This is the first in a series of monthly posts in which I share some of my favorite posts on the ethical, legal and social issues of predictive health research and medicine. A public and open discussion of these issues will increase the likelihood that individuals and communities will realize the benefits of advances in genetic and personalized medicine, human genome sequencing, predictive neuroimaging, biobanking, and health IT. PredictER Blog commends the following blogs for doing their part to inform and foster dialogue.
Listed by Topic and Date:
Biobanks
Biobanking and you. Sue Trinidad, Women's Bioethics Blog. 19 January 2008.
In the one of the first of what I hope will be long series, Sue Trinidad asks good questions about informed consent and reminds us that even "anonymized" DNA samples might be identifiers. She writes: "nothing is a more precise identifier of who you are than your so-called genetic fingerprint. Is this worrisome?"
Should genetic researchers be able to share your DNA? Sue Trinidad, Women's Bioethics Blog. 23 January 2008.
In her second post on ethical issues of genetic research and biobanks, Trinidad adds additional compelling questions, including: "If you'd consented to participate in that study at your local research university, how would you feel about your (de-identified) information being used by researchers somewhere else?" and "Say the researchers did [a] breast cancer study, and in the course of that work they noticed that there seemed to be a correlation between certain genetic patterns and alcoholism or schizophrenia. Would it be ok with you for them to pursue this line of inquiry using your genetic information?"
Consumer Genomics
American Society of Human Genetics (ASHG) Statement on Direct-to-Consumer Genetic Testing. Hsien-Hsien Lei, Eye on DNA. 2 January 2008.
Getting the month off to a good start, Hsien-Hsien Lei reviews the ASHG's policy statement [PMID: 18055737 excerpt] on Direct-to-Consumer Genetic Testing. Lei makes the following observation:"With increased competition in the field of direct-to-consumer personal genomics in 2008, I predict that only companies that can fully address the [ASHG] recommendations ... will survive .... Consumers are getting up to speed on what genetic testing can offer them and won’t settle for fuzzy, incomplete information."
Also see Lei's related posts on the subject, including: "The New England Journal of Medicine Gives Direct-to-Consumer Genome Scans Thumbs Down" (Eye on DNA, 10 January 2008).
Do I need a personal trainer or a personal genetic counsellor? Myles Axton, Free Association. 11 January 2008.In the editor's blog of the journal Nature Genetics, Myles Axton reviews the NEJM editorial “Letting the Genome out of the Bottle--will we get our wish?” (Hunter DJ, Khoury MJ, Drazen JM. N Engl J Med 2008; 358 (2):105-7. PMID:18184955 excerpt) Axton appreciates the skepticism and applauds "efforts to build genetics into every stage of medical education", but adds: "The authors have some good points, but largely ignore the unpredictable motivational potential inherent in handing people their genomes and asking them to participate in finding out more about their variation and phenotypes. Sometimes, the best doctor will say “we don’t know yet, let’s find out together”.
Privacy Issues
Your personal health: The internet and privacy. Deepak Singh, businessbytesgenesmolecules (bbgm). 2 January 2008.
Singh compares the success of Web 2.0, which relies, in part on "the forfeiture of privacy" to the rise of consumer genomics. Singh writes: "the moment you leave your footprint online, you are giving away some of your privacy. The moment you sign up for a genomic service, you are giving away some of your privacy. The question we need to answer is a simple one in a way. Is the benefit we get from being online, or getting yourself genotyped, worth the loss of privacy?" Singh has obviously traded some of his privacy for the benefits of Web 2.0; will he do the same for consumer genomics?
Respecting patient privacy preferences. John D. Halamka, Life as a Healthcare CIO. 21 January 2008.
Halamka is Chief Information Officer of CareGroup Health System and Harvard Medical School, a practicing Emergency Physician, a participant in the Personal Genome Project, and (among many more things) a vegan. Halamka writes: "One of the greatest challenges for healthcare information exchanges is to ensure continuity of care for patients while also respecting patient privacy preferences." He envisions a future in which electronic consent wizard will support a truly itemized process for sharing personal medical records and health data. Patients and research participants, might provide very specific consent statements, for example: "If I'm unconscious in an emergency room, share everything including mental health, substance abuse and HIV status data. If I'm visiting a Minuteclinic do not include my mental health and substance abuse history. If I'm sharing my data for a population-based research study, do not include my HIV status."
