ELSI Publications and Products Database

The project will carry out a multi-institutional randomized trial to evaluate whether the outcomes of BRCA1/2 testing among female mutation carriers are improved by providing a psychosocial telephone counseling (PTC) intervention in addition to standard genetic counseling (SGC). The specific aims are: (1) to evaluate the efficacy of PTC delivered in conjunction with SGC, compared to SGC only; (2) to explore the mechanisms by which the PTC impacts on psychosocial and behavioral outcomes; 3) to identify carriers who are most and least likely to benefit from PTC; and (4) to conduct an economic evaluation of the two counseling strategies. The participants in this randomized trial are 290 female carriers of BRCA1/2 mutations and 290 female noncarriers. A baseline assessment will be conducted prior to the offer of testing to collect data on background variables, moderator variables, and baseline levels of outcome variables. Following in-person pre-test genetic counseling and informed consent, participants will have an opportunity to have BRCA1/2 testing. After providing additional written consent, they will receive their results during an individual in-person session with a genetic counselor. Following disclosure of mutation status, carriers of BRCA1/2 mutations will be assigned randomly to receive either SGC follow-up only or SGC plus PTC. The PTC protocol, adapted from the previous research of the study investigators, will be delivered in 6 sessions over a 3-month period after disclosure. Sessions will include supportive counseling and provide training in coping skills to enhance the outcomes of genetic testing. Follow-up interviews will be conducted at 1-, 4-, 6-, and 12-months post-disclosure to collect data on the following outcomes; comprehension, distress, family communications and functioning, adoption of recommended cancer screening practices, and satisfaction with decisions about prophylactic surgery. If beneficial and cost-effective, the proposed PTC intervention can be disseminated to varied research and clinical settings in which BRCA1/2 testing is offered.

Despite significant efforts, African Americans continue to experience excess rates of morbidity and mortality from all forms of cancer relative to individuals from other ethnic and racial groups. Research is now being conducted to the molecular basis of cancer through genetic-based studies and to translate this information into strategies for cancer detection, prevention, and treatment. African American reluctance to participate in cancer genetics research will significantly limit efforts to apply these approaches to address racial disparities in cancer outcomes. To develop effective strategies for recruiting African Americans to participate in cancer genetics research and to enhance decisions about participation in this population, empirical data are needed on attitudes and beliefs that act as barriers and facilitators to participation. Studies are also needed to determine how barriers and facilitators may interact with attributes of the study to influence participation within this population. To address these gaps in our knowledge, the specific aims of this mixed methods study are to (1) identify barriers and facilitators to African American participation in cancer genetics research and to translate this information into a psychometrically sound instrument; (2) evaluate within group variation in barriers and facilitators among African Americans based on sociodemographics, experiences with disease, and cultural beliefs and values; and (3) evaluate the associations between participation intentions and two potential influences that include the attributes of the study and barriers and facilitators. The study will be implemented in three Phases and will include African American men and women ages 18-75. In Phase I, we will use qualitative methods to identify barriers and facilitators to participate in cancer genetics research. Phase II will consist of a cross-sectional survey to evaluate within group variation in participation barriers and facilitators based on sociodemographics, experiences with disease, and cultural beliefs and values. In Phase III, we will conduct a conjoint survey to evaluate the relative influence of participation barriers and facilitators and attributes of the study on willingness to enroll in cancer genetics research. To accomplish these goals, we have assembled a team of highly qualified investigators who are experts in the application of qualitative and quantitative methods to minority recruitment, cancer genetics, psychometrics, survey research, conjoint analysis. This study will provide empirical data that can be used to develop more effective strategies for recruiting African Americans to participate in cancer genetics research that enhance decisions about study participation.

