Chapter 3.3: Genomic research. National Statement on Ethical Conduct in Human Research (2007) - Updated 2018.

Introduction – Chapter 3.3

This chapter is about generating, gathering, collecting, conveying or using genomic data or information that has hereditary implications and/or is predictive of future health in research involving participants, relatives and other family members. It applies irrespective of the nature of the source material for the research, such as data or biological materials such as germline/ germ cells or somatic cells.

Genomic research is characterised by the original intention of the investigation and the potential hereditary and/or future health implications, if any, of the information that is collected or generated by the investigations. Genomic research is rapidly evolving and is not constrained by current methods or techniques for obtaining the information, however, a common element of genomic research is the sequencing of data or its use. Genomic information can be predictive, unchanging, sensitive and familial.

Genomic information has the unique character of being both specific to an individual and specific to relatives of that individual and, in some cases, of significance to human population groups such as groups that define themselves via their ancestral lineages.

Research results and information collected for genomic research may be significant for relatives of research participants. Relatives and other family members, such as partners and spouses, may have an interest in the participants' genomic material, or in information the research generates, because testing that material or acquiring that information may create new options for life decisions, including those with the potential to improve their health or the health of their offspring. However, some family members may prefer not to be given such information, or even not to know of its existence.

Genomic research can reveal information about predispositions to disease. Although people with such a predisposition may not develop the disease, the information may have implications for their access to employment and education and to benefits or services, including financial services such as banking, insurance and superannuation. Genomic information can sometimes be misused to stigmatise people or to discriminate against them unfairly. The information may also have similar implications for close relatives. In addition, genomic research can reveal information about previously unknown or misattributed paternity or maternity or familial relationship.

Genomic research is frequently considered to be greater than low risk, especially in the context of research involving Indigenous peoples. For this reason, relevant on-going community consultation and active agreement on the part of communities and traditional owners is an essential component of the planning and conduct of this research.

This chapter is relevant to different types of genomic research (for example, family studies, clinical research, population health research, health service research). Some research that falls within the broad description of genomic research does not involve information that is relevant to the future health of the individual participant and does not generate sensitivities for the individual, or his or her family or community. An example of this research is a population survey of preferences regarding disclosure of genomic information where identifiers related to survey results are not disclosed.

As a general principle, research including genomics will require review by an HREC, however, if no information that can identify an individual is used and no linkage of data is planned, the research may be determined to carry low risk.

In genomic investigations, there may be a strong relationship between the research and clinical contexts such that there may be clinical implications of research results or findings. Nevertheless, differences between results that are associated with research and results that are associated with clinical investigations should be clear, especially when the researcher is also a clinician and where clinical care is ongoing. Where appropriate, researchers should refer to clinical practice guidelines such as the NHMRC's Principles for the translation of 'omics '–based tests from discovery to health care and applicable legislation.

Chapter 3.3 should be read in conjunction with Chapter 3.1 and other parts of the National Statement.

Guidelines – Chapter 3.3

Element 1: Research Scope, Aims, Themes, Questions and Methods

3.3.1 Genomic research that uses sequenced information should be designed with attention to what information is necessary to achieve the aims of the research and to ensure that ethical issues that arise from activity outside the intended scope of the research are minimised by, for example, developing a list of genes that are excluded from analysis.

3.3.2 Genomic research should be designed to minimise the potential for misunderstanding and misuse of genomic information by those who may wish to use it for unrelated purposes.

3.3.3 Methods used in genomic research are not a static set, but are constantly evolving and, as they are developed and applied, may require ethical consideration on an ongoing basis. Therefore, the ethical principles and guidance in this chapter should be considered with reference to the new technologies as they are developed and applied.

Element 2: Recruitment

3.3.4 In addition to participants in genomic research identified as index cases (probands), relatives of these individuals who provide information or biospecimens for genomic research become participants in the research in their own right. Therefore, researchers should be aware of the possibility of the involvement of relatives by virtue of association with a participant or other family member who has been recruited.

3.3.5 HRECs must consider the rationale for and review the information to be used in recruiting family members of a participant.

3.3.6 Where a potential research participant is not already known to the research team, it may be ethically preferable for the participant (rather than the researcher) to make the initial contact with a family member for purposes of recruitment into research.

