The Role of ELSI Research & Policy Activities in the NHGRI Plan

Introduction

As the National Human Genome Research Institute (NHGRI) moves toward a focus on translational research, the role played by research and policy activities that explore and address the ethical, legal and social implications (ELSI) of genetic research must be considered. How should these efforts interact with other areas of genome science research or with the development of public policy? Are there valuable new opportunities to be grasped? What, if any, role should the NHGRI play in education and community outreach? And, how can the success of these ELSI research and policy activities be measured?

Two committees have joined to address these questions: the ELSI Research Advisors (ERA), a standing sub-committee of the National Advisory Council for Human Genome Research that provides advice to the council on the ELSI extramural research program; and the ELSI and Policy Planning Group (EPPG), an ad hoc group brought together to assist in the planning process. ERA and EPPG both met at the first Airlie House meeting in December 2001, and members of ERA/EPPG have participated in the planning workshops over the past year. The following report summarizes ERA/EPPG recommendations based on participation in the planning process1.

ELSI Research and Policy Recommendations

Based on the ideas generated at the planning workshops and the joint deliberations of the two committees, the following five broad recommendations have been developed:

Broaden the scope of NHGRI-supported ELSI research and policy activities.
Encourage research projects that build conceptual and definitional tools that can be used to explore the issues surrounding the next phase of genomic research.
Promote dialogue and integration among researchers working in the humanities, social sciences, genomics and clinical investigation.
Enhance the integration between NHGRI's ELSI research and policy activities
Evaluate and consider reformulating the NHGRI role in education and community outreach activities.

These recommendations are not designed to provide an exhaustive list of high priority issues that should be addressed. Rather they are meant to identify a number of broad steps that the NHGRI can take to strengthen its ELSI research and policy activities to ensure that the institute is well positioned to take on the many issues that will arise as the next phase of genomic research begins. The discussion below describes in more detail each of these recommendations. This is followed at the end of the document by a list of possible practical steps that can be taken to help operationalize a number of the recommendations.

1. Broaden the Scope of ELSI Research and Policy Activities

The breadth of the research effort involved in translating genomic discoveries into health advances points to the need to expand the scope of ELSI research and policy activities in all three of the pillars proposed for the new NHGRI plan: "genomes to biology," "genomes to health" and "genomes to society."

"Genomes to Biology" will involve considerable NHGRI resources in the creation of databases and informatics based on the collection of biological samples and clinical information from large populations. The NHGRI effort will be most successful if it interacts in a synergistic way with other public efforts (e.g., those sponsored by other NIH institutes, other agencies and other countries) and with private efforts focused on practical applications of genomic knowledge. The disciplines of political science, law, economics, history and the sociology of science will have much to offer to this effort by applying knowledge about the social structures that contribute to the development of research priorities, the factors that promote cooperation and competition, and their relative contributions toward the achievement of scientific goals that support public health. Related work could address policies related to intellectual property. In addition, perspectives from law, the humanities and the social sciences can enhance our basic understanding of how new genomic advances and new approaches to genomic research will interact with individual and cultural attitudes and beliefs. Research in these areas can provide a foundation for the development of research approaches that protect the interests and respect the rights of participants from diverse populations while ensuring the effective completion of research in the public interest.

"Genomes to Health" research involves many uncertainties related to clinical integration that can be addressed by ELSI research - for example, questions related to access to genetic services; effective and culturally sensitive counseling strategies; methods to ensure health provider education; criteria for the development of clinical practice guidelines; cost-effectiveness of genetically-based prevention and treatment; health policies related to quality assurance; privacy and discrimination; and introduction and use of reproductive genetic technologies and germ-line gene therapy. Researchers that will be needed to more fully examine these issues will include those with expertise in health economics, health systems, health disparities, behavioral sciences and public health research.

"Genomes to Society" includes broader societal questions, including the societal effects of commercial development of genetic technologies, the implications of different policy approaches to intellectual property, non-medical applications of genomic technologies, genetic enhancement, the varied cultural meanings applied to genetic risk information and the implications of the complicated relationships among the concepts of race and ethnicity and genetics. Individuals with expertise in patent law, forensics and behavioral genetics must be recruited to join the other legal scholars, philosophers, theologians, anthropologists and sociologists currently involved in examining these issues. At its center, this effort should include a rigorous assessment of the language surrounding the Human Genome Project(HGP): Is genomics, in fact, changing human society? If so, how? Is the effect consistent with expectations? Is the effect positive or negative? Is it possible to define how genomics could improve society, or cause harm, and to determine which course we are currently on?