Genetic knowledge is becoming increasingly central to the way human health and disease are understood and addressed. In order to advance the translation of medical knowledge into effective practice, it is important to know how genetic knowledge is presently understood by clinicians and patients, and applied in their routine medical encounters. Genetic information is already being translated from the abstracted world of laboratory research to the practical context of clinical practice and everyday life. At the same time, there is great interest in understanding and alleviating the unequal burden of disease affecting certain racial/ethnic populations in the U.S. Research has shown that health disparities are largely attributable to non-genetic factors such as socio-economic status, racial discrimination, inadequate health insurance, and unequal exposure to environmental hazards. Still, many believe that genetic research holds a key to explaining and addressing racial/ethnic health disparities. How clinicians translate genetic knowledge into clinical practice, how they integrate genetic and non-genetic illness understandings, and how patients in turn understand this information has not as yet been carefully studied. Using qualitative research techniques of open-ended interviewing and participant observation, the proposed study will explore how a group of primary care clinicians and their patients understand and interpret the genetic and non-genetic basis of two prominent chronic illnesses which differentially impact racial/ethnic minorities: diabetes and cardiovascular disease. The study will examine their understandings of susceptibility and management of these diseases. Comparative qualitative analysis will be used to generate specific profiles of ways that genetic information is interpreted and applied by these clinicians and their patients. The study will conclude with a national survey of primary care clinicians, designed to test the generalizability of the qualitative findings, and examine any hypotheses emerging from the analysis. Our specific aims are to: 1) Understand how genetic concepts of racial/ethnic difference are interpreted and applied by clinicians serving minority populations. 2) Understand the nature of genetic versus non-genetic factors in clinicians' understandings of the causes and management of these common chronic illnesses, which differentially impact minority populations. 3) Understand patients' interpretations of these concepts and of their own risk, health status and treatment responsibility. 4) Generate knowledge of how emerging genetics science can effectively be presented to clinicians and patients, to promote appropriate interpretation and application of genetic knowledge while avoiding possible misinterpretation and racial/ethnic stereotyping. PUBLIC HEALTH RELEVANCE: As genetics becomes increasingly central to medical care, there is a clear need for better understanding of how clinicians translate genetic knowledge into their practice, and how patients in turn understand genetic information. This is especially important in assuring appropriate interpretation and application of genetic knowledge concerning diseases that disproportionately affect racial/ethnic minority populations. This project will be contribute valuable insight into clinician and patient use of genetics concepts in everyday clinical encounters, which will yield better understanding of how emerging genetics knowledge can effectively be presented to clinicians and patients, while avoiding possible misinterpretation and racial/ethnic stereotyping.

Student Pugwash USA (SPUSA) will hold an international conference, 'Science and Social Responsibility in the New Millennium,' June 28-July 4, 1999. This event, which will bring 200 students, yound professionals, and experts from over 30 countries to the University of California's San Diego campus, will encourage talented young people to explore with senior experts the ethical, legal and social implications of the US Human Genome Project (HGP) and other developments in the field of genetics. One public plenary session will focus on genetics and the HGP and two of the ten working groups at the conference will focus on related issues. One working group will explore genetics in terms of gene therapy, the HGP, cloning, public decision- making, and patenting issues. The second will explore the interplay between computers, biotechnology, taking into consideration the role of computers in accelerating genetics research in the HGP and other initiatives, the impact of genetic databases on research around the world, possible personal freedom issues that arise from these databases, and potential impact of other emerging capabilities. The conference will foster an international network of young people committed to exploring ELSI issues and will initiate a year-long continued investigation into these issues through follow-on activities which will include: on-line discussion groups; local, campus- based activities; media outreach; and special sessions at SPUSA's regional and national events.

The Clinical Sequencing Exploratory Research (CSER) and Return of Results Consortium (RoRC) programs are designed to investigate critical questions about the application of genomic sequencing to clinical care of individual patients, from generation of genomic sequence data, to interpretation and translation of the data for the physician, to communication to the patient, including an examination of the ethical and psychosocial implications of bringing broad genomic data into the clinic. The goal of ELSI involvement in CSER is to support ELSI research required to responsibly apply personal genomic data to medical care, with a particular emphasis on the ethical, legal, and psychosocial implications of generating and returning genomic results, including returning incidental findings CSER website: https://www.genome.gov/27546194/clinical-sequencing-exploratory-researc…

