ELSI Publications and Products Database

The mission of the proposed Center for Genetics Research Ethics and Law (CGREL) is to foster sustained interdisciplinary research on the ethical, legal, and social issues involved in the design and conduct of human genetics research with individuals, families, communities, and populations. CWRU already hosts a variety of research efforts relevant to the CGREL's theme. The CGREL will integrate these efforts to launch new research collaborations and provide the resource structure necessary for their application to high priority genetics research policy questions. The basic architecture of the CGREL consists of six overlapping research groups, six research resource cores, and a research training program. The research collaborations generated by the CGREL will be harnessed to pursue four Center-wide research aims, which we believe reflect the highest priority needs in genetic research ethics and policymaking: —> To improve our understanding of the relationship between human genetics research and the humans it seeks to benefit by elucidating the cultural values and beliefs that influence different people's reactions to and experience of genetics research participation. —> To improve our understanding of the relationship between human genetics research and the human benefits it promises by elucidating the influence of translational incentives, ranging from commercial prospects to benefit-sharing agreements, on the design and conduct of basic genetics research. —> To anticipate the research ethics and science policy issues raised by new advances in genetics research by analyzing the confluence of human variation research, computational genomics, sequencing technologies, and gene transfer techniques through the lenses of contemporary research regulations and norms. —> To harness ongoing scholarship on genetics research ethics for practical application by providing evidence-based policy options for use by the scientific community, institutional review boards, and national research regulatory bodies in seeking to improve participant protections in the design and conduct of human genetic research.

This project will delineate the major ethical, legal and social issues accompanying the use of genomic information to enhance normal traits in individuals and families, and to identify the precedents that best illuminate those issues for policy-making purposes. The study will use a traditional policy analysis approach to generate specific positions on five issues of genetic enhancement policy issues: 1) Do the human subjects of clinical research on genetic enhancement interventions require special protections? 2) How should the professionally acceptable limits of genomic services be drawn? 3) What constitutes fair access to genetic enhancement services? 4) How should genetic enhancement technologies be regulated? 5) How should support for research towards germ-line gene therapy be affected by genomics' genetic enhancement capacities?

The University of Minnesota Center for Bioethics and the University's Joint Degree Program in Law, Health &the Life Sciences will complete a comprehensive investigation of the ethical, legal, and policy issues in the use of genetic information in private and public disability insurance and to recommend policies based on our findings. To achieve the goals for this project, the investigators will convene an interdisciplinary working group comprised of some of the best U.S. scholars and experts working on ethical, legal, and social issues raised by genetics, insurance, and disability. The group will include members from the field of ethics, policy and law, social science, medical science, people who live with disabilities, and the insurance industry. The Working Group will convene four times during a two-year period. In conjunction with the group's third meeting, the investigators will host an invitational national conference on the ethical, legal and policy issues raised by genetic testing and disability insurance. Through these efforts, the investigators will clarify the issues; develop a consensus about effective responses; author a consensus paper with our recommendations; and produce the first comprehensive collection of articles on the issues to be published as a journal symposium.

The aim of this project is to explore the ethical and legal ramifications of the impending collision between biological and regulatory classifications of population subgroups in American society. The project will examine the interaction between biological categories emerging from the effort to create a haplotype map of the human genome and preexisting categories specifying race and ethnicity embodied in the U.S. Office of Management and Budget's Directive 15, which governs collection of data by all federal agencies and in federally funded research. This two-year project will be led by researchers in the University of Minnesota's Consortium on Law and Values in Health, Environment &the Life Sciences with the collaboration of three Consortium members: the University's Center for Bioethics, Biomedical Genomics Center, and Institute of Human Genetics. The Project will also utilize a Working Group of scholars drawn from across the nation with expertise in law, pharmacology, human genetics, public health, anthropology, environmental health, sociology, and history. The Working Group will convene four times during a two-year period. The major goal of this project is to analyze how the information emerging from haplotype mapping will and should interact with preexisting social categories of race and ethnicity mandated by OMB Directive 15. The project will disseminate its findings through a consensus article, web-based materials, a national conference to be held during its second year, and a published symposium growing out of that conference.

