GENETIC TESTING: PRELIMINARY POLICY GUIDELINES
 

by the Council for Responsible Genetics
June 2006

 

Genetic testing has become a major component of health care. The number of genetic tests to diagnose rare diseases and to predict future health risks, for instance, has increased ten-fold in the last decade.[1] In the past four years alone, the commercial volume of genetic testing has more than doubled. [2]

But what these new technologies portend for our health and well-being is less clear. On the basis of a year-long study of genetics in medicine, the Council for Responsible Genetics (CRG) has concluded that genetic testing is inappropriate in numerous areas. Where genetic testing is appropriate, adequate insurance coverage and access to complementary services are rarely available. This report highlights these problems and points to several policy solutions to overcome them.

For a laboratory test to have utility to patients, it should provide information that contributes to an improvement of health through the prevention or management of disease and illness. Few genetic tests meet this standard (see Table 1). Despite the hype and promise surrounding so-called “predictive” genetic testing, only a handful of tests yield improved health outcomes for patients who do not show symptoms of disease.[3]

Even the two most widely touted predictive tests—BRCA 1/2 for breast and ovarian cancer and HNPCC for colorectal cancer—have been shown to improve disease prevention for only a small subpopulation of patients. BRCA 1/2 testing, for example, is commonly recommended for three categories of asymptomatic patients: women with a family history of BRCA 1/2 mutations; women with a strong family history (multiple diagnoses over multiple generations) of breast or ovarian cancer; and women with a family history of breast or ovarian cancer and an ethnic background defined as high-risk.[4] These populations are thought to collectively account for less than 10% of women who develop breast or ovarian cancer. [5]

Use of genetic tests, which lack an adequate evidence base, can result in serious harm because of inaccurate clinical indications and unnecessary medical intervention. For this reason, it is deeply troubling that so little evidence exists to support the use of many widely applied and heavily marketed tests. Market forces, rather than science, have propelled predictive tests into the health care system.

Predictive testing raises issues that are fundamentally different from those raised by diagnostic genetic tests. The latter have been used for decades to diagnose existing genetic disorders, or to identify or prevent the transmission of genetic disorders from one generation to the next; and to tailor therapies based on the genetic characteristics of a disease. Indeed, hundreds of physicians use DNA or chromosomal information every day to assess the symptoms of cystic fibrosis, sickle cell anemia, chronic myelogenous leukemia, and many other diseases. Tools such as HIV genotyping and Her2 testing for breast cancer have dramatically improved disease management.[67]

Genetics has a role to play in the advancement of medicine, but this role must be guided by a realistic assessment of its promises and limitations. CRG recommends that all genetic tests be required to show utility to patients before they are introduced into the health care system. At present, there is minimal evidence to support claims of utility to patients of many widely available and heavily marketed genetic tests. Amidst a growing push for personalized medicine, the federal government should develop a system of mandatory clinical review for all diagnostic, preventive, and pharmaco-genetic tests.

The structure and organization of health care systems shapes how genetic tests are used and the concerns that arise from their adoption. In the United Kingdom and France, for example, BRCA testing is conducted primarily by public laboratories linked to cancer treatment centers, using relatively inexpensive, non-patented techniques. Testing is also not permitted without prior physician referral and approval by a cancer geneticist.

In the United States, patients can purchase genetic tests directly from commercial vendors. Increasingly, companies such as DNA Direct use the Internet, television, and print advertising to market genetic tests directly to consumers. In 2002, for example, Myriad Genetics launched a multimedia advertising campaign in several states to promote sales of its BRCA 1/2 test for cancer susceptibility. A subsequent review of the campaign by the Centers for Disease Control (CDC) found that while the advertisements succeeded in raising public awareness of hereditary breast cancer, they tended to overstate the test’s ability to predict cancer and failed to encourage consumers to contact health care providers before and after testing. [8]

GeneLink, for example, is a company that offers a variety of products direct to consumers through a website that claims to be able to use genetic “profile information” to “recommend a specific and targeted regime of antioxidant vitamins, nutrients or skin-care formulations that have been specifically designed to compensate for predicted deficiencies.” In reality, with the exception of rare disorders detected by newborn screening, no studies have demonstrated any benefit whatsoever from using genetic information to guide nutritional choices.

