Advice on research protocols

Coding and de-identification of genetic samples and information

16.8 One area of research practice that may be an appropriate subject for guidance relates to the de-identification of genetic samples and information. The de-identification of samples and information is an important mechanism by which privacy is protected in the conduct of research.

From a privacy-protection perspective, there is a very wide distinction between personally identifiable data and truly anonymized data. But in practice the demarcation between these extremes is not sharp. Attending assiduously to where particular data lie on the spectrum between them, and especially to data that are somewhere in the middle, is a crucial protection strategy.^[13]

16.9 The National Statement makes distinctions between identified, potentially identifiable (coded or re-identifiable) and de-identified (not re-identifiable, anonymous) personal information or material.^[14]

16.10 Genetic samples and information used in human genetic research are commonly coded—that is, identifiers such as the individual’s name, date of birth or address are removed and replaced by a code. This information is potentially identifiable.^[15]

16.11 For the purposes of the National Statement, information or material is ‘de-identified’ only if the process of de-identification is irreversible—for example where the identifiers have been removed permanently or where the data have never been identified. Coded data is not ‘de-identified’ because coding, by its very nature, is intended to be reversible.^[16]

16.12 Human genetic research often requires information obtained from genetic testing to be linked to health information contained in clinical records, making true de-identification impractical. Eli Lilly Australia Pty Ltd emphasised the importance of a clear definition of de-identification because of its relation to the scope of consent.^[17]

16.13 Submissions and consultations emphasised that complete de-identification is often not a practicable solution to privacy concerns about the collection and use of genetic samples or information in research. For example, in relation to tissue banks, the Peter MacCallum Cancer Institute (PMCI) stated that:

It is important that the samples remain ‘identified’ to the managers of the tissue bank. Retaining identifiers allows the collection of follow-up information, such as survival data. A recommendation that broadly consented material should be de-identified would prevent the ongoing collection of clinical information. For certain diseases, such as breast or prostate cancer, survival outcome may not be known for years. High quality, centrally collected samples with long term outcome information are extremely valuable for testing potential markers of therapeutic response and outcome …^[18]

16.14 There are other reasons why de-identification may not be desirable in the context of human genetic research. Human genetic research may reveal information of potential importance to the future health of participants or their children. The Human Genetics Society of Australasia (HGSA) noted that:

With regard to research uses, de-identification protects privacy but does not address other interests of research subjects such as the possibility of receiving health information that comes out of the research. Obtaining consent for research that uses identified samples/information allows information to go back to participants and may place an obligation on researchers to do so.^[19]

16.15 The National Statement notes that researchers should consider carefully the consequences of storing genetic material or information in de-identified form for the proposed research, for future research, and for communication of research results to participants.^[20]

16.16 The HGSA stated that HRECs may consider it inappropriate to approve research using de-identified material or information if the research is likely to produce useful health information for the participants.^[21] Some of the dilemmas were illustrated in the HGSA’s submission to the Inquiry.

A problem may arise if the research could identify an important family condition, which may have great significance for [the family’s] health. In these cases, both the researchers and the HREC should undertake careful consideration as to which is the best way to approach the condition. For example, if a sample from a baby who had died from SIDS were found to have a genetic problem which could occur in either a parent or future sibling, would the duty of the researchers be to inform that family if further harm could be prevented? The family would then be aware that genetic research had been carried out without their consent. If the samples were anonymised initially and a subsequent research study undertaken where consent was sought, harm may have come to the family because of the delay. However, if the hypothesis about the genetic problem were wrong, is it appropriate to contact many parents about the test when there may be no benefit and potentially distress them unnecessarily?^[22]

16.17 A need to raise awareness about the issues involved in de-identification of genetic samples and information was also evidenced amongst groups most affected by genetic research. Representatives of genetic support groups in Western Australia, in a round table discussion facilitated by the Genetic Support Council Western Australia, stated that they

strongly believed that researchers should only work with de-identified samples, and that a code of practice for de-identifying donor samples should be drafted at the federal level to ensure uniformity in practice. However they noted that more information on the de-identification process and what it means would be useful for the groups.^[23]

16.18 The need for guidance on this issue was emphasised by the Department of Health Western Australia^[24] and by researchers at Westmead Hospital who pointed out that even where de-identification is preferred it can be difficult to achieve.^[25]

16.19 The Inquiry considers that advice and information on human genetic research protocols should include guidance on the different mechanisms for coding or de-identifying genetic samples and information used in research, and the relative advantages and disadvantages of each approach in different research contexts.

Managing coded samples and information

16.20 Where genetic samples or information are coded, the privacy of the samples and information is protected because they are not immediately identifiable. The level of protection afforded by coding is dependent on who has access to the identifying code and for what reasons.

