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As Genetic Tests Move Into the Mainstream, Challenges Await for Doctors and Patients

Sarah L. Zielinski

In the last decade, the list of gene mutations that have known associations with increased cancer risk has grown to more than two dozen. As more is learned about these susceptibility genes and as new ones are discovered, the promise of tailored treatments and preventive measures grows. But when it comes to testing for these genes, there are unique challenges in bringing these new tests into clinical practice for both the clinicians who order the tests and the insurance companies that pay for them.

One of the difficulties in designing clear guidelines for genetic testing is that there is no single defined protocol for testing as there is when, for example, a patient comes in with chest pains. Depending on the circumstances, cancer patients, family members, or even members of the general public may be the subject of a potential genetic test that can be initiated by primary care physicians, oncologists, or other specialists.

A starting place is the American Society of Clinical Oncology (ASCO), which in 2003 made recommendations for when genetic tests for cancer susceptibility are appropriate. Their guidelines recommend a test only when three conditions are met. First, the person being tested must have a personal or family history suggesting the possibility of a genetic susceptibility. Second, there must be a test that can be adequately interpreted, meaning that it has a high number of true-positive results and a low number of false positives. And third, the results of the test must be able to aid in the diagnosis or treatment of the individual or their family members.

However, "the ultimate arbiter of genetic testing is the proband, the patient," said Kenneth Offit, M.D., chief of the Clinical Genetics Branch at Memorial Sloan-Kettering Cancer Center in New York and head of the ASCO working group that developed the guidelines. He spoke of one patient, a Holocaust survivor who had breast cancer followed by ovarian cancer. She had no living female family members and no children or sisters, and there was no formal medical indication that a test was warranted. But the patient chose to be tested, hoping for an explanation for her own cancer, Offit said, and "genetics can tell you ‘why.’"



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Kenneth Offit

 
For others, knowing the "why" is not enough reason to be tested when there are no interventions that can offset the risk or when the diagnosis will not affect treatment; Li-Fraumeni syndrome is one example. "That's a circumstance where most families will decide at the end of a genetic counseling session that they do not want to know" if they carry a mutation, Offit said.

But there is a shortage of health care providers at nearly all levels who have adequate training in genetics. For example, there are fewer than 2,000 certified genetic counselors in the United States, and their jobs entail much more than cancer genetics.

Many physicians, both primary care and specialists, have inadequate knowledge and training for providing genetic tests to their patients, particularly when a genetic counselor is not available. A 2003 report found that only 29% of physicians considered themselves qualified to provide genetic counseling to their patients. And although more than 85% of oncologists reported feeling qualified to recommend genetic testing to their patients, only 40% of primary care physicians felt the same of themselves.

ASCO has trained at least 3,000 oncologists in cancer genetics through its continuing education program. "We've definitely increased awareness of genetics to a point that's quite noticeable," Offit said.

One of the major problems is in helping time-pressured primary care physicians to find the time to do what is necessary when considering whether a patient is appropriate for a specific genetic test, said Wylie Burke, M.D., Ph.D., professor and chair of the department of medical history and ethics at the University of Washington in Seattle.



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Wylie Burke

 
Burke is developing a Web resource for primary care physicians that will help prepare them for integrating genetic testing into their practices. One suggestion was teaching these doctors a triage version of a family history, the first two or three questions of which would, if answered "yes," indicate that a full family history should be taken.

In addition, Burke stressed the need to educate primary care physicians about the connections between genes and all of the conditions for which they may be responsible.

"In a way, it's asking a lot of a primary care physician to ... take something like this on," said Mark H. Greene, M.D., chief of the Clinical Genetics Branch in the Division of Cancer Epidemiology and Genetics at the National Cancer Institute.

Aside from physician education, public education is also a concern, both in terms of what the risks are and what the appropriate course of action should be. "Public awareness of familial cancer risk is probably not as high as it should be," Greene said. "The problem is communicating that to the public at large" without making people believe they have a genetic susceptibility when it is unlikely.

