Summary of NCEHR Listserv for July 2003



1. Consent for University Students Under the Age 18

2. Criteria to Exempt Anonymous Secondary Use of Data

3. Conflict of Interest, REB Independence and Governance

4. Consent by Clients Whose First Language is not English

5. Contacting Family Members to Participate in Research

6. Ethical Issues in Community Based Research

7. Harmonization of Practices and Procedures Between Institutions

8. ICH GCP Force of Law

9. GCP Inspection Summary: Information from Health Canada

10. Internal Audit Programs

11. The Health Canada REB


13. Role of Lawyers on REBs

14. Sponsor IRB/REB relationships

15. Storage of SAEs

16. The Death of Ryan Lucio

17. The Rise of Litigation in Human Subjects Research

18. Time frame for ethics approval and reporting requirements

19. Urgent Request for a Speaker - Cdn Quality Assurance

20. New Interagency Panel on Research Ethics Members

Files to Download

Letter from Health Canada - Regs, Drugs, Clinical Trials

Education in Research Ethics - Journal of Law, Medicine and Ethics

Ethical Issues in Qualitative Research on Internet Communities

Health Canada - GCP Inspection

Litigation and IRBs - Journal of Law, Medicine and Ethics

Office of Information and Privacy Conference Brochure

Children's Hosptial of Eastern Ontario Recommendations (The Death of Ryan Lucio)

Genetic hypercoagulability: screening should be an informed choice

Genetic hypercoagulability :prevention suggests testing family members

Health Surveillance and Research - Health Canada Proposal

Expedited Review Research for th PRE


1. Consent for University Students Under the Age 18

Currently, our REB requires all participants under the age of 18 to obtain
parental consent in order to participate in research studies.

It is anticipated that a larger number of students who are under the age of
18 will be enrolling in Ontario's and other Canadian universities as a
result of the elimination of grade 13 from the Ontario's secondary school

Many of these students will have the opportunity to enroll/participate in
research studies -- e.g., course based studies such as first year
Psychology courses or other faculty or graduate student directed studies.

Will your REB treat these students are emancipated minors? or require that
they obtain parent consent for their participation as subjects in research
studies? Will your REB(s) treat social and behavioural science studies
differently than studies emerging from health-related fields?

Does your REB have published policies or guidelines on these matters?

Deborah Van Oosten
Research Ethics Officer
Brock University
St. Catharines, Ontario L2S 3A1
phone: (905)688-5550, ext. 3035 fax: (905)688-0748

We have taken the position that anyone in tertiary education can consent to research, below that it is partly a judgement call as to whether the individual is making independant decisions and signing other documents without parental consent, and usually not living at home.

Dr Michael D E Goodyear FRACP FRCPC FACP
Assistant Professor, Division of Medical Oncology, Department of Medicine, Dalhousie University
Executive Chair, Research Ethics Board, Capital District Health Authority

From: "Dr. Peter Loewen" <> The UBC Clinical Research Ethics Board recently created a comprehensive policy around consent for participation in research by incompetent subjects

Is this policy available for members other than UBC clinical REB members? If
yes, may I ask you how and if it would be possible to get hold of it ?
Thank you.Marie Buy

From: "J.S. Russell" <>
Marie, try this link for the UBC policy on incompetent subjects:

2. Criteria to Exempt Anonymous Secondary Use of Data

Do you require works that use anonymous secondary data to undergo
ethics review? If not, what is the criteria for considering a work
as exempt?

I have some problems with exempting work that uses anonymous data as
there is no guarantee the collection was done ethically and it may
provide a backdoor for people who engage someone to collect and
aggregate the data to meet a criteria. Particularly if the criteria
focuses around defining data as secondary as in my instance.

My particular instance is the outcomes of a performance review are
being aggregated by a third party and constitute the "data". The
program director wants to present this data at a conference. Our
policy requires works that are explictly quality assurance works to
undergo ethics review if the results of the evaluation are to be
presented in the public domain (the rationale is that they are now
used for generalizable knowledge and so are now research). These
works are usually handled under an application for secondary usage
and expedited review. The data was collected for another purpose (so
is secondary data) but is being presented (so its research), but was
aggregated by a third party and so is anonymous. This is a bit of a
first because in our previous experience, the secondary usage
application contained identifying data.



From: "Richard Neuman" <>
Cam, We require ethics review for the use of anonymous secondary data. We
also request the applicant provide written assurance from the data
guardian that access to the data is acceptable. This ensures that
access is via the "front door".

Hello, We require review of anonymous secondary data, in part to ensure that it was
collected in an ethical manner. We usually also require a letter from the
people holding/owning the data that they approve of its use. The review is

Catherine Paquet
Responsable de déontologie en recherche / Protocol Officer for Ethics in
Research Université d'Ottawa / University of Ottawa

We do not require REB review of research with anonymous data since it does
not fall into the TCPS definition of "human subject research".

To do otherwise could mean that researchers would have to obtain REB
approval to work with data obtained from StatCan and the like...sounds like
a recipe for a REB to loose some credibility...

We simply ask for a statement by the researcher that the data he will be
using are indeed anonymous.


Luc Simon

From: "Laurel Evans" <>
Hi. We have a situation where the data holder is requesting ethics approval
prior to the release of encrypted data. Which comes first -- the letter
approving the use, or the ethics approval? Laurel.

From: "Cam McDermaid" <>
Hi Laurel, what we use for facility/data access is a provisional approval from
the custodian with any accompanying conditions. The REB looks at
that, then the certificate is provided to the custodian who would
release the information. It provides the REB with the information
they need and satisfies the custodian, generally.



From: "Susan Hoddinott" <>
Like Laval, we also do not require REB approval of anonymous secondary data.


From: "Richard Neuman" <>
Laurel, we have the same situation. In that case we have agreed with the data
guardian that they will grant approval in principle for data access and
final approval after ethics approval.

From: "Diann Nicholson" <>
We also require it at the IWK Health Centre. Diann Nicholson
Director, Research and
Research Ethics Administration
IWK Health Centre
5850 University Avenue
Halifax, Nova Scotia

From: "Bill Marr" <>
Cam's e-mail raises two issues: (1) the ethics review of secondary data
under TCPS rules, and (2) quality assurance projects.

At Laurier, the REB does not review research using secondary data as
long as those data contain no identifying information with respect to
the participants. As the TCPS writes on page 3.4: "This issue [the use
of secondary data] becomes of concern only when data can be linked to
individuals, and becomes critical when the possibility exists that
individuals can be identified in the published reports." So, if the
secondary data contain no identifying information, we do not review the
research; it is not a concern. Using examples from my own discipline,
economics, we would not review research using the publicly available
micro files of the Labour Force Survey or the public use data from the
1996 Census because individuals can not be identified in the data. How
those data are collected is really not an issue; in both cases
participation is compulsory, not voluntary, but our REB would not
prevent researchers from using those data on that grounds.

For quality assurance projects, we sometimes do review those because
they are someone's research or are likely to be so: collect original
data, lead to publications and presentations, generate general
knowledge, etc. We have had a few situations where a faculty member
chaired a University committee, say the health and safety committee,
that committee administered a survey, and the faculty member used those
data in a research project. That project was reviewed by our REB.

3. Conflict of Interest, REB Independence and Governance

From: "Gabrielle Miller" <>
To: <>
Subject: Re: [Ethics] Conflict of Interest, REB Independance andGovernance
Date: Wednesday, July 30, 2003 11:51 AM

At the risk of putting my foot in it, I think I should reply to this, since I have been living the conflict of interest tightrope (as Research Office and Research Ethics Board Chair) for the last three or so years (and many more as ethics administrator/research officer). (I handle it by being more firmly committed to ethics than to research.)

When we developed the institutional policy, (yes, I had my foot in there also!) we tried to give the REB responsibility to the upper levels of the University as the TCP wanted, but it just bounced down again, since those levels of the University told us they don't know the first thing about research, have lots more important things to do (at least more important to them), and think ethics review should be handled at a level which understands what is going on.

There is some truth in this (at least the understanding part): although it would be nice to have the University President's clout and prestige, and her commitment to the reputation of the University when dealing with some of the more difficult cases. It really puts us in a quandary-- how do you get disinterest without uninterest?

Gaby Miller
Research Officer/Agente de recherche
Laurentian University/Université Laurentienne
(705) 675-1151, ext/poste 3213
Fax: (705) 671-3840
Web page:

>>> 07/30/03 08:49AM >>>
Earlier in the year, Deborah van Oosten at Brock University attempted to tabulate reporting lines and other administrative items dealing with the relationship between REBs and their institutions. I am not sure what lay behind that or what was was done with the information.

In the resulting table 11 responses are listed (including Brock, and us).

Since the position of REBs in relation to their institution can be extremely important in terms of perceived institutional conflict of interest, this requires more careful examination.

It would seem that the key issues are reporting lines, accountability, appointments and funding of REBs, as well as an analysis of the potential for undue influence on the the chairs or members of the REB, and means of recourse.

Aplicable Guides and Reports
GCP (1.31) defines an IRB (or IEC 1.27) as an independent body. TCPS (1.2) requires that institutions 'ensure that REBs have the appropriate financial and administrative independence to fulfill their primary duties'. OHRP (Chapter I, Institutional responsibilities) states that 'it is vital that IRB members, department heads, and other officials with responsibility for oversight of research have open and ready access to the highest levels of authority within the institution.'

Overall the issue seems to have created more interest south of the border than north (eg DHHS 2001, AAU 2001, NBAC 2001, NHRPAC 2001, AAMC 2002).

The DHHS considers that broad representation of members from outside the institution is the most effective solution but comments that the IRB must be positioned with respect to the administrative structure to allow it to function in an autonomous manner. NHRPAC appears to support this. AAU deals more with the institution's own financial investments. The AAMC report also addresses the administrative aspects of REB (IRB) governance. It refers to several proposals to create "firewalls" around Academic Affairs (eg GAO 2001). However the task force's mandate was specifically financial interest. The NBAC report covers a wide range of topics. In addressing Conflict of Interest, it acknowledges in addition 'subtle and pervasive' conflict as being more difficult to manage.

Clearly there are more pervasive forms of influence than the obvious financial ones.

The NBAC also carried out a number of specific studies (Volume II), two of which (Fletcher, McCarthy) dealt with the role of the OPRR in relation to its parent institution, the NIH. NBAC pointed to the GAO report of 1996 which indicated an inherent conflict in that the director of NIH was responsible for both the success of the intramural programme and for enforcement of HRS protection through OPRR. Tuskagee was the most flagrant example of NIH-PHS failing. NBAC referred to 'institutional blindness' and felt that the mission and interests of the Institute and the OPPR were in fundamental conflict. It recommended transfer of the office to DHHS, which was duly executed as the reincarnated OHRP. In interviews with the respective sides it was clear that the research administration depicted OPRR as an impediment to research. In justifying both the elevation and relocation of OPRR, NBAC pointed to many other institutional conflicts such as the Atomic Energy Commission that was bo!
th promoting and regulating nuclear power.

A third paper (Peckman) specifically looked at the role of local IRBs. In the section dealing with the IRB within the institution, the two were depicted as inherently in conflict. Bell et al surveyed reporting lines and found that only 7% of IRBs reported to a level higher than a Vice President or Provost. Yet many commentators had seriously questioned whether an individual such as a VP Research who is directly responsible for research funding can also oversee a body who independently reviews research. Ironically the OPRR itself recommended elevation of the IRB 'to a higher level within the institutional hierarchy'.

