ELSI Publications and Products Database

Completing the Human Genome and the Human HapMap Projects has enabled studies associating genetic variation with complex diseases such as various cancers, coronary artery disease, and diabetes. This has led to the emergence of direct-to-consumer testing companies offering genomic profiling to inform individuals about their risk for dozens of diseases and traits. Such testing is being offered with the assumption that identification of an increased risk could lead to preventative measures to reduce a person's risk for developing disease or to improve disease outcome. Although personalized medicine is gaining clinical and policy attention and appears to be technically feasible, little is known about the public's understanding and perceptions of such care, nor about their assessment of its risks and benefits. We are proposing a project that capitalizes on the expertise of researchers at the University of Pennsylvania to investigate public response to personalized medicine. The proposed study will take advantage of the Coriell Personalized Medicine Collaborative (CPMC) conducted at the Coriell Institute in Camden, NJ. The CPMC aims to determine the clinical utility of personalized medicine by offering participants a personalized genomic risk assessment for a variety of diseases and collecting data on health outcomes. While not a direct-to-consumer company the CPMC study offers a unique opportunity to assess the social, behavioral, and ethical implications of direct availability of personalized genomic risk assessment. The specific aims of our project are to: 1) Assess motivations and perceived utility of personalized genomic risk assessment among individuals who express interest in the CPMC; 2) Explore participant understanding of their results, the use of the information, and educational needs; and 3) Develop policy recommendations for the ethical offering of personalized genomic disease risk assessment. We will use a mixed methodology for addressing these study aims. For specific aim 1, we will survey approximately 1000 individuals who register for a CPMC informed consent session, regardless of whether they actually attend or provide a sample for testing. For specific aim 2, we will interview 60 CPMC participants 3-6 months after they receive their results. For specific aim 3, we will work with members of the research-to-policy core of the Penn Center for the Integration of Genetic Healthcare Technologies (Penn CIGHT) to develop and disseminate policy recommendations for the responsible and ethical offering of genomic tests that takes into account the misperceptions, concerns, and educational needs of consumers.

Many genotype and genome-wide association studies (GWAS) are conducted using a phenotype-driven approach: cases and controls are identified based on the presence or absence of a particular condition and analyses are undertaken to identify gene variants associated with that condition. The inverse--a genotype-driven approach--is receiving increasing attention as another powerful tool for understanding the impact of genetic variation. Cases and controls are defined among existing study populations based on the presence or absence of a particular genotype, and in-depth phenotyping is then conducted to understand the relationship between observable traits and the gene variant of interest. Enabling such a bottom-up approach to identifying and recruiting participants for follow-up studies could significantly advance the pace of genomic research by expanding the existing mechanisms for studying the functional significance of human genetic variation. Such approaches, however, present ethical challenges that have not been fully addressed. Genotype-driven recruitment is inextricably linked to the complex and much-debated issue of disclosing individual research results: when individuals are recontacted, what if anything should they be told about the genotype that led to their being recontacted? There is a fundamental tension between avoiding the introduction of potentially unwanted and uncertain information, and avoiding deception when explaining to prospective participants the purposes of the research and why they are being approached for participation. The purpose of this project is to develop evidence-based guidelines for addressing the ethical issues that arise in genotype-driven recontact and research recruitment. Specifically, this project involves 3 Clinical and Translational Science Award (CTSA) sites that will collaborate to: —> Explore the perceptions of research participants who have experienced genotype-driven recontact for further research participation. —> Investigate IRB chairs experiences, opinions, and concerns about genotype-driven recontact and research recruitment. —> Formulate guidelines to assist IRBs and researchers in identifying balanced approaches to genotype-driven recontact and research recruitment.

