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National Statement on Ethical Conduct in Human Research 2007 Human biospecimens submission

ID: 
17
Personal Details
First Name: 
Colin
Last Name: 
Thomson
Additional Information
Individual Background: 
Lawyer
Specific Comments
Comments: 
Introduction

Introduction

Third paragraph: the last sentence in this paragraph appears to assume a degree of identifiability of stem cell lines that would render ethical consideration necessary.

Identifiability of human biospecimens in the research context depends on the availability of or access to information additional to the actual specimen, in the form of related clinical information or another matched dataset.

Will it only be necessary to consider stem cell lines or tissue products if they remain identifiable in this way and will stem cell lines and tissue products always have this degree of identifiability?  What will be the effect on their degree of identifiability of the increasing differentiation from original donor tissue?

Potential for identification

Potential for identification

This paragraph raises the same issue. If it is the case that human biospecimens are only identifiable through access to other information or another matched set of data, would the impracticality of such access be a stronger ground on which to base an argument for the lack of potential for identification?  Relying on considerations such as whether identity is required or cost of re-identification appears too subjective and variable a basis.

It is suggested that the concept of reasonable possibility be introduced as a criterion for re-identifiability.  This concept is very similar to proposed changes in the definition of personal information as part of amendments to the Commonwealth Privacy Act. The government has accepted a recommendation to amend the definition of personal information to be

‘information or an opinion, whether true or not, and whether recorded in a material form or not, about an identified or reasonably identifiable individual’.

The concept of reasonably identifiable is likely to include both practicality, resources and research goals and methods.

Adopting such terminology would then be applied in other contexts to which the National Statement applies in which similar considerations arise, that is, research in which re-identifiable information is used but where the researchers do not have access to the means of re-identification.  Increasingly common examples of such situations are research projects in which researchers use data that have been linked by a data linkage service.  

In the revised version of the chapter that is attached, this expression has been adopted.

Other chapters and documents that should be considered

Other chapters and documents that should be considered

Consider rewording the opening line as follows:

"Additional ethical guidance that may be relevant to research uses etc"

Consider rewording the fourth dotpoint as follows:

"Section 4: Chapters 4.1-4.8: Ethical considerations specific to participants, which offer additional ethical guidance on obtaining biospecimens from different categories of participants."

It is noted that the revision has eliminated the previous paragraph that repeated the legislative prohibiition on trade in human tissue. In order to remove any doubt that thsi remains important, consider rewording the second paragraph as follows:

"Researchers and institutions will also need to meet any relevant legislative requirements that relate to the collection, retention and use of human biospecimens, including the prohibition on trade in human tissue. “

 

Prospective collection of human biospecimens for research – paragraphs 3.4.1 – 3.4.4

3.4.1            The formatting of the subparagraphs should be amended to the same as is used in the National Statement.

b. This requires researchers to ensure that the burdens of collection are justified, but does not explain what would the relevant justification, for example, does it include the benefits of the research?  This has been assumed in the suggested re-wording.

c. This requires that researchers should ensure that those involved are suitably qualified. It should be made clear what involved means, for example, it is likely that it means involvement in the conduct of the research, but this should not be left as an assumption.

d and e:  these two subparagraphs repeat requirements of which a review body will need to be satisfied for ethical acceptability when it reviews any research project. These are contained in National Statement paragraphs 1.1 (d), (e) and (f).  Reliance on these subparagraphs, rather then repeating their import, would promote consistency in the informed use of the National Statement and would avoid the vagueness and impracticality of the requirement that researchers “have an understanding of the ethical issues”.

3.4.2  Consider changing, in the second line, the expression "consistent with" to "to conform to".

3.4.3 – although the content is relevant, when it is considered with paragraph 3.4.6, they can be combined, as has been done in the revised version attached.

3.4.4            The formatting of the subparagraphs should be changed to conform to that used in the National Statement.

Consider changing the word "people" to "potential participants".

Subparagraph (d):  instead of the expression "directly relevant to the health" it may be preferable to use expressions that have been used in very similar contexts in chapter 3.5. The expressions used “information that may be important” or “information that has potential importance” for health. This will promote consistency and the former has been adopted in the revised version attached.