This application proposes to assess the societal impact of genetic tests offered directly to consumers (DTC) and to develop policy options for DTC oversight that will balance the benefits of promoting availability of tests that can have a positive impact on public health and preventing harm to the public as a result of misleading claims, inappropriate tests, or inaccurate test results. DTC genetic testing challenges the traditional means of genetic test delivery. Some argue that genetic testing should take place only in the context of a health care provider, and that DTC genetic testing may harm consumers through inappropriate test selection, lack of counseling, and improper test interpretation. Others argue that DTC genetic testing may increase consumer awareness of, and access to, tests that can help them improve their health and make beneficial treatment and lifestyle decisions. Little is known about the legal or business landscape for genetic testing or its likely impact of DTC genetic testing on consumer behavior. Supporting research to ensure the effective and appropriate translation of genetics research to the public is a cornerstone of the ELSI program. The success of the Human Genome Project has led to the development of genetic tests for more than 1,200 diseases. A growing number of these tests are being offered DTC and there are few regulatory barriers to market entry. Therefore, we may expect to see significant growth of DTC genetic testing in the near future. The National Human Genome Research Institute has raised several significant research questions about DTC genetic testing. This project will provide the data needed to begin to answer some of these questions. It will develop a comprehensive landscape analysis of the DTC environment. It will evaluate claims for specific tests offered DTC and compare these claims to evidence of validity and utility in scientific literature. It will assess public awareness and attitudes regarding DTC genetic testing services and the experiences of consumers who have used two different DTC tests. Finally, it will develop policy options for oversight of DTC genetic testing. In all of these activities, the GPPC will serve as an expert resource for policymakers, the media and the public about DTC genetic testing. PUBLIC HEALTH REVELANCE STATEMENT This project is directly relevant to the health of the U.S. public. Advances in genomics have significant potential to benefit public health, but only if the public makes informed choices about whether to obtain genetic testing and what actions to take based on test results. The recent growth in direct-to-consumer (DTC) genetic testing presents questions, concerns, and opportunities, but little is known about its impact. Achieving the specific aims proposed of this project will provide the data and analysis needed for informed policy development for DTC genetic testing and important insights that can contribute to ensuring effective translation of discoveries in genetic research so as to benefit the public's health.

This study will examine how the public conceptualizes human genetic mechanisms and interprets and uses this information. The major goals of this study are to 1) document the general character of the public's beliefs about how genes effect human traits, 2) investigate their use in explaining perceived differences between individuals and between gender, class and racial groups, and 3) explore the association between these beliefs and social-political attitudes. Three telephone surveys will be conducted with African American and white, female and male adult respondents from a range of socioeconomic levels. Two of these interviews will involve the collection of qualitative information from 40 respondents (each) and one structured interview will be conducted with 1,200 respondents, nationally sampled. Findings from this study will 1) give guidance to those of genetic counseling and education so they may better understand the public's conceptions of genetic mechanisms, 2) increase our knowledge about the role genetic explanations may play in gender, class and racial antagonism and stereotyping, and 3) inform those in the field of human genetics about the social and ethical implications of their work.

Methodological advances now permit the use of genome-wide association studies (GWAS) to discover novel genotype-phenotype associations. GWAS offer a powerful tool for identifying genetic contributions to both common and rare diseases. At the same time, GWAS raise profound and challenging ethical questions. The most pressing questions derive from the likelihood that GWAS will uncover genetic information with the potential to be clinically meaningful to individual participants. As a result, investigators will inevitably face the question of whether individual genetic results from genome-wide scans should be disclosed to subjects. Commentators and ethics panels have addressed the question of whether genetic test results should be returned to research participants. Most policymakers advocate a cautious approach: disclosure should be limited to a narrow subset of results that meet stringent criteria related to magnitude of risk, severity of phenotype, and availability of prophylactic, therapeutic or reproductive interventions. Limited data regarding research participants' views, on the other hand, suggest a strong preference for disclosure of test results. However, because these data are based upon dichotomous responses to single questions, they do not address whether participants' views are sensitive to the factors identified by expert panels as salient to decisions about return of results. Without such information, it is impossible to know whether the gap between participants' views and policy guidance is as profound as the data suggest. The present proposal aims to bridge this gap through a factorial survey of 1800 members of the Jackson and Framingham Heart Studies, two influential cardiovascular cohort studies that conduct GWAS. Specifically, the proposed study will evaluate whether the criteria highlighted by policymakers are predictive of research participants' desires for this information. The study will also evaluate the relationships between attitudinal characteristics (e.g., views on and knowledge about genetics) and sociodemographic characteristics (e.g., age, education) and participants' desires for return of results. The findings will permit assessment of the extent to which there is concordance between the views of experts and those of research participants on this vexing topic. These data will help shape practice and policy regarding the return of individual results from genomic research.

