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From:
To:
Subject:
Date:
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[email protected]
Z-SecretariatRE
TCPS 2 (2014) Consultation Comments
January-31-17 11:15:46 PM
TPCSProposedRevisions_MUHC-CAE.pdf
To Whom It May Concern:
I would like to submit, on behalf of my colleagues at the Centre for Applied Ethics of the McGill University Health
Centre, comments on the proposed revisions to the Tri-Council Policy Statement.
We are grateful for the opportunity to offer our thoughts on the proposed revisions, and we thank you for your
consideration of these.
Please do not hesitate to contact me should you have any questions about our submission.
Sincerely,
Renaud
Renaud Boulanger, MSc
Conseiller en éthique | Ethics counsellor
Centre d'éthique appliquée | Centre for Applied Ethics
Centre universitaire de santé McGill (CUSM) | McGill University Health Centre (MUHC)
2155 rue Guy, 223.08
Montréal, Québec, H3H 2R9
514-934-1934 poste | extension 71461
[email protected] www.muhc.ca/cae
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On October 14, 2016, the Interagency Advisory Panel on Research Ethics announced the release
of proposed revisions to the second edition of the Tri-Council Policy Statement: Ethical Conduct
for Research Involving Humans (TCPS2) for public comment.
The Centre for Applied Ethics (CAE) at the McGill University Health Centre (MUHC) is pleased
to respond to this call and submit for consideration feedback on the revised draft of the TCPS2.
The CAE provides ethics services to the MUHC community in situations where competing
values raise important questions related to clinical and innovative care, research, and
organizational decision-making. It also provides support to the MUCH Research Ethics Board
(REB), which oversees all human subject research conducted within its walls and/or by
researchers affiliated with the institution.
Each iterations of the Policy Statement sheds additional light on the sort of research environment
we wish to nurture across the country, and the CAE commends the members of the PRE, as well
as of the Secretariat on Responsible Conduct of Research (SRCR), for their continued
commitment to ensuring the relevance and appropriateness of our national guidelines on research
ethics.
In what follows, we identify points we believe need additional clarification before they can be
expected to be put in action by the Canadian research community. Line numbers provided refer
to the general section in which a point is discussed.
We wish to express our thanks for the opportunity to offer these suggestions. It is with great
excitement that we look forward to the final version of the proposed revisions of the Policy
Statement.
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General comments
1. We strongly encourage the PRE and SRCR to bring back the Index in the printed version of
the Policy Statement. We note that its removal in recent versions has made it harder for our
investigators to identify rapidly the passages that are most pertinent to their projects.
2. We encourage SRCR to develop a tool for researchers detailing all that they are expected to
submit in their applications, as requirements are currently spread over the various chapters
and difficult to navigate for researchers. An example of required material is found in Chapter
11, line 377, where five components of the monitoring plan (safety, efficacy, validity) that
researchers must provide REBs are described.
3. To increase navigability, we encourage the PRE and SRCR to add hyperlink/underline terms
that are defined in the Glossary.
4. Throughout the proposed revisions, there are several definitions that could be moved to the
Glossary (e.g.: Article 2.3, “naturalistic or non-participant observational research is…”).
5. We encourage PRE and SRCR to add additional guidance regarding incidental findings and
associated obligations of researchers, particularly in light of the revisions discussed at line
579. We frequently field questions from researchers trying to understand what counts as
incidental findings and how they must be discussed in Protocols and in Informed Consent
Forms.
6. We encourage PRE and SRCR to add additional guidance regarding the offer of
compensation to parties who are not directly involved in research as participants (e.g.,
parents of minors who cannot consent).
7. We encourage PRE and SRCR to expand the existing guidance (Chapter 13, Section G) on
gene transfer studies that do not target the human germline in light of recent rapid advances
in gene-editing technologies.
8. The examples provided throughout the Policy Statement are essential to the comprehension
of some of the points being made, but moving them to footnotes or endnotes would make it
easier to distinguish normative passages (an instance of this can be found in Chapter 11 line
358: “For example, consider a trial of an experimental medication for lung cancer. The
experimental medication offers one of more advantages over…”).
Comments on proposed revisions, excluding Chapter 11
9. Line 7 (vulnerability): There is ambiguity in the use of “historically.” Instead of highlighting
what groups have “historically” been made vulnerable, it may be more productive to identify
what circumstances can be said to make individuals or communities vulnerable in the context
of research.
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10. L96 (course-based-research): The Policy Statement should clarify that course-based research
that receives a waiver from REB review cannot include research activities that involve
recruitment of patients in a clinical environment. All such research should be reviewed by the
institutional REC, regardless of the fact that it may be intended for pedagogical purposes
only (cf. L280 regarding recruitment).