3.3.7 Researchers should respect differences between and within families regarding the willingness to communicate health information, the relative importance of privacy versus sharing of health information and other matters that may reflect cultural values (whether shared within the family or not).

3.3.8 Where researchers propose to generate or collect genomic information from individuals who are chosen because of their membership of a particular community, they should consult with appropriate community representatives.

3.3.9 The recruitment process should avoid disclosure of genomic information to a potential research participant as an inadvertent consequence of that process.

Element 3: Consent

3.3.10 In considering the appropriate form and scope of consent and the most appropriate process for obtaining consent, researchers should consider:

1. (a) what information will be generated by the research
2. (b) what may be discovered by the research
3. (c) what will be deliberately excluded from the scope of the research
4. (d) which, if any, of the findings of the research will be communicated to participants and, if so, how
5. (e) what the health implications are of the information for participants and their relatives
6. (f) whether there are any other implications for participants and their families of being given this information (for example, insurance, employment, social stigma)
7. (g) the potential for the information generated by or used in the research to result in participants being re‑identified
8. (h) whether information generated by the research will be shared with other research groups
9. (i) potential future use of information and biospecimens, including commercial applications.

3.3.11 Participants should be advised that information that they may be given about the likely impact of the genomic information may change over time as new knowledge/insight is gained and how to obtain updated information.

3.3.12 Participants should be advised that publication or funding requirements may require submission of data or information to controlled access repositories that meet international security and safety standards for sharing with researchers globally.

3.3.13 Participants should be advised of the practical limitations associated with a decision to withdraw from genomic research after analysis of data has been conducted or biospecimens have been shared with other researchers as well as any other consequences that may follow from their withdrawal from the research.

3.3.14 Consent specific to the research may not be required or a waiver of the requirement for consent may be considered by an HREC if:

1. (a) the data or information to be accessed or used was previously collected and either aggregated or had identifiers removed, or
2. (b) prior consent for the use of the data or information was provided under the scope of a research program that encompasses the proposed research project, or
3. (c) prior consent for the use of the data or information was provided in the clinical context for research that encompasses the proposed research project, or
4. (d) unspecified consent has been provided.

3.3.15 An opt-out approach (see 2.3.5), should not be used in genomic research.

3.3.16 Collection of information about family history for genomic research may involve the collection of information about family members who are not aware that information about them is being collected and it may not be practicable to obtain consent from all family members in a pedigree. Therefore, researchers should consider documenting who provided the family history and any presentation of research outcomes should acknowledge that self-reported information about individuals and their families may not be accurate or complete.

3.3.17 Researchers should not presume that the decision to participate in genomic research includes a decision to receive the results of that research. Where researchers consider that the results must be provided to participants, the project should be designed to include the mandatory return of results and this condition should be clear in any information materials.

Element 4: Data collection and management

This section covers the access to and collection, use, analysis, disclosure, storage, retention, sharing and disposal of genomic data and information. The potential return of findings and results of genomic research is covered in 3.3.26 to 3.3.35, below.

3.3.18 Researchers should recognise and account for the potentially predictive and sensitive nature of genomic information.

3.3.19 Researchers should be sensitive to the contextual factors that determine the identifiability of genomic information, in particular the impact of the rarity of a genetic disorder or mutation on whether individuals or families could be identified.

3.3.20 For the purposes of a specific research project, the identification of individuals or family members can be considered impracticable if:

1. (a) there is no plan in the research proposal to link or match the information in such a way as to permit re-identification
2. (b) storage of biospecimens and project information is secure.

3.3.21 If inclusion of information in databases is a necessary component of the research or if information is to be shared for other research, efforts should be made to minimise the potential for re‑identification.

3.3.22 Researchers receiving genomic information should not undertake nor permit attempts to re-identify the material or information or otherwise reduce the protection of the privacy of the participants.

3.3.23 Information generated or collected through genomic research should not be disclosed by researchers for uses unrelated to research, however, statutory or contractual duties may require participants to disclose the results of genetic tests or analysis to third parties (for example, insurance companies, employers, financial and educational institutions), particularly where results provide information about health prospects. Participants should be advised of these duties.

3.3.24 Researchers may share genomic data or information provided that:

1. (a) sharing information is consistent with the consent that has been obtained for the research project or for clinical purposes, or
2. (b) an HREC has judged that the conditions for waiver of the requirement for consent have been met (see 2.3.9 to 2.3.10)
3. (c) the HREC has approved the transfer in principle, subject to any transfer agreement that has been established for this purpose.