In Canada the seminal work is the Law Commission of Canada report entitled 'The Governance of Health Research Involving Human Subjects (McDonald 2000). In addressing independance, McDonald stresses the vested interests dominate governance of research and that the Canadian situation is even more vulnerable than its US counterpart. He lends weight to the OIG recommendation 'for insulating IRBs from conflicts that can compromise their mission in protecting human subjects' and recommends the need for insulation as being even greater in Canada. Specifically McDonald states that "it is crucial for substantive reasons and for the sake of of appearances that REBs not report to or be appointed by offices of research". (OIG
recommendations had included 'does not report directly to the part of the institution responsible for bringing in research funds...and has recourse should it be subject to any pressure'

Specifically the report stresses the situation in Quebec, where it is stated that REBs are 'independent from both hospitals' research centres and the scientific review boards...They are attached to the hospitals' Boards of Directors which also appoint their members'. It is worth noting that in Quebec many of the principles of REB conduct and governance are enshrined in the Ministère de la santé et des services sociaux du Quebec action plan (1998)

Amongst sources quoted by McDonald are Edgar and Rothman ' Does it make sense to give the leadership of an institution, which by its very nature cannot survive without funds and fame brought in by clinical research, the reponsibility of appointing the membership of a monitoring committee'.

It is within this framework that we need to consider the recent announcement that the current executive be replaced with a nominee of the heads of the clinical departments.




OIG: Office of the Inspector-General, Institutional Review Boards: A Time for Reform (Department of Health and
Human Services (U.S.), June 1998) at 17.

H. Edgar & D.J. Rothman, The Institutional Review Board and Beyond: Future Challenges to the Ethics of
Human Experimentation (1995) 73/4 The Milbank Quarterly 489 at 490.

Dr Michael D E Goodyear FRACP FRCPC FACP
Assistant Professor, Division of Medical Oncology, Department of Medicine, Dalhousie University
Executive Chair, Research Ethics Board, Capital District Health Authority

Chairman, Canadian Brain Tumour Consortium, Credentials Committee

Spokesperson on Tobacco or Health: Canadian Oncology Societies
Porte-parole pour tabac ou sante: Societes d'oncologie du Canada

Chair, RTOG Medical Oncology Quality Control

From: "Michael Goodyear" <>
Jack, well that's certainly an interesting perspective, which although I did go through Division 5 in my review of pertinent documentation, I did not consider. I was certainly aware of the regulation you refer to, but did not read that meaning into it.

Christine, Agnes? Anyone at Health Canada want to comment?

From: "Ted Palys" <> Thanks to Michael Goodyear for identifying this issue for discussion, as
well as for identifying key sources that have addressed the issue. The
seminal volume by Michael McDonald and colleagues regarding ethics
governance identified institutional conflict of interest of REBs as THE
next issue in Canada. Little has been done about it, however, since the
release of that volume in 2000.

Another article in relation to this issue was brought to our attention by
Charles Weijer in an email to this forum on 1 July under the subject
heading "The rise of litigation in human subjects research." The article
by Mello, Studdert & Brennan (2003) from the Annals of Internal Medicine
describes a growing legal niche in an area you might call "human subject
victimizations" (all in the biomedical area, of course), and is available
online at either of these links:

It's always difficult to know to what extent trends in the litigation-happy
United States can be extrapolated to Canada, but one legal principle the
authors highlight that is as relevant here as there is that REBs and
institutions who put themselves in the situation where a human subject
complainant can legitimately raise the specter of institutional conflict of
interest are legal toast.

The article raises the question of how REBs and institutional authorities
will respond to recognition of this problem. The worrisome one for the
authors is that "While this litigation may serve a valuable
compensation function for injured subjects, it will also have profound
effects on institutional review boards, leading to a more legalistic,
mechanistic approach to ethical review that does not further the interests
of human subjects or scientific progress." I wish they would have said
"may" instead of "will," because there ARE choices here. One alternative is
to take the necessary steps to ensure that REBs are truly at arms length
from institutions and institutional conflicts of interest, something that
would in the long run be to the benefit of both research subjects and the
research enterprise. But, as the van Oosten data Michael refers to show, we
still have a long way to go. Further discussion as to how that might be
achieved would be both useful and appreciated.

Ted Palys
Simon Fraser University

From: "Jack Corman" <>
To: "NCEHR" <>
Cc: "Michael McDonald" <>
Subject: Re: [Ethics] Conflict of Interest, REB Independence and Governance
Date: Wednesday, July 30, 2003 6:02 PM

Interesting, Michael, that the one document that has legal force in Canada,
the Canadian Food and Drug Regulations, has been omitted from the postings
so far. Division 5 of the Food and Drug Regulations stipulate that the REB
and the sponsor are not to be affiliated.

Through the publication of these regulations in September, 2001, in
practical terms, there is a document with the force of law that should have
had a significant impact on the governance of clinical research in Canada by
mandating that the REB be unaffiliated with the sponsor, and defining
sponsor as the organization, individual or corporation that conducts the

I believe the intent of this regulatory requirement was to minimize research
conflict of interest, thus upholding the essential governance principle of
separation between the audit function and operations function. This
principle is well known in manufacturing, i.e., the QA function must be
independent and therefore is not to report to Manufacturing/Production. So
it stands to reason that the REB should not report to the VP Research, but
rather to the highest levels at an institution, e.g., the CEO or Board of
Trustees. Quebec has simply put this long-standing principle into effect.

The same principle should have been maintained in the Arthur Andersen/Enron
case, but was not, i.e., the revenues generated from Enron by Arthur
Andersen¹s consulting arm were so important and disproportionate to the
revenues generated by the audit arm that senior management in effect gagged
the auditors when they started to point out serious problems in Enron¹s

Jack Corman
IRB Services
14845-6 Yonge St. #328
Aurora, ON L4G 6H8
Tel 905 727 7989

From: "Luc Simon" <>
On the topic of REB autonomy, one should also consider that although the REB
has a central role in the "system to safeguard the welfare and the interests
of research subjects", other instances also have important responsibilities.
For instance, the MOU that was signed between canadian Universities and the
federal granting councils states the responsibilities of "institutions" in
the prooer conduct of research, the establishment of REBs, etc...

At the risk of receiving lots of ripe some extent, members of
the REB could be considered "research administrators" (especially chairs and
coordinators), as they participate in an institutional function that is
integral to the conduct of human subject research. That's why they are
covered by the institution's liability insurance anyhow !

Many find the question of REB "institutional autonomy" a crucial one,
especially from the perspective of conflict of interests. Curiously, there
is much less concern about the inherent "individual conflict of interest"
buit-in the REB composition where researchers have to be themselves voting
members of the REBs. It is expected that they will not participate in the
examination of protocols of their own team, or close collaborators, or...
But is their inherent professional bias in favor of "research" any less
problematic than the perceived "institutional potential undue influence" of
having the REB report to the vice-president for research office ?

I completely agree with Gaby, some pragmatism is in order. The day-to-day
conduct of REB business need to be free from undue influence, but
institutional authorities who have responsabilities in the conduct of
research should be in a position to determine policies, including policies
regarding the implementation of TCPS (for example, should research using
anonymized data be subjected to REB review !).

Regards,Luc Simon

From: "Michael Goodyear" <>
There is an ethical paradox or dilemma here in that accountability is a core value, but to whom?

A number of issues here. The relationship between the TCPS and the granting councils is problematic and has been described as inappropriate. A new home is needed.

Yes REB members are part of the process of research, but they need to be very careful as to where they are sitting and when. While REBs must be autonomous, that is exercising independent review, they should also be considered integral to research which is why they are to some extent peer reviews. Where REBs have been misplaced in the past and depicted as adversarial is where the research community has failed to take responsibility for the overall oversight, leaving the REB unfairly burdened.

In terms of individual COI one can break this down (apart from the flagrant ones of financial interest or direct involvement) into identification with the research culture (not always a bad thing) and identification with the institution (loyalty). It is in finding balance that the REB truly operates as it should. Otherwise we could take away the entire concept of local review and of 'institutional' review, by sequestering the whole process off to an outside body. There are many who believe that this is a good thing anyway. The risk (althought not mutually exclusive) is that the review will fail to take into account local conditions.

Institutional policy setting is a very touchy subject (having just encountered an institutional administrator who beleived that the REB should not be involved in policy at all, but merely implement it). While insitutions may lay down that review shall bein compliance with TCPS/and or GCP/Helsinki, we are on very thin ice when it comes to any more detailed micromanagement. That would not be independent review. If there is an insitutional 'affiliation' may be it should be to the bioethical community.

Since you touch on the 'chose du jour' of secondary analysis, it might be worthwhile examining why different institutions have different answers to the problem. Are they following policies based on careful ethical analysis, or an institutional policy determined in the way you suggest. The two have very different implications. Ok that is one 'tomate mur'. I think that in difficult situations like this it might be helpful for the research community, outside experts, the REB and the research office to sit down and see if they can develop consensual guidelines (notice that I did not say policy) along the lines I indicated earlier. The failsafe being to obtain a ruling from the REB as to whether the project should be formally reviewed. Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Michael Goodyear" <>
As a follow up to the broader issues of the place of the REB in society raised in my earlier response to this I could suggest some articles in the "Currents in Contemporary Ethics" series in J Law, Medicine & Ethics.

1. Stone TH: Federal training requirements for responsible research. Not going far enough. JLME 29(1): 94-9 , 2001

2. Anderlik MR, Elster N: Lawsuits against IRBs. Accountability or incogruity? JLME 29(2): 220-8, 2001

I have attached copies (which curiously our US counterpart will not allow).

Dr Michael D E Goodyear FRACP FRCPC FACP
Assistant Professor, Division of Medical Oncology, Department of Medicine, Dalhousie University
Executive Chair, Research Ethics Board, Capital District Health Authority

Chairman, Canadian Brain Tumour Consortium, Credentials Committee

From: "H. Weinberg" <>
Luc, I usually don't jump into these discussion but I have to say I agree
with you.

Somehow this whole issue seems to have evolved into an assumption that
there are two opposing and forces that must necessarily be in conflict the
Universities and the REB. It is almost as if it is assumed that there are
two incompatible ethical and moral philosophies that must always be in
conflict, that of the university institution and that of the REB, and that
they have to prepare for battle. I think we sometimes forget that
universities are a collection of academics - the same academics that are
responsible for the research in which they are individually engaged, and
who happen, from time to time, to be in administrative positions within
that institution. Most of the policy of the university is usually
established through an elected university Senate, including policy for
implementation of the protection of subjects in human and animal
research. I agree that the REB has to be independent of everyone,
including the university administration, but it is also true that the
university administrations almost all agree with this prescription. From
time-to time conflicts do arise but I believe we have to be careful about
assuming that, in principal, they must always arise.

4. Consent by Clients Whose First Language is not English

From: "Masood Zangeneh" <>
Hi, I am curious if anyone has any ideas/advise on how to ensure informed
consent is thoroughly understood by clients whose first language is not
English when not using an interpreter.

Masood Zangeneh, B.Sc. (UofT), M.Ed. (MSVU), M.A. (Unisa- candidate)

From: "Adela Reid" <>
Hello, our board usually requests a copy of the information letter and
consent form in both English (or French as appropriate) and in the language
of the participant. We also request that the phrasing be to the literacy
level of the target group. For example, if interviewing underprivileged
individuals in a developing nation where the level of literacy was low, we
would want the letter and form written in simple language (we would suggest
an appropriate grade level). We would ask for these changes in the English
form and for them also to be made in the translated form.

Also, we have made stipulations in the past for participants who are or who
may be potentially illiterate. We request the researcher provide us with a
written statement in the language of the participant (similar to the
information letter) of what they will read to the potential participant. We
then require the researcher to keep a written record of the date and time
this information was orally presented to the participant, and the date and
time the participant provided oral consent.

