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University of Ottawa comments on proposed revisions to TCPS 2
January 31, 2017
Who was consulted:
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REB members and chairs
Researchers
Deans and Vice-Deans, Research, who also consulted with the professorate
Office of Research Ethics and Integrity staff
Affiliated hospitals
General comments:
The comments below reflect feedback received from the groups listed above. In cases where a comment
is quoted directly, it has been put in brackets. Some comments were received in French, others in
English. When quoting comments, we did so in the original language.
In general, there was support for the proposed revisions, recognizing that many were already in the
posted interpretations of the TCPS 2.
Many people we consulted commented that the main text in French needs to be revised. Some
examples are provided below.
Main text: It would have been helpful to include more of the original TCPS 2 text, particularly where
there is reference made to other sections. For example, under Article 2.3 the new text refers to Articles
2.3 a) and b) but these are not included. It was therefore necessary to have both documents open when
revising changes in order to fully evaluate the revised text. If there is a second round of consultations, it
would be useful if a tracked version of the complete TCPS 2 were also provided.
Question from the research community, REBs and affiliated sites: Will the TCPS 2 training tools be
revised to reflect the implemented changes?
Researchers mentioned that one area where additional guidance would be useful is on autoethnographic research, or other modes of self-study, including guidance as to when these do or do not
require ethics review. In order to determine need for ethics review of auto-ethnographies, uOttawa
currently considers whether or not third parties (parents, family or others) can be identified in the
project, and what the risk level is but it is unclear that given the subjective nature of this type of
research, it is something that is appropriate for REBs to review.
Comments – Main Text
Chapter 2.1 (lines 34-36)
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Many people commented that the following sentence is unclear: “For the purposes of this Policy
pilot studies do not include the pre-testing of a particular research instrument such as a
questionnaire.” The comments were directed both to the French and English versions of the text.
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Does this sentence imply that these activities don’t require review, or only that they aren’t pilot
studies? If it means that these studies do not require review
o There is a worry that if a patient population is the one participating in the tests the risks to
them are likely the same (if not higher) as those encountered when the tool is finalized.
o It was recommended that you include translation of existing research instruments /
questionnaires (keeping in mind the comment above).
French: “La tournure de cette phrase n'est pas des plus directe ou des plus simples. À changer si
possible par : "Aux fins de la présente, l'essai préliminaire d'un instrument de recherche, tel qu’un
questionnaire, n'est pas considéré comme une étude pilote". »
New article 2.5A
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There were varying opinions on whether this change should go ahead.
Concerns:
o Despite these activities being conducted for pedagogical purposes, this is a research training
activity so there was concern that not requiring ethics review may send the wrong message
to students.
o Without the REB being involved, some particularly risky studies may be conducted by
students. We have seen for example, proposals from undergraduate courses to interview
homeless people or proposal to do research related to illegal activities, where students did
not have the appropriate experience or training to deal with potential issues.
o If the REB isn’t consulted, some projects which may need REB review (don’t fit the
exemption criteria) won’t be spotted and may go ahead without REB approval.
Arguments in support of the change:
o Even with the current system, it is sometimes difficult to ensure that the REB is aware of all
‘research-like’ activities conducted by students.
o Given the fact that these are essentially training activities, the standards cannot be the same
as for regular research projects.
If this article is kept, we recommend that stronger language be included indicating that institutions
should have guidelines in place for these types of projects, for example, that they be of minimal risk
to participants. Suggestion: revise last sentence (lines106-107) to state: “It is recommended that
institutions have procedures and mechanisms in place, other than the REB, to ensure that students
are properly trained and conduct these activities in accordance with TCPS 2 principles. This could
include procedures and guidelines which are applied institution-wide or at the department or
faculty level.”
Line 64
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The definition of ‘participant observation’ is not clear. What is meant by ‘interaction’? What
constitutes ‘influence’? If a researcher is sitting in a coffee shop quietly observing other patrons,
does this constitute participant or non-participant observation?
Article 2.10
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Recommendation: provide non-biomedical examples, such as studies where researchers are looking
at suicidal risk, death of family members, etc. There can be an emotional impact to such research
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but in many cases, the research isn’t adding to the emotional disturbance (and in some cases may
ease it). As in the other examples provided, it’s important to distinguish between existing factors
and those introduced or enhanced due to participation in the research.
Chapter 2, section B
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There was general agreement with the new content but researchers indicated that additional
guidance regarding instances where there is a disagreement between individuals and the
community, and whether one could or should be prioritized, would have been useful. For example,
the text could had referenced Article 3.6 (critical enquiry).
