Mary A. Majumder

Two cheers for GINA

The Genetic Information Nondiscrimination Act of 2008 (GINA) was recently enacted in the United States. Its supporters have applauded the passage of GINA, and they hope that it will alleviate public fear about genetic discrimination and facilitate genetic testing and participation in genetic research. Critics worry that GINA does not provide adequate protection because it fails to address discrimination on the basis of non-genetic health-related information, and it only regulates the use of genetic information in health insurance and employment. Despite these limitations, GINA represents a major step forward in US policy. Additional research is needed to assess the impact of GINA on industry practice and public opinion. In the mean time, education about GINA and its limitations can help individuals make more informed decisions about genetic testing and participation in genetic research.

Cyberbanks and Other Virtual Research Repositories

Mary Anderlik Majumder ew things seem more a part of the material world than biological specimens. Yet the processes by F which collections of specimens are assembled, translated into information, combined with more information, and distributed are taking research repositories into the virtual realm. The term “virtual” has a number of meanings, and so a research repository can qualify as virtual in a variety of ways. The term would seem to apply, for example, to (1) constructing a repository by forming a network among institutions; (2 ) using the Internet or the World Wide Web to solicit specimens and information; (3) integrating web-based technology into the operation of the bank; (4) using the Internet or web-based technology to manage relationships with donors or collection sites and recipients; and (5 ) digitizing specimens.’ The all-digital repository would seem the most virtual of all possible repositories, a true cyberbank. The common thread across all the five categories is, I think, an element of elusiveness. It may be the elusiveness of the distributed network or of the electronic medium. A series of case studies shows how these features are combined in many virtual repositories. These case examples then become touchstones for a review of ethical and regulatory concerns. Ownership and intellectual property issues are beyond the scope of this article,Z although I will conclude by noting the emergence of a strong critique linking transactions in tissue and information to a dangerous depersonalization.

An Embedded Model for Ethics Consultation: Characteristics, Outcomes, and Challenges

Background: Little has been written about models for clinical ethics consultation. By “model” we mean the way in which the engagement between the clinical ethics consultant, hospital staff, and other stakeholders is structured, with a key variable being the degree of integration with stakeholders within the institution or segments of the institution. We describe an innovative model of clinical ethics consultation, which we term “embedded ethics,” involving embedding clinical ethics consultants within clinical specialties and subspecialties based on institutional needs and areas of clinical ethicists’ expertise. Methods: The overarching methodology for this article is a case study, reporting our experience with an intervention that we evaluated using mixed methods. Results: Our results underscore the positive impact that an embedded ethics intervention can have on consultation volume and intensity, as well as clinical staff perceptions of an ethics consultation service (ECS). Conclusions: Our experience with the embedded ethics model supports several intuitions about the benefits of adopting such a model for increasing awareness (and use) of the ECS as a resource for clinicians, patients, and families and of improving clinicians’ satisfaction.

Beyond Our Borders? Public Resistance to Global Genomic Data Sharing

Prospects have never seemed better for a truly global approach to science to improve human health, with leaders of national initiatives laying out their vision of a worldwide network of related projects. An extensive literature addresses obstacles to global genomic data sharing, yet a series of public polls suggests that the scientific community may be overlooking a significant barrier: potential public resistance to data sharing across national borders. In several large United States surveys, university researchers in other countries were deemed the least acceptable group of data users, and a just-completed US survey found a marked increase in privacy and security concerns related to data access by non-US researchers. Furthermore, diminished support for sharing beyond national borders is not unique to the US, although the limited data from outside the US suggest variation across countries as well as demographic groups. Possible sources of resistance include apprehension about privacy and security protections. Strategies for building public support include making the affirmative case for global data sharing, addressing privacy, security, and other legitimate concerns, and investigating public concerns in greater depth.