16.21 There is an emerging international standard for genetic privacy protection, which provides for the use of independent intermediaries to hold the code linking genetic samples or information with the identifiers.^[26]

16.22 The National Statement recognises the desirability, in some circumstances, of intermediaries in the conduct of human genetic research by stating that ‘[w]here an HREC approves the use of potentially identifiable data that has been coded, the HREC should decide whether an independent person should hold the code’.^[27]

16.23 The Institute of Community Genetics has developed the concept of the ‘gene trustee’—an independent third party acting on behalf of persons submitting genetic samples for testing. This mechanism is described in some detail in Chapter 18.

16.24 The level of protection provided by a gene trustee mechanism may not be practical for all human genetic research projects, particularly those that are small-scale. However, at the very least it may be argued that the persons who have access to the identifying code should be specified in research protocols.

16.25 There was broad agreement in submissions and amongst those consulted by the Inquiry that the use of coded information and independent intermediaries should be encouraged in genetic research, wherever possible.^[28] However, some submissions noted that the advantages of such an intermediary would need to be balanced against the additional costs of such arrangements.^[29]

16.26 The Inquiry considers that the advice and information on human genetic research protocols should include guidance on the appropriate use of independent intermediaries to hold codes linking genetic samples or information with the identifiers.

Feedback to research participants

16.27 The possibility of providing feedback of health information to research participants has been identified as raising important ethical issues relevant to human genetic research. This issue is closely related to considerations about the coding or de-identification of genetic samples and information. The National Statement provides that:

When research may reveal information of potential importance to the future health of identified or potentially identifiable participant’s future health or the participant’s offspring, the research protocol must provide for consent procedures, counselling, support, test quality and test result confidentiality as would apply if the participant sought such information in a clinical setting. Otherwise such research may only be performed if the genetic material has been de-identified.^[30]

16.28 When consent is being sought from individuals for the collection of genetic material, the National Statement provides that they should be informed

that the researchers will endeavour to provide information about the outcome of the research. Participants should be advised when it is not intended to provide feedback. If relevant, participants should be asked whether they wish to be notified of research results which relate to them as individuals.^[31]

16.29 Nick Saunders and Paul Komesaroff referred to the complexities involved in providing individual results to research participants:

Complexities arise as a result of uncertainty about the reproducibility of results, their implications for the individual concerned or for blood relations, their effect on the ability to take out life insurance, and other matters. In recent years it has come to be regarded as a right of participants in research to receive their individual results; it is likely that this assumption will need to change.^[32]

16.30 Concerns were also expressed by researchers in submissions and consultations about the discharge of their legal or ethical duties to contact research participants about specific test results,^[33] and about the differences of opinion among researchers in population studies.^[34]

16.31 It is possible that, in some circumstances, a legal duty to contact a research participant about a genetic test result might be derived from common law principles relating to the tort of negligence and the concept of a duty of care. There is no legal authority regarding the possible imposition of such a duty.^[35]

16.32 Whatever the legal position, it is clear that some researchers are keenly aware of ethical obligations to inform research participants about the health implications of genetic testing conducted on genetic material provided by them. However, there are recognised practical and resource implications involved in providing individualised feedback to participants.

16.33 The Inquiry considers that advice and information on human genetic research protocols should include further guidance on the discharge of these legal or ethical obligations to research participants. As one submission recommended, that advice should identify ‘thresholds of impact’, which trigger the need to communicate results or outcomes to participants.^[36]

16.34 Such guidance will be useful, especially for research using large databases.^[37] One possibility would be to provide that, in appropriate circumstances, researchers’ ethical duties to contact research participants about test results may be discharged by providing general information to all research participants, for example, by way of a regular newsletter.^[38] Information provided in this way could alert research participants to the implication of test results found in the course of the research. It could also advise that, if participants are concerned about these implications, they should obtain individual medical advice about whether clinical genetic testing is indicated.

16.35 The Department of Health Western Australia noted two broader considerations that need to be recognised in the advice and information to be developed by the NHMRC. First,

the level of protection provided by such technical matters may still be compromised by failure in the integrity of the researchers and this is an important matter to be addressed by HRECs, institutions and the researchers themselves.^[39]

Second, the broader function or consequence of such regular advice needs to be recognised because

there needs to be the encouragement of a research culture and ethos which has respect for the outcomes and potential impact of the research on human subjects.^[40]

Disclosure of commercial arrangements

16.36 At least in terms of overall funding, it is clear that private sector involvement in health and medical research is significant (see Chapter 11). As a new and burgeoning area of medical research, private sector involvement in human genetic research can be expected to grow. It is express government policy to increase private funding of research and to improve Australia’s record in the commercialisation of the outcomes of research.^[41]

16.37 In consultations the Inquiry was told that it is increasingly common for universities and publicly funded research institutes to ‘spin off’ private biotechnology firms, including those engaged in aspects of human genetic research.

