policy and politics
The Regulatory Gap for Preimplantation Genetic Diagnosis by Michelle Bayefsky
T
he use of preimplantation genetic diagnosis, the powerful technique employed during fertility treatment to select embryos based on their genes, is currently unregulated in the United States—unlike in nearly all other countries where PGD is available. Of course, the analytical quality of the genetic tests, the laboratories where they are performed, and the technicians who carry them out are subject to the Clinical Laboratory Improvement Amendment requirements. And as the Food and Drug Administration prepares to begin regulating laboratory-developed tests, including many genetic tests, the clinical validity of the tests may also need to be demonstrated.1 But neither CLIA nor the U.S. Food and Drug Administration is responsible for governing medical practice,2 and state law and the relevant medical associations have largely fallen silent on the questions of when and why PGD ought to be performed.3 The result of this regulatory lacuna is that while PGD was originally intended for screening embryos for severe heritable disorders, it is now also employed for a variety of more controversial purposes, including nonmedical sex selection, selection for a “savior sibling” (that is, a child who will be histocompatible with a sick sibling and could therefore donate tissue to the sibling), and even selection for children with conditions such as deafness or dwarfism.4 In other words, in the United States, if there is a genetic test available, you can afford to pay out of pocket,5 and you can find January-February 2015
a specialist willing to order the test and perform the associated procedures, then you can do PGD for any reason. The United States is very unusual in its lack of legal guidance on the acceptable uses of PGD. Most countries where PGD is available have relevant legislation restricting the technique’s use.6 Often, PGD may be used only for medical purposes, although how “medical” is defined and what bodies are responsible for making this determination varies. For example, in the United Kingdom, the Human Fertilisation and Embryology Authority (a statutory body) is charged with the task of approving a list of conditions for which PGD is permitted, based on an assessment of the seriousness of the disease. Elective sex selection is banned outright.7 In France, the 2011 Bioethics Law specifies that PGD may be used only to select against specific diseases or to select for a tissue match for a sick sibling.8 In Canada, nonmedical sex selection is prohibited,9 and in the Netherlands, PGD is permitted only for the diagnosis of “severe and untreatable genetic conditions.”10 The absence of regulation of PGD in the United States is thus notable and worthy of explanation. Four considerations are particularly important in this explanation. They are deeply interrelated, as the political, economic, and social conditions particular to the United States are mutually determining and reinforcing. Lack of a single-payer health care system. In many other countries with advanced medical research and
treatment—and in all of the countries mentioned above—the national government plays a major role in funding, and sometimes directly providing, health care services. It is therefore necessary in these countries for government officials to weigh the applications of available medical treatments in order to determine what services ought to be covered. Although in countries with a two-tier system patients may still pay out of pocket for certain treatments, the government must at least ask the question, is this an appropriate, useful, or necessary medical application? In the United States, where private health insurers cover most people and governmentfunded health care (such as Medicare, Medicaid, and the Veterans Health Administration) does not include coverage for advanced fertility treatment such as in vitro fertilization (IVF) and PGD, the government has not been required to take a stance on the appropriate uses of PGD. Resistance of medical professionals. For a variety of reasons, medical professionals in the United States tend to resist greater government oversight. As several leaders of the American Society for Reproductive Medicine wrote in 2006 (succinctly summarizing the first point), “regulatory oversight should parallel funding.” They also suggested that government regulation might result in poorly crafted or ideologically motivated laws and that being forced to adhere to a preapproved list of conditions for which PGD may be performed—such as the one used in the United Kingdom—“would exert a chilling effect” on the development of new tests.11 Some doctors also view government oversight as an unwelcome intrusion into medical practice and a potentially inappropriate interference with patient care. In the United Kingdom, by contrast, most doctors are employed directly by the national government, and the “intrusion” of government regulation is simply a fact of life. Physician attitudes and expectations likely depend, at least in part, on a country’s health care framework. Proximity to the abortion debate. PGD, like IVF in general, involves creating and often discarding embryos, H AS TI N GS C E N TE R RE P O RT
7