It is critical that active efforts are undertaken in all three areas to engage scholars and community experts from diverse social and cultural communities. This not only will help to ensure that the scholarship undertaken has the necessary richness and breadth of perspective, but also will enable ELSI research and policy activities to address the concerns of broader segments of the world's population.

2. Encourage Basic or 'Tool Building' Research Activities

Basic research in the social sciences, law and the humanities that results in the development of more precise terms and definitions and other conceptual tools that can be used to better understand contextual issues, such as the cultural meaning applied to genomic advances, are essential to the development of effective health and social policy options. This research includes philosophical and other theoretical inquiry into the meaning of genomic science and of the world in which genomic research is progressing. It might include consideration of different worldviews, theological and epistemological systems and how they are affected by genomic advances; the conceptualization of such questions as "what it means to be human;" the implications of genomic advances for distinctions between health care and enhancement, and for concepts of equality and justice. The most urgent areas of inquiry in this domain include:

Genomics and race/ethnicity: Exploration of the factors that influence the continued reliance on and use of racial categories in genomic research; exploration of definitional and language issues (e.g., is race simply a social construct that may have profound biological consequences?); exploration of the appropriate role of ethnicity or ancestral geography in genomic research; analysis of theories of race (current and historical) and their social consequences, alongside new developments in molecular and behavioral genetics.
Genetics, economics and culture: What are the most ethical or just methods for commercializing genomic research? For providing genetically based health care? How do these, and other issues, change on the rich backdrop of other cultures, faith traditions, or countries, particularly developing countries? Will genomics create greater health care divides or have the potential to lessen them? How does/will genome research impact/prevent/or change views of health disparities in different cultural and ethnic communities?
Non-medical uses of genetics: How do we define what is "non-medical"? How does genome research impact on how we view or define health and disease? What will genomics say for defining humanness and differentiating humanness from connections with other species? How can we best study the inevitable and ongoing use of genetic information to legitimate social processes or policies?

3. Promote Dialogue and Collaboration

The isolation of researchers working in law, the humanities and social sciences, genomics and clinical investigation, is striking. Yet all are part of a research continuum that will make possible the translation of genomic discoveries into health and societal benefits. Dialogue is of great value but can also be uncomfortable: vocabulary, meanings and assumptions can differ, negative stereotypes exist - e.g., of the basic scientists who ignore the societal implications of their work, or of the "ELSI police" who impede scientific progress with frivolous fears - and experts from different disciplinary backgrounds may challenge each other's expectations, assumptions and values. Yet the concept of integration of ELSI research and policy activities with other components of genomic biological and clinical research was a frequent theme at the NHGRI planning workshops, in part because genomic discoveries are recognized to have potentially far-reaching impact on society.

NHGRI could promote dialogue and collaboration among these different domains of research in several ways:

Priority-setting. The planning process has deliberately involved diverse viewpoints and expertise. Disagreements about social and research priorities are part of the discussion and are unlikely to be fully or permanently resolved by the current planning effort. On-going cross-disciplinary discussion would contribute to the evaluation of new research opportunities as they arise, provide a forum for evaluation of controversial issues, and serve as the basis for innovative collaborative efforts. A mechanism to assure such dialogue should be developed as part of the planning effort.
Identification of crosscutting research issues. Researchers in law, the humanities and social sciences, genomics and clinical science confront a number of similar research problems. Encouraging the development of multidisciplinary collaborations to explore and address these issues will be crucial. Examples of some of the most critical cross-cutting issues include:
- Definitions of population groups for research purposes; and methods for appropriate community engagement when research involves minority or disadvantaged populations. This discussion might address issues of protection of research participants and individual or group stigmatization resulting from research within defined populations.
- Appropriate methods for family-based recruitment; secondary research participants; disclosure of research results within families. Shared efforts to provide guidance to IRBs on these issues would benefit all NHGRI-supported researchers.
- Methods for consent and protection of confidentiality in the creation of large databases.
Timely identification and integration of ethical, legal and social issues in translational research. As genome research moves forward to the development of health interventions, questions related to their safe and effective application will arise. It is essential that research exploring and addressing these questions be formally integrated into all aspects of biological and clinical research in this area. For example, the initial research to identify metabolic polymorphisms predicting drug response will not address broader social, legal or ethical issues. Although how societal resources are made available for such research is an important question. Once the polymorphisms are known, however, these questions become an important part of the research agenda: Will testing for such polymorphisms reduce adverse drug outcomes sufficiently to outweigh added costs? Are health care providers prepared to use such tests appropriately and effectively? What meaning do patients give to test results? Is test use different when polymorphism prevalence varies in different populations, and, if so, should it be? Will the tests create a genomic underclass?

