27 June 2008. Alzheimer researchers, advocates, and caregivers are giving mixed reviews to the passage into law last month of the Genetic Information Nondiscrimination Act (GINA). The new law, more than a decade in the making, prevents employers and health insurers from denying jobs or coverage to individuals based on genetic information. But it affords no protection for disability, life, and long-term care insurance—safeguards critical to the well-being of Alzheimer disease (AD) patients and their families. “After 13 years of legislative debate, the law stops short of fully protecting people with Alzheimer’s,” said patient-advocate Bill Bridgwater, a national board member of the Alzheimer’s Association.
GINA was originally conceived to address shortcomings in the Health Insurance Portability and Accountability Act (HIPAA) of 1996. HIPAA put some restrictions on using genetic information to determine premiums or eligibility in group health plans; the new law extends protections to individual policies and employer practices as well. It also prohibits health insurers from requesting or requiring that a person undergo a genetic test, and prohibits employers from requesting, requiring, or purchasing genetic information on employees or potential hires. And it bans discrimination against those who take part in, or have family members participating in, research that includes genetic testing, counseling, or education. For a freely downloadable discussion of GINA, see Hudson et al., 2008 in the New England Journal of Medicine, with a video interview with Francis Collins of the National Human Genome Research Institute in Bethesda, Maryland.
In advocating for these changes, GINA’s proponents hoped to smooth the way for the practice of personalized medicine, which relies in part on genetic testing. They also sought to encourage participation in clinical research, where fear of discrimination based on genetic information can keep prospective subjects away. On these counts, GINA is being hailed as a success.
“It’s a great step forward, something that’s long overdue,” said Robert Green of Boston University, director of the REVEAL study, which monitors the experience of healthy adult children and siblings being tested for AD risk (see ARF Live Discussion). “It reassures the public—especially the potential research subjects out there—that we are taking measures to address their greatest anxiety: that the information in their DNA will be used against them.”
“The passage of GINA removes one potential barrier to genetic testing not just for our customers, but for anyone considering this type of testing,” agreed Karen Hanson, director of clinical operations at Smart Genetics in Philadelphia, which through the online service Alzheimer’s Mirror offers direct-to-consumer testing for ApoE4, a genetic marker for late-onset AD.
Unfortunately, GINA does not remove the remaining barriers to life, disability, and long-term care insurance that relatives of AD patients currently face. Because of that loophole, “I haven’t paid that much attention to it,” admitted Misha Bairach, whose husband has early-onset AD. Unlike ApoE4, the genes for early-onset familial AD are definitive predictors of disease, and Bairach hopes her three adult children will get screened for them someday—but not before they’ve secured disability and long-term care insurance. Even in the absence of predictive genetic testing, two of Bairach’s children have already been refused coverage.
“It’s disappointing that GINA specifically excludes long-term care insurance,” says Sam Gandy, chair of the Alzheimer’s Association’s medical and scientific advisory council. “That’s certainly at the top of the list of concerns for Alzheimer patients and their families.”
Such provisions were strategically excluded from the legislation in order to secure its enactment, said Angela Trepanier, president of the National Society of Genetic Counselors. “Any time you pass legislation, there has to be some compromise,” she said. While not entirely sympathetic to it, Trepanier understands the insurance industry’s economic bind with regards to disability, life, and long-term care plans, which are preferentially sought out by people with increased susceptibility to disease. “The companies can’t provide coverage if they only have high-risk individuals,” she noted.
But Trepanier expressed concern that AD patients and their families may not recognize the law’s loopholes when they decide to get tested. Her fears could be well-founded. Even though GINA will not go fully into effect for another 18 months, business at Alzheimer’s Mirror has seen an uptick since May, according to Smart Genetics cofounder Richard Watson. While he was unwilling to disclose exact numbers on the increase, “I’ve personally spoken to people who decided to purchase their test after GINA passed,” Watson said, “including one individual who specifically waited for the law before being tested.”
GINA’s passage underscores the need for pre-test counseling to help people make informed decisions about genetic screening, Trepanier said. “It’s the Alzheimer research community’s responsibility to make sure people know those loopholes are there,” Gandy stated. For a start, people considering testing can search the National Society of Genetic Counselors website to locate a genetic counselor by specialization and geographic area.
Indeed, Gandy and others worry that the law, in combination with direct-to-consumer testing (DTC) services such as Alzheimer’s Mirror, could prompt a headlong rush to ill-considered testing and commercial misrepresentations of genetic markers. DTC genotyping companies have already been the subject of two recent state crackdowns in California and in New York (click upper right corner to skip welcome), and federal hearings on the services are scheduled for July. DTC testing could end up unduly stigmatizing the ApoE4 variant, said Gandy. Although 15 to 30 percent of the general population has inherited at least one copy of ApoE4, as do some 45 percent of people with AD, many people with the ApoE variant never develop the disease. “I don’t see the point of an ApoE test,” said Rudy Tanzi of Massachusetts General Hospital in Boston, who has advocated for GINA’s passage. “It’s not reliable except as a differential diagnostic.”
That caution doesn’t always come across in advertisements for direct-to-consumer services, and it also doesn’t seem to match the public’s perception.
“People call and say, ‘I want to be tested for the Alzheimer gene,’ and they mean ApoE4,” said Jill Goldman, a genetic counselor at Columbia University College of Physicians and Surgeons in New York, who sees families with early-onset AD. “We won’t do it, because it’s not specific enough. My fear is not so much for the people who receive a result with an ApoE4. They’re kind of expecting it. I fear for the other ones, who think they’re scot-free, and don’t make appropriate plans for the future—and that means long-term care insurance.
“We advise people to get all of their insurance before they get tested,” Goldman said. “GINA is not going to change that. But if there were effective treatment or prevention, that would change everything.”
The long-term outlook may be a different story from the immediate impact of GINA on AD-related genotyping. Tanzi, a leader in AD genetics research, notes that the information supplied by susceptibility genes will eventually help clinicians customize care for a wide variety of illness, including Alzheimer’s. “We’re entering an era where there will be more pharmacogenetics,” he said, “and genotyping may eventually be required by HMOs to determine which drugs will be effective.” Indeed, several drug trials already have hinted that AD patients carrying ApoE4 may respond less well to drugs ranging from cholinesterase inhibitors to the diabetes drug rosiglitazone to an experimental AD antibody therapy. It is important to add, however, that this pharmacogenetic result came up in post-hoc analysis, which tends to be statistically weak, and has not to date been replicated in a follow-up study designed to test it directly (see ARF related drug news story; ARF related conference story; Farlow et al., 1998).
Though its practical effects may be lackluster, GINA’s symbolic import should not be overlooked, Tanzi said. Tom Bird, a leading neurogeneticist at the University of Washington in Seattle, agreed. Bird said the passage of GINA signals a willingness on the part of national government to address the policy challenges raised by personal genomics.
“A key thing that insurers and legislators and the general population have to realize is that we all have genes that put us at increased risk of disease,” Bird said. In the coming years, the roster of those genes will continue to grow, along with the ability to interpret their effects. “It’s not an issue that’s going to go away.”—Karen Wright.
Karen Wright is a freelance writer in New Hampshire.