2
Workshop Presentations

OPENING REMARKS

Lawrence O. Gostin, J.D., L.L.D.

Committee Chair


The speed and acuity of scientific innovation since the mapping of the human genome has been marvelous. However, it is important to remember that much of this scientific innovation has only been the means to a benevolent end. That end traditionally has been improving the health of individual patients through the use of genetics and family history for diagnosis, prognosis, and clinical interventions. Genetic testing and genetic information initially provided only modest but important benefits such as reproductive counseling and life planning. Today, the potential for clinical prophylaxis and treatment, including the possibility of genetic treatment, is stunning.

At the same time that genetics offers this remarkable promise of benefit in clinical medicine, it raises a host of ethical, legal, and social concerns. For example, should genetic information be kept strictly private, and should patients receive special legal protection against discrimination in employment and insurance? Do physicians or even patients themselves have an ethical or legal obligation to inform family members who may be at risk? In focusing so much attention on the importance of genetics to health, the question of whether genetics is really different from other areas of science and medicine has yet to be addressed. Is the importance of genetics sufficiently different to justify genetics exceptionalism? Fortu-



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary 2 Workshop Presentations OPENING REMARKS Lawrence O. Gostin, J.D., L.L.D. Committee Chair The speed and acuity of scientific innovation since the mapping of the human genome has been marvelous. However, it is important to remember that much of this scientific innovation has only been the means to a benevolent end. That end traditionally has been improving the health of individual patients through the use of genetics and family history for diagnosis, prognosis, and clinical interventions. Genetic testing and genetic information initially provided only modest but important benefits such as reproductive counseling and life planning. Today, the potential for clinical prophylaxis and treatment, including the possibility of genetic treatment, is stunning. At the same time that genetics offers this remarkable promise of benefit in clinical medicine, it raises a host of ethical, legal, and social concerns. For example, should genetic information be kept strictly private, and should patients receive special legal protection against discrimination in employment and insurance? Do physicians or even patients themselves have an ethical or legal obligation to inform family members who may be at risk? In focusing so much attention on the importance of genetics to health, the question of whether genetics is really different from other areas of science and medicine has yet to be addressed. Is the importance of genetics sufficiently different to justify genetics exceptionalism? Fortu-

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary nately, Congress had the foresight to set aside 5 percent of all human genome funding to address the ethical, legal, and social implications (ELSI) of genetics. There is another, deeply important benevolent end of the Human Genome Project, and that is improving the health of the public. Until recently, genetics has been primarily interested in discrete but rare genetic diseases such as cystic fibrosis and Huntington Disease, diseases with high penetrance but relatively low prevalence in the population. However, what if genomics could help explain the causes of and responses to common chronic diseases that affect so much of the population: diseases such as cardiovascular disease, diabetes, various forms of cancer, schizophrenia, severe depression, and so on? What if genetic knowledge was used not only to benefit individual patients, but to benefit whole populations? What if genomics could help illuminate the critical interactions that science has been trying to understand for decades, those dynamics between innate characteristics and such things as diet, the environment, and behavior? This would truly be a revolution in public health, and we may be on the cusp of that revolution. Public health genomics would bring new meaning to the Institute of Medicine’s famous definition of public health as being “what we, as a society, do collectively to assure the conditions in which people can be healthy.” Public health genomics may bring new and deeper understanding of important problems in medicine, science, and public health. For vaccines and pharmaceuticals, for example, public health genomics can help us answer such questions as why vaccines and pharmaceuticals work on certain people but not on others, why they are more effective in some areas and not in others, and why they produce adverse effects in some areas but not in others. Ethical, legal, and social implications of public health genomics must also be considered. A penetrating inquiry about social justice is needed. Will the benefits and burdens of population-based genomics be distributed fairly throughout society or concentrated with a privileged few? During this workshop, these important, but very difficult questions will be asked. It is the hope of the committee that the information presented will help provide a blueprint for future research, planning, and understanding in this exciting area at the intersection of medicine, public health, law, and ethics.

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary GENOMICS AND PUBLIC HEALTH: A VISION FOR THE FUTURE Gilbert S. Omenn, M.D., Ph.D. The emerging and important field of genomics bridges many disciplines. There is an avalanche of new genomic information, including new knowledge about single nucleotide polymorphisms (SNPs), haplotype blocks, and candidate genes and alleles, as well as their association with disease. However, effective linkages with much better environmental and behavioral data sets are necessary so that ecogenetic analyses (i.e., the combination of interactions of environmental and behavioral factors with genetic variations) can occur. Ecogenetics has a long overdue role in occupational, environmental, and regulatory decision making. Credible privacy, confidentiality, and nondiscrimination policies are essential to advancing this field. Breakthrough tests, vaccines, drugs, behavioral initiatives, and regulatory actions are envisioned to reduce health risks and treat patients more cost effectively in this country and globally. Recently, a state policy guide was developed by the Partnership for Prevention group entitled “Harnessing Genetics to Prevent Disease and Improve Health.” The goals of the report were to help state policy makers protect consumers; monitor the implications of genetics for health, social, and environmental goals; and assure that genetic advances be used not only to treat medical conditions but also to prevent disease. One of the key recommendations was that genetics and genomics be integrated into existing health, social, and environmental policies rather than establishing stand-alone genetics programs. There are many reasons for integrating genetics into existing policies. First, virtually all health conditions have a genetic component. Second, most common diseases arise from gene–environment interactions; therefore, genetic advances are likely to extend and expand current practices in medicine, public health, and environmental protection. Third, some genetic variations are associated with greater health risks than others, and covering this wide variability with a one-size-fits-all genetics policy would be inappropriate. A combination of science, ideas, and technology facilitates new ways of thinking that bring about new kinds of experiments. The grand vision is one of personalized, predictive, and preventive health care and community health services in both medicine and public health. There are a number of key challenges in this genomic era. The first challenge is to strengthen the sense of commitment to prevention along our public health and clinical medicine continuum. The second challenge is to think of ways we can apply new technologies and new knowledge to global infectious and chronic disease, not just those we already recognize in this country. The third challenge—one very important to our entire

