ELSI Publications and Products Database

The major goal of this study is to determine the feasibility of a CF screening program that, while incorporating pre- and post-test education for people with negative screening tests, provides personal counseling primarily for those who test positive for CF carrier status. The Vanderbilt research team will develop written and video materials, examine various settings for provision of carrier testing and determine the preferred setting from the consumer's viewpoint for provision of CF carrier testing, determine the factors that affect a couple's decision whether or not to be tested for CF carrier status, and determine general acceptance of population screening.

New technologies are enabling the arrival of the much awaited affordable genome the ability to sequence an individuals or a tumors entire genome quickly and inexpensively [whole genome sequencing (WGS)]. WGS is now being offered in clinical care and is expected to become more widely used in the near future, particularly in cancer. However, this technological advance threatens to outpace our ability to use it effectively in clinical practice and to address the associated health policy issues. Our objective is to evaluate the potential benefit- risk tradeoffs of WGS from the perspectives of patients, providers, the health care delivery system, and society by using systematic and quantitative approaches. Our study aims are: 1) to analyze how patients and physicians evaluate WGS benefit-risk tradeoffs using a decision-theoretic model of the value of information and 2) to empirically assess benefit-risk tradeoffs of WGS at the health care system and societal levels. For Aim 1 we will measure and compare patient and physician preferences for WGS in participants of the first randomized clinical trial of WGS using a general population sample (MedSeq Project), which is being led by Harvard Medical School and a nationally representative sample using quantitative, statistically rigorous methods (conjoint analysis). Aim 2 will be accomplished using two sub-aims. In Aim 2a we will conduct a policy analysis of how benefit-risk tradeoffs are considered in health care decision making for WGS, including coverage/reimbursement decisions and clinical guideline development, and how they compare to those of more established genetic tests. In Aim 2b we will develop (1) a framework to conceptualize, identify, and define data needed to assess the value of WGS; and (2) a prototypical cost-effectiveness model of one likely finding from WGS¿identification of Lynch syndrome¿using data from Aims 1 and 2a, MedSeq, and our previous analyses. This will be the first national study to our knowledge of patient and physician preferences relevant to WGS in the general population, to compare preferences from a clinical trial to a national population, and to systematically examine implications of WGS for the health care system and society. The proposed work is significant in that it will produce evidence of how WGS can be most effectively and efficiently adopted while also understanding its limitations¿information that will be useful to patients, providers, researchers, and policymakers. Our work will have broad impact on and implications for clinical practice and health policy and will build on the research currently being conducted by our experienced and diverse team. In sum, this study will address a significant topic using innovative adaptation of methods. The study is being proposed at the right time in the development of WGS¿a time when the study results will have an impact on the emerging science, when we can leverage the resources of an ongoing trial, and when we have the right team in place to conduct the research. PUBLIC HEALTH RELEVANCE: Whole Genome Sequencing (WGS) is a new and evolving technology that is highly relevant to public health because of its potential use in risk assessment, disease diagnosis, treatment decision making and research. The implementation of WGS will involve a complex set of decisions that must consider preferences of the relevant stakeholders and the impact on patients, providers, and society - in addition to the scientific evidence about validity and utility of findings. This project is critical now to examine the translation of this technology into clinical care and health policy before technology becomes widely implemented in the population.

Testing for mutations in the BRCA1 and BRCA2 breast-ovarian cancer susceptibility genes has been performed in over 70,000 individuals. Like other sequence-based tests, the results can reveal a normal sequence, a clearly deleterious mutation or a sequence variant of uncertain significance (VUS), in which it is not known whether the VUS confers an increased cancer risk. VUS results are confusing and occur in approximately 12% of tests. Their adequate interpretation requires a basic understanding of genetic principles, the laboratory methods utilized and pedigree analysis. No studies, however, have been published that assess the interpretation and clinical recommendations of non-geneticist physicians receiving a VUS result for BRCA gene sequencing and our own clinical experience suggests that many physicians categorize all VUS results as deleterious mutations potentially leading to inappropriate management recommendations. Hypothesis: Non-geneticist physicians do not discriminate between a VUS and a deleterious mutation when making recommendations with regard to breast and ovarian cancer risk management. Study Design: We will optimize and administer to members of the Texas Medical Association (internists, family practitioners, obstetrician-gynecologists, general surgeons, and oncologists) an on-line questionnaire that presents case scenarios that include BRCA test results that are deleterious, negative or have one or more VUS. A control group of experts in cancer genetics will be included. Physicians will be queried on testing options for at-risk individuals in the family, impact of the test result on cancer risk and asked to choose among a range of management options. Statistical analysis will determine whether the "path" of responses to a VUS result is more similar to a clearly deleterious or negative result. These results will be used to develop appropriate CME-eligible educational materials and to design genetic testing report formats that decrease areas of confusion identified in the survey. Relevance: Consistent with the goals of the NHGRI to bring "Genomics to Health" it is imperative that we optimize the appropriate interpretation of sequence-based genetic tests by a variety of physician specialties for use in clinical decision making. With the increasing availability of complex testing modalities, e.g. DNA and RNA gene chips, for a variety of both rare and common diseases, appropriate reporting and physician education must accompany the development of these tests.

