The American College of Medical Genetics last week became the first professional society to release practice guidelines designed to ensure a safe and ethically responsible direct-to-consumer genetic testing service market.
Meantime, the HHS Secretary's Advisory Committee on Genetics, Health, and Society, which last week released its own final guidelines for overseeing genetic tests, noted that because the rapidly evolving field continues to confound efforts to determine how DTC genetic tests affect consumers, professional societies, such as the ACMG, should develop best-practice guidelines to help standardize the emerging DTC genetic testing services industry.
For its part, the Centers of Medicare and Medicaid Services this week told Pharmacogenomics Reporter that it plans to form public/private partnerships with the genetic-testing community to develop better educational materials for labs and the public. It also plans to better regulate labs by incorporating professional standards into its guidance for labs and lab inspectors, according to a CMS official.
In its five-point Policy Statement on Direct-to-Consumer Genetic Testing, the ACMG recommends that any genetic-testing protocol should employ and involve “knowledgeable” health-care professionals to order and interpret genetic tests; fully inform consumers regarding what a test can and cannot determine about their health; clearly present the scientific evidence upon which a test is based; conduct testing at a laboratory accredited by CMS’ Clinical Laboratory Improvement Amendment, the state, or by other accrediting agencies; and address consumers' privacy concerns.
“Geneticists and genetic counselors are the professional guides to the human genome and can help patients make informed decisions about choices related to genetic testing and provide invaluable support and guidance in interpreting test results in light of personal and family history,” Michael Watson, executive director of the ACMG, said in a statement.
“This is not an area where people should really go it alone," he added. “Our goal is to ensure that there is an organized system with well-trained and experienced providers through which consumers can ensure that the information is obtained and used appropriately.”
According to Watson, the ACMG has heard from physicians who say they are poorly equipped to interpret results from high-density genomic tests that their patients are increasingly bringing to them.
“Aside from the general prevention mantra of 'eat well and get plenty of rest and exercise,'” doctors feel they can provide little in the way of medical advice, and “often feel obligated to repeat the testing if the results have important health implications, which further increases overall costs for health-related services,” Watson said.
Although DTC genetic testing services have cropped up in greater numbers over the past year, genetic testing is still a new and little-known concept to the lay consumer.
ACMG’s “primary interest” in releasing the policy statement is to ensure “that consumers understand what differentiates a genetic test that is valid and useful from one that is of little value or not appropriately validated, as all genetic tests in clinical service are validated,” Watson told Pharmacogenomics Reporter last week.
“The tests being sold are often very expensive and consumers should be aware of what they can expect in terms of actionable information,” he continued. “Since industry is dependent on a customer, an informed customer is the best way to ensure that the products that industry sells meets their needs.”
In addition to a number of firms offering single-gene tests, several companies, including Navigenics, DeCode, and 23andMe, offer genotyping services to the general public to gauge their predisposition to complex, and sometimes fatal, diseases. With the growing prevalence of these types of services, doctor and patient groups have become increasingly concerned that the current level of federal regulation for these services is confusing and doesn’t do enough to protect the public's health.
Supporting this theory were results of a report published in Science last month by researchers from Johns Hopkins University's Genetics and Public Policy Center that uncovered inconsistencies and misleading claims made by companies selling CYP450 testing services designed to help guide treatments of certain antidepressants. In the paper, the researchers concluded that there is “clearly a need for leadership at the federal level” to ensure that genetic tests marketed to the public are safe and efficacious [see PGx Reporter 04-09-2008].
In 2006, the US Food and Drug Administration, the Centers for Disease Control and Prevention, and the Federal Trade Commission issued a joint consumer alert called At Home Genetic Tests: A Healthy Dose of Skepticism May Be the Best Prescription, which cautioned consumers to be “wary of claims about the benefits these products supposedly offer.” Yet despite that effort, regulation of genetic tests as a whole remains in flux.
Although, the FDA regulates genetic test kits and CMS oversees most laboratory-developed tests, the FDA has recently expressed its intention to regulate a subset of more complex LDTs, called in vitro diagnostic multivariate index assays. With regard to DTC genetic tests, however, for the time being the FDA is choosing to practice “enforcement discretion.”
In an e-mail to Pharmacogenomics Reporter last week, Steven Gutman, director of FDA's Office of In Vitro Diagnostic Device Evaluation and Safety, said that while the agency “is observing [the DTC genetic testing field] with considerable interest ... the FDA is currently applying enforcement discretion to DTC testing using laboratory-developed methods.”
DTC genetic testing “is not an area where people should really go it alone."
According to Judith Yost, director of CMS' Division of Laboratory Services, all CLIA quality standards apply to any DTC genetic test if the testing is done at a lab that falls under the agency's regulatory purview. CMS regulates all sites where testing is performed on human specimens for health purposes. However, the agency does not regulate claims, sale of ancillary products, advertisements, or tests not for health assessment — which also could comprise many existing DTC tests that don’t assess an individual’s health per se but merely provide a risk assessment.
“There are no plans to change” CMS' current level of oversight ,Yost told Pharmacogenomics Reporter this week. “CLIA is intended to ensure the accuracy and reliability of testing regardless of where [it is] performed.”
Although CMS has no “broad plans” to increase its oversight of genetic testing, Yost said that the agency has agreed to make some regulatory changes in the area of proficiency testing.