But when the general public becomes the subject of educational or advertising campaigns, the likelihood increases that tests will be ordered inappropriately. There is a risk that because members of the general public are likely to go to their primary care physicians first to inquire about the test, these physicians may just test a person without determining if they are the right person in their family to test or if the specific test is right for that person and their situation. "There's a potential for things just going off the rails," Greene said.

The "nice-to-know" information can lead to unnecessary tests and treatments and added stress for the individual. But beyond the choices made by the doctor and patient are those made by the insurance companies that foot the bills for any test and associated services, such as genetic counseling. For an insurance company, a genetic test can be an unnecessary expense or just another medical service to be covered, and these companies are building policies of their own to decide when to cover genetic testing services for their members.

With so many new discoveries, insurance companies are finding it difficult to know what will benefit members. "There's a lot of noise," said Joanne Armstrong, M.D., senior medical director for women's health and clinical lead for genomics for Aetna Inc., a large U.S. health insurance company.

Genetic tests can be pricy: A full-sequence DNA analysis of both breast cancer genes, BRCA1 and BRCA2, costs almost $3,000. Armstrong said that the high cost of the tests means that Aetna has to prioritize the discoveries and demonstrate their value before a test will be covered.

Aetna developed a special policy regarding genetic testing more than 5 years ago after recognizing that there were several special issues that they needed to address, including privacy issues. They also decided to make it possible for family members not covered by Aetna to receive Aetna-covered genetic testing if it is more logical to test that family member first.

To decide whether specific genetic tests are appropriate for Aetna coverage, the company maintains an in-house technology assessment group that conducts both internal and external reviews of all coverage policies, which are reviewed at least annually and sometimes more often. Internal staff also scans for new technologies, which are then reviewed by the external committee of physicians and a pharmacist. When appropriate, Aetna also sends out policies to scientific societies for review.


Genetic Tests in Cancer and Possible Interventions

Many genetic tests raise more questions than they answer; however, there are some known susceptibility genes for conditions that have feasible interventions (see below).


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Some insurance companies are still developing their policies. "We're still kind of evolving our approach to genetic testing," said Walt Hollinger, M.D., managing medical director for Blue Cross Blue Shield of Florida.

Hollinger said his company's technology assessment process relies on national technology assessment centers, such as the Blue Cross Blue Shield Association's Technology Evaluation Center and the independent technology assessment companies Hayes Inc. and ECRI. He added that they generally cover genetic testing when it falls into one of two categories, either when a national body recommends it for screening or when it is used in diagnosis and would have an impact on patient management, such as testing for breast cancer genes. "Those we cover just like any other medically necessary test," Hollinger said.

However, both Armstrong and Hollinger cautioned that, of course, even when the insurance company decides that a genetic test is appropriate for them to cover, the extent of an individual member's insurance policy determines whether they are actually covered for genetic testing.

Insurance companies and physicians receive little help in evaluating the usefulness of genetic tests because the tests are not subject to regulation by the U.S. Food and Drug Administration, as drugs are. The FDA regulates diagnostic test kits, but most genetic tests are performed in clinical laboratories that do not use these kits and instead use in-house assays not subject to FDA regulation.

Because most genetic tests, therefore, come onto the market through what Burke calls the "home-brew method," without any premarket review by the FDA, there have been several suggestions of how to improve oversight. For example, the ASCO Working Group on Genetic Testing for Cancer Susceptibility has supported strengthening the regulatory oversight of the clinical laboratories that provide genetic tests. Another approach comes from the Secretary of Health and Human Services' Advisory Committee on Genetic Testing, which from 1998 to 2002 recommended that all genetic tests be made subject to FDA oversight.

Some have even suggested that a new step may be needed between the research and clinical settings. Last year in the Journal of Law, Medicine & Ethics, Carol L. Freund, Ph.D., of Vanderbilt University in Nashville, Tenn., and colleagues proposed the introduction of natural settings trials "to provide data to guide translation of genetic tests from the research phase to clinical application." These trials would establish the clinical utility of new genetic tests and possibly improve their safety before their introduction to the clinical setting.

People may expect genetic testing to give them all the answers they need, but they are bound to be disappointed, and this is why everyone involved needs to be so careful when making decisions about these tests. "You have to be really careful to get it right," Offit said.



             
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