Future Directions for Oversight of Stem Cell Research in the United States

uman pluripotent stem cell research, meaning research into cells that can multiply indefinitely and differentiate into almost all the cells of the body, has become a minefield in which science, ethics, and politics have collided over the last decade in the United States. Presi- dent Barack Obama entered this highly charged territory when he indicated during his campaign that once in office he would issue an executive order expanding federally funded human embryonic stem cell (heSC) research and introduce rigorous oversight of it (Obama 2008a & b). Candidate Obama stated that he would require that the heSC lines involved were derived with donor consent from early embryos that otherwise would be discarded following in vitro fertilization (iVF) treatment. However, in contrast with the policy of President George W. Bush, he would do so without regard to the date of their derivation. He added that he would call upon the director of the National institutes of Health (NiH) to de- velop guidelines for federally funded heSC and other pluripotent stem cell research that would draw from the guidelines developed in 2005 by the National academies of Science (NaS) for privately funded research (National Research Council 2005). a similar policy was written into the 2008 version of the Stem Cell Re- search enhancement act, which reiterates the policy enunciated in earlier versions of this bill, passed twice by the Congress but vetoed by President Bush each time (House of Representatives, 110

Barriers to clinical adoption of next generation sequencing: Perspectives of a policy Delphi panel

This research aims to inform policymakers by engaging expert stakeholders to identify, prioritize, and deliberate the most important and tractable policy barriers to the clinical adoption of next generation sequencing (NGS). A 4-round Delphi policy study was done with a multi-stakeholder panel of 48 experts. The first 2 rounds of online questionnaires (reported here) assessed the importance and tractability of 28 potential barriers to clinical adoption of NGS across 3 major policy domains: intellectual property, coverage and reimbursement, and FDA regulation. We found that: 1) proprietary variant databases are seen as a key challenge, and a potentially intractable one; 2) payer policies were seen as a frequent barrier, especially a perceived inconsistency in standards for coverage; 3) relative to other challenges considered, FDA regulation was not strongly perceived as a barrier to clinical use of NGS. Overall the results indicate a perceived need for policies to promote data-sharing, and a desire for consistent payer coverage policies that maintain reasonably high standards of evidence for clinical utility, limit testing to that needed for clinical care decisions, and yet also flexibly allow for clinician discretion to use genomic testing in uncertain circumstances of high medical need.

Taking DNA from the dead

Using cadaveric specimens in genome research presents many benefits: investigators can study multiple organs from one individual, including those impossible to collect from living donors (for example, brains), and health risks are minimized as the individual is deceased. Several genomic research initiatives plan to collect cadaveric tissues. For instance, the Genotype-Tissue Expression (GTEx) project, a US National Institutes of Health Roadmap initiative, is seeking insights into the mechanics of gene regulation by identifying variations in gene expression that are highly correlated with genetic variation (1). Another example is the Allen Institute for Brain Sciences human brain atlases, which seek to create a comprehensive three-dimensional map of gene expression in the human brain (2). However, in many countries, including the United States, there are not adequate ethical guidelines in place for this type of research. Scandals involving the removal and retention of organs from cadavers in the United Kingdom led to enactment of the Human Tissue Act, which makes it a crime to conduct genome research using tissues from cadavers without consent (3). In the United States, cadaveric specimens can be obtained and used for most research with little regulatory oversight, no ethical review and without informed consent. Deceased individuals are not human subjects under US federal regulations (4). Although the Revised Uniform Anatomical Gift Act recommends that states require individual or family permission to retain cadaveric tissues for use in research (5), permission is not the same as providing informed consent. When an anatomical gift is made, only the purpose of the gift is specified (for example, transplantation, therapy, research, or education); no discussion of the nature of the research or its risks, benefits and alternatives is required. However, ethically, individuals retain certain interests after death, including an interest in having their bodies treated with respect and in having their ante-mortem wishes upheld (6). Living individuals whose organs may be used for research post-mortem may also suffer present harm in anticipation that their corpse will be treated in ways that violate their values or beliefs. Also, family members (whether genetically related or not) have an interest in the disposition of a loved ones remains. Finally, the use of cadaveric tissues in genome research raises additional ethical concerns about privacy. Some have argued that deceased individuals can suffer nonexperiential harm, such as loss of reputation that may result from a privacy breach after death (6), and close genetic relatives have privacy interests that deserve protection (7). Research has shown that DNA is a unique identifier (8, 9), and in some forensic cases it has been used to identify the biological relatives of a suspect (10). For these reasons, it is recommended that research on the newly dead is subjected to independent ethical review and that informed consent is obtained from the individual before death or from the legally authorized surrogate (7, 11). The informed consent process should be integrated into existing organ procurement processes to allow priority to be given to transplanting viable organs and to avoid duplicate requests, and it should include an explanation of the potential privacy risks for the sample source, as well as her or his close genetic relatives. In addition, precautions should be taken to protect privacy by limiting access to DNA data through restricted databases (12). However, independent informed consent from genetic relatives should not be required because the risks are extremely small in relation to the burdens that such a requirement would impose on research. DNA will only reveal predictive information about biological relatives, and the risk of identifiability is both uncertain and dependent upon the nature of the data and the degree of relatedness to the sample source. Further, in most cases it would be impracticable to identify and locate all potentially affected relatives, and the contact itself might constitute a breach of privacy. Further research will be needed to ensure that new policies are responsive to the concerns and perspectives of potential donors and their families. In the absence of data regarding public perspectives, we recommend a preventative ethics approach that involves institutional review board appraisal and informed consent from the individual or a surrogate. This approach may prevent future scandals and bolster public trust. At the same time, it is not overly burdensome and so should not significantly impede research.