The ethical, legal, and social issues (ELSI) underlying the development and implementation of state-sponsored birth cohort studies and their accompanying biobanks are complex and potentially volatile. Michigan and other states, such as Connecticut and California, are in the midst of investigating and deliberating on how to set up biobanks and there is a pressing need for practical ELSI research and guidelines for these historic initiatives. Consequently, to facilitate the development of state-sponsored population birth cohort databases for a wide range of studies, including genetics, research is urgently needed to address how recruitment, informed consent, and data access issues are affected by community members' hopes, expectations, and anxieties about research use of new born blood spots. Our proposal specifically addresses the Challenge Area 02-HG- 101* Informed consent and data access policies. We propose the following specific aims to investigate whether a method of ameliorating these concerns through a new health information technology adequately addresses community member's needs. Aim 1: To develop and test a multi-leveled participant-centric informed consent, privacy, and data access educational system and protocol that utilizes an already existing on-line health information technology system called Private Access. Aim 2: To evaluate the impact of participant-driven levels of informed consent and data access on potential recruitment into studies (e.g. the Michigan Neonatal Biobank) using both in-person 'Town Hall" meetings and on-line testing in 15 diverse Michigan communities in five geographical locations. Specifically, we will examine how demographics, types of research, and types of researcher (government, academic, private company), consent options, types of privacy control, and data access options affected community leaders and participants knowledge, attitudes, and consent to participate in a large birth cohort and biobanking effort in the state of Michigan.

This project will support two workshops to establish a Legal Research Agenda--a detailed and concrete statement of the science and technology associated with the Human Genome Initiative and of the legal issues that have emerged or are likely to emerge as a result of the Initiative. At the March 1991 workshop, scientists familiar with and active in the Human Genome Initiative will present detailed descriptions of the Initiative, as well as its goals, methodologies, and expected results, in a setting that permits full opportunity for questions and discussion by thoughtful representatives of the legal, ethical, and social science communities. At the May 1991 workshop, the legal, ethics, and social science participants will make presentations on the legal issues raised as a means of instigating full debate on the questions by all of the participants, including the geneticists. The principal investigator will draft the Legal Research Agenda, based on the recorded interchange at the workshops.

Biobanks that collect and store participants' clinical and genetic information have become important tools in genomic research, disseminating data to a large number of investigators conducting genome-wide association studies and other genomic research. The ubiquity of these biobanks in research and the fact that many of their uses will be undetermined at the time a participant consents pose a host of ethical challenges related to privacy rights, participant consent, and data sharing. Moreover, in an atmosphere where the promise of genetic medicine is high, considerable discussion has arisen about whether, how, and when biobanks should return individual research results to participants who want such data. A number of recommendations have been published to guide researchers on these issues, and engagement projects have measured public preferences about participating in such research. However, no systematic assessment has been conducted to measure genetic researchers' practices, preferences and beliefs about how best to inform and consent biobank participants, how to protect their privacy while sharing their data with researchers, and how to return an individual's study results to them without creating roadblocks to effective genomic research. We propose a systematic study of genetic researchers' views about the current landscape of biobank use, in order to inform policies that maximize the benefits and minimize the harms of genomic research. We will measure and analyze the current practices, preferences, and opinions of genetic researchers in the U.S. regarding informed consent, privacy protection, data sharing and the return of individual results as they pertain to genomic biobank research. We will first conduct one-on-one interviews with 25 human geneticists from diverse backgrounds as well as 15 researchers who chair data access committees for biobanks. After carrying out formal qualitative data analysis, we will develop a survey based on the interview data and field it to 4,500 U.S.-based members of the American Society of Human Genetics and 350 U.S.-based scientists who have either contributed to or used the NIH dbGAP biobank database. The survey will measure the prevalence of practices, preferences, and opinions in the human genetics community. We will compare our findings to current guidelines on the conduct of biobank research in order to identify the strategies that are being used in practice, as well as areas where researchers may benefit from additional guidance. We will also compare geneticists' attitudes and practices to our previous work on public expectations of genetic research to identify areas of disconnect that may warrant consideration in the design and implementation of biobank policies. Because of the rapidly changing nature of genomic research, we have proposed an achievable, two-year study that will inform biobank research policy in a timely way. Findings will be disseminated to human geneticists and biobank leaders, and feedback will be requested from them to guide future work.