Subparagraph (e): is it intended that participants will not have a choice as to whether or not they receive this information? If such a choice should be made available, it should be a required element of the ethically defensive plan referred to in 3.4.10 and 3.4.11 and the availability of such a choice should be made clear in 3.4.4.  These have been adopted in the revised version.

Subparagraph (f): consider using "provided" instead of "distributed".

 

Subparagraph (g): some attempt should be made to make clear in this subparagraph that once identification ceases to be practicable, then the right to withdraw will be lost.

Subparagraph (i): it may be preferable to use the expression "potential for commercial application of outcomes of the research" that is already used in the National Statement that 4.1.20 (d) instead of "foreseeable commercial outcomes arising from research".

Use of human biospecimens obtained after death – paragraph 3.4.5

3.4.5            Consider replacing the expression "senior available next of kin in accordance with" with the expression "person or persons authorized by". This would preserve the applicability of legislation regardless of the terminology that it uses to identify lawfully authorized people.

Ethical review before human biospecimens are used in research – paragraphs 3.4.6 – 3.4.11

3.4.6            Consider replacing the expression "given ethical consideration" in the second line with the expression "designed, reviewed and conducted". This is in accord with the breadth of responsibilities that the National Statement imposes on institutions and researchers and would also have the effect of incorporating the content of paragraph 3.4.3 of the draft – as has been done in the revised draft.

3.4.7            The breadth of consideration required by this very general description could be reduced by the provision of some examples of what circumstances and limitations should be taken into account.

 

3.4.8            This is a repetition of what institutions and researchers should be aware that the National Statement already provides in chapter 2.1.  Repetition is unnecessary.

 

3.4.9            The structure of this paragraph contradicts a basic procedural premise of the National Statement. This is that the decision as to whether a research project involves low risk to participants is a matter for review bodies: it is a matter of judgment and knowledge rather than of pre-determination by the National Statement.

 

Accordingly, consideration should be given to redrafting this paragraph as a set of relevant considerations to the determination by such a review body on whether research involving human bio-specimens involves low risk or more than low risk. A suggested re-structure has been adopted in the revised chapter.

 

The opening paragraph is unclear. It is not clear what "further use" means for human bio-specimens for which consent for research has already been given. Is further use another research project other than the one for which consent has already been given or is it that research project?  If the purpose of paragraph is to inform the determination of the level of risk involved, then it does not seem to matter whether the use is the first research use or a further use.  Omitting “further” would overcome this ambiguity.

 

Subparagraph (a),, whether the proposed research is consistent with the consent given, introduces a consideration not normally relevant to the determination of the risk level of research. Whether consent has been given and whether the research is within the scope of that consent is an issue that arises independently of the risk involved in the research and one that will be considered in the ethical review of the research.

Subparagraph (b): is suggested that this subparagraph be reworded, drawing on the discussion of the issue identify ability above in these comments on the introduction. An appropriate wording would be:

“(b) whether the identity of the donors can reasonably be ascertained by those conducting, or those responsible for, the research.”

Subparagraph (c):  the relevant consideration is whether there is a risk of more than discomfort.  If so, the research would involve more than low risk and would require review by an HREC.

Subparagraph (d): consistent use of language on this issue would assist in this chapter. At present, several different expressions are used about the likelihood and the nature of information arising from research and affecting donors, and the blood relatives or their community. As to the likelihood, 3.4.4 uses the expression may, 3.4.9 uses " reasonable expectation", 3.4.10 uses "likelihood" and 3.4.11 returns to "may".

As to the nature of the information, 3.4.4 (d) uses the expression "directly relevant", 3.4.4 (e) uses the expression  "potentially relevant", 3.4.9 (d) uses "relevant for", 3.4.10 uses "potential importance for the future health", 3.4.10 (a) uses "significant health consequences" and 3.4.11 uses "of potential importance to the future health".

In the case of both expressions, there seems no reason to use different terminology wherever they appear.

 

Similar considerations have already been addressed in chapter 3.5 of the national statement. There, the first expression is rendered simply by the word "may" and the second expression by "may be important for their health". 

It is accordingly recommended that similar terminology be used in the subparagraphs in the chapter under review.

3.4.10            In the light of the discussion above, it is suggested that the words "of potential importance to" we replaced by the words "that may be important for".

Subparagraph (a): again, in the light of the discussion above, it is suggested that the words "will have significant health consequences" be replaced by the words "may be important for the health of".