Researchers and institutions are ethically and legally obligated to safeguard research participants' privacy and the confidentiality of their data. Indeed, the success of the research enterprise depends on the public's confidence that private information will be vigorously protected. Certificates of Confidentiality, authorized by federal law, are an important tool for meeting this expectation. By shielding researchers and institutions from forced disclosure of identifying data in any legal proceeding, Certificates are intended to facilitate participation by reassuring prospective participants about the security of their information and thus allow research to proceed on sensitive topics critical to the public's health. In fact, Certificates are commonly believed to offer near absolute privacy protection. Their use has recently been promoted in the context of burgeoning efforts to build large-scale research platforms and new requirements for an unprecedented degree of data sharing. There is, however, a remarkable paucity of evidence upon which to base conclusions about the strength of the protection Certificates afford. A recent case that reached the North Carolina Court of Appeals suggests that the full legal effect of a Certificate is unclear. Empirical data are needed concerning when, why, and how Certificates are used, including stakeholders' understanding of the protection they provide and how that affects their assessment of research risk. The perceptions of Institutional stakeholders, including IRB chairs and institutional legal counsel, are particularly important given the central role they play in developing and implementing policies and practices for recommending or requiring that a Certificate be obtained. The purpose of this study is to examine how research institutions understand and use Certificates in protecting research participants and the role they play in assessments of risk. Specifically, the aims are to: Assess IRBs' use and understanding of Certificates and the role of Certificates in risk assessments Explore institutional legal counsel perceptions of the protections Certificates provide and their institution's experiences with legal demands for identifiable research data Analyze the legal foundations for Certificates and comparable confidentiality protections We will form a multidisciplinary Advisory Panel to provide expert guidance throughout the life of our study. At the conclusion of our research, we will hold an in-person meeting with the Panel to review our findings; identify policy priorities that could strengthen the protection Certificates afford, enhance stakeholders' understanding of Certificates, and promote the appropriate use of Certificates; and elucidate additional research needed to optimize the role of Certificates in protecting research participants. PUBLIC HEALTH RELEVANCE: Certificates of Confidentiality are an important tool for meeting researchers' and institutions' ethical and legal obligations to safeguard research participants' privacy and the confidentiality of their data. There is, however, a remarkable paucity of evidence upon which to base conclusions about the strength of the protection Certificates afford. The results of our study will provide empirical data concerning when, why, and how Certificates are used, including institutional stakeholders' understanding of the protection they provide and how that affects their assessment of understanding of Certificates and promote the appropriate use of Certificates. They will also provide a foundation for future research to aid longer term policy development that optimizes the role of Certificates in protecting research participants

A range of potential solutions has been proposed to the confidentiality challenges in genome research and how best to proceed in this era of "big data" is not known. Some advocate measures to further restrict access to genomic information. Others argue for strengthening laws that prohibit misuse. In the meantime, the strengths and weaknesses of the current "web" of protections created by federal and state law are poorly understood. In addition, emerging models are breaking from tradition by ceding control to participants over whether, with whom, and for what purposes their data are shared. There is an urgent need to better understand the existing constellation of legal protections, how they apply to a swiftly evolving research environment, and how best to inform prospective participants about the extent and limitations of these protections in different contexts. The objective of the proposed research is to gather empirical data regarding the actual scope of the confidentiality protections applicable to genome research (beyond basic security measures), as well as how these are and should be described to prospective participants. To achieve this objective, we will: (1) Conduct in-depth qualitative interviews to explore thought leaders' views of risks, benefits, and confidentiality in genome research; (2) Carry out extensive analysis of the legal tools for protecting confidentiality in genome research (e.g., genetic anti-discrimination laws, data sharing policies and regulations), including their application to realistic research scenarios encompassing both current and evolving approaches to control over data sharing; and (3) Assess current consent language and develop flexible model language that simply and accurately describes the confidentiality risks and protections in genome research. The conduct of these aims will be highly integrated, with each one informing and being informed by the others. The expected outcome will be an extensive body of complementary, high quality data concerning the strengths and limitations of legal means to protect confidentiality in genome research-including in the context of emerging approaches to control over data sharing-and how the risks and protections both are and should be described to prospective participants. These data will further support several important areas of future research, including investigation of participant opinions and understanding, genome researcher perspectives, and rigorous empirical assessment of our model consent language. PUBLIC HEALTH RELEVANCE: Genome-scale research, together with widespread sharing of the amassed data, provides unparalleled opportunities to learn more about human health and disease. Despite careful attention to data security and policy approaches to protecting confidentiality, however, resourceful investigators continue to demonstrate the ability to discover the identities of research participants whose genomic data had otherwise been considered "de-identified." The long-term goal of the proposed research is to support the development of evidence-based approaches to confidentiality in genome research that enhance public trust and facilitate scientific progress.