This project addresses ethical and policy issues regarding current genetic susceptibility testing for late-onset Alzheimer disease (AD). It also addresses ethical aspects of ongoing autosomal dominant testing in families with early-onset AD. The project's Community Advisory Board and National Study Group will take up these tasks: examine current testing developments in AD genetics, their presymptomatic applicability, and clinical usefulness; consider costs of testing, potential testing pool, and justice in access to testing; address potential impact of susceptibility testing on private long-term care insurance industry; develop ethics guidelines for apolipoprotein (APOE) susceptibility testing and APP autosomal dominant mutation testing; and develop recommendations for the Alzheimer's Association in ensuring public understanding of test developments. In addition, a pilot questionnaire study of population attitudes toward APOE susceptibility testing, to be implemented in Chicago, is included. As the introduction to this proposal indicates, this project is now urgent and timely, and proceeds in collaboration with the National Alzheimer's Association.

There is almost no systematic, empirical research on the topic of how information about genetic risk information travels through families, what family and cultural characteristics might impede or promote its dissemination, and how individuals at genetic risk conceptualize these issues. The purpose of this project is to explore these issues using risk information about breast and ovarian cancer as a model. Empirical data collection will begin with recruitment of individuals at elevated genetic risk for breast/ovarian cancer who present as patients at genetic counseling centers in Portland, OR and Seattle, WA, but an attempt will be made to look at the entire family as the unit of analysis. Data about how risk information passes through the family will be gathered by qualitative interviews, observations of clinical encounters, and family focus groups. In the last half of the grant a Policy Group will be convened to examine empirical data from the study in light of normative legal and bioethical assumptions about these issues.

Using historical methods, this project explores the relevance of eugenics to genomics for the specific case of cancer theory and policy. The project will first examine the history of eugenics to see how genetic information was used in the 1920's-1940's to stigmatize or discriminate against specific individuals or members of groups. A second part examines the history of recent cancer theory to determine the extent to which evidence has been found that cancer is genetic, in the various senses of that term. The discovery of oncogenes and genes predisposing certain individuals or groups to specific types of cancer will be traced, along with policy implications conceived to flow from these discoveries. A third and final part compares and contrasts the potential dangers implicit in the biological determinism of eugenics and genomics. Efforts will be made to assess the extent to which the biological determinism often associated with genomics will have different social consequences from the determinism of earlier eugenics.

The two specific aims for the proposed summer genetics program for nursing faculty are: (a) to increase nursing faculty knowledge about human genetics and its clinical application, and b) to increase the amount of human genetics content and clinical experiences integrated into RN preparatory programs. Baseline levels of human genetics content and clinical experiences in nursing curriculum will be measured via a national survey of all state approved RN preparatory programs. The summer genetics program specific aims will be met by offering a multifaceted educational program over two consecutive years. The program will begin with a 12 day intensive summer course in human genetics offered to 30 nursing faculty. Following the summer course, participants will receive semiannual telephone follow up initiated by nursing faculty who have expertise in teaching and integrating genetics content into nursing curriculum. As part of the continuing education aspect of the program, a semiannual nursing genetics newsletter will be sent to each participant. During the third summer, all 60 participants will attend a two day workshop on clinical application of new genetics information and technology. Participants' shared experiences with and recommendations about integrating genetics content into nursing curriculum will be consolidated and submitted to a peer reviewed academic nursing journal.

The purpose of the Newborn Sequencing In Genomic medicine and public HealTh (NSIGHT) program is to explore, in a limited but deliberate manner, the implications, challenges and opportunities associated with the possible use of genomic sequence information in the newborn period. Funds will be used to stimulate research in three component projects specifically applicable to newborn screening: 1) Acquisition and analysis of genomic datasets that expand considerably the scale of data available for analysis in the newborn period. 2) Clinical research that will advance understanding of specific disorders identifiable via newborn screening through promising new DNA-based analysis. 3) Research related to the ethical, legal and social implications (ELSI) of the possible implementation of genomic sequencing of newborns.