Subparagraph (b): consider removing the word "study" is unnecessary.

Subparagraph (c): in the light of the discussion about identify ability above, it is suggested that the word "feasible" be replaced by the words “reasonably possible".

There is no apparent provision in the considerations for the ethically defensible plan to provide participants with a choice of whether or not to receive information of potential importance for the health.  This has been provide for in the revised version.

3.4.11            It is suggested, for greater clarity, words "their use in" be inserted between "for" and "research" in the first line.

There appears no need top re-state the material; in the second sentence, because this is already provided for in 3.4.10 and the same essential premise for the defensible plan arises here.

Cost recovery for human biospecimens – paragraph 3.4.12

3.4.12            For greater elegance, it is suggested that the first sentence be deleted and the second sentence be reframed as follows:

"Any proposal to recover costs incurred in collecting, retrieving, handling, storing or distributing human by specimens must be reviewed …”et cetera

Import and export of human biospecimens – paragraphs 3.4.13 – 3.4.15

3.4.13            No comment is made on this paragraph but there does not seem to be any reason for having omitted a following paragraph to address the situation where researchers cannot establish that collection was ethical, as was the case in the original chapter 3.4. The equivalent of the original paragraph 3.4.4 (b) should be added and has been in the revised draft.

3.4.14 – no comment.

3.4.15 the following is a suggested rewording of this paragraph:

"Where human biospecimens were obtained prior to the issue of this guideline, an HREC may approve their use, even if all of the requirements of this chapter are not met, provided that:

  • there is sufficient evidence that the samples were obtained with consent and
  • that the proposed research is within the scope of that consent, or
  • the research would meet the conditions for waiver of consent (see Chapter 2.3: Qualifying or waiving conditions for consent)."

The paragraph needs to be moved above the heading about import/export to which it is unrelated. This has been done in the revised draft attached.

General Comments
Comments: 

Some general observations

Use of headings

Most chapters of the National Statement use the four values: research merit and integrity, justice, beneficence and respect, as headings for groups of guideline paragraphs.  This is done where their use can promote the role that these values play in the structure and interpretation of the National Statement.

None of these headings are used in this proposed amendment, although no reason is given for not doing so.  A suggested re-arrangement of the proposed changes, using these headings is offered for the committee’s consideration.

Role and responsibility of the NHMRC

The National Statement to which the proposal is an amendment, was issued by three agencies, the NHMRC, the ARC and UA.  Despite that, there is no reference in this proposal for change to the second or third agency.  Further, there is no reference to this proposal – or indeed to the National Statement itself – on the websites of those agencies.

This appears anomalous, at least.  It appears that there is no protocol among the agencies for amendment of the National Statement and indeed that there is no communication among the agencies about changes. Rather, it appears that the NHMRC has arrogated to itself the control and management of such changes.

An important additional consequence of this apparent state of affairs is that it reinforces the impression that, despite the assertion that the National Statement applies to all human research, its maintenance remains with only one agency whose responsibility is for health and medical research only.  This can hamper the respect for the National Statement across disciplines other than those involved in health and medical research.

A REVISED VERSION OF A NEW CHAPTER 3.4

Chapter 3.4: Human bio-specimens (revised)

Introduction

This chapter provides ethical guidance for research involving human bio-specimens. Such research is important in developing an understanding of normal development, function and disease. It does, however, often involve special ethical considerations because of:

• the way the bio-specimens are obtained

• the information they may carry and the implications of that information for the individual and blood relatives

• the significance that may be attached to the bio-specimens by individuals and/or communities.

The definition of ‘human bio-specimens’ is broad: it encompasses any material taken from a human body including, but not limited to, tissue, blood, urine, sputum, gametes, embryos and fetal tissue, and any biological material obtained from them including cell lines. It does not include extraneous material such as micro-organisms that live on or in a person.

This chapter does not cover research involving gametes or embryos, including the derivation of human embryonic stem cell lines, as the ethical issues in this type of research are covered in the Ethical guidelines on the use of assisted reproductive technology in clinical practice and research (2004, revised 2007), issued by the NHMRC; and, for fetal tissue, in Chapter 4.1: Women who are pregnant and the human fetus. However, once stem cell lines or tissue products have been derived under a licence, they should be considered in the same way as other human bio-specimens covered in this chapter.