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary understanding of human health—is to recognize the heterogeneity among patients within any diagnostic category and among populations. Another challenge is to use the interpretation and computational analysis of gene expression profiles, microarray experiments, comparative genomics, and proteomics in the development of mechanism- and evidence-based medical practice. Finally, there is the challenge of integrating genetic, environmental, and behavioral factors in preventing and treating illnesses. In chronic diseases, there is a need to know a lot more about variation, risk, and how to motivate people to take actions within their own control by providing knowledge about their risks and the modifiability of those risks. Concomitantly, credible privacy, confidentiality, and nondiscrimination policies are necessary to effectively translate genetics research into population health benefits. Supporting the whole endeavor are information sources about genetic variation. For example, the International HapMap Consortium aims to genotype at least 1 million SNPs from 270 individuals to facilitate the study of direct associations of individual SNP alleles with disease phenotypes. This will include careful analysis of the linkage disequilibrium, which represents a more powerful approach than the traditional linkage-based analyses. Another key support for translation of genetic research into population health benefits is the CDC-funded Centers for Genomics and Public Health. The leaders and staff in these institution-based centers have worked closely with the CDC to advance the whole field and are a major source of support for developing an effective public health workforce and infrastructure. Sequencing and analyzing the human genome is generating genetic information that must be linked with information about nutrition and metabolism, lifestyle behaviors, diseases and medications, and microbial, chemical, and physical exposures. Genetics must be included in protocols for health promotion and disease prevention research (e.g., host–pathogen interactions, risk factors for chronic diseases, and drug or vaccine development). Using the field of toxicogenomics as an example, risk assessment and risk management must move beyond consideration of one chemical, one environmental medium (air, water, soil, food), and one health effect (cancer, birth defect) at a time. This will require that multiple molecular signatures and biomarkers be integrated with a comprehensive public health view. It is important to take advantage of the fact that there are multiple sources for the same agent, multiple media/pathways of exposure, multiple risks/effects of the same agent, and multiple agents causing the same effects in order to understand the status and trends of disease, formulate

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary ecological models of health, and take into consideration social, cultural, and environmental justice. This is a golden age for the public health sciences. But the best way to reap the benefits of all the developments and advances in genetics and genomics is to bring this information together with other crucial non-genetic variables. One framework for pulling this all together comes from regulatory decision-making that begins with hazard identification, then moves to risk characterization, and finally focuses on risk reduction. Currently, attention is focused on identifying genetic variations and their accompanying disease susceptibilities. Regulatory laws should be used to advance the genomics research agenda. For example, the Office of Safety and Health Administration (OSHA) Act requires that health standards be set so as to protect—that is, no individual, even if exposed at the level of the standard for a working lifetime, shall suffer any adverse effect. Genetics should be used to identify and define those individuals at risk of suffering adverse effects. Another example comes from the Clean Air Act, Section 109, in which ambient air quality standards are set so as to protect the most susceptible subpopulations with an adequate margin of safety. Genetics can help define those susceptible subpopulations. There are experts on most sides of contentious genetics issues. What is needed is better science and better risk communication. One of the ways risk communication might be improved is by identifying specific molecular signatures that would tell people whether they have been exposed to the agents or combinations of agents. If they have early effects, the effects might still be highly reversible. Research by the Center for Toxicogenomics at the National Institute of Environmental Health Sciences (NIEHS) and academic centers around the country is focused on identifying molecular signatures of the model compound acetaminophen. It is important to test other compounds, especially known carcinogens and chemopreventive agents, which could guide us to new ways to take action on the preventive side. In all of this work on environmental exposures, it is very important to move beyond the traditional regulatory approach of examining one chemical, one medium, and one health effect at a time. In 1997, the Commission on Risk Assessment and Risk Management recommended that these issues should be put in broader contexts. Multiple sources of the same agent, multiple pathways of exposure, multiple risks of effects of the same agent, and multiple agents causing the same effects should be considered. Additionally, the Framework for Risk Management developed by this commission is an important model to emulate in genetics. The many different stakeholders need to be engaged from the start to put problems into their proper context, define risk assessment, investigate options, work up decisions, take action, and then evaluate what has been done.