depending on patient preferences. PGD also involves the added dimension that many discarded embryos are seen as possessing an “undesired” genetic feature. In the United States, abortion is a more contentious issue than in most other Western countries, and it is very unlikely that Congress could successfully pass a law on the appropriate use of PGD.12 Such a law would have the effect of sanctioning the destruction of some embryos. State legislatures might be able to pass a law on PGD, but given the political volatility of the issue relative to the number of cases, state legislators are probably not eager to tackle this topic either.13 Inherent limitations of the democratic process. Certain applications of PGD are extremely controversial, and reasonable people can disagree about their legitimacy and whether they should be offered. For instance, a 2006 survey of IVF clinics indicated that less than half of responding centers offered PGD for nonmedical sex selection and about a quarter offered tissue typing for savior siblings.14 The very nature of democracy in a diverse, pluralistic society makes it difficult to design regulations on such divisive topics. While the contentiousness of certain uses of PGD is not exclusive to the United States, the United States is more culturally diverse than most Western and Northern European countries,15 which may amplify the inherent challenge of developing regulations that reflect and respect the views of the electorate. Given these obstacles, it is unlikely that government bodies in the United States will implement guidelines for the appropriate use of PGD in the near future. It is possible, though, that as physicians become more accustomed to provisions of the Affordable Care Act that affect their everyday practice (such as electronic health record usage requirements and reimbursements for
8 HASTIN G S C E N T E R R E P ORT
Medicare services based on quality of care), they will become less resistant to government involvement in the kinds of services they offer. Furthermore, professional organizations such as the American Society for Reproductive Medicine and the American College of Medical Genetics could take a more active role in developing guidelines for the use of PGD. Self-regulation is not legally binding, but medical society guidelines are often cited by insurance companies weighing what procedures to cover and courts deciding whether a doctor has breached the standard of care. While medical societies may not be perfectly representative of the American population, stricter self-regulation on the use of PGD would be a positive step toward managing this potent and rapidly advancing medical technology. Disclaimer
The opinions expressed here are those of the author and do not reflect the policies or positions of the National Institutes of Health, the U.S. Public Health Service, or the U.S. Department of Health and Human Services. 1. Food and Drug Administration, “Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs),” September 30, 2014. 2. S. Baruch et al., Reproductive Genetic Testing: Issues and Options for Policymakers (Washington, D.C.: Genetics and Public Policy Center, 2004). 3. M. Bayefsky and B. Jennings, Regulating Preimplantation Genetic Diagnosis in the United States: The Limits of Unlimited Selection (New York: Palgrave Macmillan, forthcoming, 2015). 4. S. Baruch, D. Kaufman, and K. Hudson, “Genetic Testing of Embryos: Practices and Perspectives of US In Vitro Fertilization Clinics,” Fertility and Sterility 89, no. 5 (2008): 1053-58. 5. PGD itself may be covered under some health insurance plans (see, for example, Aetna, “Clinical Policy Bulletin: Invasive
Prenatal Diagnosis of Genetic Diseases,” April 29, 2014, http://www.aetna.com/cpb/medical/data/300_399/0358.html), but in vitro fertilization, which must be performed in conjunction with PGD, is rarely covered by insurance (National Conference of State Legislatures, “State Laws Related to Insurance Coverage for Infertility Treatment,” last updated June 2014, accessed December 4, 2014, http:// www.ncsl.org/research/health/insurance-coverage-for-infertility-laws.aspx), and IVF costs approximately $12,000 per cycle. 6. R. M. Isasi and B. M. Knoppers, National Regulatory Frameworks regarding Human Reproductive Genetic Testing (Genetics and Public Policy Center, 2006), http://www.dnapolicy. org/pdf/geneticTesting.pdf. 7. Human Fertilisation and Embryology Bill, Bill 6, House of Lords. United Kingdom, 2007-2008. 8. Loi relative à la bioéthique, Loi no. 2011814, French Parliament, 2011. 9. K. Speechley and J. Nisker, “Preimplantation Genetic Diagnosis in Canada: A Survey of Canadian IVF Units,” Journal of Obstetrics and Gynaecology Canada 32, no. 4 (2010): 341-47. 10. Isasi and Knoppers, National Regulatory Frameworks regarding Human Reproductive Genetic Testing. 11. J. Simpson, R. Rebar, and S. Carson, “Professional Self-Regulation for Preimplantation Genetic Diagnosis: Experience of the American Society for Reproductive Medicine and Other Professional Societies,” Fertility and Sterility 85 (2006): 1653-660. 12. See T. Murray, “Stirring the Simmering ‘Designer Baby’ Pot,” Science 343 (2014): 1208-210. 13. Whether state regulation of the use of PGD would be advisable is a separate question; laws would most likely differ dramatically around the country and could range from complete prohibitions to unhindered access to PGD for any reason. 14. Baruch, Kaufman, and Hudson, “Genetic Testing of Embryos: Practices and Perspectives of US In Vitro Fertilization Clinics.” 15. R. Morin, “The Most (and Least) Culturally Diverse Countries in the World,” Pew Research Center, July 18, 2013, http://www. pewresearch.org/fact-tank/2013/07/18/themost-and-least-culturally-diverse-countries-inthe-world/. DOI: 10.1002/hast.412 This column appears by arrangement with the American Society for Bioethics and Humanities.