One of the most important questions raised by the ongoing achievements of the Human Genome Project is how this new biological knowledge - and the powers it confers - will affect our identity and selfunderstanding as human beings. This book project focuses on one key aspect of this complex issue: exploring the extent to which human identity can be reconciled with deliberate design or partial redesign. The author proposes to shed new light on this question by comparing the debates surrounding two areas of scientific innovation that are not normally associated with each other, but that are in fact deeply related: the enterprise of human genetic intervention and the enterprise of building intelligent machines. Both these enterprises entail "pushing the limits" of traditional concepts of what it means to be human; and both ultimately confront their makers with the same core "family" of questions: What are the defining features of human personhood? To what extent can those features be modified or extended, before human personhood begins to break down? Can some (or all) of those features find embodiment in an entity other than a human being? These kinds of questions are no longer the sole province of science fiction writers, but have been taken up with increasing seriousness by mainstream scientists and technologists, as well as by a wide array of "science watchers" in academia, legislative circles, and the news media. Through documentary research and interviews, this project aims to deepen our understanding of the history and sociology of the debates surrounding these powerful new technologies, electro-mechanical and biological, that are perceived as destabilizing human identity. The intended audience for the book is a broad one: scientists and technological practitioners interested in the social and cultural reception of their research; legislators and other policymakers with a stake in the governance of science; general educated readers who are concerned about the role of science and technology in shaping our collective future.

The directors of genetic counseling training programs met to update graduate education curricula. The focus was threefold: ethnocultural issues; ethical, social and legal implications of the HGP; and strategies to address the shortage of genetic counselors. Enhancing graduate education is one critical means to meet the anticipated expansion of the roles of genetic counselors. The NSGC is the professional society which represents the vast majority of genetic counselors and is committed to maintaining a high standard of care. The development of curricula which can be widely implemented, as well as endorsed guidelines for training, will reach a large constituency of counselors-in-training and will have widespread impact on the field of genetic counseling. The community-at-large will directly benefit from comprehensively trained counselors, new models of service provision and broader appreciation for the ramifications of genetic testing.

This project addresses the ethical, legal, and social implications of Alzheimer's disease (AD) genetics from the critical perspective of a group at high risk for the disease: currently unaffected relatives in families with AD. The applicants--Mass General Hospital/Harvard Medical School and the University of Alabama--have been working together since 1990 as part of the NIMH Genetics Initiative to identify families with Alzheimer's disease for genetic linkage study. Nearly 350 such families, predominantly affected sibling pairs and over 300 of their unaffected siblings, have been collected. In the present proposal, the two centers will use both qualitative and quantitative approaches to study knowledge, attitudes, and behavior related to genetic studies and genetic testing in the unaffected individuals in these AD families and their primary care physicians, and will develop and pilot educational materials designed to address their needs for genetic information.