Adela M. Reid
Research Ethics Compliance Officer
Agent d'Éthique en Recherche et de Conformité
Office of Research, Concordia University

From: "Michael Goodyear" <>
First rule is if in doubt don't. First language issues covers a wide range of competency though, therefore it is not easy to give a simple answer.

While wishing to avoid any exclusivity in subject recruitment, enrolling patients with a poor comprehension of English (or whatever language the research is being conducted in) is fraught with hazard. Simply translating the consent form is not the answer, since the subject needs to feel comfortable communicating throughout the trial.

Dr Michael D E Goodyear FRACP FRCPC FACP
Assistant Professor, Division of Medical Oncology, Depart

From: "Adela Reid" <>
Just to clarify, in the situations where we ask for a consent form to be provided in another language, the research (often interviews) is being done in that language, not in English. The English version of the form on record is only for the benefit of the reviewers, especially if the language of choice is one of which no one on the committee has any knowledge.

Certainly participants must have a working knowledge of the language the research is carried out in. Otherwise, the consent process (and likely the research itself) is worthless.

Adela M. Reid
Research Ethics Compliance Officer
Agent d'Éthique en Recherche et de Conformité

5. Contacting Family Members to Participate in Research

From: "Hebert, Dr. Philip" <>
And Dr MZ knows he received excellent training in ethics if he went to U of
T over the past decade (as I taught most of it....), although we have only
recently taught research ethics....
PS Our website which posts our undergrad ethics curriculum is at:

Philip C Hebert MD PhD FCFPC

During my undergrad, I worked as a research assistant with a very
questionnable psychiatrist who made all the unethical decisions when it came
to recruitment. It was a genetic study and we were told to pursue patient's
family members to particiapte (no money was available to compensate them).
We were indirectly told to pressure them to participate. We were even told
to use things like "it is for the good of humanity" and for the good of
those suffering from so and so disorder. It is understanding that it is a
daunting task to continuously monitor what a PI is doing in the privacy of
his/her own research setting, but I think it is important to have such a
mechanism in place. If ERBs have shortage of manpower, universities should
come up with a plan to recruit and attract students to such a specialized
trainings. my 1.5 cents.


-----Original Message-----
From: Michael Goodyear []
1. The Problem: The researcher wants to call family members (siblings) to
get them to come in for testing and information about the proband subject's
condition. We said no, provide the subject with a letter to give/mail to
their siblings, who can contact the researcher if interested.

It didn't work, they claim, very few family members called. Either they
were not interested or the subject never passed on the information. We are
being told we are out of step, other REBs allow the researchers to call
family members directly. We have asked for documentation. We are also told
that 'geneticists do this all the time' with the subject's permission.

2. The scenario: The researcher is studying thrombophilia by taking people
who have blood clots and testing them for a predisposing thrombophilia. In
some cases this may be genetic. They propose to test the siblings and if
positive, warn them about the increased risks, especially if they need
surgery. There is no intervention.

3. Position: This is an invasion of privacy. If siblings are not responding
it is probably for a good reason. They may not be in a good relationship
with the subject or they are scared. A direct contact by the researcher
might be interpreted as harassment.

This would need to be balanced against the 'need to know', and the
potential risks of not knowing and benefits of knowing, to the sibling.

4. Questions: Who has experience with this and how have they handled it?
Even if you have not, what do you think? Does anyone else recall this
protocol and what they did? Is there a 'workaround' solution. So far no one
has come up with passive consent.

Dr Michael D E Goodyear FRACP FRCPC FACP Assistant Professor, Division of Medical Oncology, Department of Medicine,


Secretary -6054, Direct Line/ Voice Mail: -6015, Fax -6186: Pageing:
-2222, Pager 2670

Thanks Michael,

Now we at least have two sides to the discussion and ethical analyses thrive in the presence of uncertainty. I am usually the first one to raise isues about paternalism (or if we are gender correct, parentalism), so I am interested to see your concerns about this.

I should state from the outset that this protocol, which is tricouncil funded, raised issues from the outset along these lines when it was first presented to the REB at the coordinating institution, and they rejected the proposal to 'cold call'. In truth although I have been provided with some of the correspondence between the PI and their REB, I do not know exactly what was finally approved at that institution.

When it was presented to us it had been changed to a passive process (see prior discussion today on the strengths and weakness' of that approach), whereby unless family members called to register objections they were contacted by the researcher from a list provided by the proband - essentially a genetic pedigree. We rejected that and the compromise was the current one of giving the proband a letter to give to relatives inviting them to call. This did not produce recruits so they know they wish to directly approach family members.

I was interested to see that your analysis appeared to be based on a model of a therapeutic relationship, which you appropriately pointed out could be considered not to apply. Indeed the PI in their letter of protest to the 'home' REB indicated that the aim was to prevent not treat disease. A number of people have also drawn analogies with other forms of genetic testing.

In fact the concerns we had were based on privacy and respect for the individual. In particular I asked people to consider their own possible reactions to receiving such a communication from the research centre, and especially if the siblings were not close. In fact I think that the issues are quite complex, but have similarities to other research involving family members and tracing contacts with infectious diseases, which apply as much to clinical care as to research.

The first issue is the probands concerns not only about who knows that they have a specific disease (blood clot), but also now the knowledge that it might be genetic and that other family members may be at risk, with all the resulting stress that can result. (For those of you who have raised the question, yes genetic and psychological counselling is on hand, as well as regular psychological testing of all concerned, which is actually an outcome).

The next issue revolves around the relationship between the proband and the sibling, and the possible effects of transmitting such information to the sibling.

The other issues involve the sibling being approached by a third party about their health, finding that the third party has knowledge of a family medical problem that they might not be aware of, and finally that may have serious consequences for them, and that they may be involved in not only testing but also possibly a randomised trial of intensive monitoring vs observation (yes, I omitted that detail not to confuse people).

The possibility of doing harm seems considerable.

A number of compromises have been suggested as this process has played out.

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Laurel Evans" <>
I could be wrong Michael (C), but I think that information pertaining to
relationship with the proband and the relative's respective contact
information comprises "personal information" (not personal health
information) under PIPEDA. And while that Act does not apply to
commercial organizations yet, it is due to do so on Jan 1, 2004
(notwithstanding Mr. Radwanski's situation). If I am correct, then
"consent" should be obtained before the collection, use or disclosure of
the information, unless it would be inappropriate. (This is in spite of
the exceptions for scholarly study or research). In my opinion, the
process whereby the proband provides a list of family members who have
indicated that they are willing or unwilling to be contacted,
constitutes adequate "consent" to allow the researcher to then proceed
to contact the appropriate family members. All this said with the
caveat that I am not an "expert" in privacy law.

Michael Coughlin wrote:

> In the discussion about a researcher contacting siblings of
> a proband with thrombophilia, what I have not seen is a
> cogent argument against it. This is a totally different
> situation from a physician giving names of patients to
> researchers to call. The latter case involves a therapeutic
> relationship in which confidentiality is promised and
> demanded, and passing on the name of a patient to a
> researcher outside the therapeutic relationship, without
> consent, is wrong. This is the reason for having the
> clinican make the original request of patients to consent to
> be contacted. But we are not talking about a therapeutic
> relationship between proband and siblings, so whatever the
> argument is, it has to have a rationale totally different
> from that arising from the physician/patient relationship.
> To require the same process for this latter case that we use
> for handling clinican-patient-researcher contact is, I
> think, unjustified.
> If the proband, with understanding of the implications for
> self of disclosing the disease propensity to siblings (i.e.
> informed consent), gives the names and phone numbers of
> siblings to the researchers, I cannot see, absent other
> factors, why it is wrong for the researchers to contact the
> siblings. It is not unlike a "snowball" technique of
> recruitment in qualitative research. It certainly could
> become unethical if the physician-researcher somehow
> pressures the patient into giving the names, but that
> possible risk is present in most research, and we put in
> place processes to try to minimize the risk (e.g. who
> actually gets the consent).
> But other than common courtesy and possibly knowledge of
> unique personal circumstances where contact by a researcher
> might cause harm, I see no obligation of secrecy on the part
> of the proband. It has nothing to do with confidentiality,
> and I do not even see how it would infringe on privacy
> rights unless we are talking about an unlisted phone number.
> But if I've missed something, I would appreciate seeing what
> the argument would be for such protectiveness. REBs have a
> significant role to play in protecting patient welfare,
> privacy and confidentiality, but we do have to be careful of
> redefining that mandate into a new kind of unjustified
> paternalism.
> Michael
> --

From: "Michael Goodyear" <>
Point taken, Michael

In George's absence I am waiting for a reply from our in house privacy law lawyer (we are appointing a privacy commissioner here too in view of the complexities of the issues).

In the meantime I consulted our genetics department on their standard of practice, and was told that they would not allow this, even in standard clinical care. They feel the potential for harm by being contacted directly by a health care institution about your genetic background is considerable. We will explore this further.

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Michael Goodyear" <>
Just to help this discussion along a little further, many of you may remember Melissa Austin's article (attached) that was published last year - in particular what happened to the unfortunate IRB in one case she cites

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Jack Corman" <>
I respectfully do not entirely agree with Michael Coughlan. A physician
giving out names to a researcher without permission is wrong because s/he
does not have the right to do so without agreement from the patient. What if
the physician provided the names/phone numbers, etc., not of his patients
but those of his/her patients¹ siblings? Still not right. Neither does a
patient have the right (at least moral if not legal) to give out contact
information about siblings or anyone else to an unrelated person without
checking with them first. (Notifiable disease/public health laws are an
obvious exception).

The sibling is NOT the treating physician¹s patient, the patient is not the
legal representative of the sibling, and thus has no right to give out the
sibling¹s contact information without contacting him/her first to see if
it¹s OK. The situation is made more egregious if the patient is asked by the
treating physician for information about siblings because of the unequal
power relationship ­ the patient may feel compelled to provide the
information against his/her will.

Also, there is potential risk to the sibling who carries the mutated gene,
even if heterozygous ­s/he is at greater risk of health problems, and
therefore is potentially more expensive to insure or more likely to miss
work because of medical conditions, and potentially vulnerable to insurance
companies/employer punitive action. Even though this is a theoretical risk,
it is one that is borne in mind whenever genetic/pharmacogenetic research
projects are reviewed, as you point out your genetics department¹s standard
of practice.

What¹s wrong with asking the sibling¹s permission, anyway? Shows respect
for the subject, isn¹t that what we are supposed to promote?

As to PIPEDA, ³personal information² is defined as ³information about an
identifiable individual, excluding the name, title or business address or
telephone number of an employee of an organization². PIPEDA¹s provisions do
not apply to an organization whose activities are not commercial in nature,
i.e., no commercial application to the thrombophilia genetic research
project at hand, e.g., Dalhousie is not trying to develop a commercial test
for the genetic mutatiion. Hence, technically, PIPEDA would not apply in any
case. However, why not respect its privacy provisions sooner than later?
It¹s a moot point in provinces that have their own privacy laws, e.g.,
Alberta, Saskatchewan, which take precedence over PIPEDA and are already in

Jack Corman

From: "Michael Goodyear" <>
Thanks Jack:

As I delve further into this a number of interesting questions come up. Melissa Austin states that in her project FDRs (First Degree Relatives) are contacted directly "after permissin has been obtained by the proband" - I am trying to reach her (and should I also talk to her IRB?).

One issue that has come up is whether this is actually a research question at all. If the standard of practice in clinical care of thrombophilia is to contact FDRs, then technically this falls outside of the REB's purvue (but doesn't affect any ethical or legal concerns one might have). (i.e. it is not the research question, which starts after FDRs are made aware of the study, although REBs must also ask how patients were identified and recruited). The researcher could legitimately argue that patients were identified during routine screening of FDRs.