January-February 2015
The Regulatory Gap for Preimplantation Genetic Diagnosis by Michelle Bayefsky
T
he use of preimplantation genetic diagnosis, the powerful technique employed during fertility treatment to select embryos based on their genes, is currently unregulated in the United States—unlike in nearly all other countries where PGD is available. Of course, the analytical quality of the genetic tests, the laboratories where they are performed, and the technicians who carry them out are subject to the Clinical Laboratory Improvement Amendment requirements. And as the Food and Drug Administration prepares to begin regulating laboratory-developed tests, including many genetic tests, the clinical validity of the tests may also need to be demonstrated.1 But neither CLIA nor the U.S. Food and Drug Administration is responsible for governing medical practice,2 and state law and the relevant medical associations have largely fallen silent on the questions of when and why PGD ought to be performed.3 The result of this regulatory lacuna is that while PGD was originally intended for screening embryos for severe heritable disorders, it is now also employed for a variety of more controversial purposes, including nonmedical sex selection, selection for a “savior sibling” (that is, a child who will be histocompatible with a sick sibling and could therefore donate tissue to the sibling), and even selection for children with conditions such as deafness or dwarfism.4 In other words, in the United States, if there is a genetic test available, you can afford to pay out of pocket,5 and you can find January-February 2015
a specialist willing to order the test and perform the associated procedures, then you can do PGD for any reason. The United States is very unusual in its lack of legal guidance on the acceptable uses of PGD. Most countries where PGD is available have relevant legislation restricting the technique’s use.6 Often, PGD may be used only for medical purposes, although how “medical” is defined and what bodies are responsible for making this determination varies. For example, in the United Kingdom, the Human Fertilisation and Embryology Authority (a statutory body) is charged with the task of approving a list of conditions for which PGD is permitted, based on an assessment of the seriousness of the disease. Elective sex selection is banned outright.7 In France, the 2011 Bioethics Law specifies that PGD may be used only to select against specific diseases or to select for a tissue match for a sick sibling.8 In Canada, nonmedical sex selection is prohibited,9 and in the Netherlands, PGD is permitted only for the diagnosis of “severe and untreatable genetic conditions.”10 The absence of regulation of PGD in the United States is thus notable and worthy of explanation. Four considerations are particularly important in this explanation. They are deeply interrelated, as the political, economic, and social conditions particular to the United States are mutually determining and reinforcing. Lack of a single-payer health care system. In many other countries with advanced medical research and
treatment—and in all of the countries mentioned above—the national government plays a major role in funding, and sometimes directly providing, health care services. It is therefore necessary in these countries for government officials to weigh the applications of available medical treatments in order to determine what services ought to be covered. Although in countries with a two-tier system patients may still pay out of pocket for certain treatments, the government must at least ask the question, is this an appropriate, useful, or necessary medical application? In the United States, where private health insurers cover most people and governmentfunded health care (such as Medicare, Medicaid, and the Veterans Health Administration) does not include coverage for advanced fertility treatment such as in vitro fertilization (IVF) and PGD, the government has not been required to take a stance on the appropriate uses of PGD. Resistance of medical professionals. For a variety of reasons, medical professionals in the United States tend to resist greater government oversight. As several leaders of the American Society for Reproductive Medicine wrote in 2006 (succinctly summarizing the first point), “regulatory oversight should parallel funding.” They also suggested that government regulation might result in poorly crafted or ideologically motivated laws and that being forced to adhere to a preapproved list of conditions for which PGD may be performed—such as the one used in the United Kingdom—“would exert a chilling effect” on the development of new tests.11 Some doctors also view government oversight as an unwelcome intrusion into medical practice and a potentially inappropriate interference with patient care. In the United Kingdom, by contrast, most doctors are employed directly by the national government, and the “intrusion” of government regulation is simply a fact of life. Physician attitudes and expectations likely depend, at least in part, on a country’s health care framework. Proximity to the abortion debate. PGD, like IVF in general, involves creating and often discarding embryos, H AS TI N GS C E N TE R RE P O RT
7