Innovations in next-generation DNA sequencing technologies, accompanied by exponential drops in cost, have made it possible for clinicians to begin to use whole genome sequencing (WGS) to diagnose, treat, and predict disease. The extent to which WGS will improve health outcomes on a population level, however, will depend on effective oversight of its commercialization and use. The regulations that currently guide the administration of single-gene tests were not designed to address the tsunami of genomic information generated by WGS, and the uncertainties related to its interpretation, clinical utility and potential indications. New policy approaches may be required to establish a system that guarantees appropriate, broad access to high-quality sequence data and valid reports while encouraging innovation. The proposed research study, which responds directly to the program announcement PA-11-250, will begin to systematically prioritize and address the unique policy challenges involved in translating WGS into health benefits in the United States. This study will identify, prioritize and begin to address some of these policy questions using a modified Delphi process that iteratively engages a diverse group of stakeholders. An initial landscape analysis of the current and emerging WGS industry, enhanced by interviews with industry leaders about the future of clinical WGS, will serve as the basis for understanding how WGS fits into-and how it may disrupt-the current regulatory framework. This analysis will inform the drafting of an initial list of policy questions. A panel of 40 key stakeholders, drawn from the genomics industry, clinical laboratories, insurers, health care systems, providers and patient groups, will then be iteratively surveyed to add to and refine this list, and to prioritize the resulting issues by importance and tractability. Policy approaches to address three high-priority issues related to test quality and validity, insurance reimbursement, and intellectual property will then be developed. Through another series of stakeholder surveys, the research team will collect, refine and evaluate ideas which will be discussed by the stakeholder panel at an in-person meeting to identify areas of agreement and reasons for disagreement. Findings will be distributed to stakeholder and policy communities in concise, accessible formats with the goal of informing policy development. Policy briefings and follow-up meetings with select federal officials, Congressional members and staff will be used to begin focused dialogues on clinical WGS. This project will be among the first to use a collaborative, systematic approach to inform stakeholders and U.S. policymakers about policy priorities surrounding the newest generation of health care genomics. Importantly, it will result in concrete, pragmatic policy approaches developed by a diverse group of experts. PUBLIC HEALTH RELEVANCE: Patients will soon be able to learn the sequence of their entire genome-all of the DNA they inherited-and share it with health care professionals to help prevent, diagnose, and select treatments for diseases. The laws that ensure that the public has access to high- quality genetic tests were crafted before sequencing the genome was possible. This study will begin to develop a system of rules to make sure that (1) the new DNA tests are reliable and explanations of the results are accurate, (2) that people have access to these tests through the healthcare system, and (3) that new innovation in the area is rewarded without sacrificing quality or access.

How did scientists come to view organisms and molecules as information storage and retrieval systems? By which processes did life come to be conceptualized as a text written in a natural language? By posing these questions, the investigator aims to reconstruct a critical history of the development of the genetic code in relation to the concepts of information storage and retrieval. Leading to a published book, this research will focus on the years 1953-1973, when researchers unraveled salient mechanisms of DNA function, representing it as information transfer: the transcription and translation of DNA into proteins. The study will examine how this new language has altered our basic concepts of nature, organisms, health, disease, and behavior. It will also underscore the constraints that culture, language, and ideology place on the production of scientific knowledge: mediating our representations of nature and the articulation of life processes. The research methodology will include the use of primary and secondary scientific sources as well as archival records and interviews.

Educational objectives of the Human Genome Mapping Center at Stanford University will be achieved by an educational outreach program designed to provide the public with a basic, working understanding of the science behind, applications of, and ethical issues raised by the HGP. The first aim is to develop and present in high school classrooms a curriculum consisting of lab experiments and dry-lab exercises using three-dimensional models. The second aim is to reach members of the public by developing interactive exhibits and laboratory demonstrations about the HGP for use in a 'hands on' science museum. The third aim is to increase the depth and range of HGP-related subjects by providing lectures and discussions on a variety of topics of interest to groups including genetic disease support organizations, adult education classes, and high school and junior college students. The fourth aim is to demystify scientific research by bringing members of the public into a working laboratory to talk with HGP scientists and to manipulate laboratory equipment in an interactive tour of the Human Genome Mapping Center at Stanford University.