An interesting question that often comes up with reference to standard of care (and it is also a point of contention in the social justice sphere) is 'standard of care - where?'. Should the referential point be the standard in the investigator's institution, the jurisdiction, or an average across the country/hemisphere/world. Hmm.

I have unearthed a pattern of care survey (Canada), which shows that 18 of 24 centres responded. Of the 18 28% do not screen FDRs, 72% ask probands to contact FDRs, and 17% contact FDRs directly. I have become aware of two editorials arguing for and against this but have not read them yet, but I guess that creates equipoise.

As you debate this keep in mind tha a number of your institutions have already approved this protocol. The question you need to ask is what exactly did you approve and what are you going to do when your local PI comes knocking on the door tomorrow and wants to change the recruitment due to poor accrual.

The fact that an IRB was suspended over this issue helps to focus the mind a little.
Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Lori d'Agincourt-Canning" <>
I thought I would just add to this discussion by describing the strategy I
used in a qualitative study of moral/social issues arising from genetic
testing for hereditary breast/ovarian cancer. Throughout the study, I
received considerable assistance from two genetic counsellors involved in
our hereditary cancer program. They contacted individuals who had undergone
genetic counselling/testing for hereditary breast cancer, told them about my
research and asked their permission to give me their names and phone
numbers. If given, I then followed up this initial contact with a telephone
call. I described the goals and objectives of the study, what would be
involved (a one-on-one interview) and invited them to participate. This was
followed by an information letter and informed consent form, which potential
participants were asked to return to me. Patient response to this was
excellent. Recruitment of family members occurred at the same time. By this
I mean, if the participants I contacted expressed willingness to
participate, I requested their support in asking other family members
(siblings, parents, adult children, etc) whether they might be interested in
participating in the research. (I kept in mind that they mind feel pressured
to assist me and emphasized they should feel under no obligation to do so).
As with the genetic counsellors, they made initial contact with family
members and asked their permission to give me their phone numbers. If
permission was obtained, I followed up by phone in the same manner as
previously. If family members expressed interest in participating in the
study on the phone, I sent out an information letter and informed consent
form. Again, response rate was excellent (over 95% of those I contacted
agreed to participate in the research). Of course, this study was conducted
with REB approval.

Beyond the legal/ethical rights to privacy, I would also like to make one
other point with respect to disclosure of genetic information (and
researchers going outside established relationships to contact additional
family members). Clearly, genetic information differs from other types of
medical information in that it has implications not only for the individual
patient, but for family members as well. Several recent critiques suggest
that a person with a genetic disorder has a moral duty to disclose that
information to other family members. Ethical arguments favouring a duty to
disclose are based on the assumption that knowledge about genetic risk is
beneficial; that indeed, it is better to know than not know. A problem with
this approach is that it does not take into account the life circumstances
of various individuals and families. It fails to ask whether it serves the
best interests of everyone to be informed about their genetic risk status
especially when there is no effective intervention (as appears to be the
case with thrombophilia). A person who draws on certain experiences and acts
from a sense of relationship or responsibility to others, for example, might
ascertain that it is better for a particular family member NOT to know this
information; that it could, in fact, impart harm to her/him. Thus, unless
there is clear evidence that the disclosure of a person's genetic results to
others can prevent harm (e.g. physical harm or would be used to make
important life decisions), I maintain it would be ethically unjustified to
do so. This applies to both the research and clinical setting . I agree with
Michael who stated, if siblings are not responding to the research
invitation, it is probably for a good reason .

Lori d'Agincourt-Canning, Ph.D. Post-doctoral Fellow, Department of Medical Genetics, UBC Ethics Consultant, BC Cancer Agency, Vancouver

From: "Michael Goodyear" <>
Lori's thoughtful comments and experience are very much appreciated. There is clearly considerable opportunity for useful research here.

The other side of the disclosure/non-disclosure argument is what happens in the event of eventual dislosure in which it becomes evident that information was witheld. In any event there is clearly a need for appropriate counselling of all involved.

One of the nurses involved has suggested to me doing a survey based on a hypothetical construct in which the subject is asked to consider themselves a relative, and how they would feel about the various options from non-disclosure to direct contact by the physician.

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Laurel Evans" <>
I basically agree with your conclusions Jack. You may be right about
the interpretation of "commercial" activity, in PIPEDA although you
probably would need to know a bit more about the
purpose/rationale/funding for the study before you could definitively
says that the research was not for commercial purposes.

Jack Corman wrote:

6. Ethical Issues in Community Based Research

From: "james frankish" <>
Subject: [Ethics] Ethical Issues in Community-based Research Course
Hello, as part of our CIHR/MSFHR-funded, Research Training Program (Community
Partnership Research), we are teaching a new graduate course on ethical
issues in community-based research. The topics are listed below.

We would greatly appreciate any suggestions for reading lists,
bibliographies, favorite readings, articles etc. on the topics identified
below. We will gladly compile and share any identified resources.

Thanks in advance for your help. Please feel free to forward this message
to others.

Course Topics
Ethical Concerns about Research with Humans: History and Current Context

The Nature of Evidence and Its Relations to the Conduct of Community-Based

Perceptions of Risk & Benefit in Community-Based Research

Conceptions of Self-Responsibility & Implications for Community-Based Research

Defining 'Community' and Academic-Community Relations

Meaningful Participation and Community Partners in Community-Based Research

Vulnerable Populations and Cross-Cultural Issues in Community-Based Research

Participatory Research and Community-Based Research

Effective Protection for Communities: Governance and Policy Issues

Action Research, Reflective Research and Community-Based Research

Building Community Capacity-Building as an Ethical Issue in Community-Based

Ownership and Ethical Dissemination of Findings & Products from
Community-Based Research

From: "Joe Kaufert" <>
WE will be developing a module on examples of community-based research
and problems of ethics review for Aboriginal communities for the
Manitoba/ UBC ACADRE students this February. It looks like a
comprehensive outline.
Joe Kaufert

7. Harmonization of Practices and Procedures Between Institutions

From: "Francis Rolleston" <>
To: <>
Subject: [Ethics] Forgive my frustration.
Date: Thursday, July 24, 2003 8:31 PM

This listserv seems to be very good at identifying problems. The proposed
solutions then seem to be to mandate someone else to do something. That is
understandable, but is it excusable?

The people around this listserv are the most experienced and brightest
people in Canada in this general area. Perhaps we should seek to start to
address some of these problems ourselves. We really can do so, together.
Without much effort, without collecting air-miles, without spending
kilo-bucks which no-one has, not even, or perhaps especially, not Health
Canada. Just a tiny bit of mutual organization.

Let us identify a problem. Let us state the problem, and its parameters,
which with this group should be doable in 2-3 days on the listserv. Then
let's have a volunteer, perhaps the most vocal person who raises the issue,
who would propose a solution. The let's have that solution constructively
criticized on the listserv, and use that mechanism to build to a consensus
if possible. Then communicate that to the responsible authority. Then move
to the next problem.

As I have said before, I am convinced that if we work together as a country,
we can resolve problems that bug us all, but that are intractable if we
approach them individually. This would require harmonization of practices
and procedures between institutions, not dependence on someone else to
harmonize policies etc between regulatory authorities. Canada is a
desirable place to do clinical research. Perhaps decreasingly so, but still
desirable. The same issues that make our lives difficult seem also to be
those that make us less desirable. It is up to us to address them, and to
say how research will be done in our country. This may require some of us
to subordinate our cherished individual policies to a common standard. But
all policies are compromises.

I know that this sounds all very simplistic. But we all know the problems.
I see CAREB as the focus for this effort (there I go again identifying
someone else to do the work). But CAREB is all of us, and we are CAREB.

Forgive my ranting and raving, but I spent many years as the target or "why
do you not do something about my problem". Now I am on the other side, but
have not (yet) lost that part of my memory.

Michael, Elizabeth, Jack, Cam, many others, what should we try to address
together. What are the first problems that we all face? Annoying problems
that make our days much longer without adding value, yet are obviously
solvable if we work together? Otherwise you will have to rely on people
like me, consultants, who seek contracts to address issues that are really
much better addressed through joint action for free. In the end the work of
consultants needs to be taken to consensus through joint action. But most
35 page consultant reports contain 3 pages of meat, if you are lucky. (Ray's
and my report on adverse events is, of course a notable exception to this
low ratio).

Lets take the next step.

Again, apologies. But I never was a diplomat.

Francis Rolleston

From: "Francis Rolleston" <>
To: <>
Subject: RE: [Ethics] Forgive my frustration.
Date: Friday, July 25, 2003 1:56 PM

I agree in principle with big issues, but have practical reservations.
Perhaps lets start by identifying a doable issue to set out the methodology,
and get to the big leagues in due course. Accreditation is huge, and a
section of Health Canada is working on it. I am keeping in touch with them
through my work with Senator Morin and because I know a lot of the people

I would like to follow up on your re-raising of the compensation issue in an
earlier email. What about my re-opening that one and trying to push for a
consensus position? Start by asking if anyone has modified their stance,
and if people think that a consensus approach for Canada makes sense? If
there is a positive answer, then go for it? The trouble is, what is a
positive answer since so many of the people on the listserv are silent, and
summer is not a good time for such things.

Incidentally, our paths crossed in the Ocean Nutrition ragweed protocol,
which also came to us after you had finished with it since they are
receiving IRAP funds. We made some further changes, which I understand have
been passed on to you. However, I was able to assure my REB that IRB
Services was a highly reputable organization, which facilitated our review,
as did your surgery on the consent form.

Are you in Ottawa sometime? Can I take you out to lunch/coffee/whatever?

Best regards


Francis Rolleston
500 Denbury Avenue
Ottawa, ON
K2A 2N7
613 728-7163

On Behalf Of Jack Corman (IRB

Let's focus on big issues, Frances, that concern all those involved in human
subject research. Maybe that's reaching too far, given that we collectively
have not even been able to agree on detail stuff like compensation clause
wording in consent forms.

The single biggest issue in my opinion is accreditation. And not just REB
accreditation. Ryan did not die because the CHEO REB failed to conduct a
good ethics review of the study. The clinical trial in which he was
involved was knowingly conducted in contravention to Canadian law by a
prominent investigator at a prestigious institution. How did this happen?
How was it allowed to continue? We are fortunate to live in a country where,
at least historically, patients do not phone their lawyers at the drop of a

The is the listserve of the National Council on Ethics in Human Research,
not just the Research Ethics Board listserve, although most of us are
involved with or sit on REBs. We owe it to ourselves to devise a means to
assist all institutions conducting human subject research to ensure that the
research is conducted in compliance with the law, and that institutional
policies and procedures, of which some will necessarily apply to REBs, are
sufficient to provide human subject protection at all levels.

Poisson, Olivieri, NCIC (Oscar Mulder), St-Justine/CHEO (two Ryans), etc.,
are not all the fault of the REBs – there is a pattern of systemic
institutional policy and process breakdown that we should not ignore.

I for one would opt for a solution we work on collectively, as opposed to
one imposed on us from the top. Jack Corman
President/Secretary IRB Services

From: "Michael Goodyear" <>
Francis' role seems to be to keep us on our toes. You could say that the gauntlet has been thrown. I am sure whether I should be flattered at being named amongst the 4 most vocal (can one say that in e-mail?) participants.

Everything here makes sense, it is the practical implementation that requires more thought. There has been considerable discussion over listserves in the last couple of years. How many do we need? Should they be moderated or unmoderated?

What Francis is proposing would in some ways require a unique structure, and that is structure with a capital S. While the 'Gang of Four' (5 if we count Francis) may be vocal the practical question is - are they representative? If Francis wants a made-in-Canada solution, and for that to work, there has to be buy-in from all stakeholders. CAREB - how many REBs do we have in this country (does anyone know? - the last mailout from Health Canada shows that their list is not complete either - we are still waiting for ours - sorry Christine and Agnes).