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary From a policy point of view, there are many things that need to be done to facilitate translating genomics into improvements in the public’s health. For example, the case was made above for integrating genetics into existing policies. Decisions about genetics policy involve many complex issues about ethics, costs, benefits, individual interests, and societal interests. Medical care decisions must be linked to research, to insurance policies, and to broader public health policies. The intersection between genetics and public policy is both immediate and long term, warranting close monitoring and timely actions. One area that needs particular attention is the criteria for population screening using genetic tests. Several key recommendations for health policies advanced by the Partnership for Prevention should be implemented, including (1) increase consumer knowledge of genetics, (2) strengthen public health infrastructure to accommodate genetics developments, (3) add genetic competencies to licensing requirements for all health professionals, (4) increase supply of qualified genetic counselors, (5) invest in a broad genetics research agenda. Several key recommendations for state policies include (1) protect individual privacy while meeting information needs for public health tracking systems and approved research; (2) put one state agency in charge of handling reports of discrimination and privacy breaches; (3) help state universities expand genetics education and training; (4) convene insurers, employers, consumer groups, and health professionals to resolve barriers to timely availability of affordable genetic services; (5) require that genetic services financed by the state are valid, reliable, and useful; and (6) establish a coordination process to integrate genetics into policy and programs, starting with the broad public health agenda. Finally, greater effort must be made to engage communities in ethical, effective, and timely community-based studies. This includes involving community members from the earliest stages to have a real influence on the project. The research processes and outcomes should benefit the community, and community members should be part of the analysis and interpretation of the results. This type of investment should create productive partnerships that continue beyond a specific research project and should ultimately empower community members to define and initiate their own projects.

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary THE SCIENCE OF GENOMICS AND ITS APPLICATION TO COMMON DISEASES Aravinda Chakravarti, Ph.D. It has been widely predicted that genomics will soon allow us to unravel the genetics of most common diseases and will provide a mechanism for risk prediction for individuals susceptible to a variety of complex disorders. This presentation is intended to provide a background on the science of genomics while addressing the following questions: How can one gain information concerning complex disease genetics? How can this information be used in individuals and their families for risk prediction? How can this information be used to prevent disease, delay its occurrence, modify its severity, and/or develop specific therapeutic measures? In assessing the application of genomics to common diseases, there are four perspectives outlined below: the importance of genome sequence to identify genes, identifying functions of genes through comparative genomics, identifying disease genes/processes through large-scale association studies and transcript analysis, and proving function by chemical genetics. Genetics research is at a crossroads, evolving from work that focused primarily on rare Mendelian disorders to that of complex common diseases. Several old controversies have to be dealt with, including Mendelian versus biometrician approaches, the genetic load controversy, and biochemical/ molecular versus evolutionary mechanisms. The Human Genome Project and new DNA (deoxyribonucleic acid) sequencing data can provide numerous insights into disease mechanisms, and we are now beginning to understand gene function and disease pathogenesis. Common diseases appear to be caused by interactions of some genes with major effect and high penetrance, but also by multiple genes, each with small effect and low penetrance, all of which will interact with environmental factors. For these diseases, simple Mendelian inheritance will be the exception rather than the rule. For instance, research on Hirschsprung disease, which shows no simple Mendelian pattern of inheritance, indicates gender predilection and geographic and ethnic differences in prevalence. Now several genes have been identified, each with small effect, out of many that remain unknown. In addition to our current knowledge of genes, which pertains primarily to the coding sequences of the genome, many other mutations must occur in the non-coding parts of the genome, which make up the vast majority of human DNA; there is still much to learn about the effect of mutations in these areas. The HapMap project, which will enable us to pinpoint millions of SNPs and many genes with small effect, will be con-

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary cluded in a few years, enabling the study of a great amount of human genetic variation. This new technology will facilitate efforts to sequence the genomes of multiple individuals, and the interpretation of these changes will likely be based on computational biology. The interaction between these multiple genetic predispositions and specific environmental factors will provide important information about how to reduce the burden of these complex disorders on both individuals and the population. For example, recent data on the interaction of gene mutations with environmental factors in fetal alcohol syndrome show that some diseases previously considered to be totally environmentally based have differences in genetic susceptibility and may now be explained in part on molecular genetic grounds. Thus, the genetic basis of complex common diseases, the specific environmental factors involved in each of them, and the molecular/chemical basis of these interactions will be important in developing population-based approaches to disease control and eradication. BRIDGING GENOMICS AND POPULATION HEALTH Sharon Kardia, Ph.D. One of the biggest issues in the emerging genomics revolution is how to create a bridge between the great scientific advancements that are emanating from genomics and improvements in population health. Conceptually, it is necessary to consider the individual in the context of his/her environment. The genomics revolution, in the broadest sense, is bringing to our awareness the rich tapestry of the biological hierarchy, moving from the tremendous variation in an individual’s genome to its manifestation in the expression of the genome (i.e., the transcriptome) that translates into the basic metabolic machinery (i.e., the proteome) and its impact on a person’s metabolic profile (i.e., the metabolome) that underlies disease processes. It is important to recognize that the same processes that feed information from the genome to the disease process are also feeding information about a person’s internal and external environment back through the metabolome to the proteome to the transcriptome. All of this is happening within the context of people’s day-to-day lives. The scientific and technological revolutions occurring right now are breaking down the barriers to gathering the high-dimensional biological information1 needed to understand the continuum between health and 1   High-dimensional biological information is all the data (i.e., information) obtained from the “omic” science and technologies (genomics, transcriptomics, proteomics, metabolomics).