Whole Genome Sequencing
The ethical challenges of whole-genome sequencing part 1. Daniel MacArthur, Genetic Future. 22 January 2008.
In the first of a two(?) part post reviewing "Research ethics and the challenge of whole-genome sequencing" (McGuire AL, Caulfield T, Cho MK. Nat Rev Genet 2008; 9 (2):152-6. PMID:18087293), MacArthur summarizes advances in whole-genome sequencing technologies and evaluates the authors' comments on: the return of genome data to participants, the provision of clinical follow-up, and the integration of genome data and medical records. If you've read the NRG commentary, you'll be interested in this post; if you don't have a subscription to journal, you'll value MacArthur's outline of the issues. In his forthcoming part 2, MacArthur plans to "discuss the other major ethical challenges discussed in the NRG commentary: obligations to close relatives of study participants, and future uses of samples and data." Stay tuned! -J.O.
Wednesday, January 30, 2008
Saturday, January 26, 2008
A Public Cord Blood Bank in Indiana? Reviewing House Bill 1020
[In this post contributing author Katherine Drabiak shares her assessment of some of the strengths and weaknesses of Indiana House Bill 1020. The legislation was referred the Committee on Public Health on January 14th, 2008. - J.O.]
Drafters of Indiana’s House Bill 1020 proposing to establish a nonprofit operation of umbilical cord blood bank seem to have learned from the ownership battles over donations recently impeding biobank research efforts. Unlike other existing state laws relating to the property rights associated with cord blood donations, HB 1020 explicitly promulgates a waiver of ownership rights. HB 1020 proposes to illuminate the “ownership” transfer (Chapter 1 Section 7) that would ostensibly be drafted into the informed consent form templates. The current draft of HB 1020 and the proposed amendments as of January 18, 2008 unequivocally specify that any property rights related to the cord blood, including intellectual property rights developed, would vest in the Bank.
While this provision on its face provides additional legal certainty, its efficacy assumes several propositions: the informed consent form is legally sufficient and the pregnant patient truly understands the nature of the donation, the Bank’s IRB will ensure precautions to overcome potential conflicts of interest that could undermine the legitimacy of informed consent, and that property waivers will not be found to conflict with federal law.
As HB 1020 is currently drafted, Chapter 1 Section 4 relating to informed consent broadly tasks the Bank with drafting and providing informed consent forms without specific directives. Prior to donating and signing such a waiver, the pregnant patient must be adequately informed of the options to either donate the umbilical cord blood to the Bank or the possibility of using a private banking facility. Yet currently proposed amendments to HB 1020, if passed, would change the amount of information provided and only inform the pregnant patient of the value of donating to the Bank, eliminating the requirement to discuss the possibility of private banking options. This marks a significant departure from other state law practices, which typically present the pregnant patient with the options of public banking, private banking, or forgoing any donation. This departure could potentially undermine consent by insufficiently informing the pregnant patients. Efforts to promote a public bank may topple, if supported by a weakened informed consent process. Is the fact that few pregnant patients would choose (or be able to afford) a private banking facility a legitimate and prudent reason to eliminate this option in the informed consent process?
The legislation also assumes the sufficiency of potentially blanket consent (Chapter 2 Section 2) and the Bank’s adherence of allocating donations to “ethical” research protocols. The amendments to the legislation propose that the Board of Directors for the Bank would form an independent Institutional Review Board to establish and oversee the informed consent process and privacy protections which would occur separately from the allocation decisions. Per Chapter 1 Section 3, an advisory board comprised of at least 51% research scientists would be tasked with reviewing applications of parties interested in receiving nontransplantable donations. The Board and the IRB are guided by the proposition that research use of the donations shall be used “to promote medical advances, life sciences research, or biotechnology research.” (Chapter 1 Section 5) Logistically, the IRB’s representations of potential research uses of the donations to the pregnant patients should align with the allocation criteria used by the research scientists. If for some reason the majority of the Board decides (assuming research scientists would urge maximum distribution to cutting edge research) to allocate donations to a technologically forward yet ethically questionable project, this may not conform to the IRB’s representations to the pregnant patients during the donation process. The question arises whether the Bank will develop an internal mechanism to ensure the function of the IRB is preserved throughout the allocation process.