Results from several genome-wide association (GWA) studies have recently emerged showcasing the discovery of specific genetic variations found to be associated with several common, complex diseases. Leveraging these findings and fueled by the rapidly decreasing costs of performing genome-wide single nucleotide polymorphism (SNP) scans, a small number of companies have begun offering tests that aim to calculate an individual's risk for these common diseases using this genome-wide technology, direct-to-consumer (DTC) over the internet. While the offering of these tests - both at this stage of scientific discovery and directly to the consumer - has been the subject of much intense controversy, it is nevertheless the case that many individual consumers are purchasing these products. Despite this, however, relatively little is known about the characteristics of consumers of DTC personal genomics services, including why they chose to pursue this type of testing, and perhaps most critically, how they are responding to their results. The Scripps Genomic Health Initiative (SGHI) represents an opportunity to begin to address these questions. The SGHI is a large longitudinal cohort study in which participants purchase the Navigenics Health Compass DTC genomic risk assessment product at a discounted rate and are administered baseline (i.e., pre-risk disclosure), as well as 3- and 12-month follow-up (i.e., post-risk disclosure) web-based demographic, family medical history, and behavioral health assessments. In addition, items pertaining to attitudes about genetic testing and the perceived impact of the results, including distress related to receiving information pertaining to one's genomic risk profile, are administered. The SGHI is, to a large degree, exploratory in that it is one of the first studies to evaluate response to testing among individual consumers of DTC personal genomics services. To date, over 4,000 individuals have enrolled in the SGHI, and although the ongoing recruitment of individuals into the study is currently funded, analysis of the assessment data that is being collected is unfunded. Therefore, we are requesting two years of funding via the NIH Exploratory/Developmental Research Grant Program (R21) for analysis of these data. Our specific aims are as follows: First we will characterize consumers of DTC personal genomics services in terms of their demographics, baseline level of genetic risk for disease, behavioral health characteristics, and attitudes regarding genetic testing. Second, we will assess response to testing among consumers with respect to general anxiety and distress related to testing, perception of new disease risk, changes in health behaviors, and attitudes regarding the impact of results. Third, we will evaluate potential moderators of response to testing, including demographic characteristics, perception of risk, risk estimates reported in the Health Compass, and utilization of genetic counseling services. PUBLIC HEALTH RELEVANCE: The proposed project would leverage data from the Scripps Genomic Health Initiative (SGHI), a large longitudinal cohort study of over 4,000 consumers of GWAS-based DTC personal genomics services (i.e., specifically the Navigenics Health Compass product). We aim to characterize consumers of DTC personal genomics services, as well as assess behavioral and psychological response to DTC genetic testing, including potential moderators of response such as level of genetic risk and utilization of genetic counseling services. At this time there is essentially nothing known about the impact of this technology on consumers despite its relatively wide availability and the fact that many individual consumers have already purchased these products. Thus, the proposed work will provide an initial examination of these important questions to which timely answers are critical given efforts currently underway to determine how best to regulate the sale and use of these tests.

A big data ecosystem is evolving in our society in which people may have, or feel they have, little control over the flow of their personal health information, and thus their privacy. Further, although there has been significant discussion related to big data and privacy at the highest levels of government, there is little consensus among scholars and stakeholders as to what privacy actually is, not to mention a lack of data from individuals as to personal conceptions of privacy. While much has been written about the potential harms of this and the rapidity with which the divide between health-related big data capabilities and privacy controls and protections is widening, we have little systematic knowledge of the nature and impacts of individual-level privacy concerns, and no reliable and valid tools for acquiring such knowledge from patients. The goal of this project is to conceptualize, measure, and understand individual privacy affinities and responses to privacy environments in the context of health-related big data technologies. The primary deliverable of the project will be a psychometrically sound instrument: the Privacy Affinities and Privacy Environment Responses ("PAPER") scale. Privacy has been the subject of several proposed theoretical frameworks in many different fields including philosophy, sociology, and law. Considering privacy from a behavioral and psychological perspective, we propose a preliminary conceptual model in which privacy is a combination of stable individual privacy affinities or predilections and changing individual responses to different privacy environments. We propose a three-phase project using qualitative and quantitative methods: In Phase One, we will refine our conceptual model through comprehensive literature review, individual interviews, focus groups, consultation with experts, and analyses of preliminary data from two previous studies. In Phase Two, we will develop a psychometrically sound instrument to measure individual privacy affinities and privacy environment responses related to personal health data information technologies according to established practices for measuring patient-reported outcomes. We will leverage an established instrument development platform. In Phase Three, we will administer this instrument to an online patient community of over 2,000 individuals. We will explore the relationship between privacy and propensity to adopt health-related big data technologies, willingness to share personal health data for research, and disease type and stage. To accomplish these goals, we have assembled a team of experts in bioethics, law, information and computer science, clinical psychology, medicine and public health, psychometrics and instrument development, privacy theory and technology, online survey research, and health policy. Development of an instrument to assess privacy will catalyze patient- and community-engaged research on this important topic. In turn, this will inform and promote development of transparent, patient- and user-centered privacy policies and practices, which are critically needed at this time of unprecedented technological advancement. PUBLIC HEALTH RELEVANCE: The divide between health-related big data capabilities and individual privacy controls and protections is widening, and we have little systematic knowledge of the privacy concerns of individuals, and no reliable and valid tools for acquiring such knowledge from patients. The goal of this project is to refine a conceptual model of privacy and develop and test a psychometrically sound instrument to measure individual privacy affinities and privacy environment responses with respect to personal health big data

This study will use survey and case study methodologies to examine Academic-Industry Relations (AIRs) in genetics and related fields. Results will contribute to assessment of: 1) how AIRs have evolved since the inception of the biotechnology revolution; 2) current levels of involvement with industry among HGP grantees, geneticists, and other scientists; 3) whether AIRs are likely to enhance the commercial and academic productivity of university investigators (including current or potential HGP grantees), or to reduce communication in ways that may compromise scientific progress and the university environment; and 4) whether industrial relationships among HGP grantees are similar to or different from those in other fields. The study will assess the success of past efforts to manage AIRs, and make recommendations concerning whether new or different policies are necessary to enhance the benefits or contain the risks of AIRs generally, and AIRs among HGP grantees in particular.

