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National Research Council (US) Committee on Population; Finch CE, Vaupel JW, Kinsella K, editors. Cells and Surveys: Should Biological Measures Be Included in Social Science Research? Washington (DC): National Academies Press (US); 2001.

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Cells and Surveys: Should Biological Measures Be Included in Social Science Research?

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13Ethical and Social Issues in Incorporating Genetic Research into Survey Studies

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The promise of genetic studies for improvements in human health has been widely espoused (for example, Hood, 1992; Fears and Poste, 1999; National Bioethics Advisory Commission, 1999), and genetic studies have achieved added significance as the end point of the Human Genome Project approaches (Pennisi, 1999). There is the strong sense that everyone at some point in the not too distant future will be affected by genetic research, and that medicine in general is undergoing a transformation to “molecular medicine,” in which knowledge of individual genomes will aid in disease treatment and prevention.

In a recent report, Research Involving Human Biological Materials, the National Bioethics Advisory Commission (NBAC) emphasized that, in order to obtain improvements in human health, it will be crucial to collect biological samples from persons who are also willing to provide ongoing clinical information about themselves (NBAC, 1999). The potential for learning more about health and the human condition by linking ongoing and planned population surveys with genetic research is a topic of intense interest.

Others in this book and elsewhere (e.g., Wallace, 1997) have described existing population survey studies, enumerated the potential applications of population surveys for genetic study, and suggested means by which existing population surveys could be modified to render them more applicable for use in genetic studies. The purpose of this chapter is to provide an overview of the ethical and social issues associated with broadening existing household surveys to include biological sampling and associated genetic studies. The chapter provides some background on the historical consideration of ethical and social issues associated with genetic research, and discusses the particular features of genetic information and samples that give rise to these issues. Four general categories of ethical and social issues in genetic research studies are considered, including privacy, access and ownership of genetic information and materials, psychosocial risks of participating in genetic research studies, and potential group-related harms. In each of these sections, an overview of the relevant concerns associated with genetic research is provided and any special issues particular to survey studies are discussed. This chapter ends by suggesting that three general themes be incorporated into discussions about whether to include biological sampling and/or genetic research in ongoing and planned survey studies. The important topic of informed consent in genetic research is covered by Botkin elsewhere in this volume.

BACKGROUND

Several reports over the last 25 years have concerned, at least in part, ethical issues associated with molecular biology and/or genetic research. A list of selected reports appears in Table 13-1, and includes several from Presidential Commissions, most recently, Research Involving Human Biological Materials: Ethical Issues and Policy Guidance from the National Bioethics Advisory Commission (1999). In addition, other governmental agencies and working groups, such as the National Research Council, the Office of Technology Assessment, the Office for Protection from Research Risks (OPPR), and the Task Force on Genetic Testing have considered ethical, social, and policy issues associated with genetic research (see Table 13-1). Thus, there are many existing resources from diverse sources and perspectives to draw from when considering the issues associated with incorporating genetic research into survey studies.

TABLE 13-1. Selected Institutional Reports Including Reference to Ethical, Social, and/or Policy Issues Related to Genetic Research.

TABLE 13-1

Selected Institutional Reports Including Reference to Ethical, Social, and/or Policy Issues Related to Genetic Research.

Although not new, the discussion of ethical issues associated with genetic research seems to have intensified in the last 10 years. This likely is due to several factors. The U.S. Human Genome Project (HGP) officially began in 1990, and since that time rapid developments in gene discovery and technical and molecular capabilities have occurred due to the influx of funding to these areas of research. In addition, the HGP directs about 5 percent of its yearly budget into researching ethical, social, and legal issues associated with developments in genetics, attracting increased attention to these issues (Meslin et al., 1997). Also, the increasing investment of commercial interests in genetics and the burgeoning biotechnology industry have focused attention on the adequacy of regulations applicable to genetic technologies and tests and the responsibilities of biotechnology concerns in introducing those technologies to the market (Task Force on Genetic Testing, 1997; Holtzman, 1999). Other features of the current time, such as increasing public concern about the privacy of medical records, increasing concerns about access to health care, and increased attention to research ethics issues in general and gene therapy research in particular (Moreno et al., 1998; Ellis, 1999; Woodward, 1996; Marshall, 2000), have increased the attention to social and ethical issues associated with genetic information and genetic research.

IS GENETIC INFORMATION SPECIAL?

Part of the debate surrounding ethical issues in genetics research turns on a discussion of whether genetic information and research are different from other forms of medical information and research, and the implications any differences may have for protecting participants in genetic research protocols. Some have argued that genetic information is not inherently different from other types of sensitive medical information (Murray, 1997). Other forms of medical information may show strong correlation with various diseases or health states. The analogy of viral transmission has been invoked to illustrate how other forms of medical information have direct implications for individuals other than the infected person (Mehlman et al., 1996; NBAC, 1999).