Line 268-269: “A fair and equitable recruitment process is based on inclusion and exclusion criteria that
are justified by the research question (Article 4.1). It allows individuals, groups and communities to
indicate their interest in participating without risk to their privacy (Article 5.1).”
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This statement assumes that there is a desire and need for privacy in all instances, which is not
accurate. We believe that there should be an assessment of the privacy requirements and a
discussion with potential participants on this topic versus a statement regarding the absolute need
for it in all situations.
Article 3.7, lines 298-301: The first sentence is unclear. What types of risks could people be exposed
to? Examples would be useful.
Chapitre 4, ligne 370 : « Comme l’inaptitude à décider de consentir les place dans une situation de
vulnérabilité dont la situation les rend vulnérables dans le contexte de la recherche, les
participants… » Commentaire : « À réviser. La phrase est incompréhensible. »
Chapter 4, lines 373-374 : “Any prohibition or undue limitation…”
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There is agreement from all parties that research results, including negative results, should be
disseminated. However, this is a very absolute and strict statement, which leaves no room for
circumstances where dissemination and publication are not appropriate, for example, where a
researcher discovers that there was a methodological issue with the design of a study and the
results are not valid. This can happen to any study but is more likely when dealing with student
research. Other examples are where there may be a temporary limitation in cases of intellectual
property and research contracts with private business. We recommend softening the language
and allowing for contextualization.
Note: the same applies for the statement in line 299 “All findings should be published.” This is
obviously the ideal but researchers and institutions don’t have complete control as to whether
and when their findings are published.
There was concern that this change would have major practical implications for institutions and
their researchers, including financial challenges.
Many asked for examples of appropriate means / resources for dissemination as well as for
examples of what constitutes appropriate timelines.
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Comment for The Ottawa Hospital: “When results are shared in formats other than
publications, I think more guidance on expectations for disclosing of funding and of COIs would
be of value.”
Lines 387-389 “For this reason, and based on respect for participant expectations and protection of
the public good, researchers, REBs (emphasis added) and institutions have an ethical responsibility
to make reasonable efforts to publicly disseminate research findings in a timely manner and
without undue restriction.”
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The REB members were very concerned about this sentence. They do not believe the REB has a
responsibility to disseminate research findings. It has a responsibility to request information
from researchers regarding their dissemination plans and to verify if these follow the principles
laid out in Article 4.8. We recommend revising the sentence.
Article 5.1, lines 429-431, Sentence « in other situations… » is repeated.
Line 437 Suggestion: define “reportable communicable disease”; whose definition does this refer
to?
Ligne 446-447 « Tous les résultats, y compris les résultats négatifs. » Commentaire : « Il manque une
partie de la phrase. « devraient être considérés?” »
Line 472 “…the institution should establish a policy that explains how it will fulfill its responsibilities
to support its researchers.”
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Given that a policy is normally a general statement (for ex., the institution will respect the TCPS
2), what is needed is a procedure, which explains how this will be put in place (as is said in the
text). Suggestion: replace “policy” with “procedure”.
Article 5.2, line 492: Previous text (line 488) refers to an “obligation” to disclose but this line says
“reason”; it is not clear why the change was not also made to this line.
Article 6.11, line 582 & lines 584-587: Suggestion: replace “humans” with “participants”.
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Note: it is only possible to include this information in the research proposal if the researchers
know ahead of time that they will use it, which may not be the case.
Lines 665-672: The statements appearing here contradict those appearing in line 371. Recommend
modifying line 371.
Lines 702-704: There is an issue with the second sentence of this paragraph. 1) Not all research
involves humans. This statement declares the REB should oversee all confidentiality, publication
and access to data clauses. 2) The REB, at least at our Institution, is not responsible for reviewing
contracts; we have a contracts office who fulfills this role, with whom the REB communicates as
needed. Suggestion: revise the sentence to indicate that the institution can delegate this authority
to a contracts office or if there is no contracts office, where the contract involves research with
humans, to the REB.
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Chapter 7, section E: Many requested that more specific examples be provided.
Line 914 (def. of clinical trial)
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Various concerns arose around this definition, and many commented that it seemed very close to
the original.
Comments were made asking it be specified that ‘health’ include both mental and physical health.