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary disease. The availability of genome-wide and candidate gene SNP panels, gene expression array technologies, and proteomic and metabolic profiling are at an all-time high. However, the emerging data have not yet provided sufficient explanations for the chronic diseases and infectious diseases that affect the population’s health, nor have the data been fully applied to concerns about occupational health and health behaviors. In building bridges between these worlds, it is important to monitor our advancements in terms of an overall conceptual map of the intersecting continua of research and practice that affect the continuum between individual and population health. One model of genomic medicine—that is, one model of a bridge between genomics and the public’s health—is to collect all the genomic, transcriptomic, proteomic, and metabolomic information on an individual that is possible. Then it is necessary to make the information available in a user-friendly fashion so that the average physician can improve diagnosis and treatment, thus reducing health care costs and improving health outcomes. In order for this model to work, there needs to be a tremendous amount of research behind the scenes. A major scientific issue is how to get such vast amounts of integrated information across the biological hierarchy in patient and population studies to provide the evidence base for transforming medical practice. Another key question is, How must linear, single-agent based concepts of disease be revised in the face of information about the huge collection of interacting agents that underlies human biology? The “omic” technologies are revolutionizing our understanding of biology. New language and concepts are needed to convey and compress this high-dimensional data into useful information and knowledge. Molecular profiles, signatures, and patterns do not easily translate into current understandings of causality. What is causality when everything is related to everything else in the cellular milieu? This brings up new issues or principles in biology never addressed, such as redundancy in human genetic and metabolic systems or the concept of balance across multiple systems. Extensive genetic knock-out studies show that there is a large compensatory or adaptive aspect of human biological systems that must be understood in order to build a bridge between genomics and population health. Many challenges exist in attempts to bridge the worlds of genomics and population health: The challenge of etiological heterogeneity of the common diseases. The need for better methods for measuring disease processes, environments, and behavior. The ability to collect high-dimensional “omic” data far exceeds the ability to measure the core aspects of disease and the

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary external or human factors that will form the interventions of tomorrow to improve human health. The daunting complexity of considering all the possible underlying gene–environment and gene–gene interactions. The need for large, expensive, clinical and population-based cohort studies that build the necessary evidence base for translation into practice. The need for improved informatic capacity to translate and integrate diverse sources of information and data into new knowledge, as well as the informatics support for translation into practice. The lack of high-dimensional statistical methods for analysis and compression of these rich data sources. The climate of fear about genetic information among the public and health professionals. The challenge of educating health professionals so that genetic information can be used appropriately and accurately. The lack of clear evidential standards set forth by the scientific community or federal agencies that could be used by a body such as the U.S. Preventative Services Task Force to inform medical and public health professionals about the level of confidence and the utility of genetic information. Support for translating genomics into improvements in the public’s health requires development and support of an emerging public health genomics model. The United States has great public health services, departments, agencies, and organizations. Schools, churches, hospitals, and community organizations help people throughout their lives by providing connections that allow health to be promoted, prevention efforts to be enhanced, and population-based screening approaches to be implemented. There are many ways in which the established public health infrastructure and other public and private networks can be used to support the translation of genomics into improvements in the public’s health. For example, by partnering with academic institutions, departments of health can provide culturally responsible avenues for genetic research that utilize existing newborn blood spots, childhood and disease registries, and local environmental and behavioral risk assessments in order to provide research feedback about the local population’s genetic risk and disease-prevention possibilities. In addition, departments of health are ideal partners for community-based participatory research programs that can be used to fill the gaps between health professionals in the community, academic partners, and public health practice. Other types of support that are already available to help in this translational area are the population-based cohort studies such as the National

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary Health and Nutrition Examination Survey (NHANES), the Framingham Heart Study, the emerging National Childhood Study, and many others that have extensive longitudinal data and biological samples in hand. Importantly, some cohort studies already have mechanisms for distributing samples for “omic” measurements that are then compiled into central databases that can be used by the entire research community. These resources, as well as other biobanks, and data resources (e.g., clinical and behavioral intervention trials) are a very cost-effective way of conducting research critical to facilitating translational outcomes. One approach to providing a solid evidential basis for genomic medicine and public health genomics, and moving beyond linear, single-agent–based ideas of disease, is to create a risk assessment framework to guide the trajectory of scientific investigation and to facilitate decision making. The risk assessment framework used in the environmental health sciences provides a useful template for creating genetic risk assessment standards in population health research. The three main areas of research needed fall into the categories of genetic risk identification, genetic risk characterization, and genetic risk reduction. Genetic risk identification encompasses genetic epidemiological research, gene–environment interaction studies, animal genetic modeling, as well as bioinformatic research and ultimately complex system modeling. Genetic risk characterization focuses on understanding how genetic risk factors influence disease development and manifestation. This research focus necessarily involves longitudinal studies to characterize the genetic probabilities of developing disease, extensive “omic” analysis of the causal chain of events, in vitro studies of the identified processes, and development of animal models. From this evidence base, novel methods for genetic risk reduction could then be tested in clinical prevention and intervention trials, population prevention and intervention trials, and pharmacogenetic trials. In order to support this type of research, medical and public health informatic systems will need to be developed. Furthermore, there is a need for new research paradigms such as community-based participatory research to address the psychosocial aspects of performing genetic studies in the public arena. In addition, high throughput “omic” measurement centers and the availability of biological samples and high-quality data from clinical trials and cohort studies will also be needed to facilitate an overarching scientific program that begins with genetic risk identification, moves to risk characterization, and then tests methods of genetic risk reduction. The community-based participatory research paradigm is ideally suited for addressing the multitude of issues that arise in translational studies of genetics and genomics. By engaging community stakeholders in the development of research questions, in conjunction with academic