4. Enhance Integration between Research and Policy Activities

There are many research, health and social policy issues that arise as a result of the genome research supported by NHGRI. Examples include policies and IRB guidelines related to the protection of participants in genomic research; genetic test licensing; access to health care services; development of practice standards for health professionals; discrimination; genetic privacy; and questions related to intellectual property. Of particular concern are issues surrounding the relationship between genetic information and racial, ethnic or other forms of stigmatization and discrimination. At the NHGRI, research into these issues is supported through the extramural ELSI Research grant program - which funds research applications initiated by investigators at 'extramural' universities and organizations and the intramural Medical Genetics Branch - which has a number of investigators who conduct ELSI research. Policy activities are supported through the Office of Policy, Communications and Education (OPCE) located in the NHGRI Office of the Director.

Although NHGRI has participated in some important policy initiatives - notably support of efforts to develop effective federal legislation against genetic discrimination - as a federal agency responsible for funding research it has no mandate to oversee the development of policies in each of these areas. However, the institute and its ELSI research and policy programs have a crucial role to play in the development of a body of knowledge upon which such policies can be built, and the translation of these research findings into coherent options that can be considered by policy makers. For this reason, it is important that the efforts of the NHGRI policy office are closely tied to the ELSI research efforts in both the extramural and intramural research programs, not only so that the policy activities are informed by the research, but also so that the research efforts are grounded in emerging research, health and social policy concerns.

The standard PHS investigator-initiated research and peer review system are not designed to respond quickly to emerging issues. It is therefore critical that the NHGRI develop "rapid response" mechanisms that will allow the institute to quickly and effectively develop appropriate background analysis to address developing policy issues. These mechanisms could include convening expert panels or workshops, commissioning white papers or contracting for targeted research studies, and coordinating National Institutes of Health (NIH)-wide efforts to examine and address these issues. In addition, the NHGRI should make better use of its intramural research program, which has the flexibility to quickly focus its resources on the exploration of emerging issues.

Although ELSI research supported by NHGRI has produced a substantial body of data on a wide array of topics, coordinated efforts to examine a body of data in a systematic manner, and to develop a consensus among the research community as to the most salient findings and their possible implications for public, health and research policies and practices have occurred only in the cancer (BRCA1/2 and HNPCC), Cystic Fibrosis and variation research consortia. There are a number of emerging issues, such as pharmacogenetics, germ line gene therapy, genetic enhancement and the relationship between race, ethnicity, and genetics that need to be more clearly defined before additional research and policy activities can move forward. The NHGRI ELSI research and policy programs should work together to assemble diverse teams of basic science, clinical and ELSI researchers, community members, policy makers and industry representatives to explore these issues, develop precise definitions and identify the most pressing research and policy needs.

5. Evaluate and Reformulate NHGRI Role in Education and Outreach Activities

Assessing the overall value of the education activities funded through the ELSI research program is difficult. These projects have ranged from tightly focused pilot tests of health professional education curricula to somewhat more amorphous television-based public information projects. As an extramural research program that relies on investigator-initiated studies, the ELSI research program has not been in a position to develop a well-defined and systematic approach to these education projects. In addition, the research grant may not be the most effective mechanism for ensuring the development of high quality educational interventions that will be useful, effective and widely disseminated.