Even if the informed consent procedure and forms are found to be sufficient, the property waiver itself could be interpreted as potentially conflicting with federal law. The FDA has objected to the terms donation and abandonment of property rights, asserting that 21 CFR 50.20 prohibits requiring subjects to waive or appear to waive any rights as a condition for participation. Yet recent case law suggests that the drafters of HB 1020 may be on to the recent legal trend that disfavors the FDA’s interpretation and instead posits that the pregnant patient is not actually waiving any legal right by signing the "waiver" because she has no legal right to direct the use of the donation after signing the informed consent form, nor is she entitled to any potential intellectual property rights should they arise. Rather, the property waiver serves as a legal clarification to pre-empt potential disputes from spinning into costly or lengthy judicial interference.
If we assume these potential conflicts relating to the informed consent process and allocation procedure are resolved in an ethical manner, the drafters of the Bill may be initiating a trend to adopt property waivers for all banked donations. If this property waiver is adopted, it would most certainly eliminate many of the potential conflicts previously associated with donating banked specimens and, therefore, would allow the Bank to concentrate fully on maximizing its research efforts. – Katherine Drabiak
Drafters of Indiana’s House Bill 1020 proposing to establish a nonprofit operation of umbilical cord blood bank seem to have learned from the ownership battles over donations recently impeding biobank research efforts. Unlike other existing state laws relating to the property rights associated with cord blood donations, HB 1020 explicitly promulgates a waiver of ownership rights. HB 1020 proposes to illuminate the “ownership” transfer (Chapter 1 Section 7) that would ostensibly be drafted into the informed consent form templates. The current draft of HB 1020 and the proposed amendments as of January 18, 2008 unequivocally specify that any property rights related to the cord blood, including intellectual property rights developed, would vest in the Bank.
While this provision on its face provides additional legal certainty, its efficacy assumes several propositions: the informed consent form is legally sufficient and the pregnant patient truly understands the nature of the donation, the Bank’s IRB will ensure precautions to overcome potential conflicts of interest that could undermine the legitimacy of informed consent, and that property waivers will not be found to conflict with federal law.
As HB 1020 is currently drafted, Chapter 1 Section 4 relating to informed consent broadly tasks the Bank with drafting and providing informed consent forms without specific directives. Prior to donating and signing such a waiver, the pregnant patient must be adequately informed of the options to either donate the umbilical cord blood to the Bank or the possibility of using a private banking facility. Yet currently proposed amendments to HB 1020, if passed, would change the amount of information provided and only inform the pregnant patient of the value of donating to the Bank, eliminating the requirement to discuss the possibility of private banking options. This marks a significant departure from other state law practices, which typically present the pregnant patient with the options of public banking, private banking, or forgoing any donation. This departure could potentially undermine consent by insufficiently informing the pregnant patients. Efforts to promote a public bank may topple, if supported by a weakened informed consent process. Is the fact that few pregnant patients would choose (or be able to afford) a private banking facility a legitimate and prudent reason to eliminate this option in the informed consent process?
The legislation also assumes the sufficiency of potentially blanket consent (Chapter 2 Section 2) and the Bank’s adherence of allocating donations to “ethical” research protocols. The amendments to the legislation propose that the Board of Directors for the Bank would form an independent Institutional Review Board to establish and oversee the informed consent process and privacy protections which would occur separately from the allocation decisions. Per Chapter 1 Section 3, an advisory board comprised of at least 51% research scientists would be tasked with reviewing applications of parties interested in receiving nontransplantable donations. The Board and the IRB are guided by the proposition that research use of the donations shall be used “to promote medical advances, life sciences research, or biotechnology research.” (Chapter 1 Section 5) Logistically, the IRB’s representations of potential research uses of the donations to the pregnant patients should align with the allocation criteria used by the research scientists. If for some reason the majority of the Board decides (assuming research scientists would urge maximum distribution to cutting edge research) to allocate donations to a technologically forward yet ethically questionable project, this may not conform to the IRB’s representations to the pregnant patients during the donation process. The question arises whether the Bank will develop an internal mechanism to ensure the function of the IRB is preserved throughout the allocation process.
