Thursday, May 29, 2014

Don’t Do It, AMA


The American Medical Association (AMA) will soon be voting on a statement opposing the utilization of genetic testing services solely by providers who specialize in genetics (e.g. geneticists, genetic counselors) and in support of genetic testing by any provider regardless of specialty, education, or certification. The serious negative ethical, legal, financial and medical implications of this approach have been well documented (1-7). In addition, several of the statements in the proposal are inaccurate:

Proposed Statement: “Certified clinical genetic counselors and medical geneticists are in severe shortage in many areas of the country.”
Response: This is not accurate. There are many board certified geneticists practicing in the United States – many of whom have outreach clinics covering large geographic areas.  For patients without a local genetic counselor, access is no longer an issue because there are now internet, phone and satellite based telemedicine services available for genetic counseling (8,9).

Proposed Statement: “Physicians treating patients who may be suspected of genetic susceptibility to cancer are well educated as to the indications for and implications of such genetic testing.”
Response: Multiple studies spanning more than a decade have shown that the majority of physicians do not have the education, training or certification to take on this detailed and ever-evolving subspecialty (6,7,10-27).  Evidence continues to mount that the majority of physicians order either too much, or incorrect, testing in even straightforward cases (5-7). Serious, life-threatening errors have resulted from clinicians without proper training and credentials practicing generic counseling and testing (1-3).  Medical malpractice claims have been filed against such clinicians, and the number of lawsuits these clinicians will face is likely to inflate as genetic technology becomes increasingly complex (28). 

Proposed Statement: “The requirement for an independent specialist may interfere with the timing and coordination of care.”
Response: Genetic counseling centers routinely reserve appointments for urgent patients for surgical or radiation decision-making immediately, without delaying such treatment.   High standards for thorough genetic counseling, informed consent, proper ordering and accurate result interpretation will be paramount in harnessing the benefits of genetic testing and correctly incorporating this information into a patient’s medical management. 

Proposed Statement: “The ultimate decision on the medical necessity for genetic testing should be within the realm of the treating physician and his or her patient.”
Response: With an average of 20-22 minutes scheduled per patient (29), it is both unrealistic and unfair to expect the already overburdened clinician to take on the complex role of cancer genetic counseling and testing.  A more efficient approach is for the clinician to choose which patients need genetic counseling and to refer them to a certified genetic counselor. In addition, patients do not expect their clinicians to be experts in genetics, but to play a key role in referring them for these genetic services (30). 

We ask the AMA to consider these facts when voting on this upcoming proposal,that places both physicians and patients at risk.


References:

1.  Brierley, KL, et al (2012). Cancer Journal, 18:303-309.
2.  Brierley, KL, et al. (2010). Connecticut Medicine, 74(7):413-423.
3.  Bensend TA, et al (2014) Journal of Genetic Counseling. 23(1):48-63.
4.  UnitedHealth (2012) working paper 7.  UnitedHealth Center for Health Reform and Modernization.
5.  Value of Genetic Counselors in the Laboratory (2011). Lab Document. ARUP
6.  Plon SE, et al. (2011) Genet Med. 13(2):148-154.
7.  Bellcross C, et al. (2011) American Journal of Preventive Medicine, 40(1):61-66.
8.  Hilgart, J et al. (2012) Gen in Med:14(9):765–776.
10. Emery J, et al. (1999). Fam Pract, 16:426-445.
11. Wilkins-Haug L, et al. (2000). Obstet Gynecol, 95:421-424.
12. Wilkins-Haug L, et al(1999). J Genet Couns, 8:301-311.
13. Suchard MA, et.al (1999). J Genet Couns, 8:301-311.
14. Watson EK et al. (1999). Fam Pract, 16:420-425.
15. Fry A, et al. (1999).  Fam Pract, 16:486-474.
16. Suther S and Goodson P. (2003). Genetics in Medicine, 5(2):70-76.
17. Wideroff L et al. (2003) Cancer Epidemiology, Biomarkers, and Prevention, 12:295-303.
18. Burke W et al. (2009). American Journal of Medical Genetics, 149A: 349-356.
19. Brandt R et al. (2008). Genetic Testing, 12(1): 9-12.
20. Wood ME, et al. (2008). Family Practice, 25:334-340.
21. Chorley W and MacDermot K. (1997). BMJ, 314(7078):441.
22. Demmer LA et al (2000). JAMA, 284:2595-2596.
23. Giardiello FM et al. (1997). The New England Journal of Medicine, 336(12):823-827.
24. Wilkins-Haug L, et al. (2000). Obstet Gynecol, 95:421-424.
25. Greendale K and Pyeritz RE. (2001). Am J Med Genet, 106:223-232.
26. Baars MJ, et al. (2005) Genetics in Medicine,  7(9):605-610.
27. Wideroff, L., et al.   (2005). Journal of Medical Genetics, 42(10):749-755.
28. Lindor RA and Marchant GE. (2011) ASCO Annual Meeting; Chicago, Illinois. Abstract #6073.
29. Weeks WB, Wallace AE. (2003) Arch Intern Med. 163(8):944-8.
30.  Miller FA,  et al. (2010) Family Practice, 27:563–569