“We plan to change the regulations including the list of tests that require PT, the grading scheme, target values, and requirements for PT programs,” Yost said.
This appears to be a marked change in CMS' willingness to address proficiency testing for CLIA-certified laboratories in past months. In September the agency denied a GPPC petition to create a genetic specialty under CLIA, which would be a step toward making proficiency testing mandatory for all CLIA-certified laboratories. At the time, CMA said such a requirement would be too costly [see PGx Reporter 09-05-2007].
Regarding proficiency testing, “we have already developed a plan and have met with CDC, our CLIA partner, to put that plan into effect through the CLIA Advisory Committee,” Yost added.
In its final guidelines for the oversight of genetic tests, released last week, the SACGHS noted that given the rapidly evolving nature of the field, it is currently difficult to assess how marketing genetic tests to consumers will affect them. While the regulatory oversight of genetic tests as a whole is currently in flux, the committee recommended that federal agencies first work together to oversee the field and assess the impact of marketing genetic tests directly to consumers.
During a SACGHS meeting last year, Wylie Burke, chair of the department of medical history and ethics at the University of Washington, stated that the “role of statutory regulation in the oversight of genetic tests was not clear.”
However, Burke acknowledged that “at FDA there was an ongoing concern about whether there should be more regulation concerning performance of genetic tests in laboratories and uncertainty about measures that should be taken to protect consumers from DTC tests.”
According to Burke's statements, recounted in the SACGHS' final guidelines, “statutory regulation [is] a potential vehicle for standardized reporting and labeling of information about genetic tests, but ... not a route for establishing a standard of practice around the use of genetic tests.”
In the absence of more clear guidelines, Burke suggests that professional societies, such as the ACMG, step in and develop best practice guidelines to help standardize the emerging DTC genetic testing services industry.
“Professional organizations could help identify the importance of genetics issues for their members, whether in national meetings or stand-alone educational programs. They can also play an important role in laboratory oversight, working within the context of CLIA to set standards and create [performance] testing programs,” the SACGHS report says, citing Burke. Additionally, professional societies can ensure that research is being conducted and that practice guidelines follow rigorous procedures to ensure the safety of tests, Burke added.
In its report, the SACGHS acknowledged that marketing DTC genetic tests is a rapidly evolving area, and therefore it is difficult to discern how these tests may be affecting consumers. Currently, consumers can directly order LDTs in 27 states, while 10 states allow DTC testing under certain circumstances.
“While the impact of these campaigns is difficult to define at present, the increasing availability of a variety of genetic profile tests that claim to answer questions regarding cardiovascular risk, drug metabolism, and deoxyribonucleic acid (DNA)-informed diet suggests that patients will assume increasing responsibility in the interpretation and utilization of these test results,” the SACGHS notes. “This trend has raised significant ethical concerns, as well as prompting discussion of the role of both genetics professionals and clinicians who are not trained in genetics with patients who request interpretation of results.
“The issue is now well enough accepted that it has begun to appear in professional societies’ policies,” the SACGHS states. The committee added that evidence exists in scientific literature suggesting that “DTC advertising misleads consumers with claims that are unproven and ambiguous.”
Guidelines Not Enough
While professional societies might increase confidence in the genetic-testing industry, their involvement won’t solve all of its challenges. According to Burke, while professional societies “develop practice guidelines, which are a trusted source of information for doctors ... the problem with practice guidelines is that they are 'all over the map.'”
“Many different bodies provide guidelines using different processes, some of which are more transparent and evidence-based than others,” Burke added. “Professional, personal, or financial interests sometimes affect the process, and methodologies vary and are not always disclosed. Even if the processes used are good ones, the evidence may be lacking.”
Adding to the ambiguity is the fact that “currently, there is no requirement that providers of non-FDA-cleared or -approved tests disclose information to support claims about the accuracy and validity of testing, and there is no central or uniform mechanism for providing this information in an accessible format to patients and providers,” the SAGCHS pointed out.
In its report, the advisory committee encouraged federal agencies to collaborate and regulate how DTC test shops market their tests, and assess how these campaigns affect their customers.
CMS' Yost said that in line with the report's suggestion, the agency has agreed to form public/private partnerships with the genetic testing community to develop better educational materials for labs and the public. Additionally, CMS plans to develop enhanced oversight of labs by incorporating professional standards into its guidance for labs and lab inspectors.
“We also have already provided our inspectors training in GT technology and issues,” Yost added.
Also adding to the regulatory confusion is the fact that the current system of regulating DTC testing requires that the tests be indicated to make medical decisions. However, many genetic testing services claim that they are simply offering consumers information about their genes, and that the information they are providing is not intended for medical decision making.
“We are now in new paradigm in which some argue that the human genome and the tests to determine one’s genomic content is only information and only becomes health care when one acts on it,” ACMG's Watson noted. Therefore, “recreational genetic testing operates outside of [the regulatory] system by arguing that they only provide information, not a medical test.”
According to Yost, however, DTC genetic testing shops may not be able to wiggle out of CMS regulatory oversight by simply claiming that their services aren't being used for medical decisions. “CMS has an ongoing effort to ensure that those DTC testing services that fall under CLIA are properly certified. Just claiming that you are not medical doesn't do it,” she said.