The Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) on November 5 released a draft report, “U.S. System of Oversight of Genetic Testing: A Response to the Charge of the Secretary of HHS.” The report details the current state of genetic testing oversight and recommends specific ways of improving the system, many of which echo measures called for by GPPC. SACGHS invites the public to comment on the draft on or before December 21.

The report reflects several of the Center’s longstanding concerns and recommendations, including the need for increased use of proficiency testing (PT) for genetic tests. As the draft report states, “PT is currently considered to be the most rigorous form of performance assessment. In principle, genetic tests and all other high complexity tests should be required to undergo PT.” The report cites the 2006 Center survey of laboratory directors revealing that while participation in PT is linked with laboratory quality, many laboratories do not perform PT or use alternative assessments for all tests they offer.

SACGHS recommends specific means of increasing the use of PT, such as requiring laboratories to participate in available PT, and developing incentives for providers to develop more PT programs for genetic tests. The report also recommends improving enforcement by enlisting experts in the field to train genetic testing lab inspectors, and by enabling the Centers for Medicare and Medicaid Services (CMS) to hire sufficient staff to fulfill its statutory requirements under the Clinical Laboratory Improvement Amendments of 1988 (CLIA).

The committee further suggests that CMS should make a greater effort to ensure that all labs performing clinical genetic testing be certified under CLIA, and that it “make publicly available a list of laboratories that have been cited by CLIA for condition-level deficiencies.”

Center Director Kathy Hudson, who served on the task force that drafted the report, says, “We hope that CMS will also make public information on which labs are CLIA-certified so that providers and patients can ensure that they use qualified labs.”

The committee also recommends the establishment of a voluntary test registry, through an HHS-funded expansion of the existing GeneTests site, in order to “understand the universe of genetic tests being offered and to enhance the transparency of this field.” Says Hudson, “Based on the Center’s analysis and stakeholder consultation, we believe that a genetic testing registry is essential to making information available on the clinical validity of genetic tests. However, the Center believes that a voluntary registry will not be comprehensive, and would prefer to see a mandatory registry established instead.”

Another point on which GPPC and SACGHS agree is the critical role of the Food and Drug Administration’s (FDA’s) oversight of laboratory-developed tests (LDTs). The agency has not historically regulated these tests, but recently began overseeing a subset known as in vitro diagnostic multivariate index assays (IVDMIAs). The report states that “SACGHS supports FDA regulation of LDTs and the flexible risk-based approach the agency is taking to prioritize genetic LDTs…” But the report also suggested that “further analysis, deliberation, and consultation are needed to determine whether the appropriate weight has been apportioned to the risks associated with the novelty and complexity of the testing platform and technology.”

“While supporting robust, ongoing discussion and engagement with the FDA, the Center is concerned that this recommendation could be used to stall the FDA’s development of a final IVDMIA guidance document,” says Center Law and Policy Director Gail Javitt. “The FDA is well-equipped to weigh the risks of LDTs, and enabling it to do so will be a boon to public health.”

Finally, the committee expressed concern about gaps in oversight and enforcement with respect to tests marketed directly to consumers that are currently “skirting the boundaries of CLIA’s authority,” and recommended both an expansion of authority under CLIA and increased collaboration among other federal agencies.

“We are pleased that the Task Force addressed direct-to-consumer genetic testing,” says Hudson. “Since CLIA cannot address the problematic health-related claims made about some of these tests, we are happy that the report also calls for agencies such as the Federal Trade Commission to strengthen monitoring and enforcement actions regarding these claims.”

“In recognizing the need for such measures as more PT, transparency regarding laboratory performance, and a role for FDA in regulating LDTs, SAGCHS has taken an important step,” says Hudson. “Our optimism is tempered, though, by experience. Our requests to CMS and HHS to enhance PT and make more information about lab performance public have been repeatedly refused. Further, recommendations by prior HHS advisory committees to enhance genetic testing oversight have done little more than gather dust. We hope the secretary will act decisively on these recommendations once they are finalized.” – Shawna Williams


Report - U.S. System of Oversight of Genetic Testing: A Response to the Charge of the Secretary of HHS

Article - HHS ponders oversight of genetic tests

Article - CMS rejects petition to establish new safety standards for genetic testing laboratories

Issue brief - Who regulates genetic tests?

Issue brief - FDA regulation of genetic tests

Issue brief - Direct-to-consumer genetic tests: empowering or endangering the public?

Report - Public Health at Risk: Failures in Oversight of Genetic Testing Laboratories

A practice committee opinion released at the annual meeting of the American Society for Reproductive Medicine (ASRM) on October 16 concluded that evidence does not support the use of preimplantation genetic screening (PGS) for any indication. The release of the opinion, which surprised many at the meeting, spurred vigorous debate and a dissenting public statement by the Preimplantation Genetic Diagnosis International Society (PGDIS).

