLIA (33).
2006 April — The proposed rule "Quality Standards for Genetic Testing," which would add a genetic testing specialty under CLIA, appears on CMS's semiannual regulatory agenda for issuance in November 2006 (14).
2006 June — The Genetic Alliance, along with 75 signatories representing advocacy organizations, professional groups, and industry, sends a second letter to Administrator McClellan urging CMS to issue the proposed rule for a genetic testing specialty (50).
2006 June — Judith Yost, director of laboratory services at CMS, testifies at the Secretary's Advisory Committee on Genetics, Health, and Society meeting that "we do have a notice of proposed rule making in CMS clearance at this time."(29)
2006 July — In a letter to CMS, 14 women's health organizations urge the agency to issue the proposed rule for a genetic testing specialty (51).
2006 July — CMS signals apparent change in its position on the creation of a genetic testing specialty in testimony by Thomas Hamilton before the Senate Special Committee on Aging. He testifies that "[t]ests for genetic markers are dispersed throughout various laboratory specialties and the requirements for those tests are encompassed by the current quality standards"(2). He makes no mention of the agency's plans to issue a proposed rule for a genetic testing specialty under CLIA. Similarly, in a letter to the Genetic Alliance, CMS indicates that current oversight of genetic testing under CLIA is adequate (34).
2006 August — In a meeting with representatives of the Genetics and Public Policy Center, CMS confirms it has decided not to issue a proposed rule for a genetic testing specialty under CLIA. CMS officials assert that the specialty lacks sufficient "criticality" to warrant rulemaking and that existing regulations are adequate (15).
Next Week: Part III
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- Code of Federal Regulations, title 42, sec. 493.
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- Javitt, Gail pers. comm. to Judy Yost, July 15, 2005.
- Yost, Judith pers. comm. to Gail Javitt, September 15, 2005.
- Hudson, Kathy pers. comm. to Mark McClellan, November 18, 2005.
- Hamilton, Thomas pers. comm. to Kathy Hudson, Jan. 9, 2006.
- Testimony of Judith A. Yost, director, Division of Laboratory Services, Centers for Medicare and Medicaid Services, before the Secretary's Advisory Committee on Genetics, Health, and Society, June 26, 2006.
- 2006. Nutrigenetic Testing: Tests Purchased From Four Websites Mislead Consumers. United States Government Accountability Office. www.gao.gov/new.items/d06977t.pdf (accessed August 23, 2006).
- Federal Register 68 (January 2003): 3639
- 2006. Practices and Attitudes of Laboratory Directors of Clinical Genetic Testing Laboratories. Johns Hopkins IRB No. NA-00001533. Unpublished data on file with Genetics and Public Policy Center, Washington, D.C.
- Terry, Sharon pers. comm. to Mark McClellan, February 28, 2006.
- Smith, Dennis pers. comm. to Sharon Terry, July 17, 2006.