3.3.25 Subject to the requirements of good research practice, genomic information and related biospecimens should be stored or disposed of in accordance with the project-specific consent provided or the governance policies of the relevant biobank.

Element 5: Communication of research findings or results to participants

3.3.26 In considering whether to return results of research, researchers should distinguish between individual research results and overall research results. Researchers should consider how these results will be provided to participants, how the process of returning results will be managed and the risks of the return of individual research results and overall research results.

3.3.27 Return of findings and results relating to an individual participant depends on the contextual relevance of the findings; some genomic research findings must be returned, some findings may be returned and some findings should not be returned.

3.3.28 While participants may have a strong interest in their own information, researchers are not expected to return raw genomic data to participants.

3.3.29 Once there is sufficient evidence and agreement that a finding or result is clinically significant, participants should be advised that research results or findings that may be returned will first need to be confirmed according to applicable guidelines, for example, at a National Association of Testing Authorities (NATA)‑accredited laboratory.

3.3.30 When designing the research project and in considering whether to return findings to participants, researchers should refer to the Decision tree for the management of findings in genomic research and health care for the principles/framework and then refer to the guidance in the section Guidance for the Development and Evaluation of an Ethically Defensible Plan for the Potential Return of Findings and Individual Results from Genomic Research that follows for developing an ethically defensible plan.

3.3.31 Any plan to return individual research results should include linkage with a clinical service and access to genetic counselling. The plan should specify any expertise to which the project team might require access.

3.3.32 The return of results or findings of significance for the health of the participant or relative is the responsibility of the appropriate clinical service or, where such a service is not available, the participant's clinician in consultation with the research team.

3.3.33 Where a result or finding may be of relevance to one or more relatives, it is the remit of the appropriate clinical service or the participant's clinician to discuss with the participant the appropriateness of communicating these results or findings to relatives.

3.3.34 Over time there may be a substantive change in the understanding of the significance of the research results or findings. For the duration of the research project, researchers have a responsibility to provide the research cohort with the opportunity for each participant to re-consider their decision related to receiving results or findings (see 3.3.53‑3.3.55).

3.3.35 In all other cases, any obligation to further analyse or interpret genomic data related to participant information ceases at the end of the project.

National Statement Decision Tree

Note 1

Clinicians who do not request an investigation or on whose behalf an investigation was not requested or who subsequently refer a patient to a different primary treating clinician do not have an obligation with respect to management of the findings of the investigation.

Note 2

The patient must be advised of the policy +/- options addressing the return of findings including incidental findings.

Note 3

A “no” answer includes scenarios in which a non-validated test is performed in a NATA accredited lab or overseas equivalent AND in which a validated test is performed in a non-accredited lab. Situations in which this might occur include the development of diagnostic tests and research testing that has not been approved as part of a research project. In the first situation (test development), findings should not be returned. The second situation (unapproved testing) is contrary to ethical standards.

Note 4

The criteria and process must specify: 1) that any findings must be verified by a NATA accredited lab; 2) which findings will be returned; 3) who will be consulted prior to the return of the findings; 4) who will return the findings; and 5) to whom the findings will be returned.

Note 5

If the findings are not pertinent findings, then any return of findings will be based on the policy established by the research protocol and/or by international standards.

Note 6

Refer to guidance in this chapter regarding requirements related to consent for the return of findings from genomic research.

Key terms

Pertinent findings

Also known as primary findings, pertinent findings are those that were the primary objects of the investigation.

Secondary findings

Findings that were not the primary target of the investigation, but were either specifically sought or are related to the primary target and anticipated as likely to arise.

Incidental findings

Findings of potential clinical significance unexpectedly discovered during the investigation. NB: With respect to full spectrum 'discovery 'investigations and direct-to-consumer testing, one is explicitly searching for any and all findings and so no findings can be considered 'unexpected '.

Authors of this National Statement

This National Statement has been jointly developed by the National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC) and Universities Australia (UA). This joint undertaking reflects a widely shared conviction that there is a need for ethical guidelines that are genuinely applicable to all human research and it gives expression to the shared responsibility for ethically good research described above.