American Association for Clinical Chemistry
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July 2008 Clinical Laboratory News: After Long Wait, GINA Becomes Law

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July 2008: Volume 34, Number 7

After Long Wait, GINA Becomes Law
Will Labs See an Increase in Demand For Genetic Testing?

By Phil Kibak

After stalling in Congress for more than a decade, the Genetic Information Nondiscrimination Act, otherwise known as GINA, won unanimous approval in the Senate earlier this year by a vote of 95–0 and near-unanimous approval in the House of Representatives by a vote of 414–1. The act finally became law when President Bush signed it on May 21. Proponents of GINA say it will boost the demand for genetic tests performed in clinical labs because it protects an individual’s genetic privacy and bars employers from using genetic information when making hiring, firing, job placement, and promotion decisions. The new law also prohibits health insurers from denying coverage to healthy individuals or charging higher premiums based solely on the possibility of developing a genetic disease, a prospect that many considered a major stumbling block to widespread genetic testing for some forms of hereditary cancer. Supporters of the legislation described it as the first civil rights legislation of the 21st century.

Francis Collins, MD, PhD, Director of the National Human Genome Research Institute, was among those who spearheaded efforts to pass a federal law protecting genetic privacy. “This law allows more people to consider genetic testing without fears that employers or health insurers will use the results against them,” he noted. Under his leadership, scientists completed the Human Genome Project, a complex, multidisciplinary, scientific enterprise directed at mapping and sequencing the 3 billion DNA base pairs in the human genetic blueprint (See Box, below).

 Francis Collins Steps Down As NHGRI Director

Francis S. Collins, MD, PhD, the director of the National Human Genome Research Institute, part of the NIH, recently announced his intention to step down on August 1 to explore writing projects and other professional opportunities.

Collins, 58, a physician-geneticist, has served as NHGRI’s director since April 1993. He led the Human Genome Project (HGP) to its successful conclusion in 2003 and subsequently initiated and managed a wide range of projects that built upon the foundation laid by the sequencing of the human genome. Following the precedent set by the HGP under Collins’ leadership, these projects have made their data rapidly and freely available to the worldwide scientific community. Collectively, these projects and their data have transformed biomedical research and empowered researchers all around the world.

In addition to his leadership of the public effort to sequence the human genome, Collins initiated and guided a wide range of follow-up projects in large-scale genomics. He also played a leading role in applying the tools of genomics to understanding the risk factors for common diseases, such as diabetes, heart disease, various types of cancer, and mental illness.

“In the past, surveys have shown that many Americans, even including some healthcare providers, were reluctant to seek reimbursement for genetic tests or to include genetic test results in their health records because of concerns about discrimination,” Collins added. “By guarding against genetic discrimination in health insurance and employment, this law will encourage more Americans to take part in research that involves the collection of genetic information.” Collins also believes GINA will be a tremendous boon to many types of biomedical research, including genome-wide association studies aimed at uncovering the genetic risk factors for common diseases.

Gregory Tsongalis, MHS, PhD, Director of Molecular Pathology at Dartmouth Hitchcock Medical Center and President of the Association for Molecular Pathology, heads a lab that conducts a large volume of genetic tests. He agrees that GINA will encourage genetic research. “GINA certainly has the potential to open the door to expand genetic testing,” he said. “I don’t expect the floodgates will open and that there will be major increases in test volumes overnight, but I think we will see an increase in traditional genetic disease testing and screening. Also, I suspect that now people will be more willing to participate in genetics research trials.”

Useful But Not Perfect

Yet the new law has shortcomings. For example, it does not prohibit life insurance or disability insurance companies from taking genetic information into account in coverage decisions. “One could not help but assume that [GINA] is a revolutionary piece of legislation that…would provide extensive, effective, and comprehensive protection against genetic discrimination in health insurance and employment. Unfortunately, such an assessment would be incorrect,” wrote Mark Rothstein, JD, in an article titled “Is GINA Worth the Wait?” (Journal of Law, Medicine & Ethics 2008:36(1), 174–178). Rothstein is the Herbert F. Boehl Chair of Law and Director of the Institute for Bioethics, Health Policy and Law at the University of Louisville (Ky.) School of Medicine.