depending on patient preferences. PGD also involves the added dimension that many discarded embryos are seen as possessing an “undesired” genetic feature. In the United States, abortion is a more contentious issue than in most other Western countries, and it is very unlikely that Congress could successfully pass a law on the appropriate use of PGD.12 Such a law would have the effect of sanctioning the destruction of some embryos. State legislatures might be able to pass a law on PGD, but given the political volatility of the issue relative to the number of cases, state legislators are probably not eager to tackle this topic either.13 Inherent limitations of the democratic process. Certain applications of PGD are extremely controversial, and reasonable people can disagree about their legitimacy and whether they should be offered. For instance, a 2006 survey of IVF clinics indicated that less than half of responding centers offered PGD for nonmedical sex selection and about a quarter offered tissue typing for savior siblings.14 The very nature of democracy in a diverse, pluralistic society makes it difficult to design regulations on such divisive topics. While the contentiousness of certain uses of PGD is not exclusive to the United States, the United States is more culturally diverse than most Western and Northern European countries,15 which may amplify the inherent challenge of developing regulations that reflect and respect the views of the electorate. Given these obstacles, it is unlikely that government bodies in the United States will implement guidelines for the appropriate use of PGD in the near future. It is possible, though, that as physicians become more accustomed to provisions of the Affordable Care Act that affect their everyday practice (such as electronic health record usage requirements and reimbursements for
8 HASTIN G S C E N T E R R E P ORT
Medicare services based on quality of care), they will become less resistant to government involvement in the kinds of services they offer. Furthermore, professional organizations such as the American Society for Reproductive Medicine and the American College of Medical Genetics could take a more active role in developing guidelines for the use of PGD. Self-regulation is not legally binding, but medical society guidelines are often cited by insurance companies weighing what procedures to cover and courts deciding whether a doctor has breached the standard of care. While medical societies may not be perfectly representative of the American population, stricter self-regulation on the use of PGD would be a positive step toward managing this potent and rapidly advancing medical technology. Disclaimer
The opinions expressed here are those of the author and do not reflect the policies or positions of the National Institutes of Health, the U.S. Public Health Service, or the U.S. Department of Health and Human Services. 1. Food and Drug Administration, “Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs),” September 30, 2014. 2. S. Baruch et al., Reproductive Genetic Testing: Issues and Options for Policymakers (Washington, D.C.: Genetics and Public Policy Center, 2004). 3. M. Bayefsky and B. Jennings, Regulating Preimplantation Genetic Diagnosis in the United States: The Limits of Unlimited Selection (New York: Palgrave Macmillan, forthcoming, 2015). 4. S. Baruch, D. Kaufman, and K. Hudson, “Genetic Testing of Embryos: Practices and Perspectives of US In Vitro Fertilization Clinics,” Fertility and Sterility 89, no. 5 (2008): 1053-58. 5. PGD itself may be covered under some health insurance plans (see, for example, Aetna, “Clinical Policy Bulletin: Invasive
Prenatal Diagnosis of Genetic Diseases,” April 29, 2014, http://www.aetna.com/cpb/medical/data/300_399/0358.html), but in vitro fertilization, which must be performed in conjunction with PGD, is rarely covered by insurance (National Conference of State Legislatures, “State Laws Related to Insurance Coverage for Infertility Treatment,” last updated June 2014, accessed December 4, 2014, http:// www.ncsl.org/research/health/insurance-coverage-for-infertility-laws.aspx), and IVF costs approximately $12,000 per cycle. 6. R. M. Isasi and B. M. Knoppers, National Regulatory Frameworks regarding Human Reproductive Genetic Testing (Genetics and Public Policy Center, 2006), http://www.dnapolicy. org/pdf/geneticTesting.pdf. 7. Human Fertilisation and Embryology Bill, Bill 6, House of Lords. United Kingdom, 2007-2008. 8. Loi relative à la bioéthique, Loi no. 2011814, French Parliament, 2011. 9. K. Speechley and J. Nisker, “Preimplantation Genetic Diagnosis in Canada: A Survey of Canadian IVF Units,” Journal of Obstetrics and Gynaecology Canada 32, no. 4 (2010): 341-47. 10. Isasi and Knoppers, National Regulatory Frameworks regarding Human Reproductive Genetic Testing. 11. J. Simpson, R. Rebar, and S. Carson, “Professional Self-Regulation for Preimplantation Genetic Diagnosis: Experience of the American Society for Reproductive Medicine and Other Professional Societies,” Fertility and Sterility 85 (2006): 1653-660. 12. See T. Murray, “Stirring the Simmering ‘Designer Baby’ Pot,” Science 343 (2014): 1208-210. 13. Whether state regulation of the use of PGD would be advisable is a separate question; laws would most likely differ dramatically around the country and could range from complete prohibitions to unhindered access to PGD for any reason. 14. Baruch, Kaufman, and Hudson, “Genetic Testing of Embryos: Practices and Perspectives of US In Vitro Fertilization Clinics.” 15. R. Morin, “The Most (and Least) Culturally Diverse Countries in the World,” Pew Research Center, July 18, 2013, http://www. pewresearch.org/fact-tank/2013/07/18/themost-and-least-culturally-diverse-countries-inthe-world/. DOI: 10.1002/hast.412 This column appears by arrangement with the American Society for Bioethics and Humanities.
January-February 2015