Even if all REB chairs or equivalents accept a proposal from a core group, will their institutions adopt it, or are they even able to, depending on the legislation they work under. Will solutions we put forward be enshrined in national guidelines (not that we need any more), or become part of an expanding TCPS?

Francis' frustration reminds me of the fable "Who will bell the cat?". Well the only candidate put forward, and I must say, with passion (and pride?) was CAREB, and believe listserves were going to be on the agenda of the last executive meeting.

The next problem is whether in fact listserves are appropriate venues for developing policy. Let's face it, most responses to the list are knee jerk or gut reactions. National policies need careful research, and concensus building. Which of course bring us back to contracts. Not in way to be seen to be impinging on Francis' livelihood, contracts and consultants need not necessarily be synonymous. For instance for an academic base (how many non-university but academic health care REB's are run by someone whose appointment is university based as well as health sciences centre based - any?) I rely on the University departments of Bioethics and Health Law, who in turn derive their funding from contracts for people like CIHR and Health Canada.

Some sort of infrastructure is going to be required, whether it be CAREB or not. There has to be a forum that people can bring substantial problems to. The core group has to develop a list (will PRE make their shopping list public - will those who have already made submissions to PRE share them?) of priority areas and to prioritise submissions. We have what is almost an embarrassment of bodies (organisations I mean) working on research ethics questions, but how do we coordinate them all? So yes, of course consultants should be part of the overall problem solving machinery.

So who wants to take up the challenge?

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Laurel Evans" <>
I couldn't agree more Michael. It seems to me, a relative neophyte in this area, that there are almost too many players and organisations which need or want a say in research ethics, and that is why there is sometimes a difficulty in getting anything concrete accomplished. That said, I fully believe that the Canadian response of guidelines as opposed to regulations allows for a more effective response to the various issues raised. Given PRE's mandate of stewardship of the TCPS and priorities of examining policy issues and implementation concerns, I would think that that group is the most logical candidate for providing policy guidance, in consultation with the other major players such as Health Canada, NCEHR, etc. On the other hand,
CAREB has, I think, a very useful role to play in assisting with issues related to best practices in administration of REBs etc. Any concensus reached by this listserve, and indeed the dialogue on various issues by this listserve should be of benefit to both organisations as well as to the individuals on the list. When it comes to speaking as a national voice for research ethics, I suspect that that is not a feasible role for this listserve, particularly given the sometimes huge disparity in views which the membership expresses -- generally with justification/legitimacy to all points-of-view.

Michael Goodyear wrote:

From: "Michael Goodyear" <>
Which is why we need an inquiry into the whole scenario.

We have an internal review of the Lucio tragedy, or at least the recommendations, but is there an external one - there has to be. There are so many steps in this. It has to involve COG, Health Canada, the trial chair and committee.

Unfortunately change comes often from tragedy, and we must leave no stone unturned. Like a number of contributors to this list I have been keenly interested in the evolving philosophy of "error" - sorry can't think of a better word just now, and support a 'confidential' no-fault inquiry into every aspect of the tragedy. Only good can come from that.

Since this tragedy touches on the whole adverse event mess, I have been convinced from the outset that concentrating on SAEs is counterproductive, as opposed to to building toxicity handling into trial design, which means a fairly fundamental overhaul of clinical trial design. Which does not mean that there is not a place for the true SUAE whistle blow.

Michael Goodyear" <>
I think the methodology is a high priority. Compensation is something that we need a national stand on to withstand the sponsor pressures.

Summer silence - sounds like passive consent.

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Michael Goodyear" <>
Perhaps what is needed in carifying infrastructure are clear lines of communication between the respective entities. I do not think we can just assume that NCEHR, PRE, CAREB and Health Canada read everything posted on the list and convert it into internal memos for consideration in formulating national policy.

The idea of formally summarising even the diversity of opinion is not a bad one, but as I noted before, has a problem with representativeness.

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Cam McDermaid" <>
Hello Francis, I've been giving your comments some thought as well as those that
followed. I understand your frustration with the "someone should"
language that pops up from time to time.

I agree that CAREB is the best group under which any work should be
done. It, ostensibly, is an agency that represents Canadian REB's,
one of the stakeholders. That being said, I should probably join :-)

I agree wholeheartedly with Michael's comments on infrastructure and
methodology as well as buy-in from stakeholders. The development of
a best practice guideline or a position statement needs to use a
sound methodology.

I can probably finagle some resources to actively participate,
depending on where this ends up going.




From: "Susan Hoddinott" <>
Gosh - I go off-line for a few days and everyone gets these great ideas!
This listserv is getting as busy as the IRBForum.

CAREB is very open to trying to facilitate the kinds of dialogue and
consensus building that is described here.
(Cam - take the plunge and come and join us - the water is great!)

Here come the BUTS -- we are still a relatively small organization with
very limited funds and no paid staff - even the costs of teleconferences
can really add up. While we are investigating other funding sources we
currently rely on our memberships and the generosity of members'
institutions. All the Board members have 'day jobs' and their
institututions pay for their travel and local resources. We try to
maximize our resources by piggy backing on existing meetings and resources
(e.g. NCEHR listserv).

And now the CAN DO's - We can include 'hot topics' at our AGM and help
facilitate sessions at regional or pre-existing meetings. We can use our
email list to solicit comments etc from those directly involved with REB
(who may not be linked to the NCEHR listserv). We can post materials on
our website (this would be for CAREB members only) . We can use the
auspices of CAREB to push for CAREB reps to be in place on various
provincial and national committees e.g. PRE, Health Canada etc.

In order for CAREB to work and be a force to be reckoned with we need to be
truly representative of the REBs in Canada. Like Cam - take the plunge and
join us.

The Executive of CAREB meets monthly by teleconference and I will undertake
to take to those meetings any suggestions CAREB members may have for
special working groups, sessions etc. Please contact me off line at (Keep in mind s/he who has a good idea will likely be
invited to work on it or chair it ;-).



8. ICH GCP Force of Law

From: "Clark, Elisabeth" <>
At 17:29 7/23/2003 -0400, Jack Corman wrote:
"Neither country officially has adopted ICH GCP in its regulations, and,
hence, ICH GCP still officially has only guideline status on either side of
the border."

Jack, i changed the thread ...

Now i used to agree with you about the ICH GCP and its force of law in
Canada, and tpursued the question, here online and with HC staff. I don't
feel i received a clear answer.

It did always strike me as curious that Canada, as an observer to the ICH
process had adopted the guideline, before the parties to the agreement, US,
Japan, EU and the Pharma Manufacturing Ass. in their domains adopted it as

One HC staff informed that in our "Regulations" at C.05.010 "good clinical
practices" appears in lower case and does not indicate the title of the ICH
GCP document. I was assured that this was a "detail" would be corrected in
the future (whatever that means) and that "GCP is the law".

In the forward of the ICH CGP document we read "The Good Clinical
Practices: Consolidated Guideline" supersedes the Drugs Directorate's 1989
guideline ... so guidelines again ... is the problem a lack of a framework
to enforce international standards as law?

Since the ICH primarily sets the rules for the manufacturing and conduct of
clinical research leading to new drug registration, and does not exist to
call the shots for REBs, are the rules being applied selectively?

Does ICH GCP carry the force of law in Canada? Will this question fade
with summer vacation as it seems did discussion of circumstances
surrounding the on-study death of Ryan at CHEO? There are lessons to be
learned. We deal in serious matters

Elisabeth Clark
Research Ethics Officer/Human Protections Administrator
McGill University Health Center

From: "Jack Corman (IRB Services)" <>
The US also adopted ICH GCP when they were published in the Federal Register
in 1997. The HC official Elisabeth contacted may/may not have been fully
aware that Justice refused to sign off on the ICH GCP E6 because there were
certain elements in conflict with the Food & Drug Act. That¹s why ICH GCP
remains a guideline.

As the government works out a new Food & Drug Act, there will undoubtedly be
changes that affect GCP. It may be at that time that ICH GCP will in fact
become law of the land; perhaps that is what the official meant. Until then,
it¹s not.

However, not withstanding their status as guidelines, it seems more than
sensible that we adhere to them. The regulations require that clinical
trials be conducted according to GCP. If you don¹t follow ICH GCP, what
will you follow? If the Inspectorate pays you a visit, to what GCP will you
be able to show adherence if not ICH?

As to silence on Ryan, interesting contrast vs. Olivieri. There is no Apotex
to finger in this one.

Jack Corman

From: "Michael Goodyear" <>
A suitable task for PRE might include examining all the inconsistencies betwee F and D Act, Helsinki, TCPS and GCP.

Dr Michael D E Goodyear FRACP FRCPC FACP
Assistant Professor, Division of Medical Oncology, Department of Medicine, Dalhousie University
Executive Chair, Research Ethics Board, Capital District Health Authority

From: "Jack Corman" <>
Good idea, Michael. Especially the regulations and the TCPS, since they need
to be compatible. Otherwise, there may be times when researchers face
Hobson¹s choice, i.e. either break the law or violate the TCPS. Not a
tenable situation.

Alternatively, a comparison between the TCPS, Clinical Trial Regulations,
Declaration of Helsinki and Human Subject Research Codes of Conduct in
various regions might be a project for NCEHR to undertake. Maybe Health
Canada¹s Ethics Division would see merit in the idea and fund NCEHR to
conduct the review and issue a report.

Jack Corman

From: "Clark, Elisabeth" <>
Comparison between the TCPS and the other international codes seems to be
an *essential* determination for Health Canada drafters of "Canada Health
Protection Act" replacing "Food and Drugs Act" to avoid the Hobson's Choice.


little about research (pointed out by another on the List). While research
is defined in the section at F2.2 by the Budget Implementation Act, 1997 a
glaring ommission given the *protection context* is any definition for
"human subject research"

Another option for *who* would look into "a comparison" would be the PRO
Group formed by the PRE as a sub-group on procedural issues for the TCPS.
... elisabeth

From: "Francis Rolleston" <>
Preparing a report of the differences would be a useful step toward
harmonized policies, but not an end in itself. Perhaps the goal should be
revised Health Canada policies that state what will be required in Canada,
but prepared with sensitivity to the various statements that influence us.

Perhaps also listserv participants (not subjects in this case!) might
identify areas of significant disagreement on this listserv, so that people
can propose options or consensus as to what we in Canada think is the best

In 1999-2000, we tried at MRC/CIHR to identify the procedural differences
between TCPS and ICH GCP. Marianne Vanderwel’s analysis was by far the best
contribution to this.

Francis Rolleston
500 Denbury Avenue
Ottawa, ON
K2A 2N7

From: "Michael Goodyear" <>
I am afraid Elizabeth's URL got cyberassasinated - try

choose your favourite language, click on proposal then go section F!!!! Dr Michael D E Goodyear FRACP FRCPC FACP

9. GCP Inspection Summary: Information from Health Canada

From: "Laviolette, Mary-Ann" <>
To: <>
Subject: [Ethics] Information from Health Canada
Date: Wednesday, July 23, 2003 2:30 PM

Good afternoon everyone:

Dr. Raphael Saginur asked that I share the enclosed letter with you. The
letter is from Diane C. Gorman, Assistant Deputy Minister, HPFB, Health

<<03-104584-451 signed english.pdf>> <<03-104584-451 signed french.pdf>>
When I contacted Health Canada to obtain an electronic version of the above
letter, I was also provided with an electronic version of the Report on
inspections of clinical trials which were conducted last year. Once again
they are enclosed.