GINA applies only to those individuals who may have a susceptibility to develop a genetic disease but currently are asymptomatic. For example, GINA would prohibit discrimination against a woman who tested positive for one of the genetic mutations associated with an increased risk of breast cancer. But if the woman actually developed the disease, GINA would no longer apply. Likewise, in accordance with the Americans with Disabilities Act, employers may require that individuals submit to a medical examination and authorize the release of their medical records as a condition of employment. Even if GINA resulted in healthcare providers releasing only nongenetic information, there may be no practical way to do so.

But whatever deficiencies the new law has, many experts believe it will have a positive impact by creating greater ease, access, and openness about genetic testing and research.

Those who perhaps stand to benefit most from GINA are people who currently are not covered by state nondiscrimination laws who are at risk of developing a genetic disorder but are asymptomatic. “It may be presumed that these people will develop the condition, but they never do, and they are subject to discrimination. These people will gain protection,” said Rothstein.

Personalized Medicine Coalition Applauds Enactment of GINA

The Personalized Medicine Coalition—a partnership of academic, industrial, patient, provider, and payer communities that includes AACC—endorses the passage of GINA into law, saying that the privacy and protection of genetic information is essential to the progress of medicine, as well as improving the quality of care for every person.

“The guarantees provided by this legislation will encourage millions of Americans to use their genetic information to improve their healthcare and to help prevent cancer and other inheritable diseases,” said Edward Abrahams, PhD, the PMC’s Executive Director.

Only a few states have strong protections against genetic discrimination, he added, which left some individuals more vulnerable to this type of prejudice depending on where they lived. “GINA provides a national framework of enforceable protections needed to advance medical research and public health. And under GINA, there now are federal rules in place to protect those who are privately insured,” Abrahams said.

Abrahams noted that GINA’s path through Congress prompted two corporate members of the PMC—IBM (Armonk, N.Y.) and Eli Lilly (Indianapolis, Ind.)—to add genetic nondiscrimination to their employment policies in advance of the law’s passage. The organization noted that another PMC member, Aetna (Hartford, Conn.), also has publicly announced its support of the new law.

The PMC believes that GINA, along with improvements in regulatory and reimbursement policies that acknowledge the realities of genetics-based medicine, will set the stage for the discovery of new treatments and cures, as well as an accelerated path toward personalized medicine.

Why Do We Need a Federal Law?

The degree of protection against genetic discrimination provided by state laws varies widely. “GINA was needed to set a minimum standard of protection that must be met throughout the nation,” explained Collins. “As for the HIPAA, GINA goes significantly further by extending protections to individual health plans and by limiting the ability of insurers to use genetic information to raise rates for an entire group.”

At this point—5 years after the human genome has been sequenced—the average person doesn’t have a lot of genetic information in a medical record, Rothstein noted, because people without a family history of genetic illness are not subject to routine genetic testing. “But increasingly, people will have this kind of information in their medical records. The real reason GINA was enacted was to protect those people who do have a family history of genetic disease but were reluctant to undergo testing because of concern that the information would not remain private.”

That sentiment is echoed by Aravinda Chakravarti, PhD, Professor of Medicine, Pediatrics, and Molecular Biology and Genetics at the Johns Hopkins University School of Medicine (Baltimore, Md.), and President of the American Society of Human Genetics. “GINA would bring some degree of relief to those people who need to make serious decisions about serious genetic disorders, many of which are associated with effective tests. I think now there will be an increasing demand for all types of genetic tests.” He added that policy makers also might want to consider similar legislation for life insurance.

Some view GINA as an important first step to personalized medicine in the 21st century. “This is an important but initial piece of legislation,” said Kevin FitzGerald, SJ, PhD, Associate Professor of Oncology and David Lawler Chair for Catholic Health Care Ethics at Georgetown University Medical Center’s Lombardi Comprehensive Cancer Center in Washington, D.C. “As things move along, I think we’ll see other forms of legislation that are needed to steer things in the generally agreed direction of personalized medicine and to keep obstacles and problems from derailing them. For instance, a significant part of the personalized medicine promise will require large public databases of comprehensive medical records tied to biological samples. These databases will engender security and privacy issues beyond those covered by GINA. This is just one issue that may foster additional legislation. GINA is not a ‘one-bill-does everything,’ but it established a very important beachhead.”