To others, however, genetic information has certain features that render it distinct from other forms of medical information. These include its familial nature, coupled with its unique identifying characteristics (Annas, 1993; Institute of Medicine, 1994; Jonsen et al., 1996; American Society of Human Genetics Social Issues Subcommittee on Familial Disclosure, 1998). With the exception of identical twins, a person's DNA is unique to them, but at the same time, knowledge of genetic information about a person can reveal information about directly identifiable others, including their relatives and even larger groups of individuals. Another distinguishing feature of genetic information may be its predictive capabilities and the potential relevance of this information to persons other than the individual from whom this information was obtained (Institute of Medicine, 1994). Other important considerations relate to the DNA molecule itself. DNA mutations do not change over the course of an individual's lifetime (NBAC, 1999). Also, the DNA molecule is very stable. Although some information can be derived from the molecule at this time, with completion of the Human Genome Project and the deciphering of the entire DNA code, the capacity to extract information will greatly increase (Annas et al., 1995). The wealth of information in a particular DNA molecule is enormous, and in many cases DNA may provide information about predisposition to health conditions that are not yet manifesting, and some of this information may be extremely sensitive. Thus it will be possible for researchers to extract genetic information (health-related or otherwise) from stored samples at times well removed from sample collection. This information may be unknown to the person from whom the sample was taken and may be of a very sensitive nature (Annas, 1993).

These characteristics of genetic information and of DNA molecules raise concerns about genetic research that may be grouped into four general categories: privacy of genetic information, access and ownership of genetic information and samples, psychological risks, and potential group-related harms. Considerable scholarly attention has been directed to each of these areas. The following sections of the chapter provide an overview of the issues to consider in planning and executing genetic research studies in each of these four categories, and directly relate these considerations to incorporating genetic research into survey studies.

PRIVACY OF GENETIC INFORMATION IN RESEARCH STUDIES

Paramount in the conduct of genetic studies is concern about protecting the privacy of potentially sensitive genetic information generated about research participants. A number of groups have offered recommendations for protecting the privacy of study participants' genetic information (for example, Annas et al., 1995; Fuller et al., 1999; NBAC, 1999). Privacy concerns arise because many individuals, institutions, and/or organizations may have an interest in knowing a person's genetic status, and such knowledge has the potential to result in stigmatization, discrimination, and other adverse effects.

Potential Societal Stigmatization and Discrimination

Examples of insurance (e.g., auto, health, and life) and employment discrimination related to genetic information have been reported by consumers and by genetic counselors and nurses in genetics (U.S. Congress, Office of Technology Assessment, 1992; Geller et al., 1996; Lapham et al., 1996). These cases also reveal that difficulties with other societal agencies and institutions such as blood banks, adoption agencies, the military, and schools may be possible (Geller et al., 1996). It has been suggested that educational and legal institutions may have an interest in genetic status for identifying learning problems (Geller et al., 1996; Fuller et al., 1999) and deciding custody and paternity disputes (Fuller et al., 1999). Medical benefits reportedly have been denied to retirees with illnesses determined to have a known genetic basis (Fuller et al., 1999), an issue that may be particularly relevant to incorporating genetic sampling and studies into demographic studies of aging populations.

Despite these studies, the extent of the risk of genetic discrimination in health insurance and other societal institutions has been difficult to pin down. Examples of genetic discrimination, such as those included in the studies referred to above, resulted in legislation in many states and at the federal level, through the Health Insurance and Portability and Accountability Act (HIPAA) (for overviews see Fuller et al., 1999; Hall and Rich, 2000). However, current policies and existing laws to protect the privacy of genetic information are limited in number and nature and vary according to state, while comprehensive federal protections do not exist. A recent study aimed to assess the effectiveness of laws prohibiting health insurers' use of presymptomatic genetic information (Hall and Rich, 2000). The study used a variety of approaches to collect information from representatives of various groups, including genetic counselors, state departments of insurance, and health insurers. Similar data were collected from seven different states with and without laws prohibiting health insurers' use of presymptomatic genetic information. After a lengthy analysis, researchers were unable to document any substantial degree of genetic discrimination by health insurers. They were also unable to document a difference in insurers' actions between states with and without genetic-specific laws or before and after enactment of state laws in a particular state. However, they did discover that insurers were well aware of the existence and content of such laws, and suggest that the existence of such laws has served to heighten insurers' awareness of the “social legitimacy” of using presymptomatic genetic information.