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Saturday, May 24, 2014

Article Concluding the Majority of Breast Surgeons Provide Adequate Genetic Counseling Demonstrates the Opposite



An original article published online in the Annals of Surgical Oncology (Ann Surg Oncol DOI 10.1245/s10434-014-3711-9) is noteworthy for many reasons.

• This article is entitled, ‘Can Breast Surgeons Provide Breast Cancer Genetic Testing?’, and yet the methods used cannot adequately answer this question. The authors surveyed breast surgeons requesting a ‘self-assessment of skills and experience’. This methodology is flawed, to say the least, and it is difficult to believe that such an article would be published in a peer-reviewed journal in 2014.

• Fewer than 35% of those surveyed responded, with a possible selection bias toward those surgeons most interested and educated in genetic testing. And yet only half (51.6%) report that they both feel confident in their ability to provide appropriate pre- and post-BRCA test counseling and do so as a standard practice.

• Only 63% of respondents standardly obtain a 3-generation pedigree for their patient’s family history of cancer, a requirement by NCCN Guidelines as part of the breast and/or ovarian cancer risk assessment.1 This omission of a critical element of genetic counseling makes it impossible for the clinician to perform a risk assessment, order the correct genetic test, and could result in patients being denied coverage for testing.1 Such errors have been shown to result in patients having inappropriate prophylactic surgeries, inappropriate surveillance and even increased mortality, nationally.2,3,4

• This study includes no measures of knowledge, training, or education of the respondents. There is a vast body of literature showing that physicians do not have the time, education or knowledge to provide these services.5-22

• The authors conclude from their findings that “the majority of breast surgeons report appropriate practices related to assessing genetic risk, obtaining testing, interpreting the results, and providing counseling and related clinical services.” However, this study actually does not provide any data regarding how often breast surgeons interpret test results accurately, make appropriate screening and risk reduction recommendations based on test results, or provide “related clinical services”.

• Disturbingly, the authors declare no conflict of interest. Yet, at least one of the authors has worked as a speaker for Myriad Genetics Laboratory in 2014. Such conflicts of interest in choosing laboratories and influencing policy has been a subject of recent debate.23


1. NCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 1.2014. www.nccn.org. Accessed May 23, 2014.

2. Brierley KL, Campfield D, Ducaine W, et al. Errors in delivery of cancer genetics services: implications for practice. Connecticut Medicine. 2010;74:413-423.

3. Brierley KL,Blouch E, Cogswell W, et al. Adverse events in cancer genetic testing: medical, ethical, legal, and financial implications. The Cancer Journal. 2012;18(4):303-309.

4. Bensend TA, Veach PM, Niendorf KB. What's the Harm? Genetic Counselor Perceptions of Adverse Effects of Genetics Service Provision by Non-Genetics Professionals. Journal of Genetic Counseling. Feb 2014;23(1):48-63.