Prenatal testing is evolving in two important ways: first, advances in genomic medicine mean that samples of fetal DNA obtained with invasive methods (such as amniocentesis) can be analyzed using microarray analysis or whole genome sequencing, revealing far more information about the fetus's genetic make-up than was previously possible; and second, new, non-invasive prenatal tests have been introduced that isolate fragments of fetal DNA circulating in a pregnant woman's blood, making possible safe, highly accurate genetic testing much earlier in pregnancy than was previously possible. Currently the range of genetic traits that can be picked up by the new non-invasive tests is small. But it is set to expand rapidly as the technology develops, and it may one day soon extend to whole genome analysis allowing detection of the full range of traits, including those associated with increases in risk for disease, adult-onset conditions, and non-disease traits. These two changes mark the beginning of the next-generation of prenatal testing, which has the potential to dramatically alter the experience and care of the 4 million women who give birth in the United States alone each year. Thereby, these remarkable technological developments raise pressing ethical, which this project will address. First, which traits should be tested for, nd how ought testing be conducted? Second, which policies should be altered to support the ethical use of next-generation prenatal tests, and in what ways should these policies be changed? And third, what future empirical research is needed to examine how the ethics recommendations made by this project play out in practice? To address these questions, The Hastings Center has recruited experts and representatives from a wide range of sectors critical to the wise and effective use of next- generation prenatal tests, but who have not yet been brought together. Importantly, leaders from the major relevant clinical societies have agreed to participate because they realize that this project's ethical analysis and recommendations will usefully inform their organizations' future clinical guidelines. The Work Group also includes members conducting empirical research on first and second-generation prenatal testing, and members representing patients. Together, with this Work Group, the Lead Investigators will produce analysis and recommendations for clinicians, researchers, policy makers, opinion leaders and the public. A draft of this analysis and recommendations will be presented to four focus groups of pregnant women and the partners of pregnant women for their feedback. The final analysis and recommendation will be disseminated to relevant stakeholders via scholarly publications, conference presentations, a public meeting, and a project website.

This project utilizes a method of ethical analysis described as 'paradigm analysis' to develop a comprehensive and systematic framework for ethical issues raised by genomic information in clinical genetics. Several diseases with genetic bases will be used to group specific sets of ethical issues and a method for ethical analysis will be devised. The project will have three phases: 1) a working group from ethics, clinical genetics, and scientific genetics, drawing from the literature on genetic ethics, clinical experience, and prospective scientific developments, will meet on a regular basis to select and describe the paradigms; 2) the chosen paradigms will be tested for adequacy and accuracy against the records of patients in the genetics clinics of the University of Washington; and 3) the paradigms will be refashioned in response to record derived data and a report explaining the paradigmatic method will be prepared and distributed throughout the genetics and ethics community. Utility of the method for a computerized data base will be explored.

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?

In their previous project, these investigators examined the ethical and legal issues raised by the prospect of using the products of human genome research for enhancement purposes. This work identified three critical challenges to the development of social poicy in this area. First, most interventions that can be used for enhancement are likely to be initially developed and approved for therapeutic use. However, once so approved, the current regulatory structure provides no adequate means of managing the 'off-label' use of such interventions for enhancement purposes by clinicians and their clients. Second, any enhancement interventions performed on pre-implantation embryos are likely to be undertaken in the largely unregulated context of clinical reproductive biology and infertility medicine. While the previous project has allowed the investigators to outline the considerations relevant to professional ethics in this area, it is still not clear how those standards would be best enforced. Finally, the availability of either pre-implantation or post-implantation genetic enhancement interventions will also depend on policies regarding access to these interventions outside the boundaries of the U.S. This new project will undertake a close-grained analysis of these three problems as they challenge the management of genetic enhancement technologies, and will develop specific policy recommendations for public policy makers that would allow the issues to be addressed within the framework of considerations set out in the previous project. The project's methods will be primarily analytic and discursive: they will be critiquing, constructing, and proposing policy positions on the basis of literature about the closest precedents for each of these problems by continuing the regimen of regular research meetings and collaborative writing that has propelled their work to date.