In addition to genetic-specific laws and regulations, protection of participants in federally funded research is addressed by a two-pronged approach, that is, review by an institutional review board (IRB) and execution of an informed consent process. Most institutions that receive some federal funds require that nonfederally funded projects be reviewed by their IRB as well. The critical importance of the informed consent process in describing the privacy-associated risks of genetic research studies and the mechanisms in place to protect participants is discussed in detail by Botkin in this volume, as well as elsewhere (Institute of Medicine, 1994; Clayton et al., 1995; American Society of Human Genetics, 1996). For federally sponsored research, the IRB is responsible for ensuring that participants' risks are minimized, their rights and welfare are protected, and their consent to the research protocol is informed and voluntarily given (Fuller et al., 1999; Department of Health and Human Services, 1991). IRBs also consider issues related to the confidentiality of research records and how these protections are communicated to study participants. Specific suggestions about considering these issues within the context of genetic research studies are offered in the IRB Guidebook (OPRR, 1993). However, as noted elsewhere, research on current practices to protect confidentiality of research data, including genetic data, is limited, and best practices have not yet been developed (Fuller et al., 1999).

One option that may be available to genetic researchers is to obtain a federal Certificate of Confidentiality. Certificates of Confidentiality may apply to certain types of genetic research (see Earley and Strong, 1995; Fuller et al., 1999). Originally developed to provide protections for research into illegal or very sensitive activities, such as illegal behavior, sexual practices, and alcohol or drug use, Certificates of Confidentiality protect federally and privately funded institutions from being compelled to reveal identifying information about participants in a research study (OPRR, 1993). However, as noted by Fuller et al., these Certificates do not protect research participants from being compelled to reveal research data or information.

Another option available to investigators is to work with anonymous or unlinked samples, i.e., samples that cannot be linked to any identifying information. It is often difficult in genetic studies to work with unlinked samples, since matching DNA sequences with medical histories or pedigree information is integral to the research process. In addition, it may still be desirable for individuals to be able to exert some control over how their samples are used, even if the samples have had all identifying information removed (see below; Clayton et al., 1995; Botkin, this volume). However, if unlinked samples can be used, this affords protection from many privacy concerns (Clayton et al., 1995; NBAC, 1999).

A further privacy concern arises when investigators are ready to publish their research results and/or discuss their results in public, either at conferences or, increasingly, with the media. Many genetic conditions are extremely rare, and concern has been expressed that research participants can be identified by presentation of data such as pedigree data in reporting research results (Powers, 1993). Depending on the nature of the sampling and genetic research that might be linked to survey studies, this might or might not be an issue for such studies. The degree to which reporting of pedigree data is truly a risk to the privacy of research participants is a matter of some controversy and experts disagree on what, if anything, should be done to address these potential risks (Powers, 1993; Botkin et al., 1998; Byers and Ashkenas, 1998). However, most agree that researchers and IRBs should consider how study results will be reported, and should communicate any plans for publication to study participants as part of the informed consent process (OPRR, 1993; Powers, 1993).

When considering adding genetic studies to existing household demographic surveys, privacy-related concerns should be considered in light of the fact that at least some data from a number of current longitudinal U.S. household surveys are publicly available. For example, data from the Health and Retirement Study (HRS) are for public use and are available by registering at a World Wide Web site or from the principal investigators, although certain sensitive data may be restricted and proposals for use of sensitive data must be reviewed by an IRB (Willis, 1999). A publicly available, population-based database including information such as economic status and health status coupled with genetic or biological information and/or samples would be an extremely powerful and attractive resource to many investigators. However, policies on what constitutes sensitive data will need to be revisited and mechanisms of data and sample collection and sharing will need to be developed. These policies must also be clearly articulated to study participants as part of the informed consent process. Finally, existing database protections and operating procedures will need to be reexamined in light of collecting biological samples for genetic studies and sharing genetic information and/or samples. Issues associated with exploiting the accessibility of the Internet, and potential electronic security risks associated with genetic data that retains identifiers, are discussed in more detail elsewhere (National Research Council, 1997).

Protecting Individual Privacy Within Families

Protecting the privacy of sensitive genetic information also involves protecting an individual's privacy within the family unit. Family members may have an interest in knowing each other's genetic status. For example, in some genetic research studies, such as studies to identify genetic predispositions to disease, it may be necessary to first identify a gene mutation in a family member who has the disease of interest. Then, researchers can ask whether another family member with no symptoms carries a similar genetic marker. In general, this approach requires that family members cooperate and that the symptomatic family member receive genetic information about himself or herself and share it with the presymptomatic family member(s). Family members may or may not want to participate in such studies (Green and Thomas, 1997) and may or may not want to share their genetic status with each other. Recruitment methods must be carefully considered to protect the privacy of the individual participant in a genetic study (OPRR, 1993).