Most, if not all, human diseases have one or more genetic factors that contribute to cause, likelihood of occurrence, severity, and response to existing or experimental treatments. There is a general perception that the ability to define a person's genetic makeup will lead to better health, improved treatments and a better understanding of risks to other family members. However, many genetic technologies increase uncertainty and confusion in the minds of patients, relatives, doctors, health insurers and others. The Penn CEER will define these issues better and offer suggestions for reducing the problems of uncertainty. The overall goal of the Center of Excellence for Ethical, Legal and Social Research at the University of Pennsylvania (Penn CEER) is to develop tools that will help consumers, professionals, policy makers and insurers understand and cope with the scope of certainty and uncertainty that genetic technologies engender. We propose to establish three cores to support transdisciplinary ELSI research and plan to study three situations at the outset. The initial studies will be: 1) To explore the evolution of prenatal screening for Down syndrome and cystic fibrosis carrier screening through a collaboration between historians of science, medical anthropologists, reproductive geneticists, prenatal care providers and women of reproductive age; 2) To utilize the Penn Center of Excellence for Hereditary Hemorrhagic Telangiectasia to explore the impact of presymptomatic molecular testing on the economics of caring for people at risk, and patient and provider perceptions of the utility of and barriers to testing; and 3) To follow a cohort of African-American (and other minority) women who have been counseled for testing of BRCA1 and BRCA2 to assess the longer-term psychological, social, and medical impact of risk counseling and genetic testing on themselves and their family members, with a focus on uncertainty. As part of the first two projects, group deliberations in real time will be facilitated by our investigators in the Annenberg School for Communication to explore public perceptions about the results of the formal investigations. The results of each of the three initial projects, and additional studies supported by the CEER, will be considered for dissemination through the Research-to-Policy Core, directed by colleagues in the Leonard Davis Institute of Health Economics. The Training Core of the Penn CEER will provide postdoctoral stipends, through a competitive process, which will prepare fellows to obtain further funding to develop a career in ELSI research. Additionally, the Penn CEER will serve as a resource for other Penn faculty, for other CEERs, and for individuals, volunteer support groups, payers of health care services and investigators, for educating about the implications of genetic technologies in terms of the realms of certainty.

In 1992, the NRC published 'DNA Technology in Forensic Science.' It was immediately recognized as the consensus of scientific opinion for determining the admissibility of DNA typing as evidence and for specifying statistical approaches for interpreting this type of forensic information. However, the report did not quell debate over the statistical evaluation of forensic DNA evidence. Some scientists have been critical of the conservative statistical approach in the report, and forensic scientists have claimed that ambiguities of language permit lawyers to use the same evidence to arrive at very different conclusions. In the mean time, new evidence and analyses have been accumulating, some of it in response to recommendations in the report. To take advantage of this new information and to help resolve the debate, the NRC proposes to form a committee of experts to perform a study addressing unresolved issues in the statistical evaluation of DNA forensic evidence. The committee will consist of experts in molecular biology, statistics, population genetics, and other appropriate areas of expertise.

Learning more about the human microbiome is likely to change the way medicine is practiced. It may also have implications for our society and our legal system and important implications for how we conceive and address the ethics of medicine and biomedical research. The goal of our project will, therefore, be identifying the ethical, social, and legal implication raised by the study of the human microbiome so as to provide insight and guidance for scientists who will be engaged in the work and members of our society who will be asked to cooperate in the studies and to live with the consequences. Our project will bring together an interdisciplinary team of 27 health professionals, scientists, and scholars from the humanities and social sciences to explore key issues through an intense process of mutual education, group discussion, consensus formation, writing, critiquing, and confirming our views. With that background we will go on to engage a broader community in a series of discussions of the topics. This series of Community Conversations on Developing Science will be designed to provide skill-based education to our audience, to engage participants in a dialogue about the issues, and to elicit their views in a process that could be called "community consultation." Combining what we learn from our group's research and discussions with the input that we gather from community consultation, we will prepare a volume for publication on the ethical, legal and social implications of the human microbiome and a set of materials to be used by others to inform scientists and our society about these matters. The working hypothesis of our project is that the human microbiome may or may not raise entirely unique issues, but that considering theoretical issues from the vantage point of the human microbiome will allow us to reexamine policies and positions in a new light. We will be trying to locate our understanding of the microbiome within the existing rich and intricately textured social fabric by identifying relevant models and points of comparison for grounding our responses. Seeing issues from the new vantage point of research on the human microbiome will spur us to ask and answer questions about the conceptual foundation of accepted principles and distinctions, about the relative importance of previously accepted commitments, and about how they fit within the warp and weft of two broadly shared values: individual liberty and the social good. We envision several distinct ethical, legal, and social domains in which research on the human microbiome is likely to have significant implications: human subject research; sample banking and biobanking; public health; privacy; property and commercialization; personhood, personal identity, and normalcy. PUBLIC HEALTH RELEVANCE: The human microbiome is a factor in many diseases. Learning more about it through sample banking and translational research is likely advance healthcare through personalized medicine and to have an impact on public health by improving our capability in disease prevention, surveillance and tracking. Research on the human microbiome will also have repercussions for our society and our legal system and important implications for how we conceive and address the ethics of medicine and biomedical research.

