By Abbyann Lynch, Cm. PhD
Director, Ethics in Health Care Association, Toronto

Text adapted from the original audio-visual presentation

Preface

ith reference to the appropriate role of the Research Ethics Board (REB), and within the context of Section 1 of the Tri-Council Policy Statement (August, 1998), there are several areas of parti-cular interest to today’s audience:

1. Why is research ethics review necessary?
2. Whence the institutional responsibility for research ethics review?
3. What is the role of the REB in such ethics review?
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1. What is the membership of the REB to be?
2. How is the REB to function?
3. Has the REB other responsibilities?

4. What should the relationships between the REB and other groups concerned with research review (internal, and external to the one institution) be?

The intention here is to speak briefly to each of these topics, and then to offer comments for your discussion later in the day’s proceedings. As you know, the three Councils have given public notice that this Policy Statement is to be a living document (thus it is open to evolution, amendment, and flexible interpretation [within limits noted in the text]. In this Workshop setting, questions and discussion towards improvement of the Statement are thus in order. That being said, the personal comments are based on a personal reading of the Statement, and on personal reflection regarding it. They should not be taken as ‘official’ (i.e., they are not an expression of any ‘NCEHR point of view’); certainly, they do not imply personal endorsement of the Policy Statement or of the manner of its preparation.

1. Why is research ethics review necessary?

The answer to this fundamental question sets the stage for consideration of the other issues mentioned. At a preliminary level, the answer is quite straightforward: the research funders (here: MRC, SSHRC, NSERC) require such review in terms of the ethical responsibility assumed by those groups. Theirs is a responsibility to society in general, to research institutions, to researchers and to research subjects, that research funded under their mandates will be conducted according to the highest ethical standards. And why should there be such ethical concern? The simple and bottom-line response is that research subjects should not come to harm, and that research which involves such subjects should be ‘worthwhile’. Research ethics review is thus a formal way of ensuring ethical and scientific accountability on the part of those institutions and the researchers associated with them insofar as they are allowed use of public monies for research purposes.

Some might ask whether the individual researcher and the individual research subjects could not set aside such review in favour of arranging conduct of research according to their own judgment (much as physician and patient have an interpersonal agreement concerning provision of therapeutic intervention). While this might be satisfactory with reference to the ‘no harm’ standard, history provides numerous examples of ‘harmful research’; careful research ethics review by an impartial review group is meant to lessen that possibility. Further, it is well accepted that the importance of the research proposed, and of the method for obtaining the desired results is best judged not by the researcher involved, but by the researcher’s peers. Add to these two considerations the matter of social responsibility for individuals’ well-being and for the advancement of knowledge, as well as for supervision of the use of public monies, and the rationale for research ethics review becomes quite apparent.

As to the structure in which such review takes place, there are obvious differences among national jurisdictions. For example, the U.S. approach is one identified with careful and minutely-fashioned legal requirements for such activity. The Canadian approach by way of this Policy Statement has been identified as less ‘legal’ and more ‘voluntary’. That being said, the standards set out in the Policy Statement are binding in the sense that they will be used in determining responsibility of Canadian researchers regarding misdemeanours in the matter of research involving human subjects, even as they are applicable in determining the availability of funding for particular research proposals.

2. Whence the institutional responsibility for research ethics review?

Funding provided by the three Councils for particular research protocols is provided to the institution for its disbursement to those researchers within the institution whom the Councils have chosen to receive such awards. This procedure recognizes the responsibility of the institution in terms of monitoring use of the monies provided; it also emphasizes the responsibility of the institution regarding the research ethics review required as the research protocol is proposed, and as it is implemented within that institution’s jurisdiction. Since the institution has these two responsibilities, it seems reasonable that the institution should also have the responsibility for establishing the body empowered to conduct the research ethics review required.