Although close to a quarter of the ELSI budget has been devoted to educational projects, and many highly regarded educational interventions have been developed, their impact on genetic literacy among health care providers or the general public is uncertain. A comprehensive assessment of the effectiveness of the education projects funded to date is needed. Evaluation is made difficult, however, by the diversity of the projects and by confusion about their ultimate goal. Are they intended to provide rigorous education to achieve specific learning objectives for defined target audiences, or are they intended simply to communicate information about genome research and ELSI to a broad public audience, or to specific communities? There has been little educational research into the genetic literacy and information needs of various populations, or into how individuals can most effectively learn about genetic and ELSI issues. The ELSI program has rarely funded this type of research and yet there is a clear need for more data on educational needs and what works and why. Given the limitations of the ELSI research program budget and the apparent inappropriateness of the traditional grant mechanism for supporting the development and dissemination of effective educational interventions, the NHGRI should consider re-focusing ELSI resources on education research, rather than curriculum development.

In addition to the ELSI education activities, both the NHGRI Office of the Director (OD) and the Office of Science Education (OSE) are involved in a wide array of education, communication and outreach activities. However, these activities seem to be somewhat ad hoc and reactive in nature and are also rarely if ever evaluated. There is little or no coordination among the extramural ELSI, OD, and intramural OSE education activities. Assessment of all ongoing education and outreach activities at NHGRI is needed, and a mechanism for priority setting and coordination should be developed. Attention should be given to the possibility of "re-purposing" some of the ELSI research funds used to support educational and community outreach activities to other NHGRI offices to allow for a more effective approach to the development of such initiatives.

Practical Steps

Many of the recommendations identified here may require targeted funding approaches, either through Requests for Applications (RFAs) or, for those topics that require more immediate and focused attention, through contracts and commissioned studies. Consideration should also be given to using an expedited clinical trial model, such as that being used in other institutes, to study clinical integration issues. NHGRI should coordinate their efforts with those of other institutes. Workshops could be used as needed to refine priorities. Finally, careful attention will need to be given to the development of evaluation metrics to more fully measure the strengths and weaknesses of these activities. A more detailed discussion of the development of these evaluation metrics is contained in the Appendix.

The following examples of additional specific steps that can be taken to strengthen ELSI research and policy activities were gleaned in large part from the discussions at the planning workshops.

Specific activities to support a broadening of ELSI research and policy activities include:

Mechanisms to reach out to research communities that are currently underrepresented in ELSI research. (This could include workshops at institutions or professional meetings and invitations to scholars in different disciplines to participate in NHGRI-sponsored activities.)
A community engagement mechanism to strengthen interactions between ELSI researchers and communities that have particular interest in or concerns about genomic research. (This could take the form of small workshops focused on specific issues that would bring together ELSI researchers examining these issues and the members of the communities that would find the information generated by this research of greatest relevance.)
Sustained and coordinated effort to recruit and retain students from a broad range of academic disciplines and cultural backgrounds in ELSI research. (The ELSI program has established a number of new initiatives in this area, but these need to be advertised more effectively and their impact should be tracked and evaluated.)

Mechanisms to encourage dialogue and collaboration include:

Structural rewards for multidisciplinary research efforts, e.g., grant mechanisms that reward cross-disciplinary work, fellowships that involve trainees across disciplines.
Multi disciplinary workshops on topics of high priority to identify crosscutting issues.
Training efforts, e.g., one- to six-month fellowships for cross training of ELSI and genomics researchers; intensive genomics summer course for ELSI researchers; week-long summer 'camps' or workshops that would bring together ELSI and genomics researchers to get to know each other and each others' methods and approaches.
Support for projects that focus on the dissemination of ELSI research findings to the genomic research and health care communities. (Could use the model of the NCI Specialized Programs of Research Excellence (SPORE) that focus on the rapid translation and dissemination of information from molecular biology to the bedside.)

Mechanisms to strengthen tool-building research and enhance the integration of ELSI research and policy activities include:

Support for Gordon-style weeklong summer institutes focused on particular research questions and policy issues.
Development of additional topic-specific research consortia like the ELSI cancer, cystic fibrosis and genetic variation consortia, for establishing linkages among current ELSI researchers (and relevant basic and clinical science researchers), to avoid duplication of effort and initiate intra-project analysis and the development of policy options or clinical guidance.
Development of mechanisms to identify topics appropriate for consensus development processes.