5. Emery J, Watson E, Rose P, Andermann A. A systematic review of the literature exploring the role of primary care in genetic services. Fam Pract 1999; 16:426-445.

6. Greendale K and Pyeritz RE. Empowering primary care health professionals in medical genetics: How soon? How fast? How far? Am J Med Genet 2001;106:223-232.

7. Wilkins-Haug L, Hill L, et al. Gynecologists’ training, knowledge, and experiences in genetics: A survey. Obstet Gynecol 2000;95:421-424.

8. Wilkins-Haug L, Erickson K, et al. Obstetrician-Gynecologists’ opinions and attitudes on the role of Suchard MA, Yudkin P, Sinsheimer JS. Are general practitioners willing and able to provide genetic services for common diseases? J Genet Couns 1999;8:301-311.

9. Suchard MA, Yudkin P, Sinsheimer JS. Are general practitioners willing and able to provide genetic services for common diseases? J Genet Couns 1999;8:301-311.

10. Watson EK et al. The ‘new genetics’ and primary care: GP’s views on their role and their educational needs. Fam Pract 1999;16:420-425.

11. Fry A, Campbell H, Gudmundsdottir H, Rush R, Porteous M, Gorman D, Cull A. GP’s views on their role in cancer genetic counseling services and current practice. Fam Pract 1999; 16:486-474.

12. Suther S and Goodson P. Barriers to the provision of genetic services by primary care physicians: A systematic review of the literature. Genetics in Medicine 2003; 5(2):70-76.

13. Wilkins-Haug L, Erickson K, et al. Obstetrician-Gynecologists’ opinions and attitudes on the role of genetics in women’s health. J Womens Health Gend Based Med 2000;9:873-979.

14. Wideroff L et al. Physician use of genetic testing for cancer susceptibility: Results of a national survey. Cancer Epidemiology, Biomarkers, and Prevention 2003; 12:295-303.

15. Burke W et al. Genetic assessment of breast cancer risk in primary care practice. American Journal of Medical Genetics Part A 2009; 149A: 349-356.

16. Brandt R et al. Cancer genetics evaluation: Barriers to and improvements for referral. Genetic Testing 2008; 12(1): 9-12.

17. Wood ME, Stockdale A, and Flynn BS. Interviews with primary care physicians regarding taking and interpreting the cancer family history. Family Practice 2008; 25:334-340.

18. Chorley W and MacDermot K. Who should talk to patients with cancer about genetics? BMJ 1997; 314(7078):441.

19. Demmer LA et al. Knowledge of ethical standards in genetic testing amoung medical students, residents, and practicing physicians. JAMA 2000; 284:2595-2596.

20. Giardiello FM et al. The use and interpretation of commercial APC gene testing for familial adenomatous polyposis. The New England Journal of Medicine 1997; 336(12):823-827.

21. Plon SE, Cooper HP, Parks B, et al. Genetic testing and cancer risk management recommendations by physicians for at-risk relatives. Genet Med. Feb 2011;13(2):148-154.

22. Bellcross C, Kolor K, Goddard K, et al. Awareness and utilization of BRCA1/2 testing among U.S. primary care physicians. American Journal of Preventive Medicine. Jan 2011;40(1):61-66.

23. Matloff ET, Barnett RE, Nussbaum R. Choosing a BRCA genetic testing laboratory: a patient-centric and ethical call to action for clinicians and payers. American Journal of Managed Care. 2014;20 (Special Issue 7): SP229. Read more!

Tuesday, May 20, 2014

Geneticists on Both Coasts Issue “Call to Action” On Need to Share DNA Data

In the new issue of Evidence-Based Oncology, Ellen T. Matloff, MS, CGC, and Rachel E. Barnett, MS, CGC, of the Yale Cancer Center and Robert Nussbaum, MD, of UC San Francisco write that efforts by some genetic testing laboratories to grab market share in the lucrative BRCA testing market may put patients at risk, while violating ethical standards issued by the American Medical Association.

