ELSI Publications and Products Database

The UNC-CH Center for Genomics and Society focuses on newly emerging ethical, legal and social implications (ELSI) of genomics research as the field matures and shifts its focus from small efforts to those on a much larger scale. These gene discovery and disclosure activities involve large numbers of individuals from whom DNA has been collected, studies with a small number of individuals whose whole DNA sequences are being examined, and the creation of complex data sets that may be linked in a variety of ways to multiple other sources of data. DNA collected in these activities may test a population for the presence of a known genetic disorder, use genotypic data to develop guides for drug dosing, combine genotype and phenotype data for large-scale prospective studies, collect and store DNA and environmental data in genetic registries, or consolidate DNA collected by multiple investigators to create a "bank" for use in current or future exploratory studies. We argue that although large-scale gene discovery and disclosure efforts have tremendous scientific promise and the potential to lead more directly to changes in public policy or clinical practice, they also raise a wide range of ELSI issues not apparent in smaller-scale efforts. (1) "Scaling up" may change the implications of genetic information for individuals, families, or populations, particularly when genetic findings are ascribed to individuals by virtue of their membership in socially defined groups. (2) Large-scale genomic research may alter challenges to informed consent in response to shifting estimations of risk and benefit. (3) New technologies and data collection and storage capacities may pose unique ELSI issues as investigators, subjects and relevant institutions grapple with regulation of the use of DNA samples, control of data, and their dissemination. (4) All of these concerns are also integral to understanding the most efficient and judicious translation of genomic research findings into clinical or public health practice. We have assembled an interdisciplinary team of investigators to conduct a research on these ELSI issues raised by large scale genomics; offer a research ethics consultation service for genomic researchers; facilitate policy initiatives that are informed by our research findings; and provide training, education, and outreach particularly focused on underrepresented minorities, to foster continued ELSI research on large-scale genomics. In addition to our goal of addressing public health priorities in newborn screening and in the translation of other genetic technologies, inclusion of underrepresented minorities in all aspects of our Center activities highlights the importance of consultation from populations with greatest interest in and most affected by large-scale genomic studies intended to address health disparities.

This research project will collect and analyze qualitative and quantitative data about US biobanks, exploring how organizational strategies, features, and attributes affect both framing and response to ELSI and policy choices. We argue that a biobank's organizational features impact 1) policy choices directly, and 2) members' framing and response to ELSI which in turn impact policy choices. We will select 12 biobanks with diverse creation strategies (creating collections from the "ground up" (de novo), repurposing non-research collections, and networking existing specimen collections) for exploratory in-depth case studies of their history, evolution, and response to ELSI and policy choices. Using the results of the case studies, we will refine questions and hypotheses about the relationships between organizational strategies, features, and attributes, ELSI, and policy choices in order to inform a survey of 500 biobank administrators selected from a systematic sampling frame. As a follow-up to the survey, interviews with 50 administrators who reported different policy choices in key areas will be conducted to further explore our findings. Based on data from these two AIMS, we will present policy recommendations to a group of biobank stakeholders, and using a Delphi process, we will develop consensus about guidelines to present to policy makers and the US biobank community. PUBLIC HEALTH RELEVANCE: This is a study of organizations, called "biobanks," that collect, store, manage, and share human samples, such as blood or tissue, for the purpose of conducting health research. Because this is a new and rapidly evolving industry, it is important to understand how biobanks respond to ethical, legal, and policy concerns that arise from genetic research that relies upon such long term storage and use. We will interview people who work in these organizations about their experiences, in order to make recommendations about the best ways to resolve these concerns.