The Policy Statement is quite clear on this point: appointment of a group to conduct research ethics review is a governance decision. Such a decision is to be made at the highest level, whether that be the university’s Senate, or the institution’s Board of Governors. The governing body of the institution not only sets out the jurisdiction of its research ethics review body; it also determines whether there should be more than one such group, and if there are several, what the relationship among them should be.

In making these various determinations, the governing body is also to ensure that its REB(s) has financial and administrative independence.

This matter of financial independence (so important in principle) has posed difficulties for numerous REBs: what level of funding is required for acceptable REB functioning, and where is it to be found? On one side, there is discussion among university research administrators concerning the need to levy ‘overhead charges’ (a fixed amount to be subtracted from the amount awarded to each researcher) to be applied against the costs of ethics review and monitoring activity. Another approach practiced in a nearby institution: the individual named as responsible for the functioning of the REB is responsible for all the secretarial work done in this connection — calling meetings, preparing minutes, answering queries, etc. This individual receives no assistance (financial or otherwise) with this; he is expected to carry on this activity as part of his regular work!

Again, taken in a slightly different direction, this matter of financing the REB raises the question of compensation for members of the REB. So-called ‘community members’ may choose to volunteer for such activity (without compensation); on the other hand, lack of funding for compensation for these individuals may limit the numbers of community members available. The same difficulty arises in a different form within the institution. Researchers recognize the responsibility they have to ensure that the peer-review process is sustained; thus they participate in research review activity. However, some researchers do not choose to participate in such review, and many are over-burdened with requests in this area. One suggestion for remedying this situation: if monetary compensation for participation in such review is not made available, then such participation should be given suitable recognition by way of in advancement within the institution (e.g., the activity should be given specific consideration in the matter of promotion and tenure).

Finally, in speaking of financial independence for the institution’s research ethics review activity, there is some concern among institutions about apparent conflict of interest. How can the research ethics review process really independent of the institution when the institution funds that research review activity?

The matter of administrative independence for the REB poses still other difficulties. The Policy Statement notes two caveats here. First, the institution has no ‘override’ concerning a negative REB decision, except by way of an established appeal mechanism. Thus, it is possible that an REB negative decision can be overturned. Second, the Statement indicates that the institution may refuse to allow a particular protocol to proceed, even when the REB indicates that the protocol has approval for implementation. From the point of view of the institution, this provision seems eminently reasonable; the institution must determine what is allowed within its jurisdiction. At the same time, there may be apparent difficulty in speaking of an REB as being ‘administratively independent’ in such circumstances.

Finally, in terms of administrative independence, there is some concern regarding the matter of jurisdiction over work done by researchers who have status in one institution when they are pursuing research in another institution (in which they also have status). This is a question in which some clarification of the Statement, perhaps amendment of it, is required.

3. What is the role of the REB in such review?

Substantively, the REB is required to "approve, reject, propose modifications to, or terminate any proposed or ongoing research, involving human subjects, which is conducted within, or by members of, the institution, using the considerations set forth in the Policy as the minimum standard".

These activities are to be directed to all research that involves living human subjects, human remains, cadavers, tissues, biological fluids, embryos or fœtuses. Excluded from such review is research about living individuals based on public information (unless direct interview is involved, or private papers are to be used). Excluded as well: quality assurance studies, performance reviews, testing within normal educational requirements. In the event of uncertainty concerning the requirement for research ethics review, the researcher is encouraged to ask the REB for assistance. (The difficulty here: in particular cases, the REB may not be certain about the correct response.)

What are the defining characteristics of research ethics review in practice? A first response is that the REB is to review the ‘ethics aspects’ of the presented protocol. However, the ethical questions to be reviewed depend greatly on which scientific questions are to be addressed, and on the method(s) proposed for ascertaining the result(s) desired. Thus, the review of ethics and the review of science here must somehow be interactive. How this is to be achieved is not clearly stated in the Policy Statement; duplication of review should certainly be avoided, as should any ‘single disciplinary’ approach.