Direct-to-consumer marketing may be inaccurate in conveying the relevant benefits and risks of genetic testing for specific patients. Worse, this type of marketing encourages consumers to pursue testing without involvement of qualified care providers such as primary care physicians, genetic counselors, or medical geneticists.

Encouraging greater consumer involvement in health care—by providing public access to price and quality information regarding provider services, for example—can create more informed decision-making and higher quality care. But the claim that direct-to-consumer testing will help consumers take control of their health is almost always misleading and potentially harmful.

CRG recommends the development of federal regulations to restrict direct-to-consumer marketing of genetic tests and to require involvement of qualified health care providers prior to and following genetic testing.

Most patients do not have adequate access to the specialized services necessary for appropriate genetic testing. If a test is to be used at all, a variety of health care conditions must be in place to ensure that its use is appropriate: specialized personnel to perform the test and interpret the results for patients and their families; genetic counseling before and after testing; and follow-up interventions to treat affected patients. As a medical geneticist at a major managed care organization put it, “the test is just one part of a series of events that must be in place before testing is appropriate. It is like a single cog on a wheel.” [9]

The United States faces an acute shortage of medical geneticists and genetic counselors. Only 500 medical geneticists are in primary clinical practice today, and the number of new graduates is not increasing. [10] There are currently an estimated 2,000 certified genetic counselors available to face a workload that is predicted to require 20,000 to 30,000 qualified personnel. [11]

Primary care physicians need to develop greater expertise to diagnose genetic conditions, evaluate genetic risks, and understand the implications of those risks for the patients themselves and for reproductive decision-making. Current gaps in knowledge are partly attributable to inadequate attention to genetics in medical education and to limited dialogue between primary care physicians and medical geneticists. [12]

CRG recommends workforce development initiatives to increase the number of practicing medical geneticists and genetic counselors, to increase genetics education for medical students and primary care physicians, and to develop initiatives to connect genetic testing with the broader system of health care services. Integrating this community of specialists and non-specialists will help to ensure that the health care system maximizes the good and minimizes the harm created by genetic testing.

Genetic testing is likely to widen already existing health care inequalities. A recent study in the Journal of the American Medical Association, for example, showed that African-American women with a family history of breast cancer were much less likely than white women to undergo genetic counseling and BRCA 1/2 testing, even after controlling for the probability of relevant mutations. [13]

Racial and ethnic disparities in access to care have been observed for a wide range of new medical technologies.[14] Greater efforts are needed to ensure equality of access to genetic testing and to accompanying information and health care.

CRG supports many of the decisions by private insurers and the Center for Medicare and Medicaid Services (CMS) to decline coverage of genetic tests with low cost-effectiveness or limited patient value. Once a test is shown to substantially improve health outcomes, however, the interests of patients demand that it be adequately reimbursed. Research indicates that this rarely occurs. While public and private health plans pay for many genetic tests, standards of coverage widely differ and levels of payment are often inadequate to cover the actual costs of testing.

According to a survey of large medical research laboratories, payment for direct costs of genetic testing ranges from 61% to 80% among major private health plans.[15] Including the interpretation of results, payment of patent royalties, and other operational costs, these levels of payment represent less than one fourth of the actual cost of genetic testing. [16]

Repeated under-payment for genetic tests limits patient access in several ways. By undercutting the financial viability of services, it drives health care providers to discontinue testing and deters patients from pursuing medically necessary care.

For genetic tests, which have demonstrated patient benefits, CRG recommends that the Current Procedural Terminology codes, used to estimate levels of payment, be updated to incorporate the full direct and indirect costs associated with genetic testing. These codes should include the costs of interpreting test results, patient follow-up, genetic counseling, multi-laboratory analysis, and payment of patent royalties.


