The use of human participants in biomedical, clinical and social-behavioral research can provide insights and discoveries that could not be otherwise obtained using model organisms or other methods. All federally-funded research with human participants such as that supported by NIH must comply with regulations that protect the rights and welfare of the participants, and require that researchers clarify the benefits and risks of participating in the research.
Protecting Research Participants
All research with human participants supported by the United States government, including any genomics research funded by or carried out at NIH, is subject to the Federal Policy for the Protection of Human Research Subjects, or 'Common Rule' (Code of Federal Regulations, Title 45, Part 46). This regulation establishes rights and protections for participants in research.
The Common Rule requires informed consent, where an investigator must provide to each potential research participant a clear summary of the research study, including any risks to participants, and where each individual then needs to consent to permit the researcher to include them in the study. The Common Rule also requires that federally-funded human subjects research studies are overseen by an Institutional Review Board (IRB) to ensure the safety of research participants.
Prior and during World War II (WWII), there were no formal regulations governing research with human participants. In response to cases of ethical misconduct during WWII, the international scientific community established the Nuremberg Code (1949) and the Declaration of Helsinki (1964) as codes of conduct for research with humans. Despite the establishment of these ethical principles at an international level, research with human participants in the US was not formally regulated until over a decade later. Increased protections in the U.S. were only established after misconduct in domestic research studies was exposed. This included studies in which participants were not informed of the risks to their health of study participation, or were denied critical medical treatment, such as in the Tuskegee syphilis experiment. As a response, the Belmont Report was published in 1979 and articulated basic ethical principles for human subjects research in the U.S: respect for persons, beneficence, and justice. The Common Rule was first published in 1981 to align with the principles outlined in the Belmont Report which continue to guide research today.
The Common Rule underwent its first major revision since 1991 in 2017, and the final revised version was published in the Federal Register on January 19, 2017. The revisions aim to "modernize, simplify, and enhance" oversight for research with human participants in the United States to address changes in the nature of research since the original publication of the Common Rule in 1991. For more information about the revisions as they relate to genomics research, see: Highlights of Revisions to the Common Rule.
Participation in Genomics Research
The use of human participants in genomics research has facilitated significant scientific discoveries and achievements, including the complete sequencing of the human genome and identification of genetic markers for human diseases. While model organisms remain powerful research tools, working with human participants in genomics research enables scientists to study human genetic variation, to identify the genetic underpinnings of disease, and to research how genomics can be applied in the clinic. The translation of genomics discoveries from bench to bedside is ushering in the era of genomic medicine, allowing for more personalized treatments tailored to specific patients.
NIH abides by federal regulations and guidance, including the 'Common Rule', for genomics research involving human participants. Individuals are provided a description of the genomics research being conducted, the ways in which their genomic information will be used, and the risks and benefits of their participation. Given that one's genome contains personal health and other information, analyzing genomes as part of a research study raises a number of issues that the informed consent process needs to address, such as the measures in place to protect participants' privacy, and under what circumstances information might be returned to them. For more information about the informed consent process for genomics research, please see the Informed Consent for Genomics Research Resource.
Implications for Relatives
While genomic research may reveal new information about the research participant's health, the heritable nature of genetic information raises implications for the research participant's relatives as well. Information about family members not involved in the study may be indirectly obtained through the research participant. Furthermore, genomic research using family pedigrees can trace disease history and may reveal family members that are carriers of a disease or will be affected themselves. These indirect results can pose an ethical conflict between a possible duty to warn family members of research participants about health risks and the protection of research participant privacy.
The IRB Guidebook from the NIH Office of Protection from Research Risks provides guidance on addressing these issues.
Identifiable populations, which include specific racial or ethnic groups, geographically-defined communities, and members of ultra-rare disease groups, face some unique concerns with regard to privacy, stigmatization, and discrimination. For example, for some communities, close family relationships may make it nearly impossible to protect participants' privacy. Additionally, genetic information could raise questions around ancestry and family-ties that may disrupt the community structure.
Some communities may require the researchers to obtain community approval before seeking consent from potential participants, and some communities have developed resources to help their members consider the major issues that come with participating in research. For American Indian and Alaska Native communities, for example, the National Congress of American Indians Policy Research Center, in conjunction with NHGRI, developed a resource to provide information about genetics research. This includes t information about how some tribes are thinking about genetics research to assist other tribes in making decisions for their own communities.
Data Sharing and Privacy
Technological advances in DNA sequencing have made high-throughput sequencing methods significantly faster and cheaper, allowing researchers to generate larger datasets than ever before. These datasets can be used for genome-wide association studies (GWAS) that identify specific genomic factors associated with human health and disease. NIH implemented the GWAS Policy in 2008, requiring data from NIH-funded GWAS to be shared with the research community in a central data repository maintained by NIH, the database of Genotypes and Phenotypes (dbGaP). To protect research participants' privacy, access to sensitive data in dbGaP is through a controlled access policy, and NIH requires secondary use of data (i.e. use of existing data for a different study) to be consistent with the informed consent obtained from research participants during the initial study.
To further expand genomic data sharing of all types, NIH released a Genomic Data Sharing policy that has been in effect since January 25, 2015. The policy states that NIH expects investigators to obtain consent for participants' data to be used for future research purposes and to be shared broadly through databases. NIH has the same expectations for informed consent for studies using genomic data from cell lines or clinical specimens that were created or collected after the effective date of the policy. Like the GWAS policy, the GDS policy includes numerous provisions to ensure the protection of human genomic data. See http://gds.nih.gov/ for more information.
The importance of controlling data access to protect research participant privacy has been highlighted by the HeLa Genome Data Use Agreement announced by NIH in August 2013. HeLa cells are used widely in research and were first taken and immortalized from a cancer patient named Henrietta Lacks. In collaboration with the Lacks family, NIH developed a controlled access policy through dbGaP specifically for genomic data generated from the HeLa cell line. The HeLa Genome Data Access Working Group reviews HeLa genome data requests from the research community, and f HeLa genome data generated from NIH-funded research is submitted to dbGaP. For further information, see: "Nature Comment: Family Matters."
Genetic Information Nondiscrimination Act
The Genetic Information Nondiscrimination Act (GINA) prohibits health insurers and employers from requesting or requiring genetic information from an individual or an individual's family members, and further provides legal protection against discrimination on the basis of a person's genetic information. This means that individuals who participate in research are protected from insurance and employment discrimination if they contribute their genetic information to studies. GINA does not protect against discrimination in some forms of insurance, however, including life insurance, long-term care insurance, and disability insurance. HHS has issued guidance on GINA for IRBs and investigators involved with Federally-supported human subjects research. In addition, NHGRI's Informed Consent for Genomics Research resource contains model language for including information on GINA in informed consent forms. For further information on GINA, see: Genetic Discrimination
Re-identification and Privacy
DNA sequences can reveal health and other information about individuals and their families. Whether genomic information is being used for research, clinical or other uses, it is important to consider what measures are needed to ensure that individual privacy is respected. This includes issues around the use of clinical samples in research and uses in law enforcement. For more information about issues of privacy in genomics and the protections provided, please see Privacy in Genomics.