Recently, the question of who the individual is that needs to be protected, that is, who is the human subject in a particular genetic research study, has come under scrutiny. In a widely publicized case, the OPRR was contacted by a father whose twin daughter had been mailed a questionnaire as part of a genetic research study being conducted at Virginia Commonwealth University (VCU). The questionnaire included questions about parents' and siblings' histories of depression, infertility, alcoholism, and mental illness. Upon opening his daughter's questionnaire, the father complained to the OPRR about the contents and expressed his concerns about the violation of privacy associated with collection of such sensitive information about him when he had not consented to participate in the research study (Brainard, 2000). The OPRR launched an investigation into this and other research studies at VCU and subsequently suspended the research trials (approximately 1,500) at the university. The OPRR agreed with the father and has ruled that the local IRB should have considered this potential risk to family members in the design of the research study (Brainard, 2000). The American Society of Human Genetics has responded to this ruling by issuing an alert discussing the relevant federal regulations concerning waivers of informed consent (American Society of Human Genetics Executive Committee, 2000). This alert also supports the need for further discussions that the Society hopes will be directed toward developing better regulations that will protect study participants without unduly restricting human genetic and genetic epidemiology research studies. In the context of a household survey, IRBs will have to carefully consider whether the acquisition of data on other family members makes those family members human subjects and whether informed consent must be obtained from them.

ACCESS TO AND OWNERSHIP OF GENETIC INFORMATION AND SAMPLES

Biological samples from participants in a population-based survey may be an important repository of interest to many researchers and may allow previously challenging research questions to be addressed. It would be in keeping with the current policy of some U.S. demographic studies to make genetic data and/or samples generated in association with household surveys publicly accessible to all researchers. In addition to the privacy issues outlined above, issues of ownership of samples and/or genetic information and data need to be addressed in considering the collection of biological samples and the addition of genetic research to survey studies.

Commercial Interests

Issues of ownership and access are becoming increasingly prominent in the area of genetic research, especially as the international Human Genome Project nears its goal of a complete, publicly available sequence of the human genome. In one widely discussed example, the private Iceland company deCODE Genetics has been granted permission from the Icelandic parliament to create a health database for the entire population of Iceland (Enserink, 1999; Annas, 2000; Gulcher and Stefansson, 2000). This database, combined with collection of biological samples for genetic analysis, is expected to be a very powerful tool in the search for the genetic contributions to disease, including common diseases such as cancer and heart disease. However, the project has been the target of national and international concerns regarding the mechanism of consent utilized, privacy issues, and questions regarding the desirability of a private company holding exclusive rights to a database containing information about an entire country's gene pool (Enserink, 1999; Annas, 2000; Gulcher and Stefansson, 2000).

A second recent example of commercial interest in genetic research may be especially relevant to incorporating genetic research into household survey studies. Boston University (BU), sponsor of the Framingham Heart Study, has entered into an agreement with venture capitalists to create Framingham Genomic Medicine, Inc. (FGM), a for-profit company in which BU will have a 20 percent interest. According to one report, the company will use the study's voluminous collection of data, which includes genetic, clinical, and behavioral components, to create an electronic database which biotechnology and pharmaceutical companies may access after paying an annual fee. In addition to data of varying types, approximately 5,000 blood samples have been collected from study participants. Negotiations are currently under way to sort out issues of ownership and access, and include representatives of BU, FGM, and the National Heart, Lung and Blood Institute, the governmental agency that has funded a considerable proportion of the research (Rosenberg and Kowalcyzk, 2000).

It may be very instructive for those involved in survey studies to follow the Framingham discussions because of the similarities between the Framingham Heart Study and household surveys. Some household survey studies collect vast amounts of data on participants over long periods of time. The survey studies and corresponding databases this volume is concerned with are or will be established with federal funds. Similar to the Framingham study, some of the survey studies have had a longstanding policy of public availability of the data. Both deCODE and FGM are founded on the belief that biotechnology and pharmaceutical firms will have considerable interest in a population-based repository of biological samples coupled with an extensive health-related database. Policies will need to be developed regarding who and what entities should have access to what information and/or samples collected in association with survey studies. Others have discussed issues related to ownership and financial interests in research of this type (e.g., National Research Council, 1997; Knoppers et al., 1999; Annas, 2000). All of these policies must be clearly communicated to study participants as part of the informed consent process.

Study Participants

Issues of ownership of genetic information and/or samples also reside at the level of the individual study participant. The deCODE example has focused attention on the rights of study participants to opt out of participation in the database. In the deCODE example, informed consent has been waived. Unless an Icelandic citizen specifically requests their information not be included, their information can be submitted to the database. The argument supporting this approach is that obtaining informed consent from all 270,000 Icelanders would not be feasible, and in order to create a database with the desired power for health-related research, inclusion of data from as many Icelanders as possible is required. Compelling reasons must be presented to waive informed consent in genetic studies, and it does not appear that adding genetic research studies to survey studies would automatically qualify for a waiver, although this will depend very much on the nature of the genetic research under consideration. Specific situations in which waiver of consent for genetic studies might be possible have been discussed elsewhere (NBAC, 1999; American Society of Human Genetics, Executive Committee, 2000).

Once a study is ongoing, some individuals, for whatever reason, decide they no longer want to participate. In certain types of genetic studies, particularly those in which family and pedigree data are critical to the analysis, it may be very difficult scientifically to have a key participant decide to no longer continue in a study. Researchers must develop a plan, communicated to study participants prior to their enrollment in the study, regarding how the biological sample and any data generated from that sample or information provided by the participant will be handled should they decide to withdraw from the study (Clayton et al., 1995; Botkin, this volume).