Table 1. Brief Analysis of Key Genetic Tests

 
     

Test

Circumstances in which testing is recommended

Controversial Issues

BRCA 1/2

Family history of BRCA or early-onset breast or ovarian cancer; following diagnosis of breast or ovarian cancer combined with family history; high risk ethnic populations combined with family history

High-risk ethnic populations; women with limited family history of breast or ovarian cancer

Her2

Diagnosis of breast cancer

None

Hereditary Non-Polyposis Colon Cancer (HNPCC)

Family history of HNPCC; following diagnosis of colon cancer combined with family history consistent with HNPCC

Amsterdam II Criteria (three relatives affected with colorectal cancer; two generations affected; and one first or second degree relative affected before age 50)

Familial Adenomatous Polyposis (FAP)

Family history of FAP; following diagnosis of colon cancer combined with family history consistent with FAP

Family history of colorectal cancer

HIV Genotyping

Following failed HIV ART regimen

Following HIV diagnosis; HIV-positive pregnant women; population centers at high risk for drug-resistant HIV

G6PD

Family history of hemolytic anemia or G6PD deficiency; following hemolytic episode

High-risk ethnic populations

Thiopurine S-methyltransferase (TPMT)

None

Prior to thiopurine treatment

Factor V Leiden

Family history of severe blood clotting; following venous thrombosis

Prior to hormone replacement therapy (HRT) and oral contraceptive (OC) use

Factor II

Family history of Factor II; following venous thrombosis

Family history of Factor II, venous thrombosis

Methylenetetrahydrofolate reductase (MTHFR) C677T

Following venous thrombosis

Family history of MTHFR or venous thrombosis

Hereditary Hemochromatosis (HHC) / HFE mutations

Confirmatory diagnosis following phenotypic test results suggesting HHC

Family history of HHC

Chronic Myelogenous Leukemia (CML)

Following leukemia diagnosis

Prior to first-line treatment

Cytochrome P (CyP) 450

None

Prior to use of drugs metabolized by CyP450 enzymes

Oncotype DX

None

Newly diagnosed breast cancer; prediction of recurrence risk among patients following treatment for breast cancer

Apolipoprotein E (APOE)

None

Family history of Alzheimer's Disease; confirmatory diagnosis following phenotypic tests suggesting AD

Back to Guidelines

NOTES

1.  Data provided by GeneTests, an initiative sponsored by the University of Washington and funded by the National Institutes of Health (NIH). Accessed Feb. 12, 2005. [www.genetests.org]

2. Laboratory Corporation of America, 2002 Annual Report. Accessed January 24, 2005. [www.labcorp.com]; Laboratory Corporation of America, “Revenue Analysis by Business Area,” in Form 8-K. Pursuant to Section 13 or 15(d) of the Securities and Exchange Act of 1934 (Filed October 21, 2004); Laboratory Corporation of America, “Revenue Analysis by Business Area,” in Form 8-K. Pursuant to Section 13 or 15(d) of the Securities and Exchange Act of 1934 (Filed March 6, 2002); Quest Diagnostics, Investor Presentation (January 2005). Accessed Feb. 22, 2005. [phx.corporate-ir.net/phoenix.zhtml?c=82068&p=irol-IRHome]; Quest Diagnostics, “Strategic Growth Opportunities,” in Form 10-K. Pursuant to Section 13 or 15(d) of the Securities and Exchange Act of 1934 (Filed April 29, 2004).

3. For a more detailed review of the clinical utility of genetic testing, see Council for Responsible Genetics, Assessing the Use and Impact of Genetic Testing in California, Report to the California HealthCare Foundation, 2005. This report is available from the CRG by request.

4. American Society for Clinical Oncology, “Genetic Testing for Cancer Susceptibility,” Journal of Clinical Oncology 14 (1996): 1730-36; American College of Medical Genetics,Genetic Susceptibility to Breast and Ovarian Cancer: Assessment, Counselling & Testing Guidelines (1999). Accessed March 19, 2005. [www.health.state.ny.us/nysdoh/cancer/obcancer/contents.htm]; American College of Medical Genetics, Statement on Population Screening for BRCA-1 Mutation in Ashkenazi Jewish Women (1996). Accessed March 10, 2005. [www.acmg.net/resources/policies/pol-002.asp]; JP Struewing, et al., “The Risk of Cancer Associated with Specific Mutations of BRCA1 and BRCA2 among Ashkenazi Jews,” New England Journal of Medicine 336 (1997): 1401-1408.