The purpose of this study is to determine how the prospect of direct benefit to research subjects in gene transfer research (GTR) (usually called 'gene therapy') is understood and discussed by research subjects, investigators, study coordinators, and IRBs, and explained in consent forms. The research team expects to find that the prospect of benefit from receiving the investigational intervention is often exaggerated and that this exaggeration of benefit is accompanied by language confusion in consent forms, blending of the roles of physician and researcher, and other aspects of the review of research and the consent process. To investigate these issues, the researchers will interview investigators, study coordinators, and subjects in up to 40 recent GTR studies, to analyze consent forms and protocols for all GTR studies approved since 1990 (N=about 275), and to interview IRBs at institutions overseeing the 40 studies. They will develop a model that explains the variation in participants' understanding and discussion of benefit from GTR interventions, controlling for contextual factors, within and between these studies. They will separately assess variation in understanding and discussion of benefit in consent forms and by IRBs. The researchers hope to discover some ways of reducing the tendency toward exaggeration of benefit by careful attention to language in the consent form process, by education of investigators and IRB members, and by consideration of research. Based on these findings, the researchers hope to develop an improved policy standard for the presentation of benefit in GTR specifically and clinical research generally.

This sociological study is a prospective field research project on the development of the human genome initiative during the first half of the 1990's. The study is examining how the genomics community goes about trying to build a technological and social system capable of mapping and sequencing large genomes. The study is motivated by the belief that it is likely that: (a) decisions about the technological and organizational structure of the genome project will influence the social impact of the HGP; and (b) decisions about how to manage scientific collaboration on this scale will affect research ethics and practices well beyond the genomics community. For this study, topics of particular interest include the setting of policy agendas; the patterns of collaboration, competition, and data sharing in the genomics community; the selection of technological and organizational strategies; and the interaction of diverse technological cultures (such as molecular biology and computer science). The study is examining the evolution of the HGP through interviewing and participant observation.

This proposal requests funding to support an evaluation of existing regulatory frameworks and their appropriateness for the regulation of new probiotic products that are available in the market or will be available in the near future. The project will include a literature review, review of existing relevant statutes and regulations, and three day-long meetings that will each bring together 15-20 invited participants from the regulatory, scientific, biotechnology, government and academic communities to discuss whether the existing regulatory framework of foods, dietary supplements, and drugs is sufficient to ensure the safety of probiotics and accuracy of health-related claims made by sellers of products with probiotic components. The focus of the proposal is the regulation of probiotic products that are or will be available to consumers for human use without a prescription and probiotic products that are or will be available to human patients in the clinical setting. Additionally, the focus of the study will be only those commercial and clinical products that promote themselves as having, or make health-related claims based on, probiotic properties. The first meeting will focus on the science of probiotics - including the current state of probiotic research, current and future clinical applications of probiotics, current and future commercial uses of probiotics, and a discussion of the benefits and risks of consuming or using probiotics. The second meeting will focus on the adequacy of the current regulatory framework for consumer products that contain probiotics components. The third meeting will focus on developing an appropriate framework for the regulation of probiotics and making regulatory policy recommendations. Following the final meeting, the Investigators will prepare a paper or series of papers, with the help of meeting participants, that will include the following topics: a) current regulation of probiotics; b) documented benefits and risks of probiotics use; c) the adequacy of the current regulatory frameworks for the regulation of probiotics; and d) if appropriate, suggested alternative regulatory models for the regulation of probiotics. PUBLIC HEALTH RELEVANCE: The field of probiotics is a new field that may or may not fit into the current regulatory framework in the United States that is in place to regulate food and drugs for human use. As with all new technologies, it is critical that an interdisciplinary discussion of possible product risks and appropriate regulation take place before uptake of the new technology makes it too burdensome or unrealistic to impose a new regulatory structure on the new technology. This project will explore the current state of probiotics research and identify current and potential uses of probiotics in consumer products and clinical applications. The Investigators will bring together experts in the area of health policy, human microbiome science, and food and drug regulation to discuss the adequacy of the current regulatory frameworks and any potential alternatives in order to provide policy makers with regulatory options designed to protect the public from misleading claims or any potential risks that might derive from the use of probiotic products.

The rush of computers into our workplaces, homes, and institutions is drastically altering how we work and live, how we buy and sell, and with whom we communicate. Computers are obliterating traditional political and organizational boundaries, making time zones irrelevant, and bridging diverse cultures. They are fundamentally changing our culture, values, laws, traditions, and identities. The turmoil of the changes calls into question many old assumptions about privacy, freedom of speech, search and seizure, access to personal and governmental information, professional responsibilities, ethics, criminality and law enforcement. This conference aims to sort out these questions and arrive at a consensus for action through discussion and education. One session will deal specifically with genetic databanking, by providing an overview of genetic databanking, followed by a panel discussion on the tension between an individual's right to privacy and the interests of third parties. DNA forensic data banks and the use of genetic data by insurers will be explored.