PGS and preimplantation genetic diagnosis (PGD) both begin with in vitro fertilization (IVF): eggs and sperm are collected from would-be parents, and fertilization takes place in the lab. After a few days, one or two cells are taken from each of the resulting embryos for analysis. In PGD the embryos are tested for a genetic disease for which the future child is known to be at risk. PGS, by contrast, seeks to identify embryos with chromosomal abnormalities – a condition known as aneuploidy. Down syndrome is a result of one type of aneuploidy, but the majority of aneuploid embryos result in failed pregnancies. In fact, aneuploidy is the most common cause of early miscarriage, making it a seemingly logical target for IVF clinics trying to increase success rates.

The controversy over PGS centers on whether it works in practice – that is, whether screening embryos for aneuploidy increases the chances of a healthy birth. Some studies support the use of PGS, particularly for patients experiencing recurrent miscarriages. However, one recent randomized, controlled study found that PGS did not improve pregnancy or live-birth rates among women of advanced maternal age, and may in fact be detrimental. In general few data have been collected or made available on the practice of PGS in the United States – how often it is performed, for what indications, and with what outcomes. Despite conflicting studies and uncertainty about its safety and efficacy, demand for and availability of PGS are widespread.

The ASRM practice committee opinion summarizes the results of studies of PGS for four indications: advanced maternal age, recurrent pregnancy loss, repeated implantation failure, and male factor infertility. In each case, the committee found that “available evidence does not support the use of PGS as currently performed to improve live-birth rates.”

PGDIS’s response counters, “the ASRM opinions have taken into consideration neither contemporary literature nor facts that could have been provided by embryologists, geneticists and laboratories responsible for over 90 percent of these tests worldwide.” The group also states, “A beneficial effect requires experienced embryologists and geneticists who can obtain blastomeres and analyze single cells in optimal fashion. Considerable expertise is required.” This argument mirrors that in a paper a group of PGD providers published earlier in October, which made the case that poor technique accounted for the discouraging results of two recent randomized, controlled trials of PGS.

“This controversy underlines how little data we have on the efficacy of a widely-used and costly procedure,” says Susannah Baruch, the Center’s director of reproductive genetics. “We hope that in the near future we’ll have a registry of PGS and PGD procedures to help us answer such questions as whether PGS is useful, and if so, for whom.” – Shawna Williams

Preimplantation genetic testing: A Practice Committee opinion (subscription required)

Preimplantation Genetic Diagnosis International Society Refutes American Society of Reproductive Medicine Opinion

Article – Findings cast doubt on efficacy of PGD for aneuploidy

Issue brief – Oversight of preimplantation genetic diagnosis

The Center hosted on November 5 a ministerial-level delegation from China’s Ministry of Science and Technology for a discussion of U.S. genomics policy. The delegation, headed by Ma Hongjian, deputy director-general of the China National Center for Biotechnology Development, also included representatives from China’s Food and Drug Administration, the Chinese Center for Disease Control and Prevention, and Fudan University.

The visit was organized by Affymetrix, Inc., and GPPC was one of several stops in Washington, D.C. and elsewhere in the United States to gain a better perspective on public awareness and understanding about genetics in the U.S., policies to regulate genetic tests and testing, and the general business climate for genetics and genomics. Participants enjoyed a lively discussion about differences in culture and what they mean for ease or difficulty of recruitment into genetics research studies, as well as trust in government entities to ensure safety and accuracy of genetic testing. The delegation was keen to hear about differences and similarities between the proposed U.S. large-cohort project on genes and the environment, and a similar, even larger project planned in China at Chinese Medical City. The project is currently being pilot tested in Taizhou, a city of about five million residents a hundred miles north of Shanghai. – Rick Borchelt

The Center’s next Genetic Perspectives on Policy Seminar (GenePOPS), “DNA and Depression: Tests, Trust, and Treatment,” will be held at the National Press Club in Washington, DC on Monday, December 17. The program is co-sponsored by the Bazelon Center for Mental Health Law and the Centers for Disease Control. Click here to register.

Panelists will include Francis J. McMahon of the National Institute of Mental Health, Neuromark CEO Kim Bechthold, Jeffrey Botkin, associate vice president for research at the University of Utah, and Robert Bernstein, executive director of the Bazelon Center. Speakers will examine the broad policy issues emerging from growing understanding of the genetic basis of depression and other mental conditions, the ability to detect genes responsible for these conditions and offer therapy based on genetic tests, and the policy questions that genetic testing for personalized medical treatment raises more generally. Also available at the program will be copies of a new set of recommendations from the Centers for Disease Control and Prevention’s Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group regarding the use of genetic testing to guide treatment of depression, to be published Dec. 15 in the journal Genetics in Medicine.

Sara Katsanis joined the Center in October as a genetics research analyst. She is responsible for gathering, interpreting and analyzing research data to guide the development of policy options related to genetic testing and technologies. Previously, she served as the laboratory manager of the DNA Diagnostic Laboratory at Johns Hopkins University. Sara also has worked as an associate scientist at Lexicon Genetics, Inc., responsible for the management of the genotyping facility, and as a DNA analyst testing and testifying on DNA evidence for the crime lab at the Harris County Medical Examiner’s Office in Houston, Texas. Sara holds an M.S. in Medical Genetics from Brunel University, England, and a B.S. in Biological Science from Clemson University.