But which tests might be most in demand as a result of GINA? Michael Stocum, Managing Director of Personalized Medicine Partners LLC (Research Triangle Park, N.C.), a company that focuses on integrating diagnostics and therapeutics, offered his best guess. “My gut feeling is that it will be tests that are prognostic and predictive, but particularly those that may predict risk for diseases like Alzheimer’s, cardiovascular conditions, and Type 2 diabetes—illnesses that tend to occur later in life and are expensive to manage,” he noted. “On a personal note, I feel far more comfortable about subjecting myself and my family members to testing for a range of genetic markers with this new law in place.”

Chakravarti also pointed out that genetic testing is already done on a routine basis but that not many people would recognize it as such. “Newborn screening is performed in all 50 states and has been done so for decades, so there’s a very large number of Americans who have taken a genetic test. And, blood typing is another; you can’t do transfusions without knowing someone’s genotype, and that information has led to a system for donating blood, organs, and bone marrow.”

Pharmacogenomic Testing Still Faces Challenges
SACGHS Releases Final Report

Experts believe that GINA will likely involve more people in genetic testing, partly through enhanced participation in pharmacogenomic research. One challenge to this relatively new discipline has been the issue of privacy, especially when large amounts of personalized information may be just a mouse click away.

“This is where the passage of GINA into law becomes even more relevant,” noted Kevin FitzGerald, SJ, PhD, Associate Professor of Oncology and David Lawler, Chair for Catholic Health Care Ethics at Georgetown University Medical Center’s Lombardi Comprehensive Cancer Center in Washington, D.C. FitzGerald is a member of the Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS), which recently finalized its report Realizing the Potential of Pharmacogenomics: Opportunities and Challenges. He served as a member and then the chair of the task force that wrote the document, which outlines a number of recommendations and considerations in relation to pharmacogenomics research and development and its integration into clinical practice and public health. “Pharmacogenomics itself is very much still in its infancy. It’s one piece of this personalized medicine arena that is exploding around us.”

Although pharmacogenomics has significant potential to improve drug research and development, healthcare delivery, and, ultimately, patient health, it also faces considerable challenges, according to the report. For example, some healthcare payers have been reluctant to cover pharmacogenomics products due to limited evidence of their health and economic impacts, the absence of clinical practice guidelines and dosing recommendations, and a lack of education and training in genetics. And until the passage of GINA into law, the question of privacy was very much an issue.

“But perhaps the major challenge revolves around information,” FitzGerald noted. “You’ve got to have large bodies of genetic and genomic health record information, because that’s the basis on which we will come to a new and better understanding of how drugs actually work in different individuals. We know generically how things work, but on an individual basis, everyone—even identical twins—is different. So to get an answer to the question of how this particular drug works in this particular person at this particular time under these particular circumstances, we need enormous amounts of data. And GINA will help to keep that data protected.”

The next challenge, he said, is assembling that information in such a way that it is translatable to research scientists and clinicians. “And then, once we understand what we think it is that we want to know, we need to prepare a roadmap and determine the logistical hurdles that need to be addressed.” The SACGHS report is available online. 

GINA and Research Efforts

Medical researchers anticipate that GINA will pave the way for individuals to take part in research without worrying about repercussions. “GINA removes a significant barrier to participation in clinical research protocols,” said Collins. “For example, at the National Institutes of Health, fear of genetic discrimination is the most commonly cited reason that people decline to participate in research on potentially life-saving genetic testing for colon cancer and breast cancer. One-third of eligible participants have declined on this basis.”

Along with greater participation in clinical trials involving genetics, GINA is expected to have a positive impact on the growing field of pharmacogenomics, in which an individual’s genotype is used to guide drug therapy and/or dosage. Research in this field also has the potential to increase the safety and effectiveness of new, existing, and failed drugs, and could enable more drugs to reach the market by targeting them to genetically defined subgroups of patients. “People will be more inclined to undergo genetic testing for responses to medications if they know that their test results will not affect their job or health insurance status,” explained Collins.