Geneticists from both coasts have issued a “call to action” over what they say are unethical actions by some genetic testing laboratories, which seek to gain or retain market share among patients trying to understand their cancer risk.

Ellen T. Matloff, MS, CGC, and Rachel E. Barnett, MS, CGC, of Yale Cancer Genetic Counseling at the Yale Cancer Center, and Robert Nussbaum, MD, of the University of California at San Francisco, are authors of a commentary appearing in the May-June 2014 issue of Evidence-Based Oncology, a news publication of The American Journal of Managed Care.

Their commentary, “Choosing a BRCA Genetic Testing Laboratory: A Patient-Centric and Ethical Call to Action for Clinicians and Payers,” decries what they say are efforts by some doctors to steer patients to laboratories, or even “demand” that tests by done by a certain lab. “In several instances it was discovered that these clinicians were either paid consultants for such laboratories, or received speaking fees or research funding from those entities,” the authors write.

This comes nearly a year after the U.S. Supreme Court, in a June 13, 2013, ruling, stripped away Myriad Genetics Inc.’s long-held patent protection for BRCA1 and BRCA2 testing. For years, Myriad held a monopoly on testing for patients’ risk of having breast or ovarian cancer, or, for men, of passing along those risks to daughters.

Matloff has said previously that the ruling, coupled with Angelina Jolie’s announcement that she had both breasts removed due to BRCA risk, caused interest in genetic testing to soar. The ruling set off competition in the genetic testing market, with a resulting drop in prices.

Since that time, however, the authors say that Myriad has moved to retain market share in two ways: first, the company continues its decade-long practice of not sharing patients’ DNA sequences with public research databases; and, second, company officials have made statements questioning the integrity of public databases, while telling investors that the quality of its privately held DNA data represents an edge over competitors.

The authors quote Myriad’s recent third-quarter investment call, which included the statement, regarding the cancer therapy PARP inhibitors, “Our competitors’ reliance on public databases with high VUS and error rates will further restrict patient access to this life-saving medicine.”

VUS, or variant of unknown significance, is a mutation in the BRCA1 or BRCA2 gene that may or may not result in cancer, and for which further study is needed. Mature data sets with more patients’ DNA sequences are less likely to report a VUS for which cancer risk has later been determined. However, the authors assert that Myriad is overstating its superiority. In reality, they write, Myriad’s reported 3% variant rate is only slightly lower than other labs – Ambry Genetics’ rate of 4.4% is cited – so the vast majority of patients would be unaffected.

Matloff told Evidence-Based Oncology that Myriad’s decision to withhold 11 years’ worth of BRCA testing data, a period in which it had market monopoly, means that patients who are tested elsewhere may not learn their true risk level, and could be denied life-saving cancer treatment as a result.

Matloff and her co-authors write that this decision runs afoul of an AMA resolution that considers unethical any decision to use “patents, trade secrets … or other means to limit the availability of medical procedures.”

The authors and others in the field have argued that withholding DNA data from public use is wrong for the following reasons:

-It puts patients at risk.
-It denies use of the data for public benefit, even though many tests that allowed the gathering of DNA were paid for by Medicare or Medicaid.
-It risks ongoing market concentration of certain genetic tests, which will keep prices high for patients, insurers, employers, and taxpayers. Conversely, the authors write, “sharing of genetic data will benefit patient care and clinical research, which may lead to lower healthcare costs for all.”

The authors write that broadening access to DNA data “is particularly relevant for publicly funded insurers that could create incentives or make data sharing a stipulation of coverage.”

The commentary appears in Evidence-Based Oncology with two related stories: a look at efforts to reform the reimbursement system for molecular diagnostic testing, which includes Myriad’s assertion of “rights” to intellectual property; and a portrait of GenBank, the public data-sharing initiative of the National Institutes of Health (NIH).