Conclusions

The translation of the findings of genomic research into improved health outcomes will require an expansion of ELSI research and policy activities to include a broader array of expertise in such fields as public health, health economics and political science. Continued and rapid developments in the availability and use of genomic information will require ongoing efforts to explore and understand how this information interacts with concepts of cultural and individual identity and responsibility. To ensure the success of both of these efforts, it will be essential that mechanisms are developed to strengthen communication and collaboration among genomic, clinical and traditional ELSI researchers in law, the social sciences and humanities. In addition, to facilitate the translation of the findings of this expanded and collaborative research into more effective research, health and social policies and practices, the NHGRI must ensure the close coordination of their policy and research activities and the development of "rapid-response" mechanisms to address rapidly emerging and evolving issues. Also, in order to maximize the accurate and effective dissemination of new genomic information, the NHGRI will need to assess the effectiveness of its current education and outreach. Finally, with the ongoing maturation of the ELSI programs, it is essential that metrics be developed to effectively evaluate this rich and diverse body of research and policy activities.

APPENDIX

Evaluating ELSI Research and Policy Activities

The following schema for organizing the portfolio of NHGRI activities and determining the success of individual projects identifies three basic categories of research, provides examples of parallels between the three NHGRI research pillars - "genomics to biology," "genomics to health," and "genomics to society" - and suggests the criteria by which success could be measured for each category of research. Any given individual project may include activities in one, two or all three of these categories and may span all three pillars. The final "outcomes" category at the bottom of the chart includes product, policy or standard development. These outcomes represent the ultimate goal of research in all categories, but they are not within the purview of the NHGRI or NIH and cannot be used as an ultimate measure of the success of the funded research.

Type of Research	Genomes to Biology	Genomes to Health	Genomes to Society	Success Criteria
Tool-building	Maps and sequences	Delineate genetic vs. environmental factors in health	Define ethical, legal and social contexts, terms and concepts	Are results used in subsequent research or policy development?
Tool utilization and Data/Resource Development	Functional & comparative genomics; proteomics; haplotype map	Genotype/ phenotype correlation studies; prevalence/penetrance studies; clinical integration studies	Normative analysis; ethnography; legal, historical, political science and other social science analysis	Are results well-justified? Robust? Provocative? Do they improve understanding or outcomes?
Applications	$1000 genome; computational cell model	Genome based diagnostics & therapeutics	Social policy options and research practice guidance	Do benefits of the applications outweigh possible harms?
Outcomes	Biomedical products (by product-makers, i.e. industry)	Practice standards for genetically-based interventions (policy-makers& professional organizations)	Social policy and research practice standards (by policy-makers, governing bodies, OHRP, etc.)	Does the product sell? Does it improve health outcomes or policy development?

The first type of research, tool-building, can be seen in the development of maps and sequences in "genomes to biology" research, the delineation of genetic versus environmental factors in "genomes to health" research, and the development in "genomes to society" research of standard and well defined contexts and concepts for the identification, clarification and examination of the implications of genomic research. The second type of research, tool utilization and resource development, is represented in the "genomes to biology" community by research looking at how genes function (also called "functional genomics"), in the "genomes to health" community by genotype/phenotype correlation studies and in the "genomes to society" community by normative analyses to better understand the interplay between genetic information and the ethical issues and values of individuals, groups, and societies. The third area, applied research, is exemplified by the development of the $1,000 genome by "genomes to biology" researchers, the development of gene-based diagnostics and therapeutics by "genomes to health" researchers, and the development of social or research policy options by "genomes to society" researchers.

Whether one is evaluating scientific genome research or research on ELSI issues, evaluation metrics for each of these research stages across all three pillars will need to address three general questions:

Does the research provide new ideas, concepts or interventions that are used by others?
Does the use of these ideas, concepts or interventions confirm their value or improve outcomes?
Does the research or policy activity facilitate the translation of ideas into applications that promote health and other societal benefits?

For any specific ELSI project, some questions may be more important than others. Thus, foundational research is measured primarily by its capacity to generate new ideas that are used by others, while evaluation of research focusing on health applications will emphasize the outcomes resulting from new interventions. This organizational structure and set of measurement criteria can serve as a first step in the development of a much-needed comprehensive evaluation strategy for ELSI research and policy activities.

¹Given the short time frame between the final planning workshop on "Genomes to Health" and the November Airlie House meeting, it was not possible to develop a document that would capture all of the complexities of the issues raised during the year long planning process. This document should therefore be seen simply as a rough attempt to summarize a numer of the important themes that arose during this process, and not as a final consensus.

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Last updated: April 01, 2006

The Role of ELSI Research &amp; Policy Activities in the NHGRI Plan