The mapping of the human genome has allowed researchers to discover new relationships between genotype and phenotype, and has provided the basis for genome-informed medical decision-making that will lead to diagnoses and therapies that are targeted, have reduced variability, maximize efficacy, and minimize adverse effects. As information of greater health significance is generated by genomic research, there is an emerging consensus that the ethical return of genomic information will be needed. The goal of this proposal is to understand the attitudes of participants in genomic research towards the return of research results in the setting where the participant is a child and the receiver of the information is the parent. We will take advantage of a large genotype-phenotype project initiated by our group at Children's Hospital Boston (CHB) based on the Informed Cohort, a new paradigm for genomic research that we developed. The Informed Cohort is a model for the ethical recruitment of participants into a longitudinal genotype-phenotype registry and reconciles the "paradox" of maintaining participant privacy, yet providing results. We call the implementation of the Informed Cohort model at CHB the "Gene Partnership Project" (GPP). GPP is a longitudinal genotype-phenotype registry that uses a messaging system through the CHB personally- controlled health record (PCHR) to facilitate the disclosure of research results back to the participants. The "Informed Cohort Oversight Board" (ICOB) will provide the crucial oversight of the communication of results back to participants. While the enrollment of children might seem to present additional ethical obstacles, we see the natural participation of the "family unit" that occurs in pediatric hospital as an advantage for GPP. While we have implemented GPP, we do not know what factors will maximize its benefit and appeal for participants and families. We therefore propose a multi-step evaluation of the GPP and the messaging system. We do not know how parents view studies where they receive research results back on their children. To address this issue we will assess the interest of parents to participate in a genotype-phenotype study focused on their children, and determine if they would want to receive genetic information back from the study about their child. We also do not know how participants will perceive the messaging when it occurs. Thus, we will assess the use of the PCHR-based messaging system by parents of participants enrolled in GPP. Finally, a functioning ICOB will be paramount for the process of returning research results to be successful, yet we do not know how the ICOB will function. Since further work is required to ensure that the ICOB is a workable model for decision-making, we will develop the "Informed Cohort Oversight Board". The knowledge gained from the proposed project on the ethical return of research results to participants will be critical as we move towards a paradigm where individuals directly benefit from the genomic research they participate in, and eventually from genomic medicine.

When individuals are queried about whether or not they wish to receive individual research results about themselves that are discovered in the course of genomic research, the majority indicate that they prefer receiving all results, including those that are of limited validity and actionability. These preferences are in sharp contrast to the recommendations of experts who are wary of the potential for confusion and outright harm if questionable results are returned, and thus generally recommend returning only results of high validity and actionability. In this project, we will seek to resolve this tension by empirically exploring the extent to which participant preferences can reliably guide the return of individual research results, and can be incorporated into a governance structure around the return of results which minimizes harm. We are well positioned to gather data on this issue through the Children's Hospital Boston "The Gene Partnership" (TGP), a novel pediatric research registry combining genetic banking, access to CHB electronic medical records, and scalable computer-based systems to ascertain preferences for return of results from the parents of research participants and, ultimately, to return those results. TGP is also unique among large-scale genomic studies, as participants have consented to receive their individual research results. Recognizing that oversight is essential in order to ethically return research results to participants, we have established a panel of medical and ethical experts (the Informed Cohort Oversight Board, or ICOB) to advise TGP on which results should and should not be returned. As we begin to return research results, we propose to build an evidence base to resolve the tension between participant preferences and expert opinion by determining if, and how, participant preferences can be incorporated into the ICOB's oversight of return of results. Participants in our study will be randomized to one of three methods to set their preferences ("all" or "no" results, using a checklist of types of results, or an interactive educational tool and then a checklist). We will provide participants with hypothetical research results to determine whether they fully understand the implications of their stated preferences for research results to receive, and if a novel interactive educational tool helps participants set preferences that more truly reflect their actual preferences. We will also use a combination of hypothetical results and focus groups to study participants' views on the ICOB's criteria for return of individual research results. For participants in whom there are actual individual results to return from whole exome sequencing we will determine the psychological and behavioral effects on TGP participants who receive actual individual research results, and if the method of setting preferences impacts on the effects. At the end of this study, genetic research repositories will better understand the importance of incorporating participant preferences into the governance around return of research results, and the best approaches to accomplish this. PUBLIC HEALTH RELEVANCE: It is important that participants in genomic research benefit from the studies that they are participating in, especially if research results pertain to their current or future health, by choosing what types of individual research results they want to receive (setting preferences). On the other hand, experts fear that participants do not truly understand the implications of their choice of individual research results to receive, suggesting that it is unrealistic to incorporate participant preferences in the return of individual research results. In this project, we will explore the extent to which participant preferences can truly be used to guide governance around return of individual research results.

