Human genetic research involves the study of genetic factors responsible for human traits and the interaction of those factors with each other and with the environment. Research in this area includes identification of genes that comprise the human genome; functions of genes; and characterization of normal and disease conditions in individuals, biological relatives, families and groups; as well as studies involving gene therapy. Participants in clinical trials are increasingly being asked to participate in genetic studies in addition to the primary clinical trial. With the increasing prevalence of genetic research, researchers, research ethics boards (REBs) and participants should be aware of the ethical issues that this research raises.
Genetic research may have profound social impacts, both positive and negative. As genetic research advances, genes and their alleles (versions) are being identified, but the function of each gene and its relationship to disease conditions or other characteristics may not be clear. In single-gene disorders, for example, an allele of a single gene is directly related to hereditary disease. More commonly, diseases or personal characteristics are influenced by multiple genes and environmental factors.
Research may help us better understand the human genome and genetic contributions to health and disease. It may lead to new approaches to preventing and treating disease. Individuals may benefit from learning about their genetic predispositions if intervention strategies are available to prevent or mitigate disease onset and symptoms, or otherwise promote health. Genetic research also has the potential, however, to exploit or stigmatize individuals or groups, who may experience discrimination or other harms because of their genetic status.
Genetic information has implications beyond the individual, because it may reveal information about biological relatives and others with whom the individual shares genetic ancestry. The participation of an individual in genetic research may therefore have ramifications for these other persons or groups. In some cases, researchers specifically seek to conduct genetic research with members of families or communities. Such research requires particular attention to the social and cultural contexts in which participants live. Research with families or communities may raise special considerations regarding recruitment of participants, consent processes, privacy and confidentiality, and community engagement.
Article 13.1 Guidelines for informed consent, protections for privacy and confidentiality, policies for research with human tissues, and other ethical guidance described in earlier chapters of this Policy apply equally to human genetic research.
Application In developing and reviewing proposals involving genetic research, researchers and REBs should refer to earlier chapters in this Policy, including Chapter 3 (“Free and Informed Consent”), Chapter 5 (“Privacy and Confidentiality”) and Chapter 12 (“Human Tissue”). Other chapters relevant to the specific research proposal, such as Chapter 9 (“Research Involving Aboriginal Peoples”) or Chapter 11 (“Clinical Trials”) should also be consulted. This chapter does not reiterate principles set out in earlier chapters. Rather, it focuses on issues that arise specifically in the context of human genetic research and sets out ethical principles in regard to handling of information revealed through genetic research, provision of genetic counselling, participation of families and communities in genetic research, banking of human biological materials, and research involving gene transfer.
Article 13.2 Researchers conducting genetic research must:
Application The types of information that may be revealed through genetic research - and implications of this information for participants and their biological relatives - requires that researchers and REBs ensure that an appropriate plan is in place for handling both anticipated and unanticipated information. In some cases, genetic research may reveal known gene-disease associations or other information, including incidental findings, that may be clinically relevant for individuals or their biological relatives in treating or alleviating health conditions or risks. In other cases, research may reveal information that is inconclusive in its scientific, clinical or other implications. Genetic research may also reveal information about family relationships, including non-paternity.
This range of information varies in its possible implications for individuals. In some cases, follow-up clinical testing and counselling may be recommended. Information may also have implications for biological relatives and raise disclosure considerations, as discussed in Articles 13.3(b) and 13.4. Genetic information may also affect an individual’s eligibility for employment or insurance, for example, if an individual who gathers genetic information is required to disclose disease predisposition risks to participants’ employers or insurers.
The plan for handling information should take into account factors such as clinical relevance and anticipated benefits and harms for research participants and other people whose interests are implicated. Plans may include return of individual findings to participants or general notification of non-identifiable research results through newsletters, websites or other means. In regard to release or publication of research findings, the provisions of Chapter 5 (“Privacy and Confidentiality”) apply. In some cases, researchers may consider that the most ethical course of action is not to return results of genetic research to participants (for example, where clinical significance is unknown due to novelty of the genetic investigation).