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary prevention unless it is specifically prohibited by law or rule. Finally, there is a large segment of the U.S. population that has no third-party coverage. These payers have concerns. They want to know when genomics will be important, what it is going to cost, what the value added will be, whether testing will affect patient behavior, what the time frame for return on investment is, and whether there is a capable provider network. The answer to all these questions is that no one knows. Payers have to consider a number of factors: Medical care costs are escalating, new pharmacy is expensive, and new technology costs more and is additive (old technology is not eliminated when new is added). Payers must try to determine where to draw the line in terms of what is offered to an individual: Is it complete ascertainment, which is going to cost more, or is it what is reasonable for a population? Two current programs can help us think about the financial and access questions surrounding integration of genomics into health care: newborn screening and population carrier screening. Newborn screening began in the 1960s, incorporated new technologies that became available, is a public–private interaction, is present in all 50 states (although the number of disorders screened for ranges from as few as 3 in some states to more than 60 in others), and is considered a successful program. Criteria for newborn screening require that disorders have a high relative frequency in the population; in addition, tests must be easy, inexpensive, reliable, and able to be performed on a blood spot. The tests have to have acceptable positive/negative predictive value, and effective treatment or cure must be available. Disorders that meet all the criteria and are tested for include phenylketonuria (PKU), galactosemia, congenital hypothyroidism, and congenital adrenal hyperplasia (CAH). Selected population screening is also conducted, for example, Tay-Sachs, sickle cell carrier screening, and screening for Down syndrome in pregnant women of advanced maternal age. In this setting more problems begin to arise. It is sometimes the case that solutions involve highly charged issues; for example, the decreased incidence of Down syndrome in this country has been achieved by termination of affected pregnancies, which some find to be unacceptable intervention. Some insurers pay for testing only if a woman pledges to terminate the pregnancy. Other insurers are paying for pre-implantation genetic diagnosis in order to implant only those embryos that are known to be unaffected. There is also the problem that screening is extended, sometimes because of political or legal pressures, to disorders for which interventions are less effective. Lawsuits are also being used to try to expand screening. For example, the parents of a child who died of MCAD (medium-chain Acyl-CoA dehydrogenase deficiency) are suing the state, claiming that

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary the child could easily have been screened for this disorder but was not screened, and as a result the child died needlessly. Payment for screening is a blend of public and private funds that varies from state to state. Furthermore, in most states payment for follow-up treatment is provided by third-party payers, which can be problematic if treatment includes one of the standard insurance exclusions, for example, dietary supplements or hearing aids. There is great concern about the potential for discrimination. However, there have been no well-documented cases of genetic discrimination in health insurance, and many state laws already prohibit such discrimination. In summary, it is important to recognize that rather than a well-organized health care system, what exists is complicated and includes multiple systems and multiple payers. Payers do not know what to do about genetic testing. They need a paradigm for screening that includes high relative frequency in the population, and they need easy, inexpensive, and reliable tests that can be performed on a blood spot or maybe a multiplex chip. Payers also want these tests to have acceptable positive and negative predictive values, and they want effective interventions or treatments. What payers are likely to get is pressure from industry to implement tests before answers are known, political coverage mandates, and pressure from consumers and lawyers that will result in increased cost with minimal increased benefit. LEGAL AND REGULATORY Ellen Wright Clayton, M.D., J.D. with the assistance of Julie Schreiner-Oldham The focus of this section is to identify legal and regulatory barriers to ensuring optimal use of genomics to improve the health of the public, specifically in the areas of surveillance, assurance, and policy development. The provisions of HIPAA and the new interpretation of the Common Rule by the Office of Human Research Protection (OHRP) permit most surveillance activities. A number of states have passed genetic privacy laws that can be more stringent, yet they are often tempered by the state’s desires to obtain information for public health purposes. During this workshop, much has been said about the incredible importance of research that uses large databases with well-characterized clinical and exposure information. This past decade has seen much discussion about the ethical and legal controls for this type of research. Two months ago, however, OHRP issued a new guidance saying that if inves-