Even if the informed consent procedure and forms are found to be sufficient, the property waiver itself could be interpreted as potentially conflicting with federal law. The FDA has objected to the terms donation and abandonment of property rights, asserting that 21 CFR 50.20 prohibits requiring subjects to waive or appear to waive any rights as a condition for participation. Yet recent case law suggests that the drafters of HB 1020 may be on to the recent legal trend that disfavors the FDA’s interpretation and instead posits that the pregnant patient is not actually waiving any legal right by signing the "waiver" because she has no legal right to direct the use of the donation after signing the informed consent form, nor is she entitled to any potential intellectual property rights should they arise. Rather, the property waiver serves as a legal clarification to pre-empt potential disputes from spinning into costly or lengthy judicial interference.
If we assume these potential conflicts relating to the informed consent process and allocation procedure are resolved in an ethical manner, the drafters of the Bill may be initiating a trend to adopt property waivers for all banked donations. If this property waiver is adopted, it would most certainly eliminate many of the potential conflicts previously associated with donating banked specimens and, therefore, would allow the Bank to concentrate fully on maximizing its research efforts. – Katherine Drabiak
Tuesday, January 22, 2008
Cord Blood Biobanking: Indiana Legislative News
Last week at the Second Regular Session of the 115th Indiana General Assembly, Representatives Peggy Welch (District 60), Eric Koch (District 65), Kreg Battles (District 64), and P. Eric Turner (District 32) introduced House Bill 1020. The proposed legislation will establish a nonprofit corporation to operate an umbilical cord blood bank. As written the legislation also "[r]equires physicians and participating hospitals to inform pregnant patients of the option to donate umbilical cord blood". Although the primary purpose of the bank is to provide medical benefits for Indiana's citizens, it may (depending on the progress of the legislation) provide cord blood for future research studies. The bill was referred the the Committee on Public Health on January 14th, 2008.
PredictER Blog will follow this legislation and will post a more thorough commentary on the ethical, legal and social issues of this proposed biobank in the near future.
PredictER Blog will follow this legislation and will post a more thorough commentary on the ethical, legal and social issues of this proposed biobank in the near future.
Thursday, January 17, 2008
Predicting a New Disease: Pathological Consumption of Genetic Information
The current issue of the New England Journal of Medicine (10 January 2008; PMID: 18184955) contains a cleverly titled article “Letting the Genome out of the Bottle – Will We Get Our Wish?" The article, which explores the new phenomena of commercialized personal genome analysis through genetic profile tests capable of identifying several hundred thousand variations in any one genome, has drawn the attention of several astute bloggers, including: Myles Axton of Free Association, Blaine Bettinger of The Genetic Genealogist, Hsien-Hsien Lei of Eye on DNA, and Steve Murphy of Gene Sherpas. The general conclusion of the NEJM authors is that perhaps a person may get their wish, but the clinician certainly won’t. Why is that? Because the predictive value of many of the variations identified by the tests is questioned as is the utility of the information itself, i.e. what will the patient do with the information? While both of these arguments are accurate, they need to be tempered with common sense and a degree of humility rarely found when scientists address general society.
Beginning with the first point, the predictive value of these tests is limited. Lead author Dr. David Hunter develops this point in a US News and World Report interview with Nancy Shute (Why Not to Buy a Scan of Your Genome, 9 January 2008). Hunter notes that the predictive value of many of the genes or single nucleotide polymorphisms (SNP’s) found in these genetic profiles pales in comparison to the predictive value of tried and true genetic tests for specific genes like BRCA 1 and 2. To be sure, he is correct, but interestingly the predictive value of the BRCA gene is being called into question this month as well. A large population-based case-control study published in the Journal of the American Medical Association (Begg CB, et al. Variation of Breast Cancer Risk Among BRCA1/2 Carriers. JAMA. 2008;299(2):194-201. PMID: 18182601) suggests the BRCA 1 and/or 2 gene alone may not be as predictive as once thought, and that a variety of other genes may explain the strong familial clustering of breast cancer. What this means is that the more we know about genetics, the more we recognize the limits of our knowledge. How then can adding personal genome profiles adversely affect this pool of knowledge?