Article 13.3 Where researchers plan to return findings to individuals, participants in genetic research should have an opportunity to:
Application An individual’s right to privacy includes a right not to know information about himself or herself, and the principles on which this Policy is based emphasize autonomous choices regarding research participation. To permit participants to make informed choices about whether to receive information about themselves, researchers should explain the types of findings that may be revealed (as discussed in the Application of Article 13.2) and the potential implications of these findings for the participant, and should give the participant options for receiving different types of information. For example, a participant may want to receive clinically important information, but decline to receive information that is of unknown clinical significance.
Where individual results will be returned to participants, researchers must develop appropriate procedures for communicating results in accordance with the participant’s preferences or instructions. These procedures should be clearly described in the researcher’s plan. This may include direct communication of results to the participant, or communication to a specified health-care provider or other party authorized to receive the information. As discussed below, provision of research results to individuals may give rise to a need for genetic counselling.
Participants in genetic research should have an opportunity to express their preferences about disclosure of information to relatives or others, but these preferences are subject to the researcher’s duty to warn, as described in Article 13.4.
Article 13.4 Researchers may have an obligation to disclose information to biological relatives of the research participant in exceptional circumstances. This may include instances where genetic research reveals information about a serious or life-threatening condition that can be prevented or treated through intervention, even if the participant has expressed a preference against sharing information. Researchers should inform participants of this obligation in the plan for handling information.
Application As discussed in Chapter 5 (“Privacy and Confidentiality”), researchers have important obligations to maintain confidentiality of information. In genetic research, however, situations may arise where researchers become aware that a third party may be at high risk of a serious or life-threatening condition that can be prevented or treated. In such exceptional circumstances, legal or ethical imperatives may require that researchers disclose information they have obtained in a research context. Researchers should explain this to participants during informed consent discussions.
Article 13.5 Where researchers plan to return results of genetic research to participants, the research protocol should make genetic counselling available at that time, where appropriate.
Application Where the plan for handling information revealed in genetic research involves return of individual results to participants, genetic counselling may be required to explain the meaning and implications of the information. For example, genetic counselling can help explain the clinical significance of the information, whether health-care interventions or lifestyle changes are recommended, and implications of the information for biological relatives. Researchers should explain differences between genetic testing in a research context and testing in a clinical context. Clinical genetic testing may be needed to clarify or confirm results obtained in research. Where researchers disclose information to biological relatives or other family or group members, genetic counselling should be made available to them and the research participants. While the service provider need not necessarily be a genetic counsellor, he or she must have the experience or training to provide genetic counselling.
Article 13.6 Where researchers seek to recruit members of a family to participate in genetic research, recruitment processes should be respectful of privacy and other personal interests of family members. In seeking consent from members of a family to participate in genetic research, researchers should ensure that consent from each individual is free and informed.
Application Recruitment of members of a family may take place in various ways. A family group, such as parents and a child or several adult siblings, may all together receive an invitation to participate in genetic research. Alternately, researchers may ask an individual who has agreed to participate for permission to contact family members who will receive a subsequent invitation to participate. Family members may have conflicting views about participation in research, and some may have specific sensitivities or objections. Researchers should recognize the potential for conflict within families and be respectful of any known sensitivities. They should also ensure that consent from each individual is free and informed. Where researchers seek participation from children or other members of a family who may lack capacity to give consent, applicable principles in Chapter 3 (“Free and Informed Consent”) must be followed.
In some situations, researchers may seek permission from an individual participant to contact family members. Where appropriate to respect privacy interests or known sensitivities, it may be preferable for the participant to make initial contact with the family member. Alternately, the participant may identify a third party who may be asked to make initial contact with the family member to provide them with information about the opportunity to participate in genetic research. An approach by someone in a position of authority over the family member may raise concerns about undue influence or manipulation. Refer to Chapter 3 (“Free and Informed Consent”) for further guidance in regard to voluntariness of consent.