The purpose of the proposed project is to deepen empirical understanding of reproductive genetic services in rural areas, through a comparative case study of genetic counseling, testing, and related services among rural and urban residents of Kentucky. The study explicitly seeks to describe and analyze regional variation in experiences and uses of reproductive genetic services as linked to intersections of place, culture, and policy ('routes of access'). The study will address the following specific, inter-related aims: 1. To achieve a clearer understanding of how prenatal screening and genetic testing services are provided and experienced across socio-geographic regions of a substantially rural state. 2. To identify 'routes of access' (determined by intersections among place, policy and culture) to reproductive genetic services in Kentucky. 3. To identify whether and how these routes of access may be affected by the dynamics of state policy concerning health, genetic services and pregnancy termination. 4. To examine through in-depth interviews with parents who have experienced the birth of a child with a severe genetic condition issues of access to, and perspectives on, reproductive genetic services, particularly for rural residents.

A semester-long series of guest speakers discussed the Human Genome Project in relation to subjects such as federal policy for biomedical research, the scientific and medical advantages of human genomic information, its prospects and dangers to reproductive choice, to employment and insurance practices, and to the criminal legal system.

The Fred Friendly Seminars are producing a television series, entitled Our Genes/Our Choices, as the centerpiece of a vigorous public communication and education effort designed to engage the American public as well as professional and policy-making constituencies in a critically needed dialogue about the ethical, legal, medical and social implications of advances in genetic technology. This project will create extensive resources and activities for students, educators, policy makers, and professionals in science, medicine, law, business, and religion. These educational resources and outreach activities are designed to increase public awareness and understanding of genetics and ELSI issues, address common misconceptions, and ultimately, help members of the public become better informed decision makers. The Our Genes/Our Choices television series will premiere nationally on PBS, with subsequent broadcasts on other television outlets and videotape distribution. Outreach efforts will increase the television audience for the programs and expand the long-term utilization of the assembled materials. Activities include a wide-ranging National Outreach Campaign in which selected PBS affiliates as well as other Outreach Partners present discussion groups, lectures, workshops, and screenings nationwide. Complementing the campaign will be an Interactive Video Teleconference for professional trainers and educators, Discussion Guides, and a comprehensive Web Site. A formal Project Evaluation will also be conducted.

The overall goal of this project is to assess the potential and limitations of the application of genomic sequencing to testing hypotheses of human identity and relationship. The model system for this project will be direct sequencing of the highly polymorphic control region of the maternally inherited, haploid mitochondrial DNA (mtDNA) after amplification of target sequences by the polymerase chain reaction. Specifically, the mtDNA control region will be evaluated to determine the most informative portions of the sequence in American populations and the degree to which this variability permits every maternal lineage to be uniquely identified. Standardized techniques for routine sequencing will be developed to circumvent artifacts due to replication errors, contamination, and degradation of DNA. The possibility of obtaining mtDNA sequences from various human tissues, and of determining the true mtDNA sequence regardless of the tissue source of the DNA, will also be assessed. The results of this project should be of use in defining the technical and statistical limits of the genetic approach to human identification. The information and procedures developed could also be incorporated into public policy for the appropriate application of DNA sequencing to human identification.

This project proposes to address a critical gap in the literature regarding cancer susceptibility testing by examining utilization of genetic counseling and testing, and behavioral and psychosocial responses to the receipt of genetic information among a large, extended African American kindred (K2099) linked to a specific BRCA1 mutation. A prospective study of approximately 150 members of K2099 and their spouses/partners will be performed over a four year period. Genetic education and counseling will be provided when testing is offered and at the results session. Data will be collected through detailed questionnaires before and after testing on a wide range of behavioral and psychosocial measures. The specific aims are to: 1) identify predictors of the decision to choose or decline genetic counseling and testing services; 2) examine the attitudes towards BRCA1 testing among spouses/partners of adult female and male kindred members and determine how they influence BRCA1 testing decisions; 3) evaluate the effects of genetic counseling and testing for BRCA1 mutations on psychological and social well being of kindred members and their spouses/partners; 4) identify how genetic counseling and testing, and knowledge of BRCA1 mutation carrier status influences utilization of health services and health behaviors among adult women and men; and 5) describe facilitators and barriers to genetic counseling and testing and utilization of screening and preventive measures for BRCA1 mutation-linked cancers.