The objectives of this group research project are to extend the analysis of ethical and social questions raised by the Human Genome Initiative by utilizing insights and methodology recently developed in 4 new subfields of women's studies: feminist ethics, medical ethics, science analysis, and technology studies. The project will use these new approaches in an expressly collaborative methodology, to focus on hopes of, concerns of, and implications for women, especially by seeking and valuing input from potential end-users of HGI discoveries and from groups marginalized by society. During Year I, an explicitly diverse group of 60 researchers will meet in a 3-day Workshop I. A year later, the researchers will convene a final workshop. Results will be presented at a 1-day session open to the public and the media. The P.I., the co-investigators, and several participants will transmit recommendations to private and government organizations. Members will present papers at meetings and follow through on the policy recommendations.

This project will study factors influencing physician's adoption of new genetic tests and their attitudes towards how tests should be provided. It will also begin to explore consumer attitudes. The specific aims of the project include the following. 1) To use a mailed questionnaire to compare physicians who have already offered a carrier test for cystic fibrosis to physicians who adopt the test while this study is in progress and to others who have not yet used it and examine the influence of physicians' knowledge of genetics and genetic tests, their perception of their patients' expectations regarding test use, their experience with and concerns about legal liability, and their sensitivity to whether their patients' insurance can pay for the test or whether they have actually used this test. 2) To use interviews and questionnaires to learn how major health care insurers decide when to include new innovative technologies, such as genetic tests, in their benefits packages and what factors influence their decisions. 3) To develop and lead a Task Force on Genetic Testing to explore and make recommendations concerning a number of issues around the development and use of genetic tests. 4) To hold focus groups of consumers to explore their attitudes toward having presymptomatic genetic testing, their expectations of how physicians would and should respond to this technology, and discrepancies between consumers' and physicians' attitudes. Attitudes of African-American women towards genetic tests for breast cancer will be explicitly considered. The study will, therefore, identify the extent of departures from ethical norms in the diffusion of new genetic tests. It will suggest particular situations in which remedial educational interventions or policy changes could improve the safe and effective delivery of genetic tests.

This project will focus on individuals and families receiving care from a health maintenance organization. The assessment of the ethical and policy issues in CF screening seeks to determine the level of interest in learning more about CF, and factors that distinguish those who are interested in participating in a CF education program from those who are not. For those who decide to participate, the focus consists of three elements: education of the study population; determination of the characteristics that distinguish those who decide to have the CF carrier test from those who decide not to be screened; and comparison of the responses of individuals after they have been identified as CF carriers or probable non-carriers, with emphasis on the extent to which these responses are influenced by marital status, and/or carrier status of the partner. All participants who test positive for CF carrier status and a sample of those who test negative will be followed for one year.