Psychiatric genetic research (PGR) holds great promise for preventing, understanding, and treating neuropsychiatric disorders - a source of immense societal burden and personal suffering. Such research poses many ethical challenges, and failure to perform systematic study of the ethical issues surrounding PGR may threaten societal acceptance of this important scientific work. To date, NIH has not funded any work on PGR that focuses on collecting empirical data about ethical issues. To remedy this gap, we will involve well-established, transdisciplinary collaborative researchers at two sites with a national Scientific Advisory Board and a national Stakeholder Advisory Board to achieve 2 Aims: (1) to understand how 6 key stakeholder groups view important ethical considerations and safeguards in psychiatric genetic research, and (2) to develop and test a specific method for enhancing the research ethics skills of psychiatric genetic researchers and institutional reviewers of research. In the Developmental Phase, we will conduct focus groups with 100 lay stakeholders at Med Coll of Wisconsin & U of New Mexico SOM, and we will conduct key informant interviews with 20 professional stakeholders nationwide. To achieve Aim 1, we will conduct 2 hypothesis-driven mainly quantitative surveys. Project 1 will used structured interviews to collect survey data at both sites from 120 mentally ill people, 120 family members of people with mental illness, and 120 healthy people. Project 2 will be a national Web-based survey of 120 psychiatric genetic investigators, 120 IRB leaders, and 120 IRB members. Both empirical survey projects will assess ethical issues in psychiatric genetic research, emphasizing participant-oriented safeguards (i.e., consent, confidentiality, & genetic counseling) & investigator- and institutional-oriented safeguards (i.e., institutional review, conflict of interest management, tissue/sample retention, & community consent). To achieve Aim 2, we will perform a randomized controlled trial to evaluate a Web-based ethics educational module to enhance 80 researchers' and 160 research reviewers' abilities to identify, analyze, and manage PGR ethics issues. We suggest that evidence-based ethics inquiry for PGR will displace bias and fear in shaping scientific practices and public policy. Our proposed endeavor will generate new knowledge for wide dissemination and publication that can inform future evidence-based PGR ethics guidelines and generate further empirical ethics research on PGR.

The focus of this project is the question of whether couples have the right to use genetic information about their potential offspring and whether they have the right to avoid using such information. That is, to what extent do the ethical and legal concepts of procreative liberty entitle individuals to use and to ignore genetic knowledge in reproductive decisions at prematurity, preconception, preimplantation, and prenatal stages of decision making? To what extent can physicians, genetic counselors, or the government force or constrain an individual's reproductive choices? For the first time, this study will analyze the rights to ignore genetic information based on the theory of procreative liberty, taking issue with the existing state programs that strongly encourage or compel prenatal testing to avoid handicapped births. Based on Robertson's previous work exploring the ethical and legal meaning of procreative liberty, the emphasis of this project will be on legal doctrines and standards. The research methodology includes library and office study of relevant literature, analysis of court cases and statutes, and conferring with knowledgeable persons. Through publications in leading journals of diverse fields, this project will equip professionals to respect client wishes and make public policy for the use of genetics in reproductive decisions.

The purpose of this project is to produce several professional articles that identify and analyze the ethical, legal, and social issues that surround screening and altering human embryos, thus helping society and relevant decision-makers come to grips with these issues. Year 1 of the project will focus on embryo screening as a form of negative genetic selection, and its use in screening embryos for transfer based on reasons other than avoidance of severe genetic disease, i.e., for susceptibility mutations, for HLA matching, for gender, and for non-medical traits. Year 2 will then address the ethical, legal, and social issues that arise in positive genetic selection by genetic targeting of embryos. It will explore whether prevailing conceptions of procreative and family liberty include the right of prospective parents to alter or modify the genome of offspring for medical or non-medical purposes.