Because deCODE is at the initial stage of developing the database and negotiating the licensing agreement with the Icelandic government, the published discussions surrounding deCODE's plans for gene discovery using the database information do not yet include what will be done if clinically relevant genetic information is discovered. Of course, what happens in Iceland, a country with a comprehensive national health insurance system, may be very different from what happens in the United States. But an important question for genetic research in general is that of the nature of clinically relevant information and what access study participants can expect to have to such information throughout the course of a study.

Experts have discussed policies for sharing research results with study participants and some of these discussions have considered genetic research results in particular (NBAC, 1999). Some think that all research results should be shared with study participants (Veatch, 1981). Others believe that serious harms could result from sharing unconfirmed findings and that unconfirmed findings do not constitute “information” (MacKay, 1984; Fost and Farrell, 1989). In general, the consensus of opinion is that genetic research results must be scientifically valid and confirmed prior to their provision to study participants (Task Force on Genetic Testing, 1997; Fuller et al., 1999; NBAC, 1999).

This may be complicated in genetic research studies, because in general, genes, mutations, and their relationship to disease(s) are always more complex than first presumed. Even so-called “simple” Mendelian conditions, such as cystic fibrosis (CF) and Huntington disease (HD) have proven to be more complicated than originally understood. For example, cystic fibrosis, a Mendelian inherited recessive condition, has been shown to have hundreds of mutations that cause effects ranging from infertility in men, without other effects, to the classically understood symptoms of life-threatening lung and pancreatic disease (Welsh et al., 1995). Huntington disease, thought to be a clear example of an autosomal dominant neurological disorder, demonstrates anticipation, in that successive generations within a family sometimes show earlier onset of disease symptoms, particularly if the mutation is transmitted through the paternal line (Ranen et al., 1995). In addition to complexity of disease mechanism within a gene, genetic factors and genetic conditions have been shown to have unexpected associations, such as that of apolipoprotein E (APOE) alleles and Alzheimer's disease (American College of Medical Genetics/American Society of Human Genetics Working Group on APOE and Alzheimer Disease, 1995). Thus, investigators can expect both complex and unexpected findings and associations between genes and other factors (both genetic and nongenetic) to occur, which may pose challenges in communicating results to study participants.

As genetic research progresses, it can be expected that susceptibilities or inherited characteristics with much less import for disease than the examples above will be identified. For example, it is already possible in juvenile (type 1) diabetes to use genetic markers at the HLA locus to screen and identify children with an increased risk for this form of diabetes (i.e., a risk of approximately 1/80 vs. the general population risk of 1/300). Is this information relevant to study participants in any way, should it be provided, and if so, how? One solution to communicating very complicated genetic information of uncertain value that is generated in the context of a research proposal is to be very clear, in policy and communication with study participants, that interim results will not be provided to research participants.

Even if researchers do not plan to provide study participants with interim research results, circumstances may occur to cause them to reconsider this decision. Researchers may feel compelled to act on any information they discover (expected or unexpected) with clinical relevance. Also, participants may approach researchers asking for information for various reasons. While searching for a gene for susceptibility to breast and ovarian cancer, University of Michigan researchers were approached by a study participant at risk to carry a gene mutation who had scheduled a prophylactic mastectomy. She inquired of researchers if there were any new developments prior to having her surgery. According to their research results, she did not carry the gene mutation and researchers were suddenly faced with a decision about what interim information to convey to her and how to convey it (Biesecker et al., 1993; Breo, 1993).

Therefore, in planning genetic research studies, researchers must consider the following questions: What is the role of study participants in deciding about the use of their samples for research? What research results are of interest to study participants? Which, if any, research results will be provided to study participants and when will these results be provided? If future research studies generate information of potential interest to study participants, will this information be provided? How will genetic information be provided to study participants? Who will provide the information and what support will be offered to study participants in understanding the information? Researchers need to think through these questions as much as possible and have a plan in place to address them (OPRR, 1993; Clayton et al., 1995; NBAC, 1999). Some of these issues can be addressed in the informed consent process in which the agreement between researchers and study participants about what information will or will not be provided and when is clarified (Botkin, this volume). Other recommendations involve putting mechanisms in place to ensure that the information provided to research participants is valid and replicable, and having support systems for research participants in place to minimize any potential psychological risks associated with receipt of genetic information (see, e.g., Institute of Medicine, 1994; Task Force on Genetic Testing, 1997; Fuller et al., 1999).