16.38 Concerns were often expressed in consultations, and in public meetings in particular, about the involvement of commercial enterprises in human genetic research. While people who volunteer as participants in medical research generally have altruistic motives, it was seen as important that the outcomes of research enhance the public good.

16.39 While the Inquiry recognises that the benefits of genetic medicine are unlikely to be achieved without substantial private sector research investment, the commercial background to research projects is an important factor for many prospective research participants. In the absence of Australian data, empirical evidence about public attitudes to research in the United Kingdom may have some relevance in this context. A survey conducted by the Human Genetics Commission in the United Kingdom has found that levels of public trust in the responsible use of human genetic information vary markedly, depending on the nature of the individuals or bodies holding it. In particular, respondents trusted academic scientists more than health and pharmaceutical companies.^[42]

16.40 Extensive public consultation has been conducted in relation to the UK BioBank initiative.^[43] One of the reported outcomes of this research, conducted through interactive workshop sessions,^[44] was that:

The first reactions were that commercial companies should not have access [to genetic data], although some participants were quick to realise that the results [of research] would be published and therefore widely accessible to anyone. Further debate brought the realisation that if medicines are going to be developed, pharmaceutical companies must have access.^[45]

16.41 Another report on qualitative research connected with the development of the BioBank UK initiative concluded that the fact that sample collection would be a ‘publicly funded initiative and not set up as a profit-making exercise was reassuring and important in communicating its credibility’.^[46] The report indicated that

[t]here are likely to be questions from the general public and in the media about commercial access to, and use of, the samples and information. Assuming samples are donated freely by donors, there needs to be careful explanation of the financial implications of this.^[47]

16.42 Australian academics have expressed the view that, from an ethical perspective, ‘the potential for commercial exploitation’ of genetic samples and other biological materials is a very relevant consideration when individuals decide whether to consent to participate in research, given that participation is typically altruistic in nature.^[48] Similar views were expressed in some submissions.^[49]

16.43 It may be argued that there is a clear need for open and transparent disclosure, to prospective research participants, of the potential commercialisation of research outcomes and the commercial interests of the researchers involved. It has been suggested that such disclosure may protect the interests of both prospective research participants and researchers themselves:

In order to avoid feelings of exploitation, and possibly even deception, it is of crucial importance that they be given the opportunity to consent to participation in the knowledge that there is a possibility of commercial gain being made from their donated biological material. To do otherwise risks damaging the perception of research and may thereby reduce the willingness of people in the community to participate.^[50]

16.44 The National Statement contains a number of provisions relating to the disclosure of funding and financial interests. However, there is no general requirement to disclose this information, or other information about the actual or anticipated commercial arrangements connected with the research, to research participants.

16.45 The National Statement provides that a researcher must disclose to the HREC reviewing the research proposal the amount and sources or potential sources of funding for the research and must declare any affiliation or financial interest. The HREC must consider the extent to which the researcher should disclose information about funding sources to research participants.^[51] The HREC may decide that no such disclosure is justified.

16.46 The disclosure requirements in relation to clinical trials are somewhat more rigorous. A researcher must inform an HREC ‘of any business or other similar association which may exist between a researcher and the supplier of a drug or surgical or other device to be used in the trial’.^[52] Further, an HREC must examine those aspects of the budgets of clinical trials that raise ethical issues.^[53]

16.47 The Australian Academy of Sciences submitted that ‘all applications to HRECs should be required to include details of any commercial support obtained or envisaged’.^[54] It is not clear to what extent this suggestion goes further than the existing provisions of the National Statement requiring disclosure to HRECs. What seems more important is the question of disclosure to research participants.

16.48 The Centre for Law and Genetics suggested that the provisions of the National Statement dealing with disclosure of commercial arrangements to research participants should be tightened.

As a general principle research participants have an ethical right to be informed of all aspects of the research project including any commercial arrangements.^[55]

16.49 Other submissions stressed the importance of disclosure to research participants, as well as to HRECs. The Australian Red Cross Ethics Committee stated that

there should be transparent disclosure to research participants of the potential commercialisation of research outcomes, as well as any conflicts of interest. … our Committee requires disclosure of commercial arrangements for funding or product development. No researcher has ever raised any objection. In fact most researchers provide a full explanation of the commercial aspects of the research. We should also point out that our standard-model information form includes specific questions on commercialisation. There has been a general acceptance of the disclosure principle.^[56]

16.50 There is presently no ethical guidance on the desirable extent of disclosure of commercial arrangements. The Inquiry considers that the NHMRC should develop information and advice on the disclosure by researchers, to research participants, of information about actual or anticipated commercial arrangements connected with human genetic research proposals.