Lignes 1044-1048 « Ensuite, on évalue l’efficacité potentielle du médicament comme traitement de
l’hypertension artérielle. Dans le domaine de l’éducation, une étude portant sur l’efficacité
potentielle d’un programme d’études expérimental pourrait consister à mesurer un résultat précis
comme le résultat des élèves à un examen. Des enseignants spécialisés appliquent le programme à
des groupes sélectionnés comptant des élèves très motivés qui respecteront les exigences. Ensuite,
on évalue l’efficacité potentielle du programme expérimental pour ce qui est de stimuler
l’apprentissage. » Commentaire : les exemples donnés devraient inclure la notion de groupes
contrôles
Comments - Chapter 11
Overall, the University community supported the larger scope of this chapter to include high-risk
interventional studies but there was concern about the intake process for the REB office and the need
for significant revisions to processes if the proposed changes go ahead. Another issue is the likelihood
that there could be divergences of opinion (between researchers and the REB and possibly even within
the REB) as to what constitutes an above minimal risk vs. a below-minimal risk interventional study,
particularly in a non-clinical setting.
Non-biomedical researchers were concerned about the language used and the applicability of these
criteria to their fields of study.
This chapter mixes general information with principles that are to be used in ethical review of
interventional studies, which is confusing. For example, it starts with defining “interventional research”
in the scope section with a statement that for the Policy these are above minimal risk and then provides
a different definition of “interventional study” in line 27 which may include more than minimal risk.
There is also a statement that the chapter only applies to interventional research (presumably the first,
not the second definition) but certain sections speak of clinical trials (which could be minimal risk). It
was felt that additional work is needed to clarify the text.
Article 11.9 Registration of Interventional Research. Given that you define a clinical study as any study
where both the intervention and the outcome are health-related and given your definitions of an
interventional study, it seems that all interventional studies would have to be registered. This is an issue
since it is not clear where the non-clinical interventional studies can be registered, as many would not fit
the criteria for ‘clinical trial.gov’ registration. This may therefore be almost impossible to accomplish, at
least at the present time.
Catherine Paquet
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Director, Office of Research Ethics and Integrity
University of Ottawa
Ottawa, Ontario
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Appendix 1
Comment to the Proposed Changes to TCPS 2 2014
The Ottawa Hospital (OHRI Admin group, OHRI and UOHI contracts group)
Chapter 4.0: Dissemination of Research Results
Line 371: This section implies that results from all research studies, irrespective of their design,
must be made available by publication or other means (i.e., via a repository or study registry). I
truly think this is a progressive and positive step; however, I think it is critical to recognize the
practical implications this modification to the policy would have.
In my view, this addition to TCPS2 would have major implications on common practices. Who
is going to support researchers in being compliant to this change, if it is adopted? What
infrastructure demands might this create? Do suitable university/institutional repositories, with
appropriate staff support, exist to handle the anticipated increase in result deposits?
Alternatively, are external tools like the Open Science Framework going to be endorsed for the
purpose of dissemination? Researchers will need direction on how be compliant to the proposed
change as most do not currently share results in this way.
How is dissemination defined? Are there specific rules for where results must be shared if not
through a publication (i.e., in an indexed and searchable repository?). It would be of little benefit
if the dissemination policy 4.8 were not specified to ensure that findings are posted in places
other researchers, and the public, are likely to find. A list of suitable resources for this purpose
could be of benefit.
Line 385: A public presentation is noted as a suitable method of dissemination. Unless said
presentation is recorded and later hosted in an online repository that is indexed, I am not
confident this should be considered an appropriate form of dissemination. How are institutions
otherwise able to enforce their researchers’ compliance to the policy?
Line 380: Similarly states sharing should take place in ‘a timely manner without undue
restriction’. This is vague and would again present difficulties for institution to ensure and
enforce compliance. Is timely defined as 1 year as in the case for some clinical trial registries? If
so, would researchers be obligated to share results in a repository before this deadline, even if a
manuscript they intended to publish had not yet been accepted? Do journals and publishers make
allowances for pre-sharing of results, as they do with clinical trials?
When results are shared in formats other than publications, I think more guidance on
expectations for disclosing of funding and of COI’s would be of value.
As noted above, I want to reiterate that I welcome the change to the policy; I just feel it needs to
be specified in greater detail. I wonder if it would be of benefit to develop associated training or
resource materials that are made available nationally at the time of the policy update release?
Our Centre (http://www.ohri.ca/journalology/ ;[email protected]) may have capacity to
contribute to this, if this is of interest.
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Chapter 5: Privacy and Confidentiality
Article 5.1, Application
We feel that the additions to the Application section of Article 5.1 are not particularly accurate in
the context of our work. This section implies that researchers are responsible for determining
whether information should be disclosed to third parties. However, research data is typically held
by the institution; therefore, the institution decides, on a case by case basis, whether data should
be shared (exception: patient safety). As a result, we do not believe that these paragraphs should
be added to TCPS2.