To begin with the question of ‘scientific review’, it is clear that the REB is to conduct its assessment at a high scientific and scholarly level. That being said, the Statement does not list areas of particular importance in such review (presumably, there is an agreed standard for ‘peer review’). The document does make reference to exceptions in the matter of such scholarly review, for example, when such review has already been concluded by a funding agency or when such review could be conducted by an ad hoc independent peer review group, or when the institution wishes to establish a permanent peer review committee reporting directly to the REB. Each of these ‘exceptions’ presents some difficulty in the matter of interactivity between ethics and scientific review; such a gap requires further discussion in terms of ongoing refinement of the Policy Statement. That being said, there is also the question of varying approaches to the matter of scholarly review, dependent on the discipline in question. Such considerations lead to discussion of REB membership, a matter to be pursued in 3a) below.

With reference to the matter of ethics review, the Statement calls for ‘ethical probity’ (not defined) on the part of the REB. In discussion introductory to comment about such review, ‘respect for human dignity’ is identified as fundamental to consideration of the ethical aspects of human research. According to the document, this moral imperative ‘translates’ into several correlative ethical principles of interest here: respect for free and informed consent, respect for vulnerable persons, respect for privacy and confidentiality, respect for justice and inclusiveness, balancing harms and benefits, minimizing harm, maximizing benefit. While there may be some further discussion concerning the matter of ‘translation’ here, the listing certainly is representative of ongoing discussion of ethical issues in this area. Application of the listed principles in consideration of various research protocols forms the substance of much of the Statement’s text (e.g., Sections 2-10), and is thus beyond the scope of this presentation. A central notion here, however, is the requirement for risk assessment vis-a-vis the proposed research protocol (a matter to be addressed in this Workshop by Dr. Weijer, thus not to be pursued in this presentation). Closely related to this concern is the Statement’s insistence on a ‘proportionate approach’ to such review: "the more invasive the research, the greater should be the care in assessing the research." Again the matter of ‘invasiveness’ is open to interpretation (is physical intervention necessarily more ‘invasive’ than psychological intervention?), a subject not further pursued in the text. However, this question of ‘proportionate approach’ leads to the question of types of research ethics review, discussed below in 3b).

3a) What is the membership of the REB to be?

The group responsible for research ethics review should demonstrate expertise, multidisciplinarity and ‘independence’; a majority of members should be involved in research or teaching, and these individuals should have the training and expertise to make sound judgments re the ethics of human research. The group of no less than 5 members (including men and women) should include at least two persons with broad expertise in the methods and areas of research for which the REB is responsible. At least one person should be ‘knowledgeable in ethics’; in matters of biomedical research, at least one member should be knowledgeable in relevant law. Finally, the group should include at least one ‘community member’, a person who can provide ‘effective community representation’. If the number of persons required for adequate ethics review of the proposal should be greater than 5, the number of ‘community members’ should be increased proportionately.

These various membership requirements have been the subject of considerable discussion across Canada; until there is further clarification in the Statement, such discussion (read: concern, confusion) will continue. Thus, what are the characteristics of ‘sound judgment’ in this area; what constitutes ‘knowledgeable in ethics’; in what respect is ‘community representation’ judged to be ‘effective’? Further, whom does the ‘community representative’ ‘represent’, and in what way is such representation seen to advance ‘accountability’ to local communities? Considerations of the latter kind have hampered the effort of many institutions in their search for such ‘community members’; this is an area which requires further reflection and clarification by all concerned with appropriate REB function.

In contrast to the ambiguities outlined with reference to the membership positions just mentioned, the Statement’s requirements for the person knowledgeable in law are far more precise. For example, this person is to alert the REB to legal issues and their implications, not to provide formal legal opinions nor serve as legal counsel for the group. Further, "the institution’s legal counsel should not be a member of the REB".

A last point here: so as to ensure adequate expertise for the REB, ad hoc members may be appointed to the group; so as to ensure diversity and opportunity for experience, rotation of members is suggested, always with attention to continuity of REB activity.

3b) How is the REB to function?