Click here to see the original press release on PRWeb

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Friday, May 16, 2014

Choosing a BRCA Genetic Testing Laboratory: A Patient-Centric and Ethical Call to Action for Clinicians and Payers

Genetic testing laboratories are using aggressive and manipulative tactics to capture market share in the BRCA testing market. Clinicians and payers are encouraged to utilize patient-centric criteria, including open access to data, to make decisions about genetic testing laboratories.

The past 12 months in the world of cancer genetic counseling have been more notable, perhaps, than the past 12 years combined. In May 2013, Hollywood icon Angelina Jolie went public with her BRCA1+ status, thrusting the field of cancer genetic testing and counseling into the spotlight and increasing referral rates to clinics by as much as 40% (E. T. Matloff, MS, oral communication, July 2013).1 One month later, the US Supreme Court unanimously ruled against the validity of patents that lay claim to genomic DNA in Association for Molecular Pathology v Myriad Genetics, Inc.2 Within hours, multiple laboratories began offering more comprehensive genetic testing for the hereditary breast and ovarian cancer genes BRCA1 and BRCA2, and at half the cost. The battle for the multi-million-dollar BRCA testing market had begun.

This battle has resulted in some genetic counseling centers reporting that referring clinicians have begun to request, or demand, that their patients’ BRCA testing be sent to a particular laboratory. In several instances it was discovered that these clinicians were either paid consultants for such laboratories, or received speaking fees or research funding from those entities.

This is clearly a conflict of interest in violation of a physician’s ethical obligations “to regard responsibility to the patient as paramount” and to discharge their “responsibility to participate in activities contributing to the improvement of the community and the betterment of public health.”3 Concerns about such manipulative tactics led us to develop a position statement stipulating that decisions about which genetic testing laboratories to use should focus on test quality, turnaround time, cost, and whether or not the laboratory shares its data in public databases (Table 1).

Without its patent-protected monopoly, Myriad now appears to be relying on trade secrets to maintain its share of the BRCA market.4,5 The “trade secrets” are actually a database of BRCA variants of uncertain significance (VUS) derived from the thousands of patient tests they have performed over the past decade.5 The company once contributed its data to a public database maintained by the National Institutes of Health, but ceased doing so in 2004.4 Several Myriad scientists and executives have stated that the public variant databases are not properly curated and that contributing to such resources would cause more harm than good; however, by at least 1 account, Myriad disclosed that it made its decision to stop sharing data for the purpose of retaining data as a trade secret.4,6



In Myriad’s Q3 Earnings Call Transcript of May 6, 2014, the company publicly acknowledged that in the context of PARP inhibitors, “Our competitors’ reliance on public databases with high VUS and error rates will further restrict patient access to this life-saving medicine.”7 The decision to hoard patient VUS data, even while recognizing that this decision will restrict patient access to lifesaving treatment, is incongruent with the American Medical Association’s (AMA’s) policy on Genome Analysis and Variant Identification (Table 2) and is considered unethical behavior according to the AMA’s Resolution E-9.095 on “the use of patents, trade secrets…or other means to limit the availability of medical procedures.”8,9

Although variant classification is important, few BRCA tests result in a variant of uncertain significance (ie, 4.4% at Ambry Genetics10). Myriad itself reports a 3% overall variant rate, slightly lower than other labs’ and presumably attributable to the superior testing experience enabled by its patents.11 Therefore, the vast majority of patients (~95%) are not impacted by a variant of uncertain significance, although the company describes its information as “vastly superior” and leverages variant classification ability as a major differentiator.5

Other laboratories offering BRCA testing have teamed with clinicians, scientists, and patients to expand the pool of publicly available genetic information for the betterment of clinical care and research as part of the Free the Data movement (http://www.free-the-data.org). This movement recognizes that patients, clinicians, scientists, and insurers could all benefit from pooling such information.

It has gained traction in patient communities, and some patients now request that their genetic testing be sent to laboratories that share data. Many of these competing laboratories are advertising their data-sharing policies as a way to gain market share. As this movement progresses, creating public genetic databases that feature proper curation of data, transparency on how variant classification decisions are made, and open forums for discussion will be critical.