Genetic counseling provides the translational link between the new technologies of testing and the ability of individuals to engage in a process of informed decision-making. The dense and abstract nature of this information, coupled with the heightened anxiety of uncertainty and disease vulnerability that it suggests, can be overwhelming to counseling clients -- both cognitively and emotionally. Outcome studies over the past 20 years have found that a significant proportion of information is misunderstood or poorly recalled; indeed, some investigators have warned that the genetic counseling experience may be a significant psychological stressor increasing rather than diminishing disease anxiety. Despite the critical role of the counseling process to client outcomes, few outcome studies have addressed the interactive verbal and emotional processes that comprise the communication of counseling sessions. Furthermore, ethnic minorities and low literate populations are largely underrepresented among users of genetic counseling services and little is known about how to best serve these populations. The current proposal is a two-phase study designed to address these critical issues. In Phase 1, 200 genetic counselors will be recruited from meetings of the National Society of Genetic Counseling (NSGC), or through regional centers, to be videotaped while interviewing trained simulated clients seeking services related to either a) prenatal test counseling for advanced maternal age and a positive family history for cystic fibrosis, or b) susceptibility testing for BRCA1 and BRCA2 gene mutations. Simulated clients who are African American or Caucasian females will be used in interviews singly or accompanied by a male simulator acting as the client's spouse during the session. Phase 2 of the study recruits 800 subjects from ethnically, geographically, and educationally diverse populations to view the videotaped counseling sessions while imagining they are the client or the spouse being counseled. In this way, the subjects will act as analogue clients (AC) to provide a proxy for client satisfaction with the interpersonal and informational aspects of the counselor's communication, comprehension and recall and measures of anxiety.

The goal of this revised proposal is to illuminate the relationships between genetic researchers and racial/ethnic groups. Specifically, it seeks to understand how and why investigators link genetic diseases to named populations; how community organizations respond to genetic research and disease linkages; and to stimulate a dialogue between genetic researchers and community organizations on social risk, community consultation and informed consent. Four diseases that have been closely linked to named populations will be the main focus: Tay-Sachs disease, sickle cell anemia, hereditary prostate cancer, and BRCA-related hereditary breast cancer. The products of the project?s comparative approach will include materials that inform both researchers and community organizations about the implications for each of working together and of using racial and ethnic variables in genetic research.

Dr. Rothschild will complete part three of her book in progress, Engineering Birth: Human Perfectibility and the Technological Dream. The project will evaluate the bioethics and feminist literature relevant to the book's central thesis: as the new reproductive technologies interact with values and beliefs about human perfectibility, norms are being set for the 'perfect child,' recalling, yet transforming, an old ideology. The book asks why, even as the bioethics and feminist literature invokes the possibility of creating new or improved human beings, does much of this work still fail to discuss how standards are being set, the criteria themselves, and what the meaning might be for the future direction and use of such reproductive research. The project will argue that these perspectives can play a positive role in integrating ethical perspectives and in setting frameworks for meaningful dialogue between ethical evaluators and those who pursue, apply, and experience scientific and technological research.

The proposed research is a comprehensive assessment of the ethical, legal and social implications of non-forensic identity testing, with a special focus on implications for families. The research will address the following: —> different philosophical and ethical perspectives on parenthood and the parent-child relationship; —> the conceptual underpinnings of the law relevant to the family; —> the historical roots of different conceptions of the family and the demographics and economics of the family; —> empirical evidence concerning the effects of social patterns and family structures on development and well-being; —> the significance of genetic parentage and lineage in different subcultures; —> identity testing and the media; —> existing legal frameworks including areas of significant variation; —> trends in family law and the adequacy of the developing law to address the ethical and social implications of new genetic knowledge; —> the use of ad litems and alternative dispute resolution in conflicts about the testing and parentage of children; —> the implications of identity testing for other areas of law that concern the consequences of family relationship and the potential for genetic privacy laws to fill gaps in privacy protection; —> incentives created under existing and possible legal regimes; —> standards governing laboratories performing identity testing; —> laboratory quality issues; —> laboratory privacy issues; —> options for integration of counseling with testing. The research design consists of philosophical, social science, and legal methods of research and analysis. Internet searches and a survey of laboratories would supplement traditional library-based research. In keeping with a commitment to interdisciplinary work, leading experts in the relevant fields would present papers for discussion and critique at a series of multidisciplinary meetings. Selected papers would form the basis of a scholarly book. Other outcomes would include a set of recommendations on legislation and other forms of regulation, guidelines for professionals, articles in scholarly journals and professional publications, and dissemination of findings through the popular media. All lines of research would culminate in a major conference in the fall of 2002. The conference would be open to the public and structured to attract a diverse audience.