5. National Cancer Institute, “Genetic Testing for BRCA1 and BRCA 2.” Accessed March 3, 2006. [http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA]

6. Cigna HealthCare, “Antiretroviral Resistance Testing,” Coverage Position No. 0012. Accessed March 21, 2005. [www.cigna.com/health/provider/medical/procedural/coverage_positions/]; Aetna, “HIV Drug Susceptibility and Resistance Tests,” Clinical Policy Bulletin No. 0316. Accessed March 19, 2005. [www.aetna.com/cpb/data/CPBA0316.html]; Centers for Medicare & Medicaid Services, “Two New Lab Tests for the Management of HIV,” State Medicaid Directors Letter #01-005 (2001). Accessed Mar 21, 2005.[www.cms.hhs.gov/hiv/hiv01081.asp]

7. Aetna, “Herceptin (trastazumab),” Clinical Policy Bulletin No. 0313. Accessed March 19, 2005. [www.aetna.com/cpb/data/CPBA0313.html]; Blue Cross Blue Shield Association, Medical Policy Reference Manual 5.01.12; Aetna, “Tumor Markets,” Clinical Policy Bulletin No. 0352. Accessed January 21, 2005. [www.aetna.com/cpb/data/CPBA0352.html]; Blue Cross of California, “Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer,” Medical Policy 2.11.22. Accessed February 4, 2005. [medpolicy.bluecrossca.com/policies/medicine/gene_expression_breast_cancer.html]; Cigna Health, “Tumor Markers for Diagnosis and Management of Cancer,” Coverage Policy No. 0172. Accessed March 19, 2005. [www.cigna.com/.../medical/mm_0172_coveragepositioncriteria_ tumor_markers_for_ diagnosis_mgmt_cancer.pdf]

8. Centers for Disease Control & Prevention, Genetic Testing for Breast and Ovarian Cancer Susceptibility: Evaluating Direct-to-Consumer Marketing --- Atlanta, Denver, Raleigh-Durham, and Seattle, 2003, Morbidity and Mortality Weekly Report 53 (July 16, 2004): 603-606.

9. R Bachman, personal communication, February 28, 2005.

10. American Board of Medical Genetics, “Numbers of Certified Specialists in Genetics.” Accessed February 15, 2005. [www.abmg.org/genetics/abmg/stats-allyears.htm]

11. Genesage, Inc. Genetic Services Capacity: A Proprietary Study. Accessed January 17, 2005. [www.genesage.com]

12. W Burke & J Emery, “Genetics Education for Primary Care Providers,” Nature Reviews Genetics 3 (2002): 561-66.

13. K Armstrong, et al., “Early Use of Clinical BRCA 1/2 Testing: Associations with Race and Breast Cancer Risk,” American Journal of Medical Genetics 117A (2003): 154-160.

14. Kressin NR, Petersen LA. Racial difference in the use of invasive cardiovascular procedures: review of the literature and prescription for future research. Ann Intern Med.2001; 135: 352–366.

15. Andrea Ferreira-Gonzalez, “Providers’ Perspective on Reimbursement of Genetic Technologies,” Presentation to the Secretary’s Advisory Committee on Genetics, Health and Society, March 2004. Accessed March 21, 2005. [www4.od.nih.gov/oba/SACGHS/ meetings/March2004/Gonzalez.pdf].

16. DGB Leonard, “Advances in Molecular Diagnostics and Reimbursement Challenges,” Presentation to the Strategic Research Institute of New York, March 14, 2004; MS Watson, President of the American College of Medical Genetics (ACMG), Comments to the Centers for Disease Control & Prevention Genetic Forum (Laboratory Working Group), June 2, 2000.

 
 
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