This research aims to improve understanding of the Asian and Pacific Islander population in Hawaii participating in the Hemochromatosis and Iron Overload Screening (HEIRS) Study, and in turn our understanding of minority participants' reactions to and understanding of genetic testing. Using terms most suitable to the purpose and context of research as opposed to administrative categories for race and ethnicity has been recommended for public health research. The term 'Asian' has been found to be too broad and to mask important variations in beliefs and behaviors relevant to health and disease. Within the broad categories used in the HEIRS Study, Japanese, Filipinos, Chinese, and other Asian subgroups, would all mark the same 'Asian' category. However, these groups are known to differ from each other in the prevalence of health conditions, beliefs and behaviors. Specifically, differences between subgroups of Asians have been found in beliefs and behaviors related to genetic testing and counseling. In addition to known health related differences, there is also considerable heterogeneity in socioeconomic characteristics within Asian and Pacific Islander subgroups. These socioeconomic differences are particularly relevant to the HEIRS Ethical, Legal, and Social Implications (ELSI) outcomes of interest. The primary objective of this study is to assess differences in opinions about genetic testing and causes of disease using a measure with detailed Asian and Pacific Islander categories. This will be assessed among 2,761 HEIRS participants, the majority of which are Asians and Pacific Islanders. We hypothesize that there will be differences in opinions about genetic testing and causes of disease among participants originally comprising the same broad categories. We will also determine the proportion of persons who mark multiple categories and discover their primary identification. We hypothesize that at least 1/5 of participants will mark multiple categories and that among this mixed group, attitudes will be similar to those of the group with which they primarily identify. This proposal also suggests that a method of recognizing diversity among Asians and Pacific Islanders is to address groups in terms in which they self-identify. Toward this aim, a secondary outcome is to determine whether demographic questions that include more detailed, subgroup information affect the likelihood of research participation. We hypothesize that a failure to include detailed categories of Asian and Pacific Islanders on the initial HEIRS study enrollment questionnaire reduces the chance that persons of those groups completed the questionnaire.

The National Black Leadership Conference on Genetics will bring together thought, civic, and elected leaders from the black community to learn about human genetics, new developments in genetic technology, future research directions, the application of genetics to health and medicine, and the use of genetic information and technology outside of the medical context. Participants will consider issues for the black community arising from advances in genetics, explore areas of optimism and concern, and identify high priority issues for further collaborative exploration. The outcome of the Conference will be for the participants to identify and prioritize action steps to bring an important voice to the nation's consideration of the development and use of new genetic technologies. The plenary presentations and break out discussions during the two-day meeting will address questions such as why have scientists engaged in a concerted effort to uncover the genetic differences and similarities between peoples from differing geographic origins? How will this information be understood and how does it fit into an historical context? How will this information be used to improve health care? How might other social institutions use this information? What role should participating organizations play in the nation's consideration of the development and use of new genetic technologies to maximize benefits for the black community? Individuals in leadership positions in national and regional organizations focusing primarily on issues of concern to the black community will be invited to participate in the Conference. The Conference will be held in Washington DC in October 2004.

The completion of the human genome project, the creation of unique genetic research resources, and the development of robust genome analysis technology, have provided powerful tools to unravel the genetic contribution to health and disease. Yet, many human diseases are the product of complex interactions between genes and environment. The NHGRI and government advisors have identified the creation of a U.S. longitudinal study to collect environmental exposures, genetic risk factors, lifestyle, and medical experiences from hundreds of thousands of Americans as uniquely valuable. Politically, a study of such enormity and consequence requires that the public support - or at least not actively oppose - its undertaking. Ethically, such a study should be designed and undertaken in cooperation with citizens, after the hopes and concerns of ordinary citizens are sought, duly considered, and addressed. The goal of this proposal is to obtain wide societal input to inform the design and implementation of a possible large U.S.-based longitudinal cohort study of the role of genes and environment in health and disease. The project has three specific aims: 1) Develop and evaluate informational materials describing the goals and design considerations of the large cohort study; 2) Assess public attitudes about the proposed cohort study at the individual level; and 3) Engage citizens and community leaders to assess attitudes and pilot test methods of initiating community-based dialogue. This pilot project will use qualitative and quantitative methods to provide a rich and representative assessment of the public's attitudes and to engage the public in an initial dialogue about a possible large cohort study. The pilot will be conducted in five geographically and demographically distinct locations, as well as nationally using a representative sample. The project will explore specific study design elements and the perceived benefits and risks to participants, communities, and society; engage community leaders; evaluate methods of stimulating citizen dialogue and public consultation; and convene a citizens' advisory panel to provide guidance and assess the effectiveness of these methods for a large cohort study.

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.