Moving now to the second point: the clinical utility of general genome profiles is questionable. Certainly this is the case. Still, the authors need to keep "personal" aspects of these profiles in mind. This is not a test marketed to health professionals to guide treatment; it is a test marketed to guide lifestyle, a type of guidance which most physicians are admittedly poor at providing for their patients anyway. Further still, the lifestyle changes dictated by carriers of the BRCA gene may be very dramatic—possible removal of both breasts and ovaries; contrast these to the lifestyle changes encouraged by a personal genome scan indicating an increased risk for heart disease—increased exercise and proper diet.
In sum, Dr. Hunter and his colleagues are right to raise their concerns about these tests: the tests have limited capability, unknown utility, and are expensive. Still, the capability of any medical test can only be magnified by an increase in data. Furthermore, an unknown clinical utility does not mean that a person cannot derive some utility from knowing their own genome profiles. If this were the case, why would they purchase the test at all? Perhaps Dr. Hunter’s lament is in part that the human genome, once the bastion of modern orthodox medical science, now will be shared with alternative medicine in a very real and technical way. Making this point clear is what is necessary, not admonishing patients on how to spend their money. - Patrick Barrett
Beginning with the first point, the predictive value of these tests is limited. Lead author Dr. David Hunter develops this point in a US News and World Report interview with Nancy Shute (Why Not to Buy a Scan of Your Genome, 9 January 2008). Hunter notes that the predictive value of many of the genes or single nucleotide polymorphisms (SNP’s) found in these genetic profiles pales in comparison to the predictive value of tried and true genetic tests for specific genes like BRCA 1 and 2. To be sure, he is correct, but interestingly the predictive value of the BRCA gene is being called into question this month as well. A large population-based case-control study published in the Journal of the American Medical Association (Begg CB, et al. Variation of Breast Cancer Risk Among BRCA1/2 Carriers. JAMA. 2008;299(2):194-201. PMID: 18182601) suggests the BRCA 1 and/or 2 gene alone may not be as predictive as once thought, and that a variety of other genes may explain the strong familial clustering of breast cancer. What this means is that the more we know about genetics, the more we recognize the limits of our knowledge. How then can adding personal genome profiles adversely affect this pool of knowledge?
Moving now to the second point: the clinical utility of general genome profiles is questionable. Certainly this is the case. Still, the authors need to keep "personal" aspects of these profiles in mind. This is not a test marketed to health professionals to guide treatment; it is a test marketed to guide lifestyle, a type of guidance which most physicians are admittedly poor at providing for their patients anyway. Further still, the lifestyle changes dictated by carriers of the BRCA gene may be very dramatic—possible removal of both breasts and ovaries; contrast these to the lifestyle changes encouraged by a personal genome scan indicating an increased risk for heart disease—increased exercise and proper diet.
In sum, Dr. Hunter and his colleagues are right to raise their concerns about these tests: the tests have limited capability, unknown utility, and are expensive. Still, the capability of any medical test can only be magnified by an increase in data. Furthermore, an unknown clinical utility does not mean that a person cannot derive some utility from knowing their own genome profiles. If this were the case, why would they purchase the test at all? Perhaps Dr. Hunter’s lament is in part that the human genome, once the bastion of modern orthodox medical science, now will be shared with alternative medicine in a very real and technical way. Making this point clear is what is necessary, not admonishing patients on how to spend their money. - Patrick Barrett
Tuesday, January 15, 2008
GINA: Behind-the-Scenes Veto Threat
What kept the "Genetic Information Nondiscrimination Act" out of the omnibus? Apparently "Dr. No" (Sen. Coburn, the GINA's persistent foe) wasn't alone in his opposition to the legistlation. "Capitol Hill Watch" by Kaisernetwork.org relays this bit of back-room negotiating from CQ Today (14 January 2008):
A "behind-the-scenes veto threat from the White House apparently kept a popular genetics anti-discrimination measure" (HR 493) from being attached to the FY 2008 omnibus spending bill (PL 110-161), CQ Today reports. Regan Lachapelle, a spokesperson for Senate Majority Leader Harry Reid (D-Nev.), said senior administration negotiators told Senate Democrats that Bush would veto the package if the genetics measure was included. The legislation would bar employers and insurers from using information from genetic testing to determine how much a person's insurance premiums should be or other business decisions, including hiring. According to CQ Today, "Congress will work to clear the bill early this session".