<<gcp_inspection_sum_rep_e.pdf>> <<gcp_inspection_sum_rep_f.pdf>>
Mary Ann Laviolette
Ethics Co-ordinator
Ottawa Hospital Research Ethics Board

From: "Michael Goodyear" <>
since the letter is addressed, inter alia, to REBs, I am curious as to who actually received a copy, or how good is Health Canada's mailing list of REBs.

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Jack Corman" <>
All REBs that review clinical research governed by the Clinical Trial
Regulations are, or ought to be, known to Health Canada because of the
required clinical trial documentation demanded by the regulations. Health
Canada should therefore have a pretty good list, and should have sent the
fax out to all REBs that review Clinical Trials conducted under a CTA.

Those REBs that do not review biomedical research, or review biomedical
research that does not involve regulated products, would presumably not have
received the fax.

Jack Corman
IRB Services

From: "Jack Corman (IRB Services)" <>
Judith, the attachments sent by Mary-Ann Laviolette are scans of the Health Canada
fax originating from the HPFB Inspectorate. The addressees are exactly as
reproduced in the first attachment.

It might be an idea for CAREB and/or CAURA to write to the Assistant Deputy
Minister to see if Health Canada can send these sorts of things to the REB
address and contact person (e.g., either the REB Chair, the Research Ethics
Board Coordinator or Research Office Administrator/Director..

Jack Corman

From: "Michael Goodyear" <>
aha! Thank you Judith. I am still waiting for my copy!

Actually looking at the alleged circulation list I should have been peppered with copies. It sounds as if Judith's Dean's office is very efficient.

Dr Michael D E Goodyear FRACP FRCPC FACP

From: <>
Hi Michael I have checked with our Assistant Dean of Research and nothing has come in
to her office or to our REB office from Health Canada. I picked the report
up yesterday from our listserv.

Sharon Buehler
Memorial University

From: "Susan Hoddinott" <>
Hello All, I just wanted to inform this group that I have written to Ms. Gorman at Health Canada
as President of CAREB to inform her that the current 'hit or miss' method of
communication with REBs just wasn't working. Hopefully this will encourage them to at
least post directly on the NCEHR website and formally contact CAREB re distribution to
its members.

We'll see what happens next time!


10. Internal Audit Programs

From: "Mary Kate Needler" <>
Hello everybody, I was hired in June to develop a comprehensive internal audit program for the clinical research undertaken at Capital Health in Nova Scotia. I know that we are not alone in this - institutions across the country are developing audit programs or expanding their existing programs.

I have been in touch with Diann Nicholson at the IWK Health Centre in Halifax and Marleen Van Laethem at St. Michael's Hospital in Toronto, who have been very helpful. I would very much like to liaise with other Canadian clinical research auditors and, if there is sufficient interest, develop a network to facilitate interaction and collaboration.

I would be grateful for your help. Does your institution have an internal audit program? Who are the people I should talk to and how can I contact them?

Many thanks!

Mary Kate

Mary Kate Needler, MSc
Research Auditor, Capital Health
Room B23A, Centre for Clinical Research
5790 University Avenue, Halifax, NS B3H 1V7
Tel (902) 473-8549 Fax (902) 473-4497

From: "Clark, Elisabeth" <>
Mary Kate ... congratulations ... your work will enable interaction with
the dynamic collection of research ethics folk in your part of Canada.

McGill University Health Centre is currently seeking a research ethics
monitor, a different, but related focus from how you describe your position.

Once in place i will encourage our new employee to contact you.

Elisabeth Clark
Research Ethics Officer/Human Protections Administrator
McGill University Health Center

From: "April Hughes" <>
Hi MaryKate.... we have an auditing program here at St. Boniface General Hospital and have been collecting stats that we can share ... we implemented GCP based SOPs about 3 years ago and then followed with an auditing program.... all Investigators and their staff MUST sign off on the SOPs to obtain approval from the hospital for their research projects (medical, allied health, nursing, pharmacy, etc.) Terry does 2-3 audits per month involving both drug and device companies as well as academic studies ... we seem to have the biggest issues with compliance with the academic projects and have implemented extensive education programs to try to keep everyone on track (consent process and document filing are huge issues) .... please feel free to contact our auditor Terry Sawicz-Hanesiak at 204-237-2226 or at her email above......
April Hughes
Office of Clinical Research
St. Boniface General Hospital

From: "Mary Kate Needler" <>
Hello April, thank you very much for your email! I have compiled a list of 12 internal audit programs across the country, but you are the only one I know of west of Ontario. I'm sure there must be others.

I will telephone Terry to touch base.

All the best!

Mary Kate

11. The Health Canada REB

From: "Short, Donald" <>
To: <>
Subject: [Ethics] new Federal Proposal
Date: Friday, July 04, 2003 12:45 PM

I note Health Canada has added the outline of its proposed new legislation
to its web site
Not much mention of REB's that I can find....
> <<Proposal.htm>>

From: "Michael Goodyear" <>
Congratulations on joining the list Don, and thankyou for your first contribution.

This is a discussion document so feel free to comment. I would point out though that Health Canada has its own REB.


From: "Clark, Elisabeth" <>
To: <>
Subject: [Ethics] ouch ... summer hipaa
Date: Wednesday, July 23, 2003 2:45 PM

Apologies for reviving this discussion, as it may appear tedious and
irrelevant to some. But developments are worth following ...

Posted today to IRB Forum was the message below, and pdf correspondence.
No light is shed on international application of the US law, BUT i found
the language on US *guideline status* of the ICH intriguing ...

Nothing new here except if you need a reference to the fact FDA doesn't
enforce ICH domestically. One could question the relevance of binding
international guidance made uninforceable within the largest market for CT
research globally. US response is 21 CFR is *almost the same* as ICH E6,
well to negotiate CT (harmonius) rules for the rest of the world and then
say Oooops we'd rather not, seems a tad disingenuous.

begin forward --

On April 15, 2003, the director of the US Office for Civil Rights issued a
letter stating IRBs do not have to review stand-alone authorization

The letter is posted at:

FDA does not enforce the HIPAA Privacy Rule, so FDA will not be looking
separately at HIPAA documents.

From: "Michael Goodyear" <>
Dear Elizabeth (and colleagues),

Now that you have gone and dumped me into the US list (IRB Forum) and see how HIPPAA'd our US colleagues are I am glad we are all clear of this monstrosity - which does not say that I do not have to regularly take the pruning shears to pages of confidentiality clauses. Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Jack Corman" <>
I empathize - gave up on IRB Forum a while ago. Enough is enough.

Jack Corman

From: "Jack Corman (IRB Services)" <>
Thanks for your posting ­ the letter from the US Office for Civil Rights
made for interesting albeit it dense reading. One point on ICH GCP ­ its
status in the US is no different than its status in Canada. They have
regulations (e.g, 21CFR312, 21CFR50 and 56, etc. for FDA regulated studies
and 45CFR46 for US federally funded research) and we have regulations
(Division 5 of the Canadian Food and Drug Regulations). Neither country
officially has adopted ICH GCP in its regulations, and, hence, ICH GCP still
officially has only guideline status on either side of the border.

Jack Corman

13. Role of Lawyers on REBs

From: "Charles Weijer" <>
To: <>
Cc: <>
Subject: [Ethics] REB-LS
Date: Wednesday, July 02, 2003 10:56 AM

Don Short asked me to post the following:

REB-LS Rousing.


I am a lawyer, volunteer, lay member on a Canadian Research Ethics Board
(REB) in Toronto.

I believe was asked to join my board in part because the Tri-Council Policy
suggests that one of the Board members should have legal training or

I have spoken with other lawyers holding similar positions on other REB’s
and we have a sense to a degree that we are “making up” our roles as we go
along. Certainly I do NOT see my role as providing formal legal opinions and
drafting contracts for research. Rather, I think I am to alert the REB
members and the researchers to potential legal problems and issues that
could expose them (and me) as members of the Board to legal or ethical

My present challenge is that there does not appear to be a uniform standard
or definition of what our purpose or role ought to be on the REB. For
example, I personally take great exception to the absence of an independent
Data Safety Monitoring Board on some Phase One studies. It has been
explained to me that due to great caution and monitoring of Phase I studies,
that an external DSMB is not necessary. I am concerned that a number of
potential conflicts of interest can arise in such a situation. Perhaps I am
being overly concerned but at present there is no “lay legal” group to
bounce these issues off on an informal basis.

I have other concerns regarding our roles vis-à-vis the contract, the
sponsor, the Principal Investigator, and the institution. Who is “allowed”
to communicate with whom regarding clinical trials and Serious Adverse
Events and their definitions. I understand that Francis Rolleston & Ray
Saginur have made recommendations to Health Canada on the SAE management.
Until there is any new direction as a result of their work, it would seem to
me that the primary responsibility lies with the REBs to ensure appropriate
safety procedures are in place.

If anyone has REB legal member terms of reference or a model that they are
presently utilising, I would be grateful if you could make copies available
to me. If, as I suspect, there are no such tools presently extant , perhaps
we could initiate a process amongst any willing volunteers to define
practices that will best enable the achieving of the goals of the
Tri-Council Policy guidelines.

To get to the point I would like to establish at least a list of colleagues
across the country who are willing to share ideas, problems and solutions.
If we can ultimately define our roles on a clearer basis I think we, and the
system, will benefit. I would welcome a list of what we don’t need to do if
for no other reason than to protect us ,if in the future a bad research
result leads to the question, “Why didn’t you…?”.

If you interested in at least investigating these issues further with your
fellow legal participants ,I would ask that you let me know so that I will
not be the sole lonely member of what I have dubbed the Research Ethics
Board -Legal Society (REB-LS).

Any ideas and suggestions on this topic, would be gratefully received.

Don Short 416-868-3440

Charles Weijer, MD, PhD
CIHR Investigator
Associate Professor

Department of Bioethics
Dalhousie University
5849 University Avenue
Halifax, Nova Scotia, Canada, B3H 4H7

Tel. 902-494-6330
Fax 902-494-3865

From: "Michael Goodyear" <>
1. Don is correct that the role of the lawyer, and the particular training of that lawyer has not been well defined. Ideally it should be a lawyer with special training in health law, particularly governance of research ethics.

Certainly the REB lawyer is NOT the Board's legal counsel, or the institution's with regards to the contracts, but should be overseeing the compliance of the board with the applicable regulations.

2. Don needs to join this list so that he can take part in the discussions

3. To date DSMBs have not taken part in phase I/II studies. With respect to phase I it is difficult to see what their role would be other than to take over the running of the trial in which case they would not be independent. In phase I there is an elaborate series of stopping rules in place per subject and per event. Any independent board's role would be to ensure that the rules are followed. Phase II trials frequently have stopping rules based on interim safety/efficacy data, eg the 2 stage Fleming-O'Brien design. i am far more concerned about industry run phase III studies without DSMBs, but even they are not infallible, as recent events have illustrated.

4. Contracts have traditionally been between the institution and the sponsor, and are usually supervised by the research office, not the REB. The critical interplay is to ensure that contract (or Letter of Agreement) is consistent with the consent form. A common error is to craft the consent as a legal contract.

5. The more communication the better

6. Everyone agrees that management of SAEs is a mess. There is no question that the REB is responsible for safety on a trial within their own institution. The difficulties arise in interpreting data from outside of the institution, often not even connected with the trial in question. This is more appropriately a role for the regulator.

Well that is a start for lonesome lawyers

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Jack Corman" <>
The Canadian Food and Drug Regulations stipulate that someone knowledgeable
in relevant law sit on the REB ­ they do not state that it has to be a
lawyer. However, someone with legal training should be able to better know
and understand pertinent provincial and federal laws and regulations
governing research, as well as any bylaws from professional societies, etc.
that may apply. To clarify, we are talking about human research subject
protection, and not institutional protection.