PSYCHOLOGICAL RISKS OF PARTICIPATION IN GENETIC RESEARCH STUDIES

Many studies have documented psychological effects associated with receipt of genetic information. For genetic studies that plan to provide genetic information to participants as part of the study, these effects must be considered. Familial relationships and dynamics may be altered when family members receive genetic information and preconceptions of genetic status and risk are directly supported or refuted (for example, Bloch et al., 1992; Fannos and Johnson, 1995a; 1995b). Individual psychological effects of receipt of genetic information have been documented and likely vary depending on the nature of the disorder in question, among other features (Bloch et al., 1992; Marteau et al., 1992; Wiggins et al., 1992; Lerman and Croyle, 1996). A number of studies have shown depression and/or anxiety to be associated, to varying degrees, with discovery of gene mutations (for example, Wiggins et al., 1992; Lerman et al., 1996). Along with these anticipated results, unexpected effects of providing genetic information have been described (Huggins et al., 1992).

Depending on the status of the research, not all participants in a genetic study will necessarily receive informative results. This is because in the early phases of gene discovery, mutations are identified through linkage analysis and/or gene mutations have not been fully characterized and the information may be difficult to interpret. Therefore some individuals who may have expected to have their genetic risk clarified as a result of participation in a genetic study will not receive this benefit and may experience psychological effects associated with the continued uncertainty.

In addition to possible effects due to provision of genetic information generated by the study itself, investigators may also discover information with significant impact for individuals and families, such as nonpaternity, adoption, abortion, and other biological and/or social information. Concerns about psychological effects on individuals and families also extend to recruitment for genetic studies. One ongoing discussion includes whether IRBs should be concerned with how to avoid familial coercion to participate in a genetic research study (Parker and Lidz, 1994). This might become an issue in the context of demographic studies if any proposed research targets family members of the original demographic study participants.

Discussing these possibilities with study participants is an important component of the informed consent process for applicable genetic studies. As much as is possible, investigators must articulate plans to address such possibilities, and IRBs evaluating these research studies must be aware of these potential risks associated with genetic study participation and evaluate the study procedures accordingly (OPRR, 1993).

In general, if results of a clinically significant nature are to be provided, appropriate resources, including genetic or other sources of counseling, information, and/or support, must be available to study participants in order to minimize the potential for psychological risks (Institute of Medicine, 1994; Fuller et al., 1999; NBAC, 1999). For some studies, this may be a prohibitive undertaking: one estimate places the cost of counseling before and after a genetic test for 10,000 study participants at approximately $500,000 (Fuller et al., 1999). The Health and Retirement Study includes 12,600 participants (Wallace, 1997).

Finally, it is notable that the types of psychological risks described above can be used to understand the potential benefits associated with participation in genetic research studies. For some people, knowledge of genetic status can contribute to feelings of well being, can provide relief from uncertainty or anxiety (regardless of the results), can positively affect familial relationships, may help people obtain needed social benefits and/or health care, and can aid in future financial and life planning (see, e.g., Bloch et al., 1992; Wiggins et al., 1992; Biesecker et al., 1993; Breo, 1993; Holloway et al., 1994; Mitchell et al., 1996). In addition to the potential for psychological harm, the informed consent process should also allow potential study participants the opportunity to consider the possible benefits of participation in genetic research.

Both the potential psychological benefits and risks of participating in genetic research studies are not yet well documented, and further research is required to understand these effects for research participants. Survey studies (both ongoing and proposed) that follow individuals over long periods of time may be well positioned to contribute to this effort if genetic research studies are added to them. Some of these studies already maintain the infrastructure necessary to collect information regarding health-related decisions and life planning issues over extended periods of time. Questions specifically addressing the effects of participation in genetic research studies and knowledge of genetic information could be added to existing instruments and/or data collection methods. Assessing the impact of genetic information on individuals and their families in terms of the life decisions they make over extended periods of time would greatly enhance the informed consent process both in genetic research studies and in clinical genetic testing.

GROUP-RELATED HARMS OF PARTICIPATION IN GENETIC RESEARCH STUDIES

Privacy, access, ownership, and psychological risks of genetic information all must be considered within the context of cultural views of genetic and medical information and scientific research. American society as a whole places a great deal of value on information in and of itself and strongly supports research into health-related concerns. Overlaying the value we place on personal health-related information is the special regard in which we seem to hold genetic information. We seem to view it as uniquely predictive and powerful, with the ability to predict the future and to profoundly shape and affect one's life. We use genetic information to explain all kinds of behaviors and circumstances, both health-related and other (Nelkin and Lindee, 1995). The importance of genetic contributions to understanding human behavior will only increase as the entire genome is decoded and researchers begin work to understand all the genes identified.

We also relate genetic information to groups of people, raising the potential for stigmatization and discrimination of individuals who belong to those groups, as well as the possible stigmatization of the group as a whole (National Research Council, 1997). The concern is that genetic explanations might be used to support racial, gender, and other stereotypes. Thus research designed to study disease or other characteristics of a particular group may result in labeling of all members of that group, even those who did not participate in the research. This is one reason that some argue that study participants may want some control over how their biological samples are used, even if the study protocol uses samples that are completely anonymous (Clayton et al., 1995; Botkin, this volume).

