A New Era for Genetic Testing

Genetic discrimination could be a real threat and hindrance to widespread acceptance and adoption of genetic testing as a clinical tool. In the movie Gattaca, genetic discrimination takes a sinister path in a society where the genome of every newborn is mapped at birth, and the genetic information follows them throughout their lives.

In reality, genetic testing is not used for sinister purposes, but could still have very real consequences. Would you willingly subject yourself to a genetic test, knowing that the ‘wrong answer’ could reduce your ability to get insurance or a job offer? Probably not.

In fact, according to the National Institutes of Health, when offered screening for genes linked to breast or colon cancer, about a third of people eligible for the testing typically say no. The reason? These patients fear that a genetic predisposition to cancer will limit their ability to secure health insurance.

This explains why, when President Bush signed the Genetic Information Nondiscrimination Act (GINA) into law on May 21, 2008, its passage was met with great fanfare. The bipartisan bill was more than 10 years in the making, and media coverage of the event was largely positive.

Michael S. Watson, Executive Director of the American College of Medical Genetics, acknowledged the growing fear of genetic discrimination in expressing support for GINA. He said, “We believe that no American should have to choose between having a genetic test or participating in a research study that could be important to his or her life, or avoid a genetic test or furthering research to save a job or protect health insurance coverage. Fear of discrimination, prejudice or economic consequences should not be a factor in whether someone has a genetic test that could improve or save their lives.”

To prevent discrimination on the basis of genetic makeup, GINA contains a broad list of restrictions against usage of genetic information by group health plans, health insurance companies, issuers of Medicare supplemental policies, as well as employers, employment agencies, or labor organizations.

Its major provisions prohibit these entities from requiring individuals or family members to undergo genetic tests, purchasing genetic information for underwriting or plan enrollment purposes, offering coverage based on genetic information, or using genetic information as the basis of hiring decisions. It also revises the Health Insurance Portability and Accountability Act of 1996 (HIPAA) to treat genetic information as health information and prohibit its use for underwriting purposes.

Near universal acceptance

GINA had broad-based bipartisan support in both the House and Senate. The bill passed the Senate unanimously, and its lone dissenter in the House was Congressman Ron Paul. Its sponsors were a broad range of congressional leaders from both sides of the political aisle.

In a public statement on the day the bill was presented to Congress, Senator Ted Kennedy, a co-sponsor of the bill, said, “Mapping the human genome has provided extraordinary insights for modern medicine, and has opened the door to immense new opportunities to prevent, diagnose, treat, and cure disease. Its discovery may well affect the 21st century as profoundly as the invention of the computer or the splitting of the atom affected the 20th century.”

He continued: “The Genetic Information Nondiscrimination Act recognizes that discrimination based on a person’s genetic identity is just as unacceptable as discrimination on the basis of race or religion. No American should be denied health insurance or be fired from a job because of genetic testing.”

In signing the bill into law, President Bush agreed, saying that GINA “protects our citizens from having genetic information misused, and this bill does so without undermining the basic premise of the insurance industry.”

For a new law to appeal to both the political left and right is certainly an accomplishment. It also demonstrates the very high level of awareness of the subject, and the concern that genetic discrimination represents to all facets of American society.

Limitations

Despite this fanfare, GINA is an imperfect law that leaves the door open for discrimination in some circumstances and settings. It does not apply to life, long-term, or disability insurance, only to medical and health insurance. This represents a major disconnect – consumers are protected when purchasing medical insurance, but not when purchasing life or disability insurance.

So the same problems arise. Individuals with an elevated risk for Huntington’s disease or breast cancer will eschew genetic tests, fearing that they could lose their life or disability insurance or see premiums skyrocket, or they could be forced to undergo genetic tests by their life or disability insurance carriers.

In addition, since many of these insurance policies are offered through employers and, in some cases, through the same insurance carriers, consumers may run the risk of their genetic profile ending up in the wrong hands.

For example, a long-term disability carrier that also provides group health insurance at an individual’s place of employment could have access to genetic test result information that is needed and wanted by other audiences within the organization. While GINA will prevent the health insurance arm from asking for this information, the risk still exists that it may end up in the wrong hands.