11. L155 (cumulative risks): The notion of “cumulative risks” warrants defining.
12. L158 (attributable risks): Can risks attributable to research vs. risks to which participants are
exposed be as easily dissociated as suggested in this passage? It seems that some researchrelated risks only arise because of other risks to which participants are exposed. The example
of bioaccumulation and exposure to radiation comes to mind. For some individuals who are
exposed to higher levels of radiation, participation in research might be risky precisely
because of the risks to which participants are exposed outside of the study context.
13. L245 (consult Chapter 9 “when appropriate”): The Policy Statement should provide
additional guidance to researchers and REBs as to when it is “appropriate” to consult Chapter
9. Currently, it is unclear whose responsibility it is to determine when it would be
“appropriate” to do so.
14. L245 (no consent): The passage “that have been approved to proceed without consent or a
community engagement process” should be deleted as community-level interventions may
expose individuals who do not meet the study’s inclusion criteria regardless of the
community engagement process. Although important, community engagement cannot with
certainty prevent this exposure from happening.
15. L269 (participating without risk to privacy): The statement “allows individuals, groups and
communities to indicate their interest in participating without risk to their privacy” should be
changed to “without UNDUE risk [or “intrusion”] to their privacy” as the notion of absence
of risk is misleading. For instance, considering that email accounts can be hacked, the current
phrasing could suggest that attempting to recruit without risk to privacy would mean that no
recruitment could be done via email.
16. L276 (screening): It may be useful to state that “screening” activities that may precede
consent do not include clinical acts such as blood draws.
17. L373 (undue limitation): In the passage “Any prohibition or undue limitation on the
publication or dissemination of findings from research is ethically unacceptable”, it is unclear
what “undue limitation” means. The Policy Statement should provide examples or definitions
of what “undue limitation” refers to, as well as specify which party must determine whether a
limitation is undue or not (e.g., researchers vs REBs).
18. L379 (timely dissemination): Two passages refer to the idea that dissemination of findings
must occur within a given time frame: “The dissemination shall take place in a timely
manner without undue restriction” and the reference to “reasonable time” in Line 385.
However, insufficient guidance is provided regarding what “timely” and “reasonable” mean.
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The Policy Statement should set an aspirational, if non-binding, target to help guide the
research community.
19. L374 (dissemination to participants): The wording of the passage discussing the importance
of returning results to participants appears too strongly worded. While participants who
express an interest in the outcome of the study in which they participate should not face
barriers to learning about it, it is a false dilemma to try to rank dissemination to participants
vs. dissemination to the scientific community. Although the research community admittedly
generally should be spendng additional efforts towards knowledge translation, it is
counterproductive to try to oppose dissemination to participants against dissemination to the
scientific community. Emphasis should be put on lowering barriers participants face to
access study results; doing so may require more work in knowledge dissemination (including
to policy-makers), not simply a “summary of research results.”
20. L409 (availability of data): The Policy Statement encourages researchers “to make their data
available for further analysis or verification by their peers.” In Québec, the Ministère de la
santé et des services sociaux has developed a policy on the creation of biobanks and
databanks (http://ethique.msss.gouv.qc.ca/lethique-en-bref/banques-de-donnees.html). The
Policy Statement should be clearer on whether “to make data available” to other researchers
for further analysis is the equivalent of creating databanks.
21. L452 (approval): The passage suggesting that “In granting its approval for a study, the REB
engages the responsibility of the institution” should be nuanced to include the case of Québec
health centres, where research may only proceed once a personne mandatée has provided
authorisation for the research. This authorisation comes after approval by the REC, and is
essential for study initiation.
22. L519 (finding with impact on welfare): The introduction in line 519 of a new category of
finding, i.e. a finding that has “a potential impact on an individual’s welfare” that is
“significant”, is a confusing addition considering that the proposed revisions refer to
passages about incidental findings with which the research community still grapples (see, for
instance, http://www.cmaj.ca/content/186/9/655.full). In particular, the right of participants to
refuse to be informed of such findings should be clearly stated.
23. L581 (exploratory activities): The exploratory activities in this passage are described as
possibly taking place “prior to the actual design of the research” (L581). At the same time, it
is stated that the intention to use material from the exploratory activities “must be made clear
in the research proposal” (L586). These two passages seem contradictory since the very
reason to conduct such exploratory activities should be to use the information gathered doing
so (e.g., to define the study question collaboratively, tweak the study design). Not using the
information revealed by the exploratory activities would appear to be a waste of resources
and of the time of each individual involved in exploratory activities. A suggested rephrasing
might be: “If, however, the researcher wishes to use information gathered during the
exploratory activities AS FINDINGS of the study (…), this intention must be made clear
(…).”