The proposed research will study whether there should be any limits placed on life insurers' use of predictive genetic information in risk classification or medical underwriting. The research will focus on the following issues: —> the current state of the science on the use of predictive genetic information in mortality risk calculations; —> the statutory and case law addressing actuarial fairness in life insurance; —> existing and proposed legislative activity regulating life insurers' use of genetic information (including life insurers' ability to request or require genetic testing); —> the case law allowing individuals to challenge their denial of life insurance coverage or premium rates under Title III of the Americans with Disabilities Act; —> antitrust and other legal constraints on cooperation among life insurance companies with regard to their use of predictive medical information in underwriting; —> consumer attitudes toward life insurance and genetic information, including consumer perceptions of adverse selection pressures based on predictive genetic information; —> comparative law perspectives on genetics and life insurance; —> the moral mission and social function of life insurance; and —> the development of policy options and possible legislative and regulatory strategies. The research design will consist of traditional legal, medical science, social science, and bioethics research and analysis. A detailed, national consumer survey instrument will be prepared and administered by a specially selected contractor. Leading experts in the fields of life insurance, economics, genetics, insurance law, comparative law, and philosophy will research and write a chapter on their respective topics in advance of a conference in Houston, Texas. Additional invited guests at the conference will be other experts as well as representatives of the insurance industry, consumers, elected officials, and regulatory bodies. The conference will focus on building consensus and advancing understanding in areas of disagreement. The chapters, as well as the positions developed at the conference, will form the basis of a book to be published by a major publisher.

The purpose of this project is to support a coordinated and wide-ranging research project focusing on the legal and ethical issues raised by the human genome project. The nation's leading experts in the fields of genetics, law and ethics will be assembled to study the long-term legal and ethical implications of the genome project. Each expert will be assigned a topic and asked to produce a manuscript identifying the emerging issues and discussing legislative priorities and possible solutions. In March 1991, the experts will assemble in Houston for a conference to present and discuss their research findings. The conference proceedings will be published with copies distributed to members of Congress, officials of government agencies, and other interested individuals and organizations. Ten of the conference panelists will prepare more detailed legal articles to be published in October 1991 in a special genome project symposium issue of the Houston Law Review.

The overall objective of the proposed research is to study the ethical, legal, and social implications of drug responsive genetic variations, especially where significant differences have been found based upon race, ethnicity, and gender. The research will focus on four elements: —> the current and potential future use of pharmacogenomics to establish the safety and efficacy of certain drugs; —> the impact of pharmacogenomics on the legal standards applicable to the recruitment and use of human subjects in drug trials, including issues of diversity, informed consent, and confidentiality; —> the role of pharmacogenomics in providing access to appropriate health care for certain groups and the anticipated response of managed care organizations to pharmacogenomic-prescribed drugs, including issues related to the experimental nature of pharmacogenomic-based drugs, coverage mandates, and cost savings; and —> the impact of pharmacogenomics on the legal and ethical standards of care applicable to physicians and pharmacists in advising patients about genetic intolerance to or compatibility with certain drug therapies. The research design will consist of traditional legal, medical science, social science, and bioethics research and analysis. The results of the research will be used to: —> conduct a survey to determine how various racial and ethnic groups view pharmacogenomics and what they would need to know before submitting to a diagnostic test or agreeing to take drugs based upon drug responsive genetic variation; —> host a conference that brings together the key players to examine and discuss the ethical, legal, and social implications of pharmacogenomics; —> publish a book that discusses the implications of pharmacogenomics, especially as it relates to race, ethnicity, and gender, and that sets forth guidelines for the proper use of the science; and —> publish two papers, one on the future of the science and one on the survey results.