We are also of the opinion that the proposed revisions to the Application section of Article 5.1
conflate physician researchers with employees of an institution; whereas, physician researchers
hold a research appointment at an institution, sign contracts as separate parties, and have their
own CMPA coverage. Therefore, if it is determined that these paragraphs should be added to
TCPS2, we would suggest revising as follows:
“In situations where there is an attempt by legal means (e.g., warrant, subpoena) to compel
disclosure of confidential participant information, institutions are required to provide
researchers with financial and other support to may want to obtain independent legal advice or
to ensure that such support is provided. For the purposes of this Policy, "legal advice" includes
all legal services that a researcher in this situation may require, including representation. The
purpose of independent legal advice is to permit the researcher to make an informed decision as
to whether to disclose or to resist disclosure of confidential participant information. Researchers
who are considering resisting disclosure must be aware of the personal consequences of
choosing to respect ethical principles rather than legal obligations where the two cannot be
reconciled. Such advice should be independent of any advice to the institution.”
Article 5.1. As highlighted above, the proposed revisions to this Article do not take into
consideration the context within which hospitals operate; the institution holds/owns the research
data, and ‘researchers’ (which is not a well-defined term) are often independent contractors
whom the institution would not necessarily be responsible to assist.
Chapter 6: Governance and Research Ethics Review
Article 6.24
Although we recognize the desire for openness, in terms of contract negotiation, the reality is
that we need to balance the interests of industry-sponsors with full access data. For instance, U.S.
industry-sponsors may push-back quite significantly on the proposed bullet re: “permit all
researchers to access all study data in cases where no principal investigator is named”. These
terms are assessed and negotiated on a case-by-case basis. As such, we propose revising Article
6.24 to be more permissive:
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“Institutions shall are encouraged to develop policies regarding acceptable and unacceptable
clauses in sponsor-researcher contracts relating to confidentiality, publication, and access to
data. The policies should may:
(a) require that sponsor-researcher contracts be submitted to a responsible authority for a
determination of their consistency with institutional policies and this Policy;
(b) require that any ethical concerns arising in the review be referred to the REB as an integral
part of the research ethics review process;
(c) provide that all confidentiality and publication clauses:
• are consistent with the researchers’ duties to share new information from research with
REBs and study participants and to report study findings in a timely manner without
undue restriction;
• stipulate that the researchers, especially the principal investigator, will assume the
primary role and responsibility for the analysis, interpretation, and preparation of the
findings for publication;
• permit principal investigators leading multi-site studies to access all study data;
• permit researchers to access all study data collected at their respective sites; and
• permit all researchers to access all study data in cases where no principal investigator
is named.”
Article 6.24, in support of above, we feel that some of these proposed revisions reach beyond the
ethical aspects of contract negotiation into internal governance and/or business matters and might
unnecessarily limit the institution’s ability to exercise its discretion.
Chapter 7: Conflicts of Interest
Lines 702-704: Does not accurately characterize the way in which many health research
institutes operate:
“Normally, review of the ethical aspects of researcher-sponsor contract clauses related to
confidentiality, publication and access to data is the responsibility of the REB. This review may
be delegated to an individual or group with the appropriate expertise”.
In our experience, contract review is normally delegated by the institution itself to a contracts
and/or legal office, and is not undertaken by the REB. If this language is to be included in the
revised TCPS2, the REB will need to formally delegate contract review to the Contracts Office.
Article 7.4 (Financial Conflicts)
Line 738: “shall” has been replaced with “should”: “REBs should shall consider the potential for
this type of conflict because its ability to undermine the ethical conduct of research has been
empirically established”. We would recommend that “shall” be retained, and that the obligation
currently held by the REB to consider financial conflicts of interest not be watered down. Given
their potential to undermine the ethical conduct of research (as highlighted), we think it is
important that the REB be mandated to assess conflicts of this nature. Moreover, these conflicts
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can arise in the context of a specific project and might not be captured by broader institutional
oversight over conflicts of interest.
Chapter 11: Interventional Research (formerly Clinical Trials)
Line 35: To clarify the second sentence under the definition of Intervention (line 37): “The
conditions may be such things as a task, an activity, a treatment, exposure to stimuli, or a change
to environment.” Does this list also include additional testing for the study participant? Perhaps
the participant is following standard of care treatment (observational), however the researcher is
interested in assessing a specific outcome, which would not normally be assessed as part of the
patient’s standard care, e.g., blood results, results of a stress test, additional imaging, etc. This
seems to extend beyond the definition for observational research; however, it is unclear if it truly
meets the interventional definition. The outcomes being assessed are not “affected by an
intervention in the context of research” as per lines 48 and 49. Also, in some cases this
additional testing may fall into the minimal risk category, and therefore exempt the study from
the requirements of this chapter, however subjecting a cardiac patient to a stress test for example,
may expose them to more than minimal risk, rendering this chapter applicable.