If you don¹t know the law and whether the proposed research is within it,
the REB can¹t do a proper job of reviewing the study. Doesn¹t HAVE to be a
lawyer, but, if not a lawyer, who?

Jack Corman

From: "Michael Goodyear" <>
In other words, when is a lawyer not a lawyer. A frequent and contentious topic is what happens if the lawyer leaves the room for a few minutes, or has to go before business is completed. We were advised that all activity stops or we are in violation of TCPS. I was also advised that not any lawyer would do but it must be one with extensive training in health law and in particular qualified in Research Ethics Governance (wel we do offer a course on that here).

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Francis Rolleston" <>
This extensive discussion about lawyers cold also be held for ethics. Why
not require an ethicist? What is an ethicist. What is “knowledgeable in
ethics? Shades also of definition of “community member”

I probably am biased, but I have not yet heard of any other wording that I
think is preferable to what is in the TCPS. In the end, the REB is a part
of the mechanisms that the institution uses to manage its responsibilities
in research. I feel that a considerable degree of flexibility is needed to
allow this to happen effectively and efficiently.

Francis Rolleston
500 Denbury Avenue
Ottawa, ON
K2A 2N7

From: "Michael Goodyear" <>
Thanks Francis, I knew instinctively someone was going to point this out sooner or later. I would certainly think that the degree of ethical expertise varies enormously.

Dr Michael D E Goodyear FRACP FRCPC FACP

14. Sponsor IRB/REB relationships

From: "Michael Goodyear" <>
I was asked about the appropriateness of the following scenario:

Sponsor has interested an investigator in a study concept, but investigator has not yet seen protocol. Investigator indicates interest. Sponsor then asks for Name, Telephone number and Fax number of REB chair who will be reviewing study.

While Sponsor-Board relationships are addressed from time to time it is usually in the context of REBs contacting the sponsor after review to try and expeditiously iron out some problems. This one is new to me.

What do you think?

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Susan Hoddinott" <>
At UWO this info is not a secret - our REB membership and contact info
is on our website so anyone can look it up at any time. My guess is
they want the info for the Health Canada CTA.



From: "Cam McDermaid" <>
Hi Michael perhaps I'm naïve, but I see no rationale for a sponsor to directly
contact an REB chair. Any issues with relation to the review of a
protocol etc. can be handled adminstratively. Even though the
contact may not represent a conflict of interest, it may be seen as
such, which is just as important.

Our chair will speak with investigators from time to time, but the
that's different.



15. Storage of SAEs

From: "Saginur MD, Raphael" <>
To: <>
Subject: RE: [Ethics] Storage of SAE's
Date: Wednesday, July 02, 2003 11:10 AM

It would be of service to the REB community for the Health Canada
Inspectorate to give a regulatory opinion regarding the duration of SAE
report retention by REBs: is this different from their general 25 year rule?

Raphael Saginur

-----Original Message-----
From: Judith Abbott []
Sent: June 27, 2003 4:49 PM
Subject: Re: [Ethics] Storage of SAE's

About a year or two ago we made a decision that external SAEs would be
destroyed when the study was closed. We retain the letter of notification,
any summary list that's provided, and our acknowledgement, but the MedWatch
reports, etc. go in the shredder. Reports of local SAEs are retained with
the rest of the file, which is archived 2-3 years post-closure at our site.

This decision was made basically as a space-saving measure, when we realized
we would be archiving files with huge stacks of SAE reports. These reports
are retained in the PIs files, and can be retrieved by us if necessary. I
have never, in 8+ years, been asked to go back and review one.

Judith Abbott

16. The Death of Ryan Lucio

From: "Gentile, Carole" <>
To: <>
Subject: RE: [Ethics] the death of Ryan Lucio
Date: Thursday, July 24, 2003 2:05 PM

Recent comments regarding the silence surrounding Ryan's death have
motivated me to say a few words about our experience.

Nine senior staff members from different disciplines were appointed by the
hospital to investigate the circumstances surrounding the Ryan's death.
This committee (SPRC - Special Protocol Review Committee) produced a report
that can be found on the CHEO website.

The committee focused primarilly on the medication error, which in our view
was completely opportunistic. Having said that, the CHEO REB has fine-tuned
its skills in scrutinizing protocols as a result of this experience. One
document that we've found informative and useful is the CTEP guidelines for
treatment regimens.

Additionally, we are now keenly aware of human fallibility and how group
discussions/decisions can be inconsistent and less than comprehensive. For
this reason, we've developed a checklist (of sorts) to guide our
discussions, which is included in our application form for researchers.

The Health Canada angle to Ryan's story remains difficult from an REB
perspective. The trial was not approved and yet the regulations require
that the Sponsor/investigator first secure REB approval prior to their
application to Health Canada. Further, there is no direct correspondence
between between Health Canada and the individual sites involved in the study
(unless the Sponsor is also a local investigator). We now require evidence
of the Health Canada NOL prior to issuing the final approval. If the
Sponsor of a trial is also a local CHEO investigator, I sign off on the
application only if there are minor modifications required of the protocol.
This seems to be a good compromise that works for us. As well, we have been
much more forceful in educating our local investigators about the specifics
of the Health Canada regulations.

Dr. Carole Gentile,

From: "Clark, Elisabeth" <>
Dr. Gentile ... thank you for posting this very relevant information to the
List that affirms the CHEO REB committment to the ethical principles
governing human research. I'm certain that each of us comprehends the
difficult nature such communnication poses, at the same time its
transparency will enable the community to learn.

The common thread binding REBs that review biomedical research is Health
Canada, about which you told us the following:

>The Health Canada angle to Ryan's story remains difficult from an REB
>perspective. The trial was not approved and yet the regulations require
>that the Sponsor/investigator first secure REB approval prior to their
>application to Health Canada.

At the MUHC we are under the impression that HC's review of a Clinical
Trial Application (CTA) resulting in a No Objection Letter (NOL) is issued
*prior* to the REB review of the study. To do otherwise in theory, would
waste REB review time should HC's review reveal deficits necessitating
sponsor's modification to the study design, or other feature requiring a
protocol amendment, or new version.

HC post-review timing of the NOL is consistent with the Medical Device
Regulation requirement for Investigational Testing Authorization, but we
believe not so with investigational drug evaluation.

HC might be well advised to remove the contradiction within its internal
review structure and thereby create consistency of timing for issuing NOLs
for both types of CTs. For me that would be easy Lesson #1.

Dr. Gentile, may i enquire how was the CHEO REB informed of the
"regulation" to secure REB approval, prior to issuing an NOL for the study?

thank you ... elisabeth


From: "Gentile, Carole" <>
Health Canada conducted a recent audit of all our clinical trials at CHEO.
During the audit, there was considerable discussion of the new procedures
instituted by our REB in an effort to avoid having a trial approved at the
local level that had not first secured the Health Canada NOL. It is
probably more accurate to say that the REB and Health Canada process is
independent, but Health Canada does require the names of the REBs that have
approved the protocol (if known at the time of the application).

From: "Agnes V. Klein" <>
That is correct! REB review and approval has to be carried out, but the
regulations do not stipulate the timing with respect to the filing of a
Please remember that the new CTA regulations require the filing of an
application for all activities that are carried out with therapeutics that
are either not marketed (NOC'd) or where activities are carried out outside
of the limits of an approved Product Monograph.

From: "Michael Goodyear" <>
Thank you very much, I will forward the information to the appropriate bodies in our own institution. We make all of our approvals conditional on Health Canada 'no objection' letters now.

I think that I speak for all of us on this list in terms of feeling how much pain this must have caused you and your colleagues, indeed for that reason I hesitated about bringing up the issue at all.

I think it is a pain that all of us in the REB community should share, because we all know at heart, that it could have happened to any of us. I am sure that the tone of any comments on the list regarding the events surrounding this chid's death will respect the feelings of Dr Gentile and all of the staff and patients at CHEO.

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Michael Goodyear" <>
If anyone is trying to find the CTEP document referred to by Dr Gentile - it has been moved to

Dr Michael D E Goodyear FRACP FRCPC FACP

From: "Christine Nestruck" <>
To: <>
Cc: "Siddika Mithani" <>; "Ivo Hynie" <>
Subject: RE: [Ethics] the death of Ryan Lucio
Date: Friday, July 25, 2003 9:07 AM

Dr. Gentile,
Your message was sent to me by Dr. Mithani for comment. Please note that
both authorization of a Clinical Trial Appication by Health Canada and
approval of the protocol and consent information by the local Research
Ethics Board must be obtained before a clinical trial sponsor can initiate
the trial. However, these are independent approvals; i.e., one approval
dose not depend on the other. We encourage sponsors to apply to HC and the
REB in parallel such that the time to trial start-up is not unnecessarily
I hope you will share this information with you colleagues and fellow
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
A. Christine Nestruck, M.Sc., Ph.D.
Clinical Trials and Special Access Programme
Therapeutic Products Directorate
Tel: (613) 941-0570 Fax: (613) 952-9656

From: "Gentile, Carole" <>

The difficulty with the independence as applied to our situation was that
there was a perception on the part of the media (and public) that the
hospital had sanctionned a clinical trial that was 'illegal'. As a result,
we now require the NOL before granting final approval.

From: "Clark, Elisabeth" <>
While REBs are mandated by their instutions to safeguard the rights of
human volunteers in research, the responsibility is nontheless understood
by all stakeholders to be "shared" among Sponsors, Investigators, REBs and
Health Canada (HC).

While Canadians wait for a full accounting of the issues and corrective
actions HC needs to introduce in response to the tragedy, the research
ethics community would be remiss not to offer constructive solutions to
ongoing problems highlighted in the wake of the tragedy [recently suggested
by Dr Rolleston on this List].

One such issue is the timing of REB review relative to HC authorization.
Drs. Klein, Mithani and Nestruck confirm for us that "the regulations don't
require HC to "secure REB approval prior to filing". This is true for drug
research, but untrue for medical device research. HC has a separate
Division reviewing each type of research, with the *green light* to go in
Canada issued as No Objection Letter (NOL).

>From Dr. Nestruck's comments HC's suggestion that parallel submission (HC
and REB) is ideal because "the time to trial start-up is not unnecessarily
prolonged." With respect to that view speedy initiation of research does
not trump the regulator's responsibility to guarantee measured review of
experimentation. This is the protections Canadians deserve. Further,
prior federal oversight pinpoints the type of guarantee over-worked REBs
need from central regulatory review.

To re-focus the question, two types of sponsor applications for HC review:
. drug trials = Clinical Trial Application (CTA);
. device trials = Investigational Testing Authorization (ITA)
. HC review of CTA = *either* before or after REB approval;
. HC review of ITA = *always* after REB approval;

Last year i contacted an HC device reviewer for an explanation of the
inconsistency. My question was, " Why should an REB use its time to review
a device trial that was not first authorized by HC?

My question was answered with a question, "Why should HC use it's time to
review a trial that would not be approved by an REB?"

Now putting aside the absurdity of that federal regulator's response, i
prefer to think the view represented the opinion of one person, rather than
the prevailing attitude of those charged with Canadian oversight of medical
device research..

Online we have heard Drs. Gentile and Goodyear inform us that as a result
of CHEO's experience with unauthorized research, NOLs are now manditory at
their institutions, prior to the issuing of ethical approval.

Since Dr. Rolleston asked for problems and solutions i humbly suggest
*removing ambiguity* in the timing of the HC reviews to begin to address
the potential for more deaths on unauthorized studies. Two HC Divisions
may operate in separate areas, however the responsibilities of federal
regulator are identical. Inconsistency produces confusion, and confusion
serves no one's interest where research is concerned.