Given the current and anticipated capabilities to perform prenatal diagnosis, the medical profession, and society more broadly, must decide how these technologies should be used. Specifically, what prenatal diagnostic tests should professionals offer prospective parents or provide on request? Should there be limits on the tests made available to prospective parents or should choices be unlimited, restricted only by the individual values of informed couples? This project will analyze the literature relevant to the development of professional standards for the application of this technology. Particular attention will be paid to literature from the disability community as well as the broad range of medical and bioethics literature. The principal product of this two year project will be a book titled 'The Transparent Womb: Prenatal Diagnosis and the Biologic Selection of Children.' The book will be written for the educated lay community, as well as for the medical profession and bioethics communities. This project will develop a clear proposal on the appropriate uses of prenatal diagnosis and will foster a broad debate on these important issues.

Newborn screening (NBS) is conducted on virtually every child born in the U.S. primarily through state-based public health programs. Following testing, there is blood leftover on each child that is retained by many state health departments. Residual samples have been used for a variety of purposes including quality assurance for the NBS programs, forensic testing, and for research. Our project will focus on the potential use of residual samples for biomedical research. Many states are experiencing requests from investigators in academia and industry for access to residual NBS samples. Surveys of state programs reveal that there is wide variability among states in how long residual samples are retained and on a variety of other aspects of policies on sample management. As a result of the pressure for access to these samples and uncertainty over best practices in their management, there is a significant demand for guidance on the policy issues. The management of residual NBS samples is complicated by the lack of informed permission for newborn screening in almost all state programs. The lack of effective informed permission for retention and use of the specimens, particularly for research projects unrelated to NBS, raises serious ethical challenges. For both practical and ethical concerns, informed permission for the storage and use of residual NBS samples is not feasible in the foreseeable future under most programs. With this assumption, the broader goal for our project is to assess the feasibility of several methods for obtaining informed public input about sample use in research. While addressing the uses of residual samples is important in its own right, a better understanding of methods to engage the public on NBS issues will be useful for addressing a range of important questions for these rapidly expanding programs. Our proposed project will conduct a comprehensive assessment of policies in the Mountain States region on the management of residual samples. Second, we will compare public attitudes on the retention and research use of residual samples using 3 methods: telephone/paper surveys, focus groups, and internet-based surveys and focus groups using a Knowledge Networks(r) panel. Third, we will organize a working group of regional and national experts and lay individuals to address model policy elements for the retention and use of residual samples and to evaluate methods to obtain informed public input. Given the close working relationship of the primary investigators with the Mountain States Regional Genetics Collaborative, our project will focus primarily on state programs and populations within this region (UT, CO, MT, WY, TX, NM, AZ, NV). However, components of the project will evaluate whether the Mountain States region differs from other state programs and respondents nationally on key issues. We anticipate that our results will have relevance to NBS programs across the country. PUBLIC HEALTH RELEVANCE: The retention and use of residual newborn screening samples by state health departments is an important and potentially controversial topic. This project will conduct interviews and surveys of health department staff and the general public about the retention and research use of residual samples. The project also will compare 3 methods of obtaining public input on this important set of issues. The project is directly relevant to policies in public health departments that affect virtually every newborn in the country.