IRBs can play vital roles in observing and responding to research integrity (Rl) issues among principal investigators (Pis), yet how these boards view and approach these roles has not been seriously examined. Our pilot data indicate that IRBs commonly are involved in monitoring and responding to Rl problems (e.g., PI non-compliance, conflicts of interest (COI), adverse events, and problems in multi-site collaborations). But IRBs wrestle with uncertainties, and differ in how broadly they define their roles concerning Rl. In an institution, IRBs are often the only detailed reviewer of protocols, and thus have potentially important roles concerning Rl. But IRBs may be affected by institutional, social, educational and psychological factors as barriers or facilitators. Members range in background, training, values, and group norms. Unfortunately, little empirical research has been conducted on IRBs. and we have found none on how they view and approach these pressing Rl issues (e.g., what Rl problems they confront, and how frequently, how they respond, or feel they should, and what needs they may have for further guidelines, training or resources to maximize Rl). This study aims to identify and describe the range of views, problems, barriers, facilitators, and approaches concerning Rl among IRBs, in order to improve education of IRBs, Pis and others, refine guidelines, and foster further research. Research Questions: 1) How do IRBs differ in monitoring and responding to lapses in Rl? 2) What Rl issues do they encounter? 3) What factors are involved? 4) What are the implications for education and guidelines? Specific Aims: 1) Documenting and understanding the types and frequencies of Rl issues IRBs face, focusing on: non-compliance, adverse events, and COI; 2) Documenting and understanding the types and frequencies of IRB responses to Rl problems, focusing on: auditing, sanctions against Pis, and reporting of Rl problems to institutional or external entities; and 3) Documenting and understanding factors involved in IRB responses, focusing on characteristics of: i) the institution (eg., size, past Rl violations), ii) the IRB. (e.g., staff support, logistics, views of IRB roles, responsibilities, and standards, and relationships with compliance offices, COI committees, and institutional leadership), and iii) protocols with Rl problems (e.g., the PI, and funding). We will conduct in-depth phone interviews with 80 IRB chairs and 40 members for 2-3 hours each, using a semi-structured instrument, sampling and comparing IRBs from larger, research intensive vs. smaller institutions. We anticipate that the data from this study will serve as a significant foundation in assisting future research and the improvement of Rl through guidelines, education and other capacity building.

The increasing availability of genetic information on individuals raises a series of critical questions concerning privacy and confidentiality that have not been fully explored. The rise of computers, the Internet, and managed care all threaten the privacy of individuals' health information; and the sequencing of the human genome makes these issues particularly acute. Sharing genetic information may lead to stigma, discrimination, and threats to jobs and life and health insurance. Former President Clinton released privacy regulations, and some states have genetic privacy laws, yet numerous questions and controversies remain. The implementation of such safeguards remains unclear, and patient advocates feel further policies are needed. It is also unclear how privacy concerns and such regulations may affect behavior (e.g., participation in genetic testing) and to what degree new safeguards will allay patient concerns. It is critical to understand patients' underlying conceptions, views and approaches to privacy, and to policy and threats to privacy, and factors involved in these views. Yet no published research has investigated in-depth the perspectives and experiences of individuals confronting genetic diseases, concerning these issues. The aims of this study are thus 1) to explore views of privacy issues among individuals who are at risk of or have genetic disorders concerning privacy of genetic and other health information, threats to privacy, possible policies, and tradeoffs between privacy and benefits that might accrue from sharing genetic information (e.g., for research); 2) to explore the experiences of these individuals concerning privacy and disclosure - to whom they have disclosed that they confront a genetic disease (e.g., to health care professionals, family members, coworkers, employers, and insurance companies); when, why and what they disclosed; what reactions (e.g., stigma and discrimination) they have encountered; and how they view and make these privacy and disclosure decisions; 3) to explore the relationship of these views of privacy to health behaviors (e.g., delaying or avoiding diagnostic tests or treatment); and 4) to assess how type of genetic or other illness, or other factors may affect these views and experiences. We will conduct in-depth semi-structured interviews with 160 individuals -40 each who confront Huntington's Disease, genetically linked breast cancer, alpha 1 antitrypsin deficiency, and, as a comparison group, coronary artery disease. We have chosen the first 3 of these disorders because our pilot work suggests that critical privacy concerns arise with all 3 of these genetic diseases, but are related to different aspects of these conditions. The findings of this study can enhance further policy, professional and public education, and future research in this area.

