Alston, Bruce --- "Regulation of Human Genetic Research" [2002] ALRCRefJl 28; (2002) 81 Australian Law Reform Commission Reform Journal 74

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Reform Issue 81 Spring 2002

This article appeared on pages 74 – 78 & 89 of the original journal.

Regulation of human genetic research

By Bruce Alston*

This article summarises some of the ethical, privacy and related issues discussed by the Australian Law Reform Commission (ALRC) and Australian Health Ethics Committee (AHEC) in DP 66 Protection of Human Genetic Information concerning the use of genetic samples and information in the conduct of medical and other research involving humans.

The present regulatory framework for the ethical conduct of research is centred on the National Health and Medical Research Council’s (NHMRC) National Statement on Ethical Conduct in Research Involving Humans (the National Statement)¹ and on review of research proposals by Human Research Ethics Committees (HRECs).

In addition to the ethical principles and procedure for ethical review of research set out in the National Statement, the regulatory framework includes:

• statutory restrictions on dealing with personal information (which may include genetic information) including those under the Privacy Act 1988 (Cth) and related guidelines;²

• common law duties to exercise reasonable care owed by researchers, research organisations and HRECs to those with whom they have a proximate relationship, including duties to participants in research;³ and

• standards for the scientific validity of research, notably the Statement and Guidelines on Research Practice issued by the NHMRC and the Australian Vice-Chancellor’s Committee.⁴

The adequacy of the existing regulatory framework has been the subject of much comment and discussion in the course of the Inquiry to date.

The National Statement

The National Statement is endorsed by the Australian Vice-Chancellors’ Committee, the Australian Research Council, the Australian Academy of the Humanities, the Australian Academy of Science and the Academy of the Social Sciences in Australia. Briefly, the National Statement:

• contains ethical principles relevant to all research involving humans;

• requires that particular matters are to be addressed when research involves children and young people, persons with an intellectual or mental impairment, persons highly dependent on medical care, those in dependent or unequal relationships, collectivities, and Aboriginal and Torres Strait Islander people;

• requires that specific matters be addressed in the consideration and approval of research involving radiation, assisted reproductive technology, clinical trials, epidemiology, human tissue samples, genetics; and

• sets out the formation, membership and functions of HRECs.

The primary function of an HREC is to protect the welfare and rights of participants in research. An often overlooked secondary purpose is to facilitate research that is or will be of benefit to the researcher’s community or to humankind.

The National Statement provides that research proposals involving human participants must be reviewed and approved by an HREC and sets out requirements for institutions or organisations in establishing HRECs, researchers in submitting research proposals to HRECs, and HRECs in considering and reaching decisions regarding those proposals and in monitoring the conduct of approved research. The National Statement places clear responsibilities upon institutions and researchers as well as providing the framework upon which HRECs are based.

What is human genetic research?

A major topic of DP 66 is the regulation of ‘human genetic research’. Human genetic research is broadly defined in the National Statement as a process that ‘enhances our understanding of how genes and environmental factors interact to influence the health of individuals and populations and, in doing so, generates knowledge with the potential to improve individual and community health’.⁵

Some human genetic research can be conducted without the need for genetic information that can be related to specific persons or communities. Research on molecular processes can explore genetic processes and the production of enzymes or proteins. Research can use anonymous population data to examine patterns of human inheritance of disease or conditions.

When discussing the protection of privacy interests in genetic samples and information, the focus of DP 66 is on human genetic research that needs to use or will develop information that is either identified or potentially identifiable to a particular individual. Privacy interests are not generally implicated where information is not about an individual whose identity is apparent or can reasonably be ascertained from the information.⁶

However, ethical concerns may be raised by the collection or use of genetic samples and information in human research, even where the samples or information are to be de-identified. Basic ethical principles, such as integrity and respect for persons⁷ should be observed even where samples or information are to be de-identified or where the research involves a community.

The importance of human genetic research

In 1999, the Wills Report referred to the need to take advantage of advances in biotechnology to improve the health of the Australian population, to build the economy, and to create valuable jobs.⁸

Human genetic research generates knowledge with the potential to improve individual and community health. Research can also reveal information about an individual’s susceptibility to disease and hence about the individual’s future health. Such information may be of interest and benefit to research participants especially if preventive strategies exist.