The complex questions of how groups define themselves, how researchers define groups to study, and the implications of determining how or if the genetic characteristics of a group align with the socially defined characteristics of the group, have been discussed in detail elsewhere (National Research Council, 1997; Juengst, 1998; Reilly, 1998). These questions will arise if genetic research is incorporated into survey studies. Because the large demographic studies currently being conducted in the United States are representative of the population as a whole, they will include individuals for whom group-related issues may be very important. Second, researchers may be particularly interested in studying subsets of individuals from the larger population-based sample that belong to a particular group defined by the researcher. Third, a consideration of whether the elderly constitute a “group,” and the potential for group-related harms to the elderly, may arise. One goal of some current survey studies is to understand the health-related needs of the U.S. population as it ages (Wallace, 1997). The potential for stigmatization and discrimination of the elderly in our society is real, particularly as the population continues to age and the costs of health care associated with conditions of age continue to increase. These questions of identification of populations and groups are directly relevant to demographers and identify an intersection between genetic research and demography that bears further research and analysis.

A thoughtful consideration of mechanisms to address potential group-related harms will be important if genetic research is incorporated into survey studies. The report “Evaluating Human Genetic Diversity” by the Committee on Human Genome Diversity, National Research Council (1997), made a number of recommendations for conducting research studies on human genetic variation in a multinational, multicultural setting that can be extrapolated to genetic research within survey studies. The Committee made recommendations relevant to considering genetic research studies in general as well as recommendations that specifically address group-related harms. The latter include the importance of accurate identification of populations through consultation with local communities and other experts, processes for handling “community withdrawal from a genetic study,” and a discussion of individual vs. group consent to research processes.

The issue of individual and group consent for participation in genetic research focuses on the informed consent process and the necessity, desirability, and/or practicality of obtaining group or population consent for the genetic research in question (Foster et al., 1998; Juengst, 1998; Reilly, 1998). Clearly the nature of the population or group under consideration dramatically affects how one approaches the informed consent process, and this aspect of research proposals must be considered on a case-by-case basis.

Consultation with members of the group to be studied is a crucial component of designing research studies that has been used in genetics research in the past—for example, in providing Tay-Sachs screening programs (Beck et al., 1974)—as well as recently. Consultation with the Ashkenazi Jewish community in the Baltimore-Washington area was an important part of planning the anonymous testing research directed at determining the frequency of mutations in BRCA1 and BRCA2 (breast cancer genes) in that population (Hartge et al., 1999). An example of community consultation in a genetic research study on diabetes in a Native American population has been described in detail (Foster et al., 1998). Community consultation allows the views of the group and its individuals about privacy, the body, bodily substances, genetic information, and research in general to be identified and incorporated into research designs. It also allows groups to express their interests, financial or otherwise, in the genetic information, samples, and/or gene sequences that are generated with their research participation. The diabetes study referenced above describes an approach to sharing of financial proceeds with the tribe (Foster et al., 1998). Community consultation is an approach of increasing importance in genetic research as well as in research with human subjects in general.

NEW DIRECTIONS

Coupling ongoing and planned survey studies with biological sampling for genetic studies holds considerable potential to contribute to our understanding of human diseases, conditions, and aging. In considering how to best utilize these potential resources and at the same time effectively address the specific issues itemized in this chapter, three general themes should infuse discussions of the issues.

Research Participants as Research Partners

Genetic research is causing us to rethink the relationship between the researcher and the study participant. Henry Greely (1998) has suggested that participants in genetic research be regarded as “somewhat limited” partners in that research. Several observations indicate that, at least in genetic research, there is a move toward more of a partnership between these two roles. First, there is now a presumption in favor of providing to research participants more detailed information about all facets of the study and the researchers involved. The chapter by Botkin in this volume documents this phenomenon.

Second, support groups and patient advocacy groups have become more involved in the research process in genetics. For example, the Alliance of Genetic Support Groups has produced a brochure on informed consent for participation in research studies, entitled Informed Consent: Participating in Genetic Research Studies (1993). This brochure advises potential study participants on the areas they should consider and the questions they should ask prior to agreeing to participate in a research study. In a second example of the involvement of research participants in the research process, the National Institutes of Health (NIH) is recommending, although not yet requiring, that its institutes include patient advocates in their research study sections (Agnew, 1999). Several institutes have implemented this recommendation already, and this is a model that has been used by the Department of Defense to review applications for its breast cancer research funding (Agnew, 1999).