State laws

In many ways, states have been ahead of the curve in identifying the potential societal risks associated with genetic testing. The first state laws appeared in the 1970s and 1980s, protecting job applicants who had the sickle cell trait, with Wisconsin being the first state to outlaw genetic testing in the workplace. Today, 34 states and the District of Columbia have laws against genetic discrimination in the workplace.

Regarding insurance, only two states do not have some form of protection for consumers on the books: Missouri and Pennsylvania. Existing state laws run the gamut. Some cover group policies only, others cover individual policies only, and still others cover both group policies and individual policies.

Most state laws prohibit determination of eligibility based on genetic information and use of genetic information for risk selection and risk clarification purposes. Many also prohibit insurance companies from requiring genetic tests.

Clinical issues

But all of this legal action is a moot point if genetic testing does not actually lead to real improvements in the prevention, diagnosis, and treatment of genetic diseases. This latter point has been presupposed in many ways.

A 2004 study of genetics research examined 627 newspaper articles on 111 scientific papers, and concluded that there was an overemphasis of benefits and almost complete absence of risks and costs in both newspaper articles and scientific papers.

The reality is that genetic testing is a promising but expensive technology that has largely unproven benefits. At Hayes, we have evaluated the clinical evidence behind 12 genetic tests for a total of 33 different uses, using methodology based on the Center for Disease Control and Prevention’s ACCE model. We anticipate evaluating another 40 tests over the next 12 months. The ACCE model considers:

• Analytical validity, or the ability of a genetic test to accurately and reliably measure the genotype of interest.
• Clinical validity, or the ability of a genetic test to detect or predict the associated disorder (phenotype).
• Clinical utility, or the ability of a genetic test to improve health outcomes.
• Ethical, legal and social implications, including safeguards and impediments considered in context of other components.

After the evidence for each of these elements has been evaluated, we score the genetic tests with a Hayes rating, as follows:

For the 12 tests evaluated to date, only eight out of 33 (24%) of the uses have obtained Hayes Ratings of B or higher. This is not because the technology is not promising. Rather, in many cases, it is because an insufficient number of high quality clinical studies have been performed to validate that these uses of the genetic tests lead to better patient care.

Indeed, 18 out of 33 (55%) of uses received a Hayes Rating of C or D2, indicating that there is insufficient published evidence to evaluate those particular uses of the test. Over time, as additional clinical studies are performed, these ratings may change, and therefore we monitor the literature regularly and reports are updated as appropriate.

For example, the PathFinderTG test might have promise as a predictor for breast cancer. However, a Hayes review of the literature indicates that there is insufficient published evidence for us to even perform a health technology assessment of this test. The main evidence deficiencies for the PathFinderTG test include lack of a description of how the test works and how it is applied to breast cancer, and an absence of any data on analytical validity, clinical validity, or clinical utility. In our view, this makes the test, which costs $4000 to $5000 per application, too early in its life cycle to be recommended for clinical use.

Compare this with genetic tests for BRCA1 and BRCA2, which have been in use for nearly a decade. For 5% to 10% of breast cancer patients, a strong family history is indicated by multiple site-specific cases or prevalence of both breast and ovarian cancer. Genetic alterations in BRCA1 and/or BRCA2 are thought to account for 45% to 90% of BRCA1-related cases and 35% of BRCA2-related cases with a strong family history of breast/ovarian cancers.

With a long history of usage and a large body of knowledge from clinical studies, a Hayes review of the evidence regarding BRCA1 and BRCA2 tests indicated that clear clinical benefits could be derived from using the test for some patients. Individuals found to carry an alteration in one of these genes can take preventive measures to reduce the risk of cancer, such as increased surveillance or prophylactic mastectomy or oophorectomy.

Future use

Now that GINA has become law, it is anticipated that consumers will be much more comfortable with genetic testing in general. This will only accelerate test usage, which has already been exacerbated by direct-to-consumer advertising.

However, healthcare executives need to proceed with caution. There is great disparity in proven clinical benefit among tests. The scientific evidence for each test must be examined on a test-by-test basis to determine its real benefit in a clinical setting.

While GINA represents a much-needed step in the right direction, the healthcare industry must grapple with even bigger issues relative to genetic testing; the clinical validity and utility of each of the different tests, and the growing cost of these tests.