The objective of this project is to address the content, timing, efficacy, and impact of prenatal education about newborn screening generally and bloodspot sample retention specifically. This project has the following specific aims: Specific Aim 1) To determine what pregnant women, young mothers, and their partners want to know regarding the retention and use of residual bloodspot samples ' Methods include 15 focus groups conducted in five states (NY, CA, UT, MN, WA). Specific Aim 2) To create multimedia educational tools to be used in the prenatal care environment that will provide basic information about NBS and the core information determined through Specific Aim 1 about residual sample retention and use. ' Methods include the development of state-of-the-art video, printed materials, and web-based tools Specific Aim 3) To determine the impact of the prenatal education tool on parental knowledge, attitudes, and decisions regarding NBS services and the retention and use of residual samples. 3a. To determine the impact on knowledge and attitudes about NBS and the retention of residual samples ' Women at 30 - 36 weeks gestation will be provided the educational interventions in the prenatal environment. 1. Intervention Group A will have education provided on the two topics (NBS education only and NBS education plus education on sample retention and use) at separate prenatal visits while Group B will receive this education at a single visit. 2. A control group will receive standard information that is provided to new parents in the OB and/or newborn nursery environments ' Participants will be surveyed at 3 - 6 weeks post delivery about their knowledge and attitudes about NBS and sample retention and use. ' A subset of partners (N=150) will be surveyed at 3 - 6 weeks post delivery regarding their knowledge and attitudes 3b. To determine the impact on parents' decisions regarding NBS services and the permission for sample retention ' Intervention versus control groups will be compared with respect to decisions to opt-out of the retention and use of NBS residual samples and refusals of NBS altogether. Specific Aim 4) To examine the normative/ethical implications of the results of SA 1 and SA3 for the conduct of state NBS programs. Recommendations on the content and timing of parental NBS education will be developed. PUBLIC HEALTH RELEVANCE: Project Narrative Our broad objective is to improve parental knowledge about newborn dried bloodspot screening and the use of residual specimens. We will address the content, timing, efficacy, and impact of prenatal education about newborn screening and sample retention. In this project, we will compare new mothers' and their partners' knowledge and attitudes about newborn screening and residual specimens following an educational intervention for the mothers with the knowledge and attitudes of mothers in a control group who receive information routinely provided in the nursery environment. We also will evaluate the rate and reason parents opt out of newborn screening and retention of the residuals samples.

The University of Utah Center for Excellence in ELSI Research (UCEER) will conduct strategic planning for ELSI research, training and mentoring, and conduct two pilot projects. The focus of the UCEER will be population screening for genetic conditions in the health care of women and children. Our specific focus will be prenatal genetic screening and newborn screening. We will build on our strengths and experience to develop a collaborative, transdisciplinary center for research and training in ELSI issues. Prenatal and newborn screening services impact millions of individuals annually and represent important elements in pediatric and obstetric health care. Specific Aim 1: Develop a Strategic Plan for Transdisciplinary/Trans-institutional Research a) We will organize and coordinate a transdisciplinary team of investigators and support staff across the collaborating institutions; and b) Develop a strategic plan for at least two R0I level projects that addresses cutting-edge ELSI issues in prenatal and newborn genetic screening. Specific Aim 2: Develop a Strategic Plan for a multidisciplinary ELSI Training and Mentoring a) Conduct a needs assessment of faculty and students at the University for education, training, and mentorship in ELSI issues. b) Develop a strategic plan for educational, training and mentoring opportunities. c) Develop a strategic plan for education and scholarship of students from regional underserved communities. Specific Aim 3: Pilot Studies a) To identify how aneuploidy screening information and choices are communicated to couples by providers b) Using the unique resources of the Utah Population Database, we will describe the rates of prenatal screening in the population of pregnant women in Utah. PUBLIC HEALTH RELEVANCE: This project will establish a Center of Excellence for research and training in the ethical, legal and social implications of genetic research. Our proposed focus is consistent with priorities established by the National Human Genome Research Institute.

This research project will offer genetic testing to approximately 400 adult men and women who belong to a large kindred which has been found to have markers on chromosome 17q that are tightly linked with the BRCA1 gene, and provide them with individual results and counseling within a structured, multidisciplinary clinical environment. Women and men who are both gene positive and gene negative will be evaluated before testing and 1 week, 3 months, 1 year, and 2 years after testing to assess the psychosocial impact of the information on individuals and families. In addition, the use of preventive health services and individual health related behaviors will be evaluated pre and post genetic testing. The findings of this study will be important for our understanding of the psychological and behavioral responses to predictive testing for breast and ovarian cancer. The results also may assist in the development of predictive genetic testing protocols for other serious, adult onset conditions.