The NIH Draft Guidelines on Human Stem Cell Research

New guidelines have positive aspects, but challenges remain in relation to previously approved stem cell lines, informed consent, oversight, and research embryos. With new draft guidelines to govern federal funding of human stem cell research, including human embryonic stem cell (hESC) research, the National Institutes of Health (NIH) have again taken on one of the most contentious endeavors of the day (1). There are positive aspects of the guidelines (2), but concern is growing that prior approvals of many widely used cell lines may not be in accord with specific wording requirements in the draft guidelines; such cell lines would need to be “grandfathered in” if research is to continue unimpeded (3). There are also several surprising omissions, surprising because they come in areas that are thoroughly addressed in the guidelines of the U.S. National Academies of Sciences (NAS) (4–6), which have become the gold standard for the conduct of stem cell research in the United States. Further, there has been little comment on the kind of initiative that would support future policy development.

Myriad take two: Can genomic databases remain secret?

Trade-secrecy laws clash with a right to ones health data An ongoing legal challenge to the business model of Myriad Genetics highlights how recent policy developments have contributed to a collision between individual interests in access to personal health data and commercial interests in trade secrecy. Following a landmark ruling by the U.S. Supreme Court invalidating its patents on BRCA1/2 genetic variants (1), which increase the risk of female breast and ovarian cancer, Myriad now faces efforts to dismantle the proprietary database of variants and their clinical interpretation that it began developing when it was the exclusive provider of BRCA1/2 tests. Although the competing claims that anchor this dispute are hard to reconcile, we see room for legal compromise and opportunity for policy innovations to incentivize companies to invest in test development while ensuring that their findings can be used by others.

Creating a data resource: what will it take to build a medical information commons?

National and international public–private partnerships, consortia, and government initiatives are underway to collect and share genomic, personal, and healthcare data on a massive scale. Ideally, these efforts will contribute to the creation of a medical information commons (MIC), a comprehensive data resource that is widely available for both research and clinical uses. Stakeholder participation is essential in clarifying goals, deepening understanding of areas of complexity, and addressing long-standing policy concerns such as privacy and security and data ownership. This article describes eight core principles proposed by a diverse group of expert stakeholders to guide the formation of a successful, sustainable MIC. These principles promote formation of an ethically sound, inclusive, participant-centric MIC and provide a framework for advancing the policy response to data-sharing opportunities and challenges.