The completion of the first mapping of the human genome has opened huge potential for research into the ways that these genes are related to human conditions, capacities, diseases, impairments and susceptibilities. The scope of such research may be illustrated by reference to the current activities of just one major Australian genetic research organisation. The Murdoch Childrens Research Institute is conducting research into the underlying genetic causes of neuromuscular disorders, inherited hearing loss, attention deficit hyperactivity disorder, cancers, ataxias and addiction.⁹

It seems likely that human genetic research will become an increasingly important component of medical research generally. One indication of this is that clinical trials of new drugs increasingly include genetic sub-studies. It has long been known that drug toxicity and efficacy has a genetic component and these sub-studies are intended to investigate genetic causes of individual variations in clinical response to drugs.

Balancing interests

The ALRC/AHEC Inquiry aims to develop proposals that will enable human genetic research to be fostered while providing sufficient reassurance to the community that such research is subject to proper ethical scrutiny and legal control.

Any reform proposals need to balance the interests of researchers – who need access to human genetic samples and information from many sources – and the needs of individuals and their relatives – whose rights to autonomy and privacy must be respected.

Individuals whose samples or information is held want to assert their right to human dignity and autonomy (for example, through consent) and need to be confident of the privacy of that information.

Genetic researchers need to be able to secure the willing and active participation of many volunteers. The ability to conduct human genetic research may be prejudiced if potential volunteers fear that participation in research will generate information that they may subsequently be required to disclose to insurers, employers or others.

In human genetic research, the interests of the genetic relatives of participants may also need to be considered. A particular feature of many human genetic research studies is that they require the participation of families, rather than individuals. Individuals may be asked to provide family histories and genetic samples that will be used in research, the results of which can be related back to them and to other family members.

Research results and genetic material and information collected for research may be of significance to the health of genetic relatives, including those who have not participated in the research and who may not have been aware that the research was being done. These family members may have an interest in their relatives’ genetic material or information that the research generates, because testing that material or acquiring that information may create new options for life decisions, including those with potential to improve health.

However, some family members may prefer not to be given information that may provide knowledge of future health or health risks. In addition, other family members who are not genetic relatives, such as partners and spouses, may have an interest because of concerns about the health of offspring. The information generated by such family research may also be of relevance to people in the community unrelated to participants or their families but whose family histories or health condition may be similarly related to genetic effects. Not all of this information will be of positive benefit to families.

Indeed, in certain situations, such as incidental evidence of non-paternity, the implications of the information may be highly negative.

Reform of the regulatory framework for human genetic research

The Inquiry has received a wide range of views and comments about the adequacy of the regulatory framework for human genetic research. These views extend from those that are highly supportive of the existing framework through to those suggesting a broad agenda for change. In many cases the changes proposed were broadly applicable to all medical and other human research and not limited to addressing issues raised by human genetic research proposals specifically.

Enforcing compliance with the National Statement

The enduring value of the National Statement was highlighted in a number of submissions, including those that also suggested changes to its scope or content. The National Statement has persuasive authority based on the standing and representativeness of AHEC members, has been reviewed at appropriate intervals and has proven responsive to past challenges in medical research.

However, the requirements for institutions or HRECs to be registered with the NHMRC or to follow the processes set down in the National Statement are incomplete. In particular, there is currently no obligation upon private research bodies to adhere to the provisions of the National Statement.

Submissions identified the increasing commercialisation of human genetic research as an important background development. In response, the mechanisms by which compliance with the National Statement is enforced may need to be strengthened. In particular, the Inquiry is proposing that the National Health and Medical Research Council Act 1992 (Cth) be amended to prohibit the conduct of human genetic research other than in compliance with the National Statement.

Human genetic research and consent

The concept of consent is fundamental to the legal and ethical regulation of medical and other human research and to the protection of privacy and was referred to often in submissions and consultations. The National Statement generally requires consent to the use of human tissue samples, genetic material and genetic information in medical research, other than in limited and defined circumstances.

Submissions received by the Inquiry have raised concerns about various aspects of consent. In particular, it was questioned whether privacy is adequately protected by the current provisions which permit an HREC to waive consent requirements (in specified circumstances) when granting ethical approval for research proposals. A related issue is the extent to which researchers are able to obtain meaningful consent from research participants for the use of their genetic samples or information in relation to unspecified future research.

DP 66 makes a number of proposals, and asks further questions, with the aim of enhancing the reporting of HREC waivers of consent and providing more guidance on consent requirements, through changes to the National Statement.