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary tigators have access to coded information that they believe cannot be traced back to an individual, then that information is not covered by the Common Rule; there need be no Internal Review Board (IRB) review even if the researchers abstract the information from an identified medical record. Furthermore, OHRP stated that because such research is not subject to IRB review, they recommend that health care institutions identify someone or some entity that would assure the coding was actually done in a way that protected the privacy of individuals. However, the OHRP exemption does not apply if one is creating a repository for research purposes, thereby creating incentives to use a hospital database or clinical record because it will be easier. This OHRP guidance is a radical change that presents us with two major problems. First, individuals want to know when information about them is being used and, more importantly, they want ethical oversight. The change will undermine public trust in a major way. Second, good phenotypic information is important. However, all clinicians know that information in a clinical record is not very good; there are many mistakes. Given that this new guidance will move us toward using hospital pathology samples and clinical information, our data will not be as accurate. Major problems exist in ensuring the appropriate use of genomic information. There is a long history of efforts to create guidelines for testing: the Watson/Holtzman committee of the mid-1990s; the Secretary’s Advisory Committee on Genetic Testing (SACGT), which was dissolved and replaced by the Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS); the efforts of the Institute of Medicine; plus the efforts of various professional groups such as the Cystic Fibrosis Foundation and the American College of Medical Genetics (ACMG). However, efforts to develop enforceable guidelines for the use of genetic tests have repeatedly failed. A major issue is ensuring that information about genetic variation is used in ways that improve the health of individuals and the public. Furthermore, regulators need access to information about the impact of genetic variation. For example, if companies have pharmacogenetic information, they need to submit such information to the Food and Drug Administration (FDA). Finally, patients and providers must have access to reliable data about genetic tests. Currently there is a great deal of bad information and false and misleading advertisement. The FDA has declined to regulate in this area even though it has been urged to do so on many occasions. The result has been a proliferation of direct-to-consumer advertising and even sales. Both litigation and advertising to providers have fueled demand for genetic information. However, in some cases, tests simply are not commercially available. In other cases, tests may be costly as a result of intel-

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary lectual property claims or are not covered by third-party payers. Furthermore, without major changes in the legislative background, it will be impossible to obtain uniformity in insurance coverage for genetic testing. At the same time, individuals’ interest in using genetic tests has been dampened by fear they will suffer discrimination if they learn about their genetic makeup. Can the law require that people use genomic information for health promotion, for example, information about a susceptible worker who will be made sick by going into the workplace? Important issues in this instance are the validity of the information, who receives the information, and who gets to decide what to do in response to the information. Does the employee get to decide, or the employer? The fact is that genomics will enable us to stratify, and the risk of stratification is always that the information will be used in ways that are socially unacceptable or discriminatory. Although many assert that genetic discrimination is not a major problem, it has not been easy to address in the legislative arena. The result is a patchwork of policies that are not consistent either internally or with each other. The legal and regulatory framework exists to explore the impact of genetic variation on health and disease. However, more work needs to be done to ensure that providers and patients have access to clinically useful tests and accurate information. Furthermore, it is necessary to create a system in which people feel free to use this information to improve their health and to define the conditions under which third parties can appropriately use this information to constrain individual choice. Overall, what is needed are efforts to address problems from a systems perspective, recognizing that the dilemmas posed by genetics are not unique, but rather intersect with and parallel many of the great debates currently going on in our society about how to treat others. COMMENTARY Ruth Katz, J.D., M.P.H. Genomics promises to be both exciting and complex for the field of public health over the next several years. What happens in genomics and public health will be determined as much by what policy makers do as by what genomic researchers and other experts discover. But not one of the panelists in this workshop is a policy maker who will be involved in making many of the decisions on issues such as medical coverage, access to care, confidentiality, FDA regulation, discrimination, training of public

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary health officials, public information campaigns, and genomic-related research. The development of the integration of genomics and public health presents a rare opportunity to involve policy makers from both the federal and state levels. It is important to make sure that policy decisions are based upon data and real science. Rushing to judgment, including judgment about providing funding for research, is not appropriate. Policy makers should not repeat some of the problems associated with bioterrorism funding, that is, providing public health departments with money for genomics, but taking away much-needed funds from other important public health activities. Policy makers must be involved from the beginning in all discussions and debates. We heard previously that public health professionals need training in genomics. So, too, do members of Congress, members of state legislatures, and other policy makers so that they can be better prepared to deal with the myriad complex and difficult issues facing the integration of genomics and public health. Like all potentially controversial advances in public health, this issue will need real champions in the policy-making arena. There can be no doubt that policy makers will influence this field as much as any other type of player. They must be invited to the table as soon as possible, because public health champions today are very hard to come by. Judith Feder, Ph.D. At the same time that genomics has an enormous potential for expanding what is known about disease and about what can be done for people to improve our health as a population and individually, it also has the potential to increase inequities in our society and in access to health care, in part because of our voluntary insurance system. Testing provides information that, in this voluntary insurance market, can cause harm. Given the way our system operates, increased costs threaten cuts in benefits and coverage, thereby decreasing access to care. Employer-sponsored health insurance is the way most Americans obtain health insurance. Although employers cannot explicitly discriminate against an individual in terms of health insurance based on an individual’s disease, they can discriminate in terms of whom they employ. They can make employment conditions untenable for certain kinds of people, and they can manage company health insurance in ways that make it difficult for people who have health conditions to obtain the care they need. The more pressure there is and the more legitimacy there is to testing and to technology in general, the more likely it is that our health care costs