One active area of pharmacogenomic research centers on using genetic information to reduce the high incidence of adverse drug reactions, Collins added. “Consider the example of warfarin. Healthcare providers have found this anticoagulant drug notoriously difficult to administer because its dose requirements vary widely among patients and because of its relatively narrow margin for error, with either too much or too little of the drug triggering potentially life-threatening problems. Now, thanks to the identification of two genetic variations that appear to account for much of the differences in warfarin sensitivity, the National Heart, Lung, and Blood Institute is launching a clinical trial to evaluate a pharmacogenomic strategy for warfarin that will weigh the potential safety benefits with the costs of genetic testing.”

So far, FDA has approved label changes for two drugs based on pharmacogenomic data. In 2005, the agency approved label changes for the chemotherapy agent irinotecan to include a warning that patients with a particular UGT1A1 genotype should receive a lower initial dose of the drug. And in 2007, the Coumadin (warfarin) package label was updated to provide information about genetic testing for warfarin sensitivity. Although the FDA stopped short of requiring genetic testing prior to taking the drug, it recognized that adverse bleeding events could be reduced in patients with certain variations in the CYP2C9 and VKORC1 genes involved in metabolism and uptake of the drug. Now that the barrier to individual genetic privacy has been lifted, both patients and clinicians could become more comfortable with using genetic information for drug dosing. This, in turn, could result in an increased demand for such tests.

Testing for Inherited Breast Cancer

One of the most highly impactful areas of genetic testing involves inherited forms of breast cancer. Gregory Critchfield, MD, President of Myriad Genetic Laboratories, Inc. (Salt Lake City, Utah), the first company to offer testing for the BRCA1 and BRCA2 genes that are linked to breast cancer, is optimistic about GINA’s effect on genetic testing. “There have been some patients for whom potential insurance discrimination was an issue, and the passage of GINA removes that barrier. I think the new law will have a positive impact on genetic testing in general.”

Critchfield noted that Myriad’s revenues have increased despite not having a national nondiscrimination law. “Revenue growth for our company was 44% last fiscal year and has increased thus far this year,” he said.

Myriad’s success is based in large part on the BRCA1/2 genetic tests, which have been commercially available in the United States since 1996. According to the National Cancer Institute, more than 192,000 women each year learn that they have breast cancer, and about 5–10% of them have a hereditary form of the disease. A woman’s lifetime chance of developing breast and/or ovarian cancer increases if she inherits a mutated BRCA1 or BRCA2 gene.

Myriad’s list price for the comprehensive test, which analyzes the entirety of the gene for sequence changes and structural rearrangement is $3,120. There are two other testing options: once the mutation has been found by the comprehensive screening test, family members can be tested for the mutation at a cost of $350; and analysis for a panel of three mutations that are common in people who have Ashkenazic Jewish ancestry is $415.

“Insurance coverage for BRCA analysis testing is excellent, with well over 2,500 insurers who reimburse for the test,” explained Critchfield. “And as we remove barriers to testing, there are more people who will decide to make use of these predictive assessments.”

Time to Gear Up?

Although tests involving genetic mutations won’t soar overnight now that GINA has become law, labs may want to take another look at expanding their menu of genetic tests. “Labs need to prepare for potential new tests and any anticipated increase in volume,” Tsongalis recommended, adding that such tests may be “a good marketing tool for the larger reference labs.”

A similar opinion was voiced by Gualberto Ruaño, MD, PhD, President of Genomas, Inc. (Hartford, Conn.) and Director of Genetic Research at Hartford Hospital. “GINA is very salubrious for personalized medicine. It will not change the day-to-day operations of genetic testing in 2008, but it is very positive in terms of growth of the field for the rest of this decade and beyond. However, one of the biggest concerns people have about these tests is whether or not the cost will be reimbursed,” he said. “This is one of those factors that affect the translation of scientific research to real-world medicine. And these tests need to demonstrate economic value to assure reimbursability.”

To read more about GINA, as well as the text of the legislation, go to the Thomas web site