This project will organize a 5 day workshop of scholars from diverse disciplines to address the potential applications of genetic testing and screening for psychiatric illnesses in the health care system, the education system, and the justice system. The purposes of the workshop will be to identify potential applications of these technologies and provide basic guidelines for their appropriate use. Forty scholars from the disciplines of genetics, health care, health policy, education, law, history, philosophy, medical ethics, sociology, and journalism will participate in the workshop. Lay participants include representatives from mental health interest groups. The first two days of the workshop will address key aspects of the history, philosophy, sociology, and genetics of mental illness. Participants will address the potential applications of genetic technology in health care, education, and the law. Breakout groups will prepare guidelines for the application of genetic testing and screening for mental health disorders in these three societal areas. The guidelines will be expanded and refined by faculty members of the University of Utah following the workshop. The background papers, written commentaries, and guidelines will be published as a book. The workshop is being funded in part by the Snowbird Institute.

This project will address problems in maintaining privacy and confidentiality in the publication of pedigrees in the biomedical literature. The study will: (1) conduct a survey of scientific journal editors to assess their policies and practices with respect to confidentiality in the publication of pedigrees; (2) conduct a survey of investigators who have published pedigrees recently with respect to their practices and attitudes related to confidentiality and the publication of pedigrees; and (3) conduct a two day consensus conference of investigators, editors, ethicists and lay representatives to develop specific guidelines for IRBs and policy recommendations for medical journals. The results of the surveys and consensus conference will be published in a peer reviewed journal. Additional strategies for enhancing awareness of the resulting guidelines and policy recommendations will be developed at the conference.

This study will evaluate different methods of counseling for women with a family history of breast cancer. The study will take advantage of an existing breast cancer cohort to identify family members who are candidates for counseling concerning their risk for breast cancer. Subjects from these high-risk families will be offered genetic counseling and DNA-based linkage studies to test for the presence of a BRCA1 mutation accounting for cancer risk within the family. A total of 400 other subjects will be randomized to one of 3 counseling interventions or to a comparison group. These interventions are: genetic counseling, group psychosocial counseling, or primary care provider counseling. Comparisons among study arms will be made to assess the effect of different counseling strategies on: perceived breast cancer risk, breast screening behavior, anxieties and fears about breast cancer, and other health-related feelings and behaviors. A qualitative assessment of participants' reactions to the counseling process and opinions about the risks and benefits of genetic testing will also be included. Study data will provide a broad public health perspective on the counseling needs of women with a family history of breast cancer, as well as information on the needs of high-risk families.

Biomedical research involving humans generates results that fall on a continuum of potential interest to participants. Some results, such as blood pressure, have obvious clinical utility, and elevated blood pressure is actionable by taking blood pressure medication. At the other end of the continuum, results from research on the genetics of complex diseases holds great promise for future clinical management; however the results are not immediately actionable and may only be of scientific interest. Research scientists conducting Community-Based Participatory Research (CBPR) have an obligation to communicate research outcomes without implying more benefit than is actually present, and a unique opportunity to elucidate how this obligation can be met in studies that generate genetic research results. The proposed study seeks to determine how to communicate research results ranging from conventional clinical measures to genetic and genome-scale research findings within an established CBPR project conducted by the Center for Alaska Native Health Research (CANHR) at the University of Alaska Fairbanks. The CANHR study is a CBPR project partnering with >1,300 Yup'ik Eskimos and their health care providers at the Yukon Kuskokwim Health Corporation (YKHC) in Southwest Alaska. The CANHR study is focused on the identification of, and interaction among, genetic, behavioral, and nutritional risk factors that lead to obesity, diabetes and cardiovascular disease in Yup'ik Eskimos. In collaboration with investigators at the Center for Genomics and Healthcare Equality at the University of Washington, we propose an interdisciplinary partnership that will establish a Community Planning Group (CPG) of Yup'ik Eskimo representatives to collectively define a culturally meaningful framework that categorizes CANHR results, as well as to determine a communication plan that matches dissemination activities with research result categories. The framework and communication plan will be refined through an iterative series of consultations with the CPG, Yup'ik leaders with research expertise, and health care providers and health care promotion program leaders at the YKHC. We will then test the portability of the framework and associated communication strategies in an HMO research setting. In addition, all research partners will meet with a select group of stakeholders having expertise in CBPR, education, and genetics research at the beginning and end of the study to provide input and feedback based on their own unique research contexts and experiences. Finally, we will develop a guide that is based on the results of our collaborative studies, to assist other researchers and community partners in determining an appropriate plan for communicating research results. Public Health Relevance: The long-term potential for genetic and genome-scale research to contribute to health care delivery and disease prevention is high, but most current results have limited clinical utility. Although research participants generally express interest in receiving research results, little is known about what they would consider meaningful communication about complex genetic research, the research process and questions it seeks to address, or actual research findings. This study will use community-based participatory research methods to develop a framework for defining different categories of research results and appropriate communication plans, assess the generalizability of the framework, and develop a guide that can be used by other researchers seeking to develop appropriate strategies for returning complex research findings to participants.