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary are going to rise. Employers are already increasing the amounts individuals must pay out-of-pocket for health insurance. They are reexamining their formularies to determine the kinds of prescription medications they will or will not offer, thereby making it difficult for individuals with certain conditions or medication needs to find adequate insurance. Even greater problems arise with insurance obtained outside employer-sponsored plans. Insurers want to make a profit: maximizing the premiums paid while minimizing the benefits distributed. In the small-employer market, there are real risks to insurers knowing what one’s health status is because either one pays more, insurance is unavailable, or insurance is available but not for any body part that might remotely be affected by the gene or any other preexisting conditions. There is shrinking availability of insurance, so employers cut benefits. Individuals who are likely or believed likely to be susceptible to illnesses that are expensive to treat have difficulty obtaining coverage. Furthermore, such discrimination is not necessarily based on hard science. Medicaid, which covers some but not all poor people, is a “squeezed” program with variation from state to state in the services it provides and criteria for eligibility. As costs rise, many states are trying to determine how to cut back their benefits. Therefore, even if Medicaid covers genetic tests, recipients will not benefit unless they can also obtain treatment under the Medicaid program. Of course the 45 million to 50 million uninsured will not have access to anything. The more health care costs rise, the more we are going to see a shrinking in the affordability of health insurance, resulting in an increase in the numbers of people without insurance. In summary, there is a problem because there is not full access to health care. Without full access for everybody, including the poor, disparities will increase. Many believe that insurance coverage for everyone is affordable without additional investments, that it is a matter of finding the will to provide such coverage. Providing such coverage would require a perspective change from one in which each person fends for himself to one that recognizes that everyone is in this together. LESSONS LEARNED, PLACES TO GO James G. Hodge, Jr., J.D., L.L.M. The challenges identified during the workshop are significant and include those that are conceptual, legal, ethical, political, cultural, economic, organizational, and clinical. The presentations looked at these challenges through varying disciplinary approaches, including internal

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary medicine, biochemistry, psychiatry, genetic counseling, public health science, public health practice, biotechnology, law, ethics, economics, philosophy, psychology, and sociology. The varying tools used for interacting and intervening at the intersection of public health and genetics include the principles of science, research, practice-oriented methods, education, counseling, law and ethics, economics, technology, and informatics. All of these come together at the intersection of public health and genetics. Interconnected factors must also be considered. Human genomics is significantly interconnected with proteomics, non-human genomics, and ecogenetics. There are also interconnected factors related to genomic information in general: nutrition and metabolism, the varying diseases and behaviors that people contribute to their potential susceptibility to a genetic condition, environmental exposures, and medications. Each of these factors must be systematically examined and understood in order to devise plans for connecting public health and genetics. Clinical medicine, public health practice, and pharmaceuticals are also relevant. A failure in any particular area or a lack of resources or lack of opportunity affects the other areas. Finally, within public health itself, interconnected factors include core services, surveillance and research methods, vaccination policy, testing, screening, epidemiological investigations, and education. Education is only as good as the surveillance accomplished. Research is only as effective as the information obtained through our epidemiological investigations. The interplay of factors is important. There are a series of critical observations and goals that pervade our collective disciplines that justify our tools and interventions. What is at present known about the science of genetics and genomics and proteomics and ecogenetics is quite impressive. We have made tremendous strides. However, what knowledge is needed to use genetics effectively to protect the public’s health remains uncertain. What is currently perceived as a good idea is identification of a single “biomarker,” an identified genetic susceptibility that may work or may benefit a particular individual. But that is not what is needed in terms of the future for public health. Multiple factors and multiple interactions must be examined. Understanding must come in terms of whole populations, not just one individual. What a few know concerning the potential for genetics in public health is what, in the future, others must know, especially those people who can benefit from the advances being made. Critical observation tells us that money can often influence objectives and interventions, but allocating resources to inappropriate or inefficient programs must be avoided. Resources must be allocated as equitably as possible. Genetic testing that is available to some because of wealth or

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary insurance benefits should be available to all. Finally, the concerns of many individuals (e.g., protection of sensitive identifiable genetic information) must be addressed responsibly. With these multiple challenges, tools, interventions, observations, and goals, what must be done to develop meaningful plans and to translate possibilities into realities? We must assess our present knowledge, resources, and capacity. This workshop has provided key lessons in five major areas: genetic science; genetics and public health; genetics, information, and behaviors; public health infrastructure; and ethical, legal, and social issues. The genetic science lesson is that the genetics revolution has produced a wealth of new information. Scientific and technological advances in genetics, proteomics, comparative genomics, ecogenetics, toxicogenomics, bioinformatics, and computational biology have the potential to improve public health outcomes. How can the potential be marshaled? Causality is complicated; multifactor components underlie virtually all genetic conditions. Predicting the functional effect of various genetic sequences is critical, but again complicated. Additional research is essential to further identify and validate genetic variants. What key lessons have been learned about genetics and public health? One thing is to suggest that the framework for genetic risk assessment for population health research definitely requires three elements: risk identification, risk characterization, and risk reduction. Community-based participatory research can contribute to widespread knowledge and awareness. Progress is being made to identify and prevent gene–environment interactions with correlating benefits. Continued research, funding, and education enhance the ability of public health authorities to incorporate genetics into public health. Existing public health approaches to genetic diseases (e.g., population screening, universal diagnosis) can at times be inappropriate or inefficient. The ability to address these issues in a cost-effective way will be critical. In genetics information and behaviors, we have learned several key lessons. Primary care is critical to delivering genetic services to individuals and the population. These services are not, for the most part, going to be delivered through public health. The health care sector is an important partner in this endeavor. Furthermore, we lack the necessary information and research to make evidence-based decisions about the use of genetic tests. Cost-effectiveness analysis involving an assessment of opportunity costs can help determine whether a genetic intervention is either over- or underutilized. Lack of integration of genetic technologies into clinical and public health settings affects the cost-effectiveness of genomic medicine. Individual medical behaviors are the most important factors in public health improvement, and yet much remains to be learned about how to