The conference, which will be held in Montreal on September 5-8, 1996, is designed as the first international, comparative forum for the examination of the broad issues of 'controlling' human genetic material and information. The purpose of the conference is to promote discussion and cooperation and facilitate policy development among representatives from many nations. It is anticipated that the conference will attract a large and diverse audience (300-500 attendees from around the world) including the academic community, the biotechnology industry, patient advocacy groups, policy developers at the scientific and governmental level, and individuals involved in genetic research. Conference Proceedings which include summaries of the plenary sessions along with the papers of the speakers, will be published and disseminated. In addition, the conference will serve as a forum for the critique of the results of a two year Canadian Genome Analysis and Technology (CGAT) research project," Research and Human Genetic Material: Persons, Property, Patents and Policy in Canada." The conference is not designed to provide consensus on each plenary session topic, however, the publication of conference proceedings should provide tangible outcomes that can be drawn upon by those who seek to formulate meaningful DNA sampling policy.

The general aim of the project is to research and develop instructional material on business ethics decision making for those involved in commercializing biotechnology and genomics products. There are four specific aims. They are (1) to research and identify the ethical and social issues that are raised when biotechnology and genomic research is commercialized, (2) to develop an analytical business ethics decision making model or process that can be used by pharmaceutical and biotechnology corporations when their managers face these ethical and social issues, (3) to develop comprehensive ease studies in business ethics based on past pharmaceutical and biotechnology corporate behavior, and (4) to apply the decision making process to these case studies as examples of how corporate managers can/incorporate ethical reflection, debate, and analysis into business practices. The results of this research project will be directed primarily to pharmaceutical and biotechnology corporate executives, managers, board members and attorneys. The detailed case studies developed through collaboration between the Center for Biomedical Ethics and the Graduate School of Business will be utilized within Stanford University's Executive Education Program. The case studies developed will also be available to augment business ethics curricula at Stanford University and of other graduate schools of business. Case material will be distributed via the World Wide Web and eventually through a conventional text book format.

Dr. Korngiebel's long-term goal is to become an independent researcher at the intersection of bioethics, informatics, and genetic testing. To work toward this goal, she will receive rigorous training that includes 11 courses supplemented by directed tutorials in order to complement her qualitative research skills with proficiency in genetics-related bioethics, informatics pertaining to Electronic Medical Record Health Information Technology, and quantitative data analysis. The research project will allow her to apply the knowledge gained through formal instruction. During the mentored career development award, Dr. Korngiebel will be based in the Department of Biomedical Informatics and Medical Education at the University of Washington School of Medicine, an institution uniquely situated to facilitate training and research in bioethics, informatics, and genetic testin. Using her qualitative skills and the expertise gained through training, Dr. Korngiebel will be responsible for producing the main deliverable of the research project: a computerized Clinical Decision Support tool for Lynch Syndrome testing. Genetic tests are important tools for identification and mitigation of heritable cancer risk. An example is testing to identify Lynch Syndrome, a condition which confers a high lifetime risk of colorectal cancer. The Evaluation of Genomic Applications in Practice and Prevention program recommends screening for Lynch Syndrome in individuals newly-diagnosed with CRC as a means to improve health outcomes in both patients and family members. However, this approach's success is dependent on execution of an effective testing process, including a robust follow-up program. In implementing this complex process, health systems must determine informed consent procedures at different steps in the testing process and their responsibility toward family members receiving care in other systems. In this complicated scenario encompassing both genetic test choices and unaddressed ethical issues, a computerized clinical decision support tool can offer a timely means of guiding ordering clinicians through the testing process and follow-up with patients and families. Therefore, the research project will comprise the following aims: 1. Identify through interviews with key content experts and decision-makers the critical health system elements and decision points for adaptation of colorectal tumor testing in two hospital settings within UW Medicine; 2. Identify through interviews and targeted surveys of geneticists and non-geneticists the barriers, facilitators, and priorities for successfully deploying a local clinical decision suport tool for diagnostic genetic tests that leverages the Electronic Medical Record; and 3. Test the decision support tool to evaluate clinical utility and appropriateness through evidence-based usability methods. PUBLIC HEALTH RELEVANCE: The proposed computerized Clinical Decision Support tool would tackle a health-care system-wide issue of tailoring routine clinical care to accommodate local needs, reflect a nationally developing standard of practice for universal colorectal cancer tumor testing for Lynch Syndrome, and address bioethical issues of informed consent and returning findings to patients and their families concerning heritable colorectal cancer. The improvement in care and information conveyance could, ultimately, save lives and deliver on the promise of personalized genomic medicine.