Congress will work to clear ... that's a rather vague forecast. - J.O.
A "behind-the-scenes veto threat from the White House apparently kept a popular genetics anti-discrimination measure" (HR 493) from being attached to the FY 2008 omnibus spending bill (PL 110-161), CQ Today reports. Regan Lachapelle, a spokesperson for Senate Majority Leader Harry Reid (D-Nev.), said senior administration negotiators told Senate Democrats that Bush would veto the package if the genetics measure was included. The legislation would bar employers and insurers from using information from genetic testing to determine how much a person's insurance premiums should be or other business decisions, including hiring. According to CQ Today, "Congress will work to clear the bill early this session".
Congress will work to clear ... that's a rather vague forecast. - J.O.
Monday, January 14, 2008
PredictER News Brief - 14 January 2008
The latest edition of PredictER News Brief (14 January 2008) is now available online. PredictER News Brief is a biweekly digest of news, blogs, and research publications relevant to the ethics, law and policy of predictive health research. The current issue features: a synopsis of recent news coverage of the genetics of autism, a list of several upcoming events and conferences, and references blog entries from Brandon Keim at Wired Science, Jacob Goldstein at The Wall Street Journal Health Blog, Myles Axton of Free Association, and Blaine Bettinger of The Genetic Genealogist.
To received PredictER News Brief as an email newsletter send an email to listserv@listserv.iupui.edu with "subscribe PREDICTER-L" in the message body. - J.O.
To received PredictER News Brief as an email newsletter send an email to listserv@listserv.iupui.edu with "subscribe PREDICTER-L" in the message body. - J.O.
Tuesday, January 8, 2008
Biomedical Research Ethics 2.0: MySpace and Pediatrics
Much of the excitement about the future of personalized medicine revolves around the creation of consumer managed, personal health records. To acquire a measure of the anticipation, revisit the blogging blitz inspired the by implicit competition between Microsoft's HealthVault and Google Health (see, for example, David Hamilton's reviews of HealthVault at Venture Beat and Bertalan Meskó's coverage of Google Health at ScienceRoll). Although most are interested in the potential these Web 2.0 developments hold for enhanced, individualized health care, others have speculated that personal health information may become a more common feature of social-networking sites. The big names in social-networking (MySpace and Facebook) already host user-generated groups for individuals with shared health conditions; others, such as iMedix and MyOpenCare (for more examples visit Medicine 2.0) have entered the market with an obvious interest in health 2.0 and shared, personal medical records.
Although many worry about how advertisers might data mine personal information to target potential customers, these networks also offer a new source of information for medical research data and research recruitment. With this in mind, "Research Ethics in the MySpace Era" (Moreno MA, Fost NC, Christakis DA. Pediatrics 2008;121;157-161. PMID:18166570) is a very timely publication. The authors explore the ethical implications of using MySpace profiles as: a source for observational research (potentially exempt from IRB oversight); a tool for research recruitment; and a platform for health intervention studies. Although the authors are particularly interested in the risks and benefits of social-networking sites for pediatric research, the investigation could easily be generalized for research with adult users. The authors, however, do not address the ethical implications of using shared, genetic information. Imagine a day in which users update their profiles and replace zodiac signs with significant genetic biomarkers. How would this "shared" information challenge the ethical framework proposed by Moreno, Fost and Christakis? - J.O.
Although many worry about how advertisers might data mine personal information to target potential customers, these networks also offer a new source of information for medical research data and research recruitment. With this in mind, "Research Ethics in the MySpace Era" (Moreno MA, Fost NC, Christakis DA. Pediatrics 2008;121;157-161. PMID:18166570) is a very timely publication. The authors explore the ethical implications of using MySpace profiles as: a source for observational research (potentially exempt from IRB oversight); a tool for research recruitment; and a platform for health intervention studies. Although the authors are particularly interested in the risks and benefits of social-networking sites for pediatric research, the investigation could easily be generalized for research with adult users. The authors, however, do not address the ethical implications of using shared, genetic information. Imagine a day in which users update their profiles and replace zodiac signs with significant genetic biomarkers. How would this "shared" information challenge the ethical framework proposed by Moreno, Fost and Christakis? - J.O.
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