The objective of this proposal is to begin to anticipate, analyze and address the ethical, legal and social implications of the use of new genetic information and technologies in a critical non-health care setting, namely the workplace. Genetic technology in the form of genetic testing of workers is already being used in the workplace, and its use can be expected to grow over time. Recent examples that have come to regulatory attention have cast doubt on the ability of the occupational health work force to adequately deal with this issue in ways that best insure worker health and safety and are in the best interests of the workers and society. It is likely that occupational medicine physicians are directly involved in the development and implementation of employer policies regarding the use of such genetic technology in the workplace, as well as the interpretation and control of the resulting information. Therefore, it is critical to understand how occupational medicine physicians are employing this technology and to ensure that they are well-informed of the ethical, legal and social implications of its use. Thus, in this project, we propose to survey occupational medicine physicians to determine the extent of their use of genetic testing in the workplace and their level of knowledge and concern regarding the ethical, legal and social implications of such testing. The results of this study will provide information that will have direct utility in the development, implementation and evaluation of appropriate educational interventions targeting occupational medicine physicians in subsequent proposals. This is therefore a necessary first step in anticipating, analyzing and addressing the potentially adverse ethical, legal and social effects arising from the expanded uses of emerging genetic technologies in the workplace.

The purpose of this project is to educate state policy makers about the Human Genome Project, and to stimulate their interest and increase their knowledge about the social, ethical, and legal implications of the research. This will be accomplished through a series of four regional meetings on the subject in conjunction with existing meetings of regional and national organizations of state officials. In addition, a 'State Government Policy Maker's Guide to the Human Genome Project,' which will introduce lay officials to the Project, will be produced. The meetings will be followed by Proceedings, which will be distributed widely in state governments and to other interested parties.

This project will examine decisions about the use of prenatal diagnostic testing made by Mexican immigrant and Mexican-American families found to be at risk for having a child with a disability. The specific aims are: to identify the considerations Mexican immigrant families take into account when deciding whether to undergo amniocentesis after having been told they are at increased risk of having a child with a disability based on maternal serum alpha-fetoprotein (MSAFP) prenatal screening; to understand the role genetic counseling plays in shaping Mexican immigrant and Mexican-American families' understandings about prenatal diagnostic testing, their decisions about its use, and their experiences with the tests; to assess the influence of genetic counseling and the decision to accept or decline amniocentesis on Mexican immigrant and Mexican-American families' subsequent experiences of that pregnancy and any succeeding pregnancies during the following four years; and to investigate how Mexican immigrant and Mexican-American families reach consensus about whether the woman should undergo amniocentesis and how differences are resolved when they occur.

Using a combined qualitative-quantitative approach, this renewal project will explore clinicians strategies for communicating prenatal genetics information and service options to Mexican-origin clients in California and Texas, where Mexican-origin women constitute a large and growing proportion of women in prenatal care. The study will focus on clinicians with different professional backgrounds working in diverse practice settings within distinct regulatory contexts. Our specific aims are: 1) to identify the sociocultural factors which clinicians report affect their strategies for providing prenatal genetics information and service options to low income Mexican-origin clients, 2) to identify the institutional, practical, economic, and professional factors clinicians perceive as affecting their strategies for communicating prenatal genetics information and service options to such clients, and 3) to contrast the experiences and perspectives of clinicians providing prenatal genetics services to low income Mexican-origin women in California, which has a legal mandate regulating such services and Texas, which has no such comprehensive legal mandate.