This project will study the role of patient preferences and other factors in choices regarding use of prenatal screening for and diagnosis of chromosomal disorders in a racially/ethnically diverse population. The study will collect detailed information regarding the distribution of individual preferences for test characteristics and outcomes by racial/ethnic group, as well as other factors which may be related to choices regarding the use of these tests. The study will use both decision-analytic and regression techniques to compare 'predicted' choices (based on expected utility theory) to actual choices made. The study will also explore the cost-effectiveness of current and proposed age-and risk-based guidelines for prenatal testing, and will compare them to the estimated cost effectiveness of a preference-based guideline. Information generated in this study will ultimately be used in the development of a decision-assisting technology to help women of diverse backgrounds make informed choices regarding testing that reflect their underlying preferences, and in the delineation of guidelines for use of prenatal diagnostic services that place greater emphasis on patient preferences and values, in addition to risk.

Building on the experiences and products of the Human Genome Education Model Project (1993-1997), Georgetown University Child Development Center and the Alliance of Genetic Support groups plan to use the collaborative (consumer and health professional) education model to educate allied health professionals through their respective national organizations. The overall goal is to derive optimal benefit from development of the Human Genome Project for allied health professionals and the clients they serve. The specific aims are: 1) to conduct surveys to assess needs, determine education priorities, and identify resources of the respective organizations; 2) to use information from the surveys to adapt the collaborative education model to educate and sensitive health professionals about genetics, the HGP and its ethical, legal, and psychosocial issues and implement education for national staff, practitioners, and educators; and 3) to evaluate each level of education and disseminate information about the project. HuGEM II is designed to be carried out over a three-year period. An Advisory Committee will provide expertise in medical genetics, ethics, law, consumer issues, social policy, and health education.

This project employs a multi-method, transdisciplinary approach that combines ethnographic participant- observation, interview research methods, ethical, legal, and public policy analyses. The two goals of the present project are 1) to identify the ethical, legal, and policy challenges that the field of psychiatric genomics will face when trying to translate the findings of large-scale GWAS into clinically useful information, and 2) to make evidence-based recommendations about how to address these challenges. To achieve these goals, I will use, as a case study, one of the first attempts to translate large-scale psychiatric genomics GWAS findings, the Genomics of Treatment-Resistant Psychosis (GTRP) study. GTRP will perform whole exome sequencing (WES) in a sample of 1,000 institutionalized patients who suffer from treatment-resistant psychosis (TRP). GTRP's goals are to identify genomic variants associated with TRP, and ascertain whether any clinically actionable information emerges from these genomic tests that could help improve mental health care for particular patient-participants. I propose to study GTRP's experience to address three research aims critical to understanding the challenges faced in translational psychiatric genomics research with severely mentally ill patients. Aim 1 will be the mentored research phase of the project, and Aims 2 and 3 will be the independent research phases. Aim 1a employs ethnographic participant-observation and interview methods to study the factors that influence GTRP researchers' decision-making process while designing and conducting the WES consent process and the return of results (RoR) components of their study. Aim 1b employs ethical analysis to evaluate the design of the GTRP study, including the WES consent process and RoR components. Aim 1c employs legal and policy analyses to examine the regulatory framework currently in place to protect institutionalized severely mentally ill patients who participate in translational psychiatric WES research. Aim 2a is an empirical examination informed by Aim 1 that employs interview methods to study the views and preferences of GTRP patient-participants, patient-participants' legal guardians or authorized representatives (LG/AR), patient-participants' mental health clinicians, and officials of the mental health institutions in which GTRP will take place. The interviews will assess their perspectives regarding how to handle the WES consent process, selection of results to return, RoR consent process, actual RoR procedure, and the Post-RoR management of WES findings. Aim 2b employs legal analysis to examine what kind of legal responsibility, if any, LG/ARs, clinicians, and mental health institutions, assume regarding the management of WES findings once these are returned by researchers (Post-RoR management). Aim 3 employs ethical and legal analyses to explore the implications of applying a legal Fiduciary Relationship Model (FRM) for defining the ethical responsibilities that different parties hold towards patient- participants in translational psychiaric genomics research. This work will be informed by the data collected in Aims 1 and 2. PUBLIC HEALTH RELEVANCE: This project will identify the ethical, legal, and policy challenges that genomic scientists face when attempting to convert the identification of genes associated with mental health disorders into information and technologies that can improve treatment and prevention. The identification and analysis of these challenges will allow this project to generate evidence-based recommendations about how to protect the interests of the mentally ill patients who participate in these studies. The protection of vulnerable populations that participate in research is a fundamental requirement of any study. Therefore, this project will advance psychiatric genomics medicine by providing guidance to scientists and other relevant parties involved in translational psychiatric genomics research.