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary influence personal behavior. Linked, multi-part interventions are needed to promote positive behavioral changes. Genomics will expand the opportunities and widen the disparities. As Dr. Foege indicated, there will be unbelievable opportunities and unbelievable inequities. Our discussion of the public health infrastructure also brought forth some key lessons. Assuring the conditions in which people can be healthy is an objective of an ecological model for public health. Genetics underlies the essential services and functions of the public health system, it pervades everything done in public health, and it cannot be ignored. The heterogeneous public health system is, unfortunately, not organized to accomplish goals in genomics and public health; it is not tailored to providing essential services to the population in an equitable fashion. Biobanking offers significant benefits for understanding the contribution of genetic variation to health and disease, but the lack of harmonization and legal, ethical, and social complexities inhibit its full development. Public attitudes concerning genetic research are affected by public confidence, perceptions of utility, moral beliefs, and terminology. Furthermore, the capacity for public health genomics is closely tied to the competencies of the members of the public health workforce and academia. Significant genetic data collections arising from technology do not necessarily offer direct benefits for public health practice. Finally, financing for the provision of genetic tests and services is challenged by payer concerns and mindsets, as well as limitations in existing tests. There are important lessons about ethical, legal, and social issues for genomics and public health. Significant concerns exist regarding information privacy and discrimination. The protection of disease-specific groups and other vulnerable groups is not significantly addressed in laws. The HIPAA Privacy Rule, which applies to identifiable genetic data, allows public health authorities to collect such data for public health purposes. There are significant additional issues in genetic privacy, such as the duty to warn, that are increasingly being addressed through litigation. The recent statement by the Office of Human Research Protection (OHRP) exempting human subject research using coded data from the application of the Common Rule could lead to broader epidemiological research without adequate consent or oversight and could potentially undermine public trust. Laws can facilitate (and complicate) access rights of providers and patients to genetic test results. Fears of discrimination alone, regardless of realities, may sustain needs for affirmative antidiscrimination protections. Stratification invariably leads to distinguishing individuals from each other—the objective is to avoid invidious discrimination. Well, where does one go from here? What should be explored in the future? One key issue is to unravel the advances in genetic science and research to identify clear objectives for public health. The application of

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary these advances must be enhanced for public health methodology and practice. Another major issue to explore is the assessment of infrastructure improvements that are essential to integrating genetics into public health. Additional issues include Funding and development of genetic, medical, and public health research to support and measure improvements in public health outcomes. Melding social and behavioral research and methods into public health genetics. Bridging health care and public health practitioners (and others) within the intersectoral public health system. Developing techniques for integrating genetics into public health practice that overcome challenges of limited funding, technology, and knowledge. Assuring access to public health genetics in ways that are equitable and sensitive to existing health disparities. Translating genetic information within and outside public health programs. Building public trust for public health genetic data collections through attention to culturally relevant factors and complex legal and ethical issues. Developing effective public education on public health genetics through specific objectives, targeted audiences, multiple channels, and sufficient exposures. Assuring that the public health workforce and its partners are capable of using genomics in real practice settings. Innovating to develop enhanced collections of longitudinal medical and genetic data to support multiple clinical and public health initiatives. • Recognizing the effect of fiscal realities that suggest underwriting of existing genetic testing, pharmaceuticals, and services is limited. Reformating the legal regulatory framework to address issues in public health and genetics: Ensuring greater access to genetic tests. Mobilizing individuals to use genetic information for individual and communal health. Defining the conditions for third parties to use identifiable data. Engaging further review and study of these and related issues at the intersection of public health and genetics through roundtable discussions, full committee reports, or other long-term efforts. There are several conclusions to be made from what has been presented during these past two days. First, the idea of benefits and risks pervades everything. What are the benefits and what are the risks? There

OCR for page 3
Implications of Genomics for Public Health: Workshop Summary are no easy answers, but there is methodology available to begin to provide answers. Second, there is the promise of genetics, and there is the reality. Realistic ideas for the future are needed. Third, there is the debate about exceptionalism. Should things be done in an exceptional manner for genetics or can lessons be learned from other legal frameworks, other ethical norms, other public health sciences? Finally, the current status of the genetic revolution has been compared to the germ theory ideas of the early 1900s. Right now is the time, because of heightened public health awareness in this country, to marshal this revolution for the benefit of the health of the public. The opportunity exists to achieve the desired end: measurable improvements in public health outcomes through the use of genomics.