Other observations I have made come from my participation as co-investigator in NIH-funded studies to examine how best to offer testing for inherited susceptibility to breast cancer. In 1994, these studies formed a group called the Cancer Genetic Studies Consortium (CGSC). Representatives of the National Breast Cancer Coalition (NBCC) have been involved in cancer genetic research in several ways. These include: authoring and publishing in a prominent journal a position statement on whether such genetic susceptibility testing should be offered clinically or only under research protocols (Visco, 1996); participating in NIH CGSC meetings (at which the advocate representative sat at the head table with NIH representatives); and coauthoring (with NIH investigators, including Francis Collins, head of the U.S. Human Genome Project) papers that describe issues associated with genetic research in general and research on genetic susceptibility to breast and ovarian cancer in particular (Clayton et al., 1995; Burke et al., 1996; Geller et al., 1997). Most recently, NBCC representatives coauthored a paper on privacy issues in genetic research (Fuller et al., 1999).

There is room right now for discussion of how a new relationship between researchers and participants in genetic research should look, a discussion that should involve both parties. Incorporating genetic research into survey studies may provide an opportunity to engage the general population in this discussion. Rethinking the relationship between the parties in genetic research will also force examination of the researcher-participant relationship in general, and will require a reexamination of the nature of genetic information and research and how they are similar to or different from other types of medical information and research.

Responding to Change

In genetics, the one constant seems to be change. What is understood about genes and the genetic mechanisms of disease changes over time with further research. Data regarding the potential risks and benefits associated with participating in genetic research change. Laws affecting access to insurance and other social goods change. Federal regulations affecting genetic tests and patent decisions change. The capacity for clinical intervention in various diseases changes. Some sort of mechanism is needed to respond to these changes and to provide advice to researchers and participants in genetic studies.

It is unrealistic to expect the IRB system, with its current level of support, to bear the responsibility for responding to the constantly shifting sands of genetic research. Others have recommended that a national advisory committee on genetic testing be formed (Institute of Medicine, 1994; Task Force on Genetic Testing, 1997). As a result, the Secretary's Advisory Committee on Genetic Testing (SACGT) was recently established, and provides recommendations to the Secretary of Health and Human Services on genetic testing and research issues. The SACGT may address “the development of guidelines, including criteria regarding the risks and benefits of genetic testing, to assist Institutional Review Boards in reviewing genetic testing protocols in both academic and commercial settings” (http://www4.od.nih.gov/oba/sacgt.htm). As policy makers and investigators consider adding a genetic component to existing and planned demographic studies, they should look to the recommendations of this body and others. For large household surveys with already existing advisory committees, one way to do this would be to expand committee membership to include people who are familiar with ethical, legal, and social issues associated with genetic research. The advisory body could then provide oversight and advice on the collection of samples; the informed consent process; privacy and confidentiality issues; and the interplay of various study procedures and ethical, legal, and social issues.

A Research Agenda

This chapter has described various areas in which further research would help define the best protocols by which to conduct genetic research in association with household surveys. The need for research on how best to conduct genetic research cannot be understated, and is a current focus of the federal HGP (Collins et al., 1998; http://www.nhgri.nih.gov/98plan/elsi/). Many of the presumed risks and benefits associated with genetic research have only limited data to support them as either risks or benefits. For example, the limited and conflicting nature of data on insurance discrimination against people with genetic diagnoses or predispositions has been noted. There are very few data on the impact of genetic testing and research on the family unit. The lack of data poses challenges for the informed consent process in genetic research studies because it makes it difficult to give potential study participants good information about the true nature of the risks and benefits associated with their participation in a given study. Little is known about how potential study participants perceive these risks and benefits or about their motivation for participation in genetic studies. Little is known about the effectiveness of the informed consent process for genetic studies.

Survey studies that consider including a genetic component have an exciting opportunity to address some of these questions. Pilot studies of attitudes toward including a genetic component in household surveys would provide information about attitudes toward genetic research and research in general, and about motivations for participation in research. Informed consent forms could be piloted with study participants and would provide important data about the informed consent process for genetic research. Educational methods and materials could be developed to help the general population, in its ethnic and cultural diversity, understand genetic studies. Many survey studies have the infrastructure in place to follow participants over long periods, affording an opportunity to assess the experience of being in a genetic research study and potentially receiving genetic information over an extended time. In addition, given the nature of the information collected by some of these surveys, participant reports of effects of receiving genetic information can be correlated with other information independently obtained, such as various economic and/or health data.

A recent analysis of the Ethical, Legal and Social Implications (ELSI) Program of the HGP has identified a number of areas in which the ELSI program could strengthen its research portfolio. Specifically, the ELSI Research Planning and Evaluation Group recommended that ELSI “encourage activities that employ new theoretical perspectives … that promote cross-fertilization between ELSI research and other areas of the social sciences, law, and the humanities,” and that investigators be recruited “from a broader array of disciplines, such as economics, anthropology” (ELSI Research Planning and Evaluation Group, 2000). It seems that the time is ripe for a merging of the many disciplines, approaches, and resources that would be involved if genetic studies were appended to survey studies. If approached in a thoughtful and systematic fashion, expanding survey studies to include a genetic component has the potential to address many questions directly relevant to the introduction of genetic information and genetic services to the population as a whole.

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Copyright © 2001, National Academy of Sciences.
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