This chapter also does not cover therapeutic products, other derived products, medical devices or pharmaceuticals; these are considered in Chapter 3.3: Interventions and therapies, including clinical and non-clinical trials, and innovations. Research involving the derivation of embryonic stem cell lines or products from a human embryo will need to be considered by a Human Research Ethics Committee (HREC) as part of a licence application to the Embryo Research Licensing Committee (see Part C of the Ethical guidelines on the use of assisted reproductive technology in clinical practice and research (2004, revised 2007)).

Sources of human bio-specimens

Sources of human bio-specimens include voluntary donation, material taken for clinical purposes, and post-mortem. These materials are commonly collected and distributed by researchers, biobanks, pathology services and commercial entities.

Human bio-specimens collected during clinical investigations are commonly provided to pathology services for diagnostic and other testing. The National Association of Testing Authorities Australia accredits pathology centres according to compliance with the National Pathology Accreditation Advisory Council requirements. One criterion for accreditation is that pathology centres retain human bio-specimens for designated periods. Some jurisdictions may also have legislation that requires pathology practices to retain human bio-specimens. Such stored bio-specimens have been and will continue to be a resource for research and teaching. These uses may raise ethical considerations and are also covered in this chapter.

Potential for identification

Human bio-specimens that include all or part of a human genome contain markers that are unique to the individual donor. However, they will constitute personally identifiable or re-identifiable data (see Chapter 3.2: Biobanks p. 29) where the identity of the donors can reasonably be ascertained by those conducting, or those responsible for, the research.

 

Other chapters and documents that should be considered

Additional ethical guidance that may be relevant to research uses of human bio-specimens is provided in:

Chapter 3.2: Databanks

Chapter 3.3: Interventions and therapies, including clinical and non-clinical trials, and innovations, which provides ethical guidance on the use of human bio-specimens for therapeutic purposes

Chapter 3.5: Human genetics, which offers additional guidance on specific aspects of the use of human bio-specimens for research purposes

Section 4: Ethical consideration specific to participants, Chapters 4.1-4.8; which offer additional guidance on ethical issues arising from obtaining specimens from different categories of participants.

Researchers and institutions will also need to meet any relevant legislative requirements that relate to the collection, retention and use of human bio-specimens, including the prohibition on trade in human tissue.

Values, principles and themes that must inform the design, ethical review and conduct of all human research are set out in Sections 1 and 2 of this National Statement and are applicable to research involving human bio-specimens.

Guidelines

Research merit

3.4.1 Those proposing to collect human bio-specimens prospectively for research should:

a. have a sound scientific basis for doing so; and

b. ensure that the burdens of collection are justified by the potential benefits of the research; and

c. ensure that those involved in the conduct of the research are suitably qualified.

 

3.4.2 Institutions and researchers have a responsibility to ensure that any research involving the collection and use of human bio-specimens is designed, reviewed, approved and conducted in accordance with this National Statement.

3.4.3 Ethical consideration regarding the use of human bio-specimens has to take into account the circumstances in which they were obtained, and any known limitations on use.

3.4.4 Where proposed research using human bio-specimens may reveal information that may be important for the future health of the donor(s), their blood relatives or community, researchers should prepare an ethically defensible plan to disclose or withhold that information. This plan must be approved by an HREC and include consideration of the following:

a. the likelihood of generating information that may be important for the health of the donors and for which a recognized intervention exists that can benefit or reduce the risk of harm to the individual;

b. whether participants will be given a choice of whether or not to receive such information;

c. the terms of the consent for the research ;

d. whether it will be reasonably possible to identify and recontact the donor(s), their family or the community, taking into account the relationship between the researchers and the donors, if any;

d. the research context, for example, whether the research results will be generated in the primary researcher’s laboratory or through secondary analyses by other researchers;

e. the potential for sampling or coding errors and, in the case of research using human bio-specimens and data, how certain the researchers will be that the human bio-specimens and/or data came from a particular donor;

f. whether the findings have been produced or validated in a laboratory that has been accredited by NATA Australia or equivalent for the specific test being undertaken;

g. who will undertake the feedback of information and who will take responsibility for any subsequent care requirements;

h. the resource requirements and infrastructure in place to return clinically significant results in an ethically appropriate manner.