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24. L610 (pilot studies): It is unclear that it would be truly helpful for REBs to “ensure that
recruitment and consent materials provide this information and describe how the findings of
the pilot study will be used to determine the feasibility of conducting a larger study.”
Recruitment material, such as posters, generally needs to be concise to be effective. Having
to fit in an explanation of how “the findings of the pilot study will be used to determine the
feasibility of conducting a larger study” seems unnecessarily burdensome.
25. L702 (contract review): When the proposed revisions to the Policy Statement refer to
delegation of the contract review to “an individual or group with the appropriate expertise,” it
is unclear what the “appropriate expertise” refers too. Is proof of familiarity with the Policy
Statement required, for instance?
26. L706 (contracts and consultation): The proposed revisions state that the contract review
“must conform to the mandate and purposes of REB review and involve consultation with the
REB.” It is recommended that the end of this passage read “consultation with the REB, when
necessary.” Requiring competent, well-equipped contract offices, such as those found in
large university health centres, to consult REBs for every contract would add unnecessary
delays to the review process.
27. L767 (community and COI): The use of a new expression, “community conflict of interest,”
warrants a clearer definition, as well as the provision of concrete examples. In addition, the
requirement that “researchers must inform the community” should be spelled out to explain
what “informing the community” means and how this can be done. Much has been written on
the difficulty of informing communities in the context of emergency research; it is necessary
to clarify whether this sort of approach is what the Policy Statement has in mind.
28. L821 (observational studies): The change from “are” to “may be” exempt from REB review
is unhelpful without reference to clear criteria on when it is not and details regarding who
applies these criteria. Submitting every observational study to request a waiver will burden
the research ethics oversight infrastructure unnecessarily.
29. L964 (smoking): Attention should be paid not to unnecessarily stigmatise individuals in the
Policy Statement. Framing the issue of smoking vs. not smoking as simply a matter of
“choice made by the participants” is simplistic and risks stigmatising further individuals who
struggle with an addiction.
Comments on proposed revisions to Chapter 11
30. L2 (definition): The renaming of Chapter 11 is an important step forward. However, the use
of a term (“interventional studies”) that is commonly used to refer to a particular research
design rather than a risk level introduces unnecessary confusion. It is unclear what ‘minimal
risk studies that are interventional by design’ should be referred to using the newly
introduced terminology.
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31. L120 (responsibilities): The statement that “A researcher has greater responsibilities towards
participants than those of a health professional to a patient” is controversial and deserves
further explanation. The proposed revisions suggest that the reason this is the case is because
“research is not premised on providing participants a direct benefit.” Because informed
consent processes ensures that participants understand this, it seems counterintuitive to
suggest that responsibilities are increased. To put this statement in action, teasing out what
having “greater responsibilities” entails would be necessary. This expression is also used line
203 when describing the difference between interventional research and observational
research.
32. L140 (incidental findings): Contrarily to with unanticipated events and adverse events, it is
unclear why REBs should receive information regarding incidental findings – or what they
are expected to do with this information. Note that article 11.8 (line 570) is similarly
unhelpful in identifying what REBs should do with reports of incidental findings. It is
unclear, for example, how incidental findings related to one participant might “affect the
welfare or consent of participants” in the study.
33. L137/551 (multi-site studies): Some of the responsibilities attributed to investigators in the
proposed revisions of the Policy Statement contrast with the recent multi-centric mechanism
put in place by the Ministère de la santé et des services sociaux in Québec
(http://ethique.msss.gouv.qc.ca/lethique-de-la-recherche/recherche-multicentrique/cadre-dereference.html). Under this mechanism, local site researchers do not inform their local REBs
of changes to the study, as the review is done by one evaluating REB and the REBs at local
institutions are not involved in the review process. The Policy Statement should qualify
statements relevant to multi-site studies to ensure they are relevant to the Québec context.
34. L224 (foreseeable risks and benefits): The Policy Statement should specify more clearly what
benefits should be considered in this case as several fringe benefits to participating in a study
may exist but are not currently considered by REB reviews. For instance, friendly bonding
between participants may be a benefit of studies that bring participants together (e.g., focus
groups), but are not normally considered. The phrasing “Researchers and REBs shall: a)
identify all reasonably foreseeable risks and potential benefits” could be changed to
“Researchers and REBs shall: a) identify all reasonably foreseeable risks and identify
potential benefits that are significant.”