In particular, DP 66 notes that the National Statement is currently being interpreted by at least some HRECs to permit researchers and research organisations to obtain consent for as yet unspecified future research, as approved by an HREC, and without the need for later, specific, consent. However, no detailed guidance is provided to HRECs on this issue.

There are differing views about the application of the concept of consent where people cannot be informed in any detail about the nature of the research. It has been suggested that the language of consent should, in some contexts, be augmented by the concept of ‘donation’ or ‘gifting’. It should be recognised that individuals may choose to ‘gift’ samples for research purposes – for example by leaving their body to science or where donating blood to the Red Cross.

Those involved in the development and ongoing operation of Australian human genetic research databases submitted that the use of tissue banks, with a structure of broad patient consent for research on prospectively collected samples and controlled access to samples through HRECs is the best way to protect the rights and privacy of patients as well as facilitating research.

However, there may be valid distinctions to be made between allowing major centralised tissue banks to obtain broad consent to the use of the samples they collect in future research, and permitting individual researchers to do the same – and to maintain their own private holdings of genetic samples.

DP 66 considers whether research databases should be licensed or registered. This may be a means to ensure that major research collections of genetic samples apply best practice collection, storage and security standards, with access to samples under the control of standing management and ethics committees.

Licensed human genetic research databases might be expressly authorised to use genetic material and information for research approved by their HREC, without further consent from the donors. However, whether or not additional regulation of major research databases is recommended, the Inquiry proposes that the National Statement needs to deal more clearly with the issue of consent to future research.

Encouraging best practice in human genetic research

Based on extensive consultations with researchers, the Inquiry believes that it may be useful for AHEC to augment the National Statement with model research protocols for human genetic research, as well as to provide guidance on the drafting of consent forms for use in human genetic research.

The intention is to promote international best practice in the conduct of human genetic research, provide further guidance to researchers and HRECs, and achieve greater consistency across the nation. The possible content of these model or template documents is discussed in detail in DP 66.

The Inquiry suggests that particular attention needs to be paid to transparent disclosure to research participants of the potential commercialisation of research outcomes and of any conflicts of interest.

Strengthening ethical review by HRECs

Submissions and consultations suggested a range of possible reforms aimed at strengthening the current system for ethical review of human genetic research proposals and the role of HRECs within that system.

These possible reforms, some of which may require changes to the National Statement, include reporting by HRECs on the review of research proposals, monitoring by HRECs of the conduct of approved research, the structure and membership of HRECs, the review or accreditation of HRECs, the education and development of HREC members, payment of HREC members, and mechanisms for funding medical researchers’ compliance costs.

DP 66 also considers ways in which HREC oversight may be strengthened, including through more rigorous reporting requirements under the National Statement, on-going monitoring of approved research by HRECs, the review or accreditation of HRECs, and the ‘skilling-up’ of HRECs through changes to membership or providing additional training and resources to members.

* Bruce Alston is a Senior Legal Officer with the ALRC working on the Genetic Information Inquiry.

Endnotes

1. National Health and Medical Research Council, National Statement on Ethical Conduct in Research Involving Humans (1999), NHMRC, Canberra.

2. National Health and Medical Research Council, Guidelines Under Section 95 of the Privacy Act 1988 (2000), NHMRC, Canberra; National Health and Medical Research Council, Guidelines Approved Under Section 95A of the Privacy Act 1988 (2001) National Health and Medical Research Council.

3. In accordance with the common law relating to the tort of negligence.

4. National Health and Medical Research Council and Australian Vice Chancellor’s Committee, Statement and Guidelines on Research Practice (1997), NHMRC, Canberra.

5. National Health and Medical Research Council, National Statement on Ethical Conduct in Research Involving Humans (1999), NHMRC, Canberra, Ch 16.

6. See eg Privacy Act 1988 (Cth) definition of ‘personal information’, s 6.

7. National Health and Medical Research Council, National Statement on Ethical Conduct in Research Involving Humans (1999), NHMRC, Canberra, para 1.1-1.2.

8. Health and Medical Research Strategic Review, The Virtuous Cycle, Working Together for Health and Medical Research (1999), Commonwealth of Australia, Canberra, 1.

9. Murdoch Childrens Research Institute, Gene Identification and Expression, <http://murdoch.rch.unimelb.edu.au/pages/lab/gene_identification/overview.html> , 25 June 2002.