The test you don’t want patients to pass is around the corner
Alzheimer’s disease is newest candidate for genetic testing
Ethics committees could be faced with the newest genetic testing dilemma as a recently discovered indicator might identify late-onset Alzheimer’s disease. The dilemma facing ethics committees, however, could have more far-reaching ramifications than genetic researchers realized. Primarily, issues that ethicists will have to decide are who should conduct counseling with patients and how to keep potentially damaging information confidential. And patients themselves are having unsettling, and some say chaotic, reactions to national media reports about the ability to predict’ the fate of the disease.
What’s more, the issue of informed consent could come into play for patients who received a test for a cardiovascular ailment in the past. That’s because the indicator on chromosome 12 that shows a strong correlation with the development of late-onset Alzheimer’s disease (AD) also is linked to a patient’s ability to move cholesterol in the blood.
"The test for the Alzheimer’s protein marker was previously done by cardiologists when it looked like that genetic link was strong, but it’s not as common now," says Henry Greely, JD, co-director of the program in genomics, ethics, and society at Stanford University Center for Biomed-ical Ethics in Palo Alto, CA. Stanford, in conjunction with the Veteran’s Affairs Palo Alto Health Care System and other organizations, developed an Alzheimer’s Working Group that drafted a set of recommendations on genetic testing for AD. The final recommendations will be presented in early 1998. (Visit Stanford’s Web site for information on obtaining a copy. See Laura McConnell’s entry in source box, p. 4.)
Protein is key in identifying disease
Researchers in 1993 found that patients who inherited a common version of a gene known as apolipoprotein-E, commonly referred to as apoE, could be biologically linked to the development of late-onset AD. The AD association is correlated to the apoE’s fourth allele, or apoE-E4. Researchers still don’t know exactly what causes AD, however. More than four million Americans are affected by the disease, which costs $40 billion in ancillary and nursing home costs, according to the Bethesda, MD-based National Institute on Aging (NIA).
The issue facing ethics committees now is whether patients who took the test under a cardiologist’s care should be advised of the correlation, says Eric Juengst, PhD, associate professor of biomedical ethics at Case Western Reserve University in Cleveland.
"I’ve never seen an institutional ethics committee deal with this kind of issue, but in theory, they could be approached by cardiologists wondering if they have any obligation to explain this new association to previously tested patients."
In addition to the debate over whether cardiologists are obligated to disclose the information is who should provide the counseling, adds Juengst. He points out that the NIA urges clinicians with both neurological and genetic counseling expertise to help inform patients of the results of tests.
"Of course, that reflects the make-up of the National Institute on Aging’s consensus panel, but if it counts as the professional standard of care in this area, then it is what cardiologists should try to live up to as well if they are going to try to explain the AD implications of an apoE test result," Juengst explains.
A concensus statement on genetic testing for AD was published in the March 12 issue of the Journal of the American Medical Association.1 The concensus statement was funded by the National Human Genome Research Institute of the National Institutes of Health in Bethesda, MD. (For patient information on genetic testing, see the Alzheimer’s Disease Genetic Fact Sheet, inserted in this issue.)
In fact, the NIA in a public policy statement, in conjunction with the Chicago-based Alzheimer’s Association, discourages using the apoE test as a patient screening or predictive method. Instead, the groups propose that apoE testing be used for diagnostic purposes only in conjunction with other tests during medical evaluations of patients who show AD symptoms. (For more on genetic counseling precautions, see story, p. 4.)
Both the NIA and the Alzheimer’s Association support genetic counseling before and after testing because the meaning of the results is complex and the results are hard to understand. (For more on available Alzheimer’s resources, see box, p. 3.)
The impact of the apoE-E4 link to AD is still unclear because there is no definitive evidence that patients with the protein will develop AD. A Boston study, for example, found a twofold increased risk of developing AD associated with apoE-E4 in which 13.7% of the tested patients had AD attributable to the allele.2 But the test is not recommended for people without dementia, which is just one symptom of the difficult-to-diagnose disease, cautions Stephen Post, PhD, associate professor of biomedical ethics at Case Western Reserve University in Cleveland. Post is chairman of a national study group that has met over the last year to review emerging information about new genetic tests for AD.
Recommendations are available
Ethics committees do have a resource to help establish a policy or procedure on genetic testing for AD. The Stanford University Program in Genomics, Ethics, and Society’s draft executive summary of recommendations for genetic testing and AD provides assistance. A final version of the recommendations will be available in early 1998.
Key points in the executive summary include:
o Professional organizations and others should continue to draft and refine guidelines for whether and when genetic testing is appropriate.
o Genetic testing programs must provide a comprehensive process, including adequate informed consent, access to pre- and post-test genetic counseling, and multidisciplinary follow-up care, including psychological counseling for the individual and family when appropriate.
o Genetic counseling can be provided by a wide variety of competent professionals, but it should be performed only by those who have received specialized training in genetics, genetic counseling, and preferably the particular disease or disease category.
o Improved knowledge about genetics is essential to appropriate testing programs. Education programs must be developed and implemented for people at risk, the general population, health care providers, and policy-makers and should not be controlled by those with a financial interest in testing.
o Federal and state laws should ban the use of information about genetic testing in health insurance or employment decisions, and these prohibitions should be coupled with privacy legislation that limits the ability of insurers and employers to acquire genetic information the fact that a genetic test has been administered should be protected in the same way as the information gained from the test.
o Patents on genetic material, information, or inventions should not be allowed to be a significant barrier to research or to the disclosure of clinically relevant information.
o The commercial availability of genetic tests should be determined within a regulatory framework. That framework should require proof of ability to detect accurately a genetic trait with a significant link to the existence or risk of a condition or disease in a defined population, and it should include a long-term data collection component to prove medical efficacy and psychological safety.
One certainty in the AD genetic testing debate is the need for further research and clarification about who should be tested. "There’s a lot of confusion, and the chaotic reaction of some people is the crux of the issue," Post says.
References
1. Post S, Whitehouse P, Binstock R, et al. The clinical introduction of genetic testing for Alzheimer disease. JAMA 1997; 277:832-836.
2. Evans D, Beckett L, Field T, et al. Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons. JAMA 1997; 277:822-824.
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