35. L255 (role of researcher): The Policy Statement’s position regarding the role of the research
appears to be in stark contrast with much of the literature on global health ethics, which
advocates for a responsibilisation of researchers. By stating that “The role of the researcher is
to address the research question – to discover if a particular intervention is beneficial or less
harmful than the status quo. It is the role of advocates, policy makers and service providers to
use the findings of research to ensure the equitable distribution of potential benefits” the
Policy Statement misses an opportunity to emphasise the crucial role researchers must play in
knowledge translation. It is suggested that the phrasing be changed to: “The role of the
researcher is to address the research question – to discover if a particular intervention is
beneficial or less harmful than the status quo – and to ensure the adequate dissemination of
findings to facilitate uptake by advocates, policy makers and service providers, such that they
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can use findings of the research to ensure the equitable distribution of potential benefits.”
This passage would be better placed in the Introduction of the Policy Statement, such that it
grounds the entire orientation of the research enterprise.
36. L336 (placebos): The statement “The use of placebos must be necessary to address the
research question” should be replaced with “The use of placebos must be necessary to
address the research question or the only alternative (i.e. no standard of care).”
37. L419 (other requirements): It is unclear why the statement “It is the responsibility of
researchers to be aware of any additional guidelines that apply to their research and to adhere
to them for the safety and benefit of participants” is found under Chapter 11. Although there
are generally more regulations for clinical trials, there are other sources of requirements that
researchers conducting non-interventional studies may need to be aware of. The statement
should be moved to a section of the Policy Statement that applies to all researchers. In
addition, it should specifically discharge REBs of the responsibility to ensure that researchers
have done due diligence to ensure they are compliant with other requirements applicable to
their research (e.g., in international contexts).
38. L477 (DSMB): It is unclear why criteria must be used to determine whether a data safety and
monitoring board (DSMB) must be used and whose decision it is. If the Policy Statement
intends to provide this decisional power to REBs, it should more clearly state so.
39. L511 (information sharing): Greater clarity could be brought to the statement “This
information may also need to be with participants and, possibly, other relevant third parties
(e.g., family members, circle of care), as indicated by the nature of the information.” It is
unclear from the current drafting whose responsibility it is to determine what information
warrants disclosure to which party. If this statement alludes to mandatory disclosure of
certain diseases, for instance, it should state so explicitly. In addition, consideration should
be given to the impact this may have on the wording of informed consent forms.
40. L565 (end of study): It is unclear why the definition of the end of study is found in Chapter
11. The statement: “Typically, the end of the study will be the last contact with the last
participant for the purposes of collecting data or human biological materials” could be moved
to an earlier section of the Policy Statement, as it applies to non-interventional studies too.
41. L642 (registries): The use of the word “trial” should be abandoned considering the clear
aspiration of the Policy Statement that all interventional studies be registered. For example,
the sentence “Updates to the registry are also required for any changes to the trial that require
REB review and approval” could instead read “Updates to the registry are also required for
any changes to an interventional study that was registered that require REB review and
approval.”
42. L756 (Phase IV): It is counterintuitive for Phase IV to be discussed in this Chapter, since
they do not involve the prospective assignment of participants. It would be best if they were
discussed in a more relevant chapter and a note was put at line 756 referring readers to the
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right section. The creation of an Index would also make it easy for readers to find
information about Phase IV.
43. L764 (financial terms): The Policy Statement should clarify whether it expects REBs to
review final versions of the contracts between researchers/institutions and sponsors. In earlier
passages of the Policy Statement, it is stated that the review of contracts may be delegated to
non-REB members. However, the passage “REBs should carefully consider the financial
terms between sponsors and investigators associated with these trials” obfuscates this.
44. L811 (psychotherapy trials): The statement regarding recruitment of participants with
“specific psychological profiles” from the same institution as the researcher would probably
benefit from being qualified, as its applicability in the clinical setting is unclear (e.g.,
recruitment of patients from a hospital). The expectation that “Issues of participant privacy
and confidentiality may receive closer scrutiny” in clinical settings is unclear.
45. L813 (compensation): In light of the expectation that researchers provide details of how their
compensation practices will not threaten participants’ confidentiality, examples of deficient
compensation procedures would be helpful.
46. L853 (communities and cluster trials): The statement regarding the representativeness of
community members appears somewhat circular. If researchers identify individuals as
“representing the community,” then it implies that the identification process led to a sort of
vetting of those individuals. The expectations set in the Policy Statement seem rather high –
how are researchers expected to demonstrate that the “community” “regards” those
individuals as representatives? Is the Policy Statement calling for a vote of confidence or
elections of some sort? A more straightforward way to state that researchers cannot appoint
anyone as representative of the community would be to state: “Researchers must use a
reasonable process to identify individuals who legitimately represent the community.
Researchers must provide details of this process to the REB.”
Thank you for your time and consideration.
END