Advances in the molecular genetics of cellular aging raise the prospect of intervening in the human aging process to dramatically extend the human life span. The development of such interventions would confront society with the challenge of interpreting, using and regulating the ultimate genetic enhancement technology: a technology that could allow us to change a basic constant of human life at the cellular level. This project is designed to combine the work of two ongoing research programs to begin to address these challenges. The first is the research that Eric Juengst, Maxwell Mehlman and Thomas Murray have been conducting on the ethical and public policy challenges that are posed generically by genetic enhancement technologies. The framework for ethical analysis and public policy development generated by that research would be applied here to the case of anti-aging interventions, both as a test of the framework and to see what it yields in this case. The second resource is the work of the other co-investigators, Stephen Post, Peter Whitehouse and Robert Binstock, on the clinical and social meanings of the human aging process. That research will be used to identify the issues to analyze in this project, by providing the landscape of contemporary social practices, values and beliefs that radical life extensions could challenge. Collaboratively, the two groups will seek to anticipate the issues that anti-aging interventions could raise for three constituencies: the individuals and families that might use them, the health professionals that might provide them, and the public-policy makers that will shape the context in which they might become available. The project's methods will be analytic and discursive: the investigators will be critiquing, constructing and proposing arguments on the basis of existing information and previous work, through a regimen of regular research meetings and collaborative writing. This work will be overseen by an expert group of advisors; Carol Donley, Co-director, Center for Literature, Medicine and the Health Profession at Hiram College; Michael Fossel, Editor, Journal of Anti-Aging Medicine; Linda George, Associate Director, Center for the Study of Aging and Human Development, Duke University; and Thomas Murray, President, The Hastings Center.

"Personalized genomic medicine" (PGM) is being promoted as a "new paradigm for health care" and a major goal for translational genomic research (TGR). In addition to overcoming TGR's remaining scientific hurdles, achieving that goal will involve addressing a number of ethical, legal, and social challenges. Some of those challenges reflect the ways that different social policies and health care economies will complicate TGR's ability to realize PGM as a viable health care paradigm. But other challenges might emerge from the goal itself, depending upon how PGM is interpreted by those who shape it as a social practice. This project explores this suggestion by documenting how PGM and its most attractive virtues are interpreted by those involved in defining them for TGR and society, and the challenges and choices they are encountering in the process. PGM is a goal that unites a wide array of biomedical initiatives, from medical sequencing, gene expression, and pharmacogenomics research to public health, clinical, and commercial services. Its promissory virtues are precision diagnosis and risk prediction, individualized therapy, prevention, health promotion, and patient empowerment. Different proponents of PGM interpret and rank these promises differently, with different implications for the realization of PGM as a health care paradigm. We focus on four sets of interpreters that will have particularly important roles in shaping the way PGM emerges as a social practice: (1) the scientists, research sponsors, companies, and policy organizations that promote PGM as a biomedical paradigm; (2) the journals, public review bodies and educational institutions that mediate the implementation of this paradigm; (3) the health care institutions and professionals that pioneer the paradigm by providing PGM services in practice; (4) the patient-based organizations that increasingly help shape its public reception. Our empirical studies of the views of these social co-producers of PGM will then be used to generate an analytic map of their different visions, designed to draw out their ethical, legal, and social implications for TGR and health policy. The "translational pipeline" of genomic research will have many branches towards its distal end. This project is designed to anticipate the directional choices that these branches will require, so that the PGM that TGR finally delivers into the complicated plumbing of our society is as clean and safe as possible. PUBLIC HEALTH RELEVANCE: A major goal of genomic research is to develop health care tools that can achieve more precise diagnoses and risk predictions, individualized therapy, prevention, health promotion, and greater patient empowerment. The proponents of these advances call their goal "personalized genomic medicine." But many different parties are involved in shaping this vision for health care, and their different interpretations of its virtues carry different ethical, social, and legal implications. The purpose of this project is to study how some of the most influential parties who are promoting, implementing, providing, and using "personalized genomic medicine" understand its promises and potential pitfalls. This understanding will allow us to define the policy choices that lie ahead for researchers, health care providers, and the public as translational genomic research moves closer to its goal.