With the growing number of laboratories offering testing, insurers are beginning to contract with particular laboratories for BRCA testing, designating certain laboratories as their in-network providers.12 Before negotiating such partnerships, payers and regulators have the opportunity to choose to partner only with high-quality laboratories that pledge to share all past, present, and future data in public databases.

As Cook-Deegan et al write, “National health systems and insurers, regulators, researchers, providers, and patients all have a strong interest in ensuring broad access to information about the clinical significance of variants discovered through genetic testing.”3 This is particularly relevant for publicly funded insurers that could create incentives or make data sharing a stipulation for coverage.4,13

Our patients deserve for decisions regarding where their genetic testing is performed to be unbiased, free of conflict, and based upon considerations unrelated to the clinician’s self-interest. Moreover, sharing of genetic data will benefit patient care and clinical research, which may lead to lower healthcare costs for all moving forward. The choice to use only laboratories that are committed to quality, efficiency, and facilitating progress for all through sharing of data represents an important opportunity as our healthcare system evolves.


Ellen T. Matloff and Rachel E. Barnett: Yale Cancer Genetic Counseling, Yale Cancer Center, Yale School of Medicine. Robert Nussbaum, MD: Division of Medical Genetics, University of California, San Francisco School of Medicine.
References

1. Jolie A. My medical choice. The New York Times. http://www.nytimes.com/2013/05/14/opinion/my-medical-choice.html/?_r=0. Published May 14, 2013.

2. Supreme Court of the United States. Association for Molecular Pathology v Myriad Genetics, 2013 WL 2631062 (June 13, 2013).

3. American Medical Association. Principles of medical ethics. http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/codemedical-ethics/principles-medical-ethics.page. Accessed May 7, 2014.

4. Cook-Deegan R, Conley JM, Evans JP, Vorhaus D. The next controversy in genetic testing:clinical data as trade secrets. Eur J Hum Genet. 2013;21:585-588.

5. Pollack A. Despite gene patent victory, Myriad Genetics faces challenges. The New York Times. http://www.nytimes.com/2011/08/25/business/despite-gene-patent-victory-myriad-geneticsfaces-challenges.html?pagewanted=all&_r=0. Published August 24, 2011.

6. Ray T. In tackling the VUS challenge, are public databases the solution or a liability for labs? Pharmacogenomics Reporter. http://www.genomeweb.com/clinical-genomics/tackling-vuschallenge-are-public-databases-solution-or-liabilitylabs. Published February 12, 2014. Accessed February 27, 2014.

7. Seeking Alpha. Myriad Genetics’ (MYGN) CEO Peter Meldrum on Q3 2014 Results - Earnings Call Transcript. http://seekingalpha.com/article/2196503-myriad-genetics-mygn-ceopeter-meldrum-on-q3-2014-results-earningscall-transcript?page=3. Published May 6, 2014. Accessed May 7, 2014.

8. American Medical Association. D-460.971 Genome analysis and variant identification policy statement. www.ama-assn.org. Published June 2013. Accessed May 2, 2014.

9. American Medical Association. Amendment to Opinion E-9.095 Trademarks, patents, copyrights, and other legal restrictions on medical procedures.www.ama.assn.org. Published November 2007. Accessed May 6, 2014.

10. Ambry Genetics. BRCA 1/2 Test Information Fact Sheet. http://www.ambrygen.com/tests/brca1-and-brca2. Accessed May 6, 2014.

11. Eggington JM, Burbidge L, Copeland K, et al. Current variant of uncertain significance rates in BRCA1, BRCA2, and Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM) testing. Poster presented at the European Society of Human Genetics (ESHG) Congress 2012.

12. National Society of Genetic Counselors. Cancer Special Interest Group listserv postings. www.nsgc.org. May 2 and May 5, 2014.

13. News Briefs. Genetics in Medicine. 2014; 16(5):357-358.

Click here to see the original article on AJMC.com

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