The National Human Genome Center at Howard University seeks to establish the Center on Genomics and Social Identity in the African Diaspora. The mission of the proposed CEER is to increase understanding of the complexities surrounding social identity within the African Diaspora and its interface with genomics in the improvement of health and well-being. Specifically, the CEER will focus on how individuals and communities within different regions of the African Diaspora conceptualize various aspects of social identity and how these perceptions influence and/or interact with interpretations, attitudes, and behaviors regarding genetics/genomics and health in general. The research of the Center will be linked to genomic/biomedical research with the ultimate goal of facilitating improved health and well-being of African Diaspora populations, in particular, and humanity as a whole. Prior to the preparation of a P50 Center grant, however, it will be necessary to begin to build the infrastructure required for Howard to acquire and sustain the Center. The three-year planning process, presented in this P20 exploratory grant, includes the involvement of a multidisciplinary cadre of internal and external experts to advise, consult, and assist with its implementation, leading to the preparation and submission of a competitive P50 after two years. The Specific Aims of this P20 proposal are to: 1) Establish and prepare an interdisciplinary team of investigators at Howard University to conduct state-of-the-art ELSI research and other activities focused on the application of social identity to genomics, health, and well-being in African Diaspora populations; 2) design the three major components of the P50 program plan - research, training, and public policy and information dissemination; and 3) identify and/or begin to develop core resources to support the activities of the CEER.

Personal genetic and genomic information is becoming more widely available and affordable, generating increased discussions on the merits and dangers of direct-to-consumer (DTC) genetic testing and appropriateness of using personal genetic information in various contexts (e.g. clinics, research laboratories, courtrooms, and classrooms). While attention has focused predominately on health-related testing, conversations about DTC genetic ancestry testing and information are intensifying as well. Scholars have highlighted scientific limitations and potential ethical, legal, social, political, and psychologicl implications of genetic ancestry testing and information; however, there is a dearth of empirical data on (1) perceptions and experiences of participants in genetic ancestry testing and (2) public awareness of genetic ancestry tests. The bundling of genetic ancestry testing with health-related genetic testing by some DTC companies raises questions about perceptions of the relationship between ancestry and health. Moreover, genetic ancestry testing exacerbates concerns about misrepresentation of the relationship between ancestry and race; race and genetics; and genetics, ancestry, race, and disease risks. The central objective of this project i to broaden current understanding of the public's comprehension of, attitudes toward, and experiences with genetic ancestry testing and information. The specific aims are to 1) assess the long-term impact of genetic ancestry testing on prior participants in ancestry testing; 2) examine the conceptions and implications of genetic ancestry testing in a community-based setting, and 3) explore perspectives of the general public on genetic ancestry testing and the value of genetic ancestry information in understanding ancestry, race, identity, and health. We will use a mixed methods approach, including (1) in-depth interviews with prior research participants who had genetic ancestry testing six to eight years ago in four US cities; (2) in-depth interviews and focus groups with leaders and members of Freedmen and Tribal communities in Oklahoma; and 3) a national survey on public awareness and perceptions of genetic ancestry testing and information. Empirical data from this study will facilitate a deeper understanding of public perceptions of and responses to genetic ancestry testing and information. The findings will guide development of strategies for enhancing public education about the meaning and implications of different types of genetic information; will be valuable in shaping standards for DTC genetic ancestry testing companies; and will inform policies regarding the regulation and use of genetic ancestry testing and information in other contexts. PUBLIC HEALTH RELEVANCE: Although genetic ancestry testing is typically viewed as "non-health-related" or "recreational", limited data indicate that some consumers seek genetic ancestry information for health reasons. This study will provide individual, community-based, and national data on personal, demographic, cultural, social, and other factors that might influence consumer knowledge, attitudes, behaviors, and experiences concerning genetic ancestry testing and personal genomics as a whole. These findings will inform recommendations for more comprehensive oversight of DTC genetic services, thereby improving accountability in the personal genomics industry.