Article 13.7 Where researchers intend to recruit participants for genetic research based on their membership in specific communities, it may be appropriate for researchers to consult with community leaders or representatives, in addition to seeking free and informed consent from individual participants. In these cases, researchers must provide details to the research ethics board about their proposed methods for seeking engagement or consultation.
Application Some genetic research seeks to explore genetic variations within specific groups or communities. Such research may raise ethical concerns regarding stigmatization or exploitation of groups, as well as social disruption in communities, especially if individual members disagree about participation in research. Researchers may have an ethical obligation to seek the engagement of leaders or representatives of the community or to consult with community members about the proposed research. This duty will depend on factors such as the objectives of the proposed research (in particular, the extent to which membership in, or characteristics of, the community are a key aspect of the research), the potential benefits and harms of the research to the community, the nature of the community from which participants will be recruited, and the community’s organizational structure.
Individuals within a community may have conflicting views about participation in research, including disagreements between leaders and members. Such conflicts may involve attempts by some to influence or coerce choices of others about whether to participate in research. Researchers should recognize the potential for conflict within groups and ensure that consent and consultation processes foster free and informed decisions by individual members of a community. Refer to Chapter 3 (“Free and Informed Consent”) for further guidance in regard to voluntariness of consent.
Chapter 9 (“Research Involving Aboriginal Peoples”) articulates specific applications of the principles relevant to research involving Aboriginal peoples, which arise from historical examples of inappropriate treatment of Aboriginal peoples in research. Researchers who propose to conduct genetic research within Aboriginal communities or to use materials obtained from Aboriginal peoples and that have implications for Aboriginal peoples should refer to the detailed discussion in that chapter for further guidance.
Application As discussed in Chapter 12 (“Human Tissue”), collection of human tissues and genetic material and their retention in biobanks provides an increasingly important research resource. Principles for research involving human tissue (see Chapter 12) apply to banking of genetic material. Section C (“Tissue Storage and Banking”) of Chapter 12 provides guidance for prospective creation of biobanks of genetic material, and Section D (“Secondary Use of Previously Collected Tissue”) addresses access to and use of previously collected genetic material. Researchers who intend to bank genetic material should inform participants of the potential for secondary use. Principles regarding secondary use set out in Chapter 5 (“Privacy and Confidentiality”) are also relevant.
Principles set out in Chapter 11 (“Clinical Trials”) apply to clinical trial research involving gene transfer. In the context of gene transfer research, researchers and REBs should pay careful attention to the need to assess safety, minimize risk, and avert therapeutic misconception. Researchers have obligations to share new information that may be relevant to continuing consent, and to follow up with participants to identify adverse events.
Article 13.9 Gene transfer research that involves alteration of human germline cells is governed by statute in Canada under the Assisted Human Reproduction Act and its regulations. Researchers must be aware of how these apply to their work.
Application Gene alteration involves the transfer of genes into cells to induce an altered capacity of the cell. Viruses are commonly used vectors (carriers) to introduce the gene into the host genome. Gene alteration is irreversible: the cell and its descendants are forever altered and introduced changes cannot be removed. The possible use of germline alteration in the embryo implies changes that could be transmitted to future generations.
In other research situations, the special circumstances of gene transfer must be explained to potential research participants (or authorized decision-makers) during the process of free and informed consent. This includes providing information about uncertain and potentially latent risks of gene transfer and any processes for long-term follow up of participants. Principles regarding inclusion in research (see Chapter 4 [“Inclusion in Research”]) should be followed where gene transfer research involves children or others who may lack capacity to consent for themselves.
Scientific research in these areas - and associated ethical debate - is evolving rapidly, and researchers must be aware of current law and also be guided by the core principles of this Policy.