With regards to imaging, the question is more complicated. If the additional test is a PET scan,
conducted under Division 3 as a basic science radiopharmaceutical project to assess the
tracer/scan, is this considered an interventional study? Given that we are exposing patients to a
tracer they would not normally be exposed to, this seems to meet the interventional definition.
However, there is no participant outcome assessed, thereby not meeting the “Outcome”
definition.
Section A: Key Concepts
Line 136: Suggest adding the definition of Qualified Investigator as this chapter also covers
regulated clinical trials and Health Canada does not define the term Principal Investigator.
Line 142: Suggest adding to the key concepts section that study wide stopping rules require
sufficient data to be available for analysis as mentioned on line 467.
Article 11.5:
Line 378: Suggest adding an additional bullet to specifically state monitoring for “regulatory and
GCP compliance if applicable”. This supports the statements made on line 417.
Article 11.6: Suggest adding additional point after line 449 to indicate that an independent
DSMB may be applicable when safety concerns are particularly acute, i.e. phase I trials. This
supports the statements made in lines 714-715.
Article 11.7 (Reporting New Information)
In the context of industry-sponsored research. We would suggest that this Article be revised to
read: "Researchers shall promptly report new information revealed during the conduct of the
study that might affect the welfare or consent of participants to the REB to a publicly accessible
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registry and or to other appropriate regulatory or advisory bodies". We feel that the obligation
to report new information to a publicly accessible registry would place researchers in a difficult
position where they are contractually obliged by a sponsor to hold such information in
confidence. We build language into our clinical trial agreements that allows us to report new
information to participants where it affects their safety/welfare, the REB, the DSMB and the
regulatory authorities (where serious adverse events are concerned); however, we often receive
significant push-back from sponsors regarding these terms and I cannot imagine that a
requirement to disclose the information to a public registry would be well received.
Article 11.10: Suggest adding additional point after line 639 to indicate that researchers are
responsible for ensuring that the registry is updated in a timely manner with "results". This
supports in the information provided in lines 647-650.
Line 647 specifies that researchers are required to update their trial registry with results when
they become available. It is noted that to be compliant researchers can provide lists of
publications, links to publications, or even a link to the trial website. In my view, these changes
do not reflect a positive dissemination strategy.
As already outlined in the TCPS2 document, one reason for ensuring that researchers provide
results to their studies is to prevent publication bias. However, it is well known that many
researchers fail to report all trial outcomes in their publications, or switch outcomes in their
manuscript (i.e., report the secondary outcome as the primary outcome). There is an extensive
literature on this topic which I am happy to share, if this is of interest. As journals do not check
registered outcomes, if publication is considered the criteria for results reporting, this could
potentially mean many results in fact go unreported.
In addition, clinical trial participants are often told that they can obtain results from the study
they participated in, or any other completed trial, via publicly available registries. Should the
TCPS2 revisions not require that results be uploaded to the registry itself, it may mean many
members of the public (those who pay tax dollars to fund much of clinical research) may not
actually be able to access results, as many publications are still behind paywalls. In addition,
links to trial websites are likely not to be permanent records. These sites may be taken down (i.e.,
when researchers move institutions), and are unlikely to be monitored after trial completion. In
addition, there would need to be strict rules for websites about COI and funding disclosures.
It is absolutely essential that the results be provided via publicly available registries to ensure
transparency and accountability to the public.
Article 11.12:
Lines 756-770: The description of phase IV trials is not consistent with that of Health Canada.
Health Canada defines phase IV as:
“All studies performed within the approved indication after the drug has been approved by the
regulator for the market. These studies are often important for optimizing the drug's use. They
may be of any type but must have valid scientific objectives. Commonly conducted studies
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include safety studies and studies designed to support use under the approved indication (e.g.,
mortality and morbidity studies, or epidemiological studies).”
It is true that pharmaceutical companies will conduct phase IV surveillance/observational studies
for long-term safety data, however, academic research institutions tend to conduct a large
amount of phase IV research that uses prospective assignment.
Suggest adding a new section for pragmatic trials as many academic researchers are conducting
trials using this design. In a pragmatic trial, the design mimics as closely as possible ROUTINE
clinical practice, with the exception that patients are randomly allocated to treatment.
Conducting pragmatic trials raises ethical issues related to informed consent. It would be helpful
for TCPS2 to touch on these important issues.
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