A significant proportion of patients who pursue testing for BRCA gene alterations are of reproductive age. Many are actively engaged in decisions about family planning or will be in the future. A prime concern of this population is minimizing the impact of hereditary cancer on their children. Genetically-enhanced assisted reproductive technologies (ART), such as preimplantation genetic diagnosis (PGD), as well as prenatal diagnosis (PND) followed by consideration of selective abortion, may enable individuals and couples to avoid passing genetic mutations on to their children. However, their use for later onset, potentially treatable or preventable conditions such as hereditary breast/ovarian cancer, raises new ethical and social questions and concerns. The objective of this investigation is to explore BRCA1/2 mutation carriers' attitudes towards the use of PND and PGD. The investigators seeks (1) to develop a patient-centered understanding of the benefits and drawbacks of PND/PGD, (2) to explore the ethical and social acceptability of each technology to screen for BRCA1/2 mutations, and (3) to elicit patient opinions about the presentation of ART in genetic counseling. Approximately 30 BRCA mutation carriers of reproductive age will be presented a brief, standardized educational presentation on reproductive options for BRCA gene alteration carries, including discussion of PND/PGD followed by an in-depth, semi-structured interview addressing childbearing plans, and attitudes towards the use of PND and PGD to screen for BRCA gene alterations. Participants will also complete a brief questionnaire before and after the education session to assess awareness (pre) and understanding of core concepts (post). A team of qualitative research experts will analyze interview data using grounded theory techniques. Findings will contribute to the current ongoing debate among clinical genetics and associated professionals regarding the role of ART in managing the impact of BRCA1/2 alterations on patients and their families. At present, there is considerable interest and concern about the integration of ARTs and genetic technologies, particularly PGD of late onset, treatable disease (cancer) in the United States, where the regulatory environment (or lack thereof) raises special concerns. Members of the research team have been active in the past decade in building consensus and shaping policy regarding use of genetic testing for cancer risk. Our future plans for research include a parallel study of genetic counselor's attitudes regarding PND/PGD for BRCA, assessing their experience with patients considering these procedures and their ideas about whether and how reproductive options should be integrated into genetic counseling sessions. The current study, coupled with a complementary study of genetic counselors, will be disseminated through the team's participation in key organizations such as the American Society of Human Genetics (ASHG, National Society for Genetic Counseling (NSGC), American Society for Clinical Oncology (ASCO) and others that have a stake in developing professional and informed consent guidelines regarding the use of ART for adult onset cancer syndromes. PUBLIC HEALTH RELEVANCE: The study aims to elicit BRCA1/2 gene mutation carriers' attitudes towards the use assisted reproductive technologies (ART) to screen for BRCA mutations, focusing specifically on beliefs about their ethical and social acceptability. This study meets ELSI's goal of studying the translation of genetic technologies into improved health. Findings from this study will inform development of professional guidelines regarding the use of genetically-enhanced ART for adult onset hereditary cancer syndromes, and may provide physicians, genetic counselors and mental health professionals with a template for discussing deeply personal and highly emotional decisions about assisted reproduction.

Advances in psychiatric genetics are likely to offer major diagnostic and therapeutic benefits, but also legal and social-related risks, to individuals who were diagnosed with, or have a proclivity for, psychiatric disorders. In response, courts and policy-makers will have to ensure that psychiatric genetic data are used to promote, and not to obstruct, equality, justice, and social inclusion. However, few studies have queried how such data might impact judicial decision-making; none have explored this question in civil proceedings about parental rights, children's education, and responsibility for behavior in tort. This K01 proposes to study the impact of psychiatric genetic data on these 3 prominent areas of litigation and its relationship to stigma to better understand the implications of new discoveries in psychiatric genetics for law, society, and individual rights, and to inform policy-makers about this knowledge as they devise responses to these advances. The study's aims are: 1) To survey appellate court decisions in family law, education, and torts to determine the extent to which courts are considering psychiatric genetic data, and how they use such data in their decisions; 2) To investigate judicial views about the use of psychiatric genetic data and how such data may affect judges' and public perceptions of parental capacity, educational decisions, and civil responsibility for behavior in tort cases; and 3) To assess the association between psychiatric genetic data and stigma by studying if such data affect judges' and public perception of broader civil legal incapacity and treatment options, and the relationship to judicial bias against persons with psychiatric conditions. For Aim 1, I will use a mix of qualitative legal analysis and empirica methods. For Aim 2, I will use a vignette methodology, administered in 3 waves, with samples, respectively, of family court judges, parents, and state trial court judges and the jury-eligible general population. For Aim 3, I will use existing legal and sociological literature on psychiatric related stigma to develop measures of explicit stigma, and a computer-based measure designed to detect implicit bias, administered as part of the vignettes, to assess the relationships among psychiatric genetic data, judicial decisions, and stigma. Findings will be published in peer-reviewed medical, psychological and policy journals. Complementing these studies will be an intensive training program comprised of didactic courses, tailored training, clinical exposure at the NY State Psychiatric Institute, and mentored experience. My primary mentor Dr. Appelbaum, co-mentors Drs. Link and Ottman, collaborator, Dr. Phelan, biostatistician, Dr. Goldsmith, and consultant, Dr. Parens will train and monitor my progress as I attain my training goals to: 1) develop the skills necessary for conducting empirical research; 2) learn about the clinical aspects of psychiatric disorders; and 3) build and expand national and international professional collaborations with scholars in psychiatry, genetics, social sciences, bioethics, and law. This training will culminate in R01 grant submission to further study the intended and unintended consequences of psychiatric genetic data on law, equality, and social inclusion.