3.4.5 Any proposal to recover any costs associated with the collection, retrieval, handling, storage and distribution of human bio-specimens must be reviewed by an HREC who must be satisfied that the proposed cost recovery is ethical, that it is subject to transparent and accountable reporting and that full disclosure is made in the consent process (see paragraph 3.4.xxx)).

 

Beneficence

3.4.6             In determining whether research involving the use of human bio-specimens involves low risk or more than low risk to participants, the following considerations will be relevant:

(a)            whether the identity of the donors can reasonably be ascertained by those conducting, or those responsible for, the research;

(b)            whether the research involves any risks that are more than discomfort, and

(c)            whether the research may give rise to information that may be important for the health of the donors, the blood relatives or their community.

 

Respect

3.4.7 The consent of donors should be obtained and recorded when collecting human bio-specimens specifically for research, consistent with Chapter 2.2: General requirements for consent.

3.4.8 Before people consent to donation of their bio-specimens, they should be given information about:

(a)          the research for which those bio-specimens are to be used and, where extended or unspecified consent is sought, sufficient information to meet the requirements of paragraphs 2.2.1 (page 19) and 2.2.16 (page 21)

(b)          for how long the bio-specimens will be stored or used;

(c)           the extent to which their bio-specimens will be identifiable, and how their privacy and confidentiality will be protected

(d)          whether or not research using their bio-specimens may provide information that may be important to their health or to the health of their blood relatives or their community

(e)          if information of the kind referred to in (d) is likely to be revealed, whether or not they will have a choice as to whether this information will be provided to them, their relatives or their community;

(f)         if they will have a choice and choose to receive the information, how this will be done (see paragraph 3.4.xx)

 (g)           if they will not have a choice and the information will be provide to them, how this will be done (see paragraph 3.4.xx);

(h)          whether their human bio-specimens and associated data may be provided to other people, including those outside Australia, for research (see paragraphs 3.4.13 – 3.4.15).

(i)           their right to withdraw their consent for the continued use of their bio-specimens or associated data in research (see paragraph 2.2.6 (g), page 20), and any limitations there may be regarding such withdrawal of consent; for example, due to the loss of identifiability or distribution and use of the bio-specimens

(j)          any cost recovery arrangements that may apply to the collection, retrieval, handling, storage and distribution of their bio-specimens (see paragraph 3.4.12).

(k)         any potential for commercial application of outcomes of the research arising from research involving their bio-specimens, how these will be managed and to whom the benefits, if any, will be distributed.

3.4.9 Where identifiable human bio-specimens were obtained without consent for their use in research (e.g. in a clinical investigation), or where the proposed research is not consistent with the original consent, the human bio-specimens may be used only if an HREC is satisfied that the conditions for waiver of consent are met (see Chapter 2.3: Qualifying or waiving conditions for consent).

3.4.10 Where human bio-specimens were obtained prior to publication of this guideline, an HREC may approve their use, even if all of the requirements of this chapter are not met, if there is sufficient evidence that the samples were obtained with consent and that the proposed research is within the scope of that consent, or if the research would meet the conditions for waiver of consent (see Chapter 2.3: Qualifying or waiving conditions for consent).

Use of human bio-specimens obtained after death

3.4.11 Any wish expressed by a person about the research use of their human bio-specimens obtained after death should be respected. If no such wish is discovered, researchers seeking to obtain human bio-specimens after death should obtain consent from the person or persons authorized by relevant legislation.

Import and export of human bio-specimens

3.4.12 Where human bio-specimens are imported from another country for use in research in Australia, researchers must establish whether these human bio-specimens were obtained in a manner consistent with the requirements described in this National Statement and relevant Australian legislation.

3.4.13 Where it cannot be established that human bio-specimens were obtained in a manner consistent with the requirements described in this National Statement and relevant Australian legislation or there is reason to believe that they were not so obtained, the bio-specimens should not be used in research in Australia

3.4.14 Where human bio-specimens obtained in Australia are to be sent overseas, those sending them must take reasonable steps (e.g. through the use of a material transfer agreement) to ensure that those to whom the bio-specimens are being sent will use them in a manner consistent with the requirements described in this National Statement and any relevant local legislation.

 

Page reviewed: 3 June, 2013