In terms of formal activity, REB members are to meet (face-to-face) on a regular basis, with membership adjusted in the case of any member’s continuing absences from such meetings. As well, appropriate records of REB meetings are to be maintained, with documentation of decisions and dissents, and the reasons for such dissents. Minutes "must be accessible to authorized representatives of the institution, researchers and funding agencies". In all of its activity, the REB must act, and be seen to be acting ‘fairly and reasonably’.

Again, there has been some discussion as to researchers’ access to the minutes of relevant REB meetings; there are implications here in terms of potential conflict of interest between REB members and researchers, even as such access may be an important consideration with reference to appeal of an REB’s decision (See#4).

Of particular interest in the matter of REB functioning, are the Statement’s comments re different types of research ethics review. The default position is that there should be full-member review unless a) such review is to be expedited in some fashion, or b) a special exception is made in the case of undergraduate students’ research. How is the decision to allow expedited review of research proposals made? Four illustrative scenarios are provided, so that expedited review is acceptable if: a) the research protocol is seen to involve no more than minimal risk; b) this is an annual review of an approved project in which there has been little or no change made; c) this is a matter of review of patient records by hospital personnel; d) the REB is assured that the protocol in question meets its review requirements. Each of these ‘exceptions’ is the source of continuing discussion, since in each case, expedited review could be used to circumvent the original intent of required research ethics review (i.e., assurance of high standards of research and of ethics regarding that research). At the same time, full REB review may not always be required, and insistence on it might tax REB resources unduly. Further experience with this method of review is required, together with some assurance that research on it be made available for full discussion in the near future.

Notable in consideration of REB functioning here is the attention given to review of undergraduate research. The Statement allows such review to be done at the departmental level, provided such review is consistent with the standards set out by the REB, and provided appropriate record keeping is in place. This is an area of concern for the REB held accountable for such departmental review (how to ensure that review is done in acceptable fashion; how to prevent conflict of interest in this area?). At the same time, there is concern that many REBs are already in an overload situation with regard to the number of protocols to be reviewed, so that adding to the overload another responsibility (for ethics review of undergraduate research) does not appear to be an acceptable alternative. Many institutions have similar concerns about graduate research; with the apparently increasing number of such protocols, the question of ‘expedited review’ for them (together with its various problems) is being raised more insistently.

In terms of actual decision-making within the REB (and this as its major function), the Statement says very little. Should the group act by way of consensus, e.g., is majority vote (secret ballot or not) appropriate? Exactly how should dissents be registered (so that ‘adequate’ recording of them against future appeal is possible)? For many REBs, evolution of the Statement should ensure further guidance in this area.

3c) Has the REB other responsibilities?

In this context, REBs are required to assume at least two other responsibilities: monitoring of ongoing research, and education (of REB members in the first instance, of researchers and the institutional community in more general terms). Each of these requirements is the subject of discussion and concern in the communities affected.

Exactly how is ongoing research to be reviewed? Minimally, an annual report by the researcher could be acceptable. However, in the case of research in which the threshold of minimal risk is exceeded, the Statement refers to the principle of proportionate review already noted, outlining several particular areas in which review might be suitable. These include: review of the consent process (formal or random), review of reports of adverse events, review of patients’ charts, review of documents already generated by a third party.

This matter of required ‘monitoring’ has been the subject of interminable debate within the research community. In general, two main concerns are expressed. First, given the onerous work-load of many REBs, together with limited financial and administrative assistance, how can that group really promise (and perform) adequate monitoring of ongoing research within its jurisdiction? Second, if monitoring is to be more than a façade, what is really required, and which person(s) can be identified as adequate to the task? A subset of this concern is the fear that any ‘careful monitoring’ may result in a breakdown of collegiality among peers, since such activity could be perceived as ‘spying’, perhaps tainted with ‘conflict of interest’. This portion of the Statement’s commentary certainly requires further reflection and amendment.