The purpose of this project is to expand clinical applications of the principles of genetics and health promotion among nurse educators. Two previously field-tested genetics educational programs will be combined to form four practice-based, teacher-assisted genetics curriculum modules suitable for baccalaureate and advanced practice nurse educators to provide helpful and appropriate genetics resources to nursing students. Nurse educators from three schools of nursing within Maine and two schools of nursing that serve broader populations of urban and minority students will be enlisted to participate in field-testing the modules. Nurse educators will be provided with case studies, a family history questionnaire, educational materials, and clinical management guide and teacher-assisted activities for field testing. Additional educational support to nurse educators will be provided through a week-long educational session, and development of systematic access to local and regional genetics services and resources. Evaluation of the project will be ongoing and will include both periodic formative evaluations to improve project activities and a summative evaluation. Modules will be adapted and refined for printing and distribution through national nursing organizations including Web sites. The project will be summarized for submission to a peer reviewed academic nursing journal.

This ethnographic study examines the social and ethical implications of the use of categories of race and ethnicity in human genome research. The specific goals of the proposed research are: 1) to trace the history of public discourse on categories of race and ethnicity within biomedicine as it has contributed to the design of current genetic research; 2) to identify the sociopolitical stakes in discovering difference between groups identified as racial and/or ethnic in the search for single nucleotide polymorphisms (SNPs); 3) to critically examine the racial categorization of cell repositories and the use of human variation panels in genetic research; 4) to analyze the meaning of 'community' in current efforts to include racially and ethnically identified populations in the discourse surrounding genomic research and technology; and 5) to discover the ethical implications of the deployment of race and ethnicity in genomics research and to identify culturally appropriate mechanisms in protecting both individuals and communities from potential research related harms. This study will utilize anthropological methods of participant observation, semi-structured interview, survey administration and archival research.

The Mentored Scientist Development Award in Research Ethics will fulfill three main goals: 1) to obtain a broad and in-depth foundation in research ethics and to develop research skills in ethical reasoning and analysis in order to become a resource for those pursuing biomedical research; 2) to build a research program on the ethical implications of human genetic variation research for social distributive justice; and 3) to become an independent investigator in the field of research ethics upon the completion of this career development award. These goals will be accomplished through mentoring, formal coursework, faculty collaborations, and empirical research. The research plan focuses on social distributive justice in human genetic variation and pharmacogenomics research. The ethical principle of justice requires that medical research provide equitable distribution of benefits to human subjects. This project investigates whether pharmacogenomic research involving racially identified populations fulfills this principle in the fair, equitable and appropriate distribution of health benefits to all populations within the United States. The specific aims of the proposed project are: 1) to critically examine the assumptions and practice of human genetic variation research and its impact on current trajectories of pharmacogenomics research and to identify the major prospective recipients of these studies.; 2) to identify the meaning of justice for various stakeholders, including scientists, prospective human subjects, industry leaders, and policymakers, in pharmacogenomics research; 3) to examine the implications of pharmacogenomics research on the status of health disparities between racially identified populations; and 4) to develop an ethical framework in which to address social distributive justice in pharmacogenomics research that will lead to specific guidelines for those who apply this research to practice. The research will consist of an ethnographic study involving participant observation, in-depth interviews, and archival analysis.