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Revised Draft 2nd Edition of the TCPS (December 2009)

Chapter 13

HUMAN GENETIC RESEARCH

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; the characterization of normal and disease conditions in individuals, biological relatives, families and groups; and 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, especially whole-genome 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 stigmatize individuals or groups who may experience discrimination or other harms because of their genetic status, or to treat them unfairly or inequitably.

A. Application of Core Principles to Genetic Research

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  Guidance regarding proportionate review, consent, privacy and confidentiality, research with human biological materials, 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 consent in Chapter 3, privacy and confidentiality in Chapter 5 and human biological materials and materials related to human production in Chapter 12. Other chapters relevant to the specific research proposal should also be consulted, such as Chapter 9 about research involving Aboriginal peoples or Chapter 11 on clinical trials. This chapter does not reiterate guidance set out in earlier chapters. Rather, it focuses on issues that arise specifically in the context of human genetic research and provides guidance for 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.

B. Plans for Handling Information Revealed through Genetic Research

Article 13.2     Researchers conducting genetic research shall:

(a) in their research proposal, develop a plan for handling information that may be revealed through their genetic research;

(b) submit their plan to the REB; and

(c) advise potential participants of the plan for handling information revealed through the research.

Application The types of information that may be revealed through genetic research – and implications of this information for participants and their biological relatives – require that researchers and REBs ensure that an appropriate plan is in place for handling 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 adoption and 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 Article 13.3(b). 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, risks and potential benefits for research participants and other people whose interests are implicated. Plans may include sharing individual findings with participants or notification of general,non-identifiable research results through newsletters, websites or other means. In regard to release or publication of research findings, the provisions of Chapter 5 apply. In some cases, researchers may consider that the most ethical course of action is not to share results of genetic research with participants (e.g. where clinical significance is unknown due to novelty of the genetic investigation).

Article 13.3 Where researchers plan to share findings with individuals, researchers shall provide participants an opportunity to:

(a) make informed choices about whether they wish to receive information about themselves; and

(b) express preferences about whether information will be shared with biological relatives or others with whom the participants have a family or group relationship.

Application An individual’s right to privacy includes an interest in not knowing information about himself or herself. Further, the core 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 to 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.

Where individual results will be shared with 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, sharing research results with individuals may give rise to a need for genetic counselling.

Participants in genetic research should have an opportunity to express their preferences about sharing of information with relatives or others. These preferences are subject to overriding considerations that may warrant disclosure of information to relatives in exceptional circumstances where genetic research reveals information about a serious or life-threatening condition that can be prevented or treated through intervention. Articles 5.1 and 5.2 provide guidance on researchers’ ethical duty of confidentiality and situations where researchers may have a requirement to disclose information to third parties.

Chapter 5 also requires researchers to provide details to the REB regarding their proposed measures for safeguarding information through its full life cycle, including dissemination, and to guard against risks of re-identification. Funders of human genomics research may have policies requiring researchers to make genome sequence data publicly accessible. Where such policies apply, researchers must advise the REB and participants of data-sharing requirements and measures for protection of personal information. See Articles 5.2 and 5.3 for further guidance. Publication of aggregated data from genome-wide association studies has raised concerns about individual re-identification.1 This example underscores the need for researchers and REBs to ensure that measures for safeguarding information are responsive to risks that arise from continuing advances in genetic research and data linkage.

C. Genetic Counselling

Article 13.4 Where researchers plan to share results of genetic research with 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 sharing individual results with 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 share information with biological relatives or other family or group members, genetic counselling should be made available to them and the research participants. The service provider must have the appropriate experience or training to provide genetic counselling, but need not necessarily hold a diploma, degree or professional designation in genetic counselling.

D. Genetic Research Involving Families

Article 13.5 Researchers who seek to recruit members of a family to participate in genetic research shall:

(a) ensure recruitment processes respect privacy and other personal interests of family members; and

(b) seek consent from individual family members.

Application Recruitment of members of a family may take place in various ways: through (a) the researcher, (b) an individual participant, or (c) a third party on behalf of an individual participant. A family group, such as parents and a child or several adult siblings, may all receive an invitation at the same time from the researcher to participate in genetic research. Alternatively, researchers may seek permission from an individual participant to contact family members to invite participation. Where appropriate to respect privacy interests or known sensitivities, it may be preferable for the participant to make initial contact with the family member. The participant may prefer to identify a third party to provide the family member 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 for further guidance in regard to the voluntariness of consent.

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. Where researchers seek participation from children or other members of a family who may lack capacity to consent, applicable provisions in Chapter 3 shall be followed.

E. Genetic Research Involving Communities

Article 13.6 Where researchers intend to recruit participants for genetic research based on their membership in specific communities, it may be appropriate for researchers to discuss the research with community leaders or representatives, in addition to seeking consent from individual participants. In these cases, researchers shall provide details to the REB about their proposed methods for engaging in discussion.

Application Some genetic research seeks to explore genetic variations within specific groups or communities. Such research may raise ethical concerns regarding stigmatization, unfair or inequitable treatment of groups, as well as social disruption in communities, especially if individual members disagree about participation in research. Engaging in discussion with leaders or representatives of the community may be appropriate. This determination 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 risks and potential benefits 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 community discussion processes foster free and informed decisions by individual members of a community. Refer to Chapter 3 for further guidance in regard to voluntariness of consent.

Researchers who propose to conduct genetic research involving Aboriginal participants or communities, or to use human biological materials identifiable as originating from Aboriginal peoples, should refer to the detailed discussion in Chapter 9 for further guidance.

F. Genetic Material Banks

Article 13.7

(a)  Researchers who propose research involving collection and banking of genetic material shall indicate in their research proposal, and inform potential research participants, how they plan to address the associated ethical issues, including confidentiality, privacy, storage, use of the data and results, possibility of commercialization of research findings, withdrawal by the participant, and future contact of participants, families and groups.

(b) Researchers who propose research involving secondary use of previously collected and banked genetic material shall, likewise, indicate in their research proposal how they plan to address associated ethical issues.

Application Collection of human biological materials, including genetic materials, and their retention in biobanks provides an increasingly important research resource. Guidance for research involving human biological materials (see Chapter 12) applies to banking of genetic material. In Chapter 12, Section D provides guidance for creation of biobanks of genetic material, and Section C addresses access to and use of previously collected genetic material. Researchers who intend to bank genetic material shall inform participants of the potential for secondary use. Guidance regarding secondary use set out in Chapter 5 is also relevant.

G. Gene Transfer

Guidance set out in Chapter 11 applies 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 ongoing consent, and to follow up with participants to identify adverse events.

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 germ line alteration implies changes that could be transmitted to future generations.

Gene transfer research that involves alteration of human germ line cells is governed by statute in Canada under the Assisted Human Reproduction Act2 and its regulations. Researchers should be aware of how these apply to their work.

The special circumstances of gene transfer must be explained to potential research participants (or authorized third parties) during the consent process. This includes providing information about uncertain and potentially latent risks of gene transfer and any processes for long-term follow up of participants. Guidance regarding inclusion in research (see Chapter 4) should be followed where gene transfer research involves children or others who lack capacity to consent for themselves.

Endnotes


1. In 2008, the U.S. National Institutes of Health amended its policy on publication of and access to data from genome-wide association studies. See National Institutes of Health, Modifications to Genome-Wide Association Studies (GWAS) Data Access, August 28, 2008, http://grants.nih.gov/grants/gwas/data_sharing_policy_modifications_20080828.pdf

2. Assisted Human Reproduction Act (2004, c. 2), http://laws.justice.gc.ca/en/A-13.4/