REBs are also required to engage in education, first of REB membership. Numerous, inventive and successful approaches are evident in this area. At the same time, questions of members’ availability and funding for such activity are continually raised. As the mandate is extended to include education for researchers and the community more generally, greater difficulty in compliance can be anticipated. That being said, other groups have begun to address these questions (e.g., the RCPSC), and this route should be explored further. The burden of educational responsibility here is appropriate not only to the institutions in which research is being done; the professional groups to which researchers are affiliated also have an interest in ensuring that such education is available to their members. Similarly, some joint effort between the institutions and the researchers’ organizations should be encouraged in order to ensure further ongoing education of the wider community in matters of research ethics.

4. What should the relationships between the REB and other groups concerned with research review (internal and external to the one institution) be?

Just as the institution has the responsibility to provide a mandate (with defined jurisdiction) for its REB, so the institution should identify the number of REBs it requires, if workload or disciplinary considerations require more than one. Unnecessary duplication of REBs is to be avoided, but if more than one such group is required, well defined means for consistency, collaboration and communication among them are essential. ‘Fewer is better’, with overlap avoided, and with transfer of responsibility among these groups easily arranged.

Each institutional REB should have an established procedure for responding to a request for re-consideration of the decisions made. Further to this point, the institution should make provision for appeal from an REB decision by way of a single institutional ‘REB Appeal Committee’ with clearly identified processes and responsibility (This is the only route available, since the Statement clearly noted that no such appeal will be considered by the granting agencies).

Turning to external relationships, the Statement suggests that smaller institutions might join with each other to share a common REB. Such union could benefit each constituency in terms of lowered resource use and elimination of duplicated activity. At the same time, careful consideration of authority for such a grouping is required in order to ensure that individual institutions retain appropriate responsibility for research done in their jurisdictions, and so that the desired educational aspects of REB activity are implemented at each site.

The matter of appropriate research ethics review for multi-centred research proposals is discussed in the Statement, with suggestions made for dealing with the contentious issue of local jurisdiction in this area. Again, this is an area requiring further research and possible amendment to the Councils’ document.

A related issue is that of research ethics review of proposals generated in one jurisdiction with an understanding that the proposals are to be implemented in another national jurisdiction. The Statement requires ‘double review’ in such cases, on the understanding that each jurisdiction has ethical responsibility for research which is proposed, funded or implemented within its area. Coordination of procedures for review and implementation of such research can be a problem for all concerned, as can delineation of appropriate responsibility in each case. Again, with proliferation of such ‘international research’ on the increase, this is an area in which the Statement must surely be amended in the future.

Conclusion

The overall purpose here has been to provide a basis for further discussion of REBs’ operational aspects (with a view to assisting in the promised evolution of the Councils’ Policy Statement). In that context, there are several more general observations to be made.

First, there is some discussion within the institutions as to the relationship between the Councils and the institutions; the Councils’ particular view here is not explicitly stated, but whatever its identity, it serves as grounding for some of the Statement’s procedural directions. In this regard, there is no question that the Councils have the clear right to determine how monies allocated for their use, under their supervision, should be used. Equally, there is no question that the institutions concerned also have a clear right to local autonomy, and can thus determine what is to be done in the matter of any externally required ‘institutional procedures’. This question of ‘dual jurisdiction’ cannot be well resolved by way of any ‘external’ document’s fiat; continuing good-faith negotiating about matters arising in such a context is essential. As part of such negotiating, the relationship between the parties concerned here should be re-explored, with the scope of authority for each party clearly identified and agreed to.

Second, the Statement provides very little discussion concerning the need for continuing review of local REB function. "How best to review the reviewers’?" While there will be little argument about the necessity of such REB activity, the Statement could be more helpful in providing comments re suggestions or directions for its implementation.

Finally, the Councils have made it clear that evolution and flexibility will characterize their approach to the Statement’s interpretation, implementation and amendment. Not clear yet is the way in which this flexibility is to be managed, in the matter of limits, method or timing. To ensure the reality of the promised commitment, early clarification in this regard is imperative.