Elisabeth Clark
Research Ethics Officer/Human Protections Administrator
McGill University Health Center

tel: 514-934-1934 x-34720
fax: 514-843-1486

17. The Rise of Litigation in Human Subjects Research

From: "Charles Weijer" <>
To: <>
Cc: <>
Subject: [Ethics] The rise of litigation in human subjects research
Date: Tuesday, July 01, 2003 1:01 PM

Hi all --

Here is a fascinating article on recent trends in litigation and human

Mello MM, Studdert DM, Brennan TA. The rise of litigation in human subjects
research. Annals of Internal Medicine 2003; 139: 40-45.

Abstract: Owing to widespread public concern about the adequacy of
protections for human research subjects and recent instances of serious
injury to subjects at several major research institutions, lawsuits against
investigators, institutional review boards, and academic institutions are
becoming increasingly common. Several claim-promoting conditions are ripe to
promote the further growth of this litigation and raise the stakes for
research institutions. While this litigation may serve a valuable
compensation function for injured subjects, it will also have profound
effects on institutional review boards, leading to a more legalistic,
mechanistic approach to ethical review that does not further the interests
of human subjects or scientific progress.

Full text:

Charles Weijer, MD, PhD
CIHR Investigator
Associate Professor

Department of Bioethics
Dalhousie University
5849 University Avenue
Halifax, Nova Scotia, Canada, B3H 4H7

Tel. 902-494-6330
Fax 902-494-3865

For rapid assistance, please contact my administrative assistant:
Carla Farmer

18. Time frame for ethics approval and reporting requirements

From: "Monica Blais" <>
To: <>
Subject: [Ethics] Time frame for ethics approval and reporting requirements
Date: Monday, July 21, 2003 7:40 PM

For the list serve

The University of Victoria's Human Research Ethics Committee is a
behavioural REB.

At present our ethics approval for a research project involving human
participants is granted for three years. If after the first year of the
three-year approval the researcher is still collecting data, he/she is
required to submit a request for continuation form. If after the second
year, the researcher is still collecting data, he/she is again required to
submit a request for continuation form. However, if the researcher has
completed the data collection, he/she is not required to submit a
continuance. If after 3 years, the researcher has not completed the research
project (e.g. data collection), he/she must reapply for ethics approval.

We are interested in moving to a system where a project is approved for its
duration, and in which annual reporting is required. We would like to know
how other universities are handling the period of approval (e.g. three
years, five years, for life of project) and what type of reporting and/or
renewal is required.

Thank you for your assistance.

Monica Blais, MA
Human Research Ethics Facilitator
University of Victoria


From: "Joan Stevenson" <>
Dear Monica, we have a one year reporting with a simple one page renewal form.

Joan Stevenson
Chair General Research Ethics Board
Queen's University

From: "Butler, Eleanor" <>
Hi Monica, the Interdisciplinary Committee on Ethics in Human Research here at Memorial
grants ethics approval for one year. The researcher is required to file an
annual report on the anniversary of that approval and following acceptance
of this report, approval is extended for a further year.


Eleanor Butler
Co-ordinator (Ethics and Internal Grants)
Office of Research
Memorial University of Newfoundland
Tel: 709-737-8368
Fax: 709-737-4612

From: "Joan Stevenson" <>
Dear Monica, we have a one year reporting with a simple one page renewal form.

Joan Stevenson
Chair General Research Ethics Board
Queen's University

From: "Butler, Eleanor" <>
Hi Monica, the Interdisciplinary Committee on Ethics in Human Research here at Memorial
grants ethics approval for one year. The researcher is required to file an
annual report on the anniversary of that approval and following acceptance
of this report, approval is extended for a further year.


Eleanor Butler
Co-ordinator (Ethics and Internal Grants)

From: "Michael J. Wilson" <>
Monica, at McMaster we keep track of approvals in an Access database and send out
annual renewals every month. In addition, we follow up with those reports if
we don't hear back from the researcher. If the researchers don't respond
after our third request for annual reporting, we send a letter indicating
that their accounts will be frozen if they don't return the annual report.

We have established a precedent that protocols that have been approved for
four years must be resubmitted if they are still active. We also require
resubmission of a protocol if there have been more than 4 addendums or
changes. The Access database has protocols logged going back to 1995,
before the TCPS and the monitoring requirement. The 1995 and 1996 protocols
were archived and considered closed but we have been contacting PI's by
email for the years 1997 and 1998 asking them to let us know if their
research is still active, because their protocols have not been monitored,
being pre-TCPS.


From: "Cam McDermaid" <>
Hi Monica, our approvals are for one year with annual renewal. Changes to the
protocol that may affect participants or changes in the investigative
team are reported prior to implementation within an approval period
and are summarized on the renewal form with a progress summary.
Significant changes that are planned may require re-review. This
puts the trigger for re-review as a change rather than a time period.

When the data is locked, the investigator submits a closure form and
the ethics approval is considered expired. We require ongoing
renewal until the data is the locked.



From: "Susan Hoddinott" <>
At UWO investigators are required to provide a project start and end date. In
general, the approval will remain valid until the noted end date assuming no
changes and timely and acceptable responses to the REB's request for
surveillance and monitoring information (e.g. annual reporting). Occassionally
if the project is high risk or the end date is too far in the future the REB
will limit the period of its approval and require further information if the
project is to be extended. This method reduces the workload in our office and
the number of approval notices that we have to print and send out. If
investigators want to extend the end date they must submit a 'request for a
revision' form and explain why.



From: "Susan Blum" <>
Dear Monica, the policy at the University of Saskatchewan is as follows:

8.3 For above minimum risk research protocols, ethics certificates
are issued for one-year. If the project continues beyond one year,
the researcher must submit a completed "Status Report Form" to the REB
prior to the one-year anniversary approval date. If the Status Report
Form is not submitted by the one-year anniversary approval date, the
ethics certificate will automatically expire. Any research funds
associated with this research project will be withheld.

8.3.1 If no substantial change has been made to the research plan
or research protocol, the Chair of the REB may issue a one-year

8.3.2 If, in the opinion of the REB Chair, the research plan or
research protocol has been substantially changed, re-submission and
review by the REB is required.

8.4 For minimal risk protocols, ethic certificates may be issued
for up to five-years. On the yearly anniversary date of the original
approval, the researcher must submit a completed "Status Report
Form". If the Status Report Form is not submitted by the yearly
anniversary date, the ethics certificate becomes invalid. Any
research funds associated with this research project will be withheld.

8.5 If a study extends beyond a five-year period, the Chair will
review the protocol that was originally submitted. If there have been
regulatory changes that need to be addressed in the original
submission, the Chair will ask that a new ethics application be submitted.

8.6 Researchers must maintain all documentation related to the
study during the period of ethics approval. As a monitoring process
for ethics compliance, REBs and other duly constituted bodies of the
university may conduct periodic audits.

8.7 The researcher shall promptly notify the REB when the project
is complete by submitting a Status Report Form.


From: "Lindley, Pat" <plindley@Kilcom1.UCIS.Dal.Ca>
HI Monica and others, like others, our approvals are good for 12 months. We send out an annual
renewal report form to the researchers about 6 weeks prior to the expiry of
the approval. As part of the form we ask that they submit a copy of the
consent form they are currently using. We cross-check this against the
approved version of the form in the file, prior to approving the renewal.

The approval letter they get initially indicates that any changes to the
protocol or the consent form must be submitted as amendments, for

In spite of all our efforts to help researchers meet this requirement (lots of
time allowed, form supplied, reminder emails sent) we still get individuals
who do not respond. We don't review clinical trials, but it is still a concern
when researchers operate without a current approval... kind of makes a
mockery of the requirement for approval in the first place. Not infrequently
our annual forms unearth changes that have been made which were not
submitted for review, and also we have had responses to our query "have
any subjects expressed concern or had difficulties in the study?" which
have been very enlightening. We follow up on these with the researcher if
we want a fuller explanation than the one they provided on the form.

Pat Lindley

From: <>
Pat, we request an annual update as well. WE had problems with late or no repsonse
to our requests for the annual update. We now send a second letter a month
after the first advising reserachers that failure to return a completed annual
update form within two weeks will result in pulling approval and closing the
file. This appears to focus the mind as we seldom end up pulling a file. We
experienced an initial problem with student researchers whose address was not
valid. We solved this problem by copying the supervisor the requests for an
annual update as well.

From: "Clark, Elisabeth" <>
Hello List -- this discussion on an approval time frame is prompting me to
question something i had until now taken for fact. Perhaps the answer
turns on perception of minimal risk, prorportionate review or perhaps it
changes according to biomedical vs behaviorial research, BUT

Does the TCPS permit an REB to provide approval for research for a period
greater than 1 year?

Longer than 1 year approval periods seems to be what some of us have
posted, i.e., Monica wrote, "We are interested in moving to a system where
a project is approved for its duration, and in which annual reporting is
required. We would like to know how other universities are handling the
period of approval (e.g. three years, five years, for life of project) and
what type of reporting and/or renewal is required.

What's confusing me is how could a TCPS-compliant REB approval extend
beyond 1 year when at TCPS Art 1.13 (c) it says:
"Normally, continuing review should consist of at least the submission of a
succinct annual status report to the REB."

Is the duration of REB approval missings in the TCPS?

At lot of us have understood continuing review to be consistent with the US
CFR definition for "IRB approval" that can be in force no longer than 1
year from previous review, i.e. permission to conduct the study expires, if
not approved again, following continuing review at an interval no greater
than 1 year ... elisabeth

From: "Cam McDermaid" <>
To: <>
Subject: Re: [Ethics] Time frame for ethics approval and reporting requirements
Date: Tuesday, July 22, 2003 4:07 PM

Hi Elisabeth

This is a good point, but I think it may largely be a semantic one.
In the example Monica provided, although an approval is "provided"
for three years, annual reports are required. I think that, in
reality, this consitutes an annual review process, regardless of how
it is stated, and I presume approval would not be in place in the
absence of the report. The three year window until full resubmission
is a default point at which reports would be inadequate.

"Approving" a project for an indeterminate period and still requiring
annual reviews seems to be a bit of a non sequiter, presuming you'd
withdraw approval in the absence of report. It seems to me to really
be annual review. It should probably be stated as such, for the very
reasons you've identified. A better way to state the question,
perhaps, would be "At what point is a full resubmission be required
instead of a report?"



19. Urgent Request for a Speaker - Cdn Quality Assurance

From: <>
To: <>
Cc: "Deborah Dragoon" <>; <>; "Keith Burch" <>; <>; <>; <>; <>; <>
Subject: [Ethics] Urgent Request for a speaker at Canadian Chapter of the Society of Quality Assurance Meeting
Date: Thursday, July 17, 2003 10:26 AM

Dear Ethics Forum members,

I have been an observer on your forum for a short while. My interests are
mainly Research Ethics ( animal and human ), so alot of what goes on here
is a little above me , but I find it very interesting none the less.

I am the Vice President of the Canadian Chapter of the Society of Quality
Assurance ( We are having a meeting this week ( Friday and
Saturday AM) unfortunately one of my speakers just cancelled on me and I
need to fill a spot relatively quickly.

If there are any of you in the Ottawa area that would be willing to give a
talk about research ethics boards or how the privacy laws in Canada and the
US affect Human Research please do not hesitate to give me a call at
514-624-9080 or 514-918-2089. Alternatively you could respond to this

I apologise for soliciting the forum like this but I am in kind of a bind.


Janine Johnson, B.Sc., RQAP-GLP
Compliance Specialist
Cato Research Canada

20. New Interagency Panel on Research Ethics Members

From: <>
To: <>
Subject: [Ethics] Announcement of New Members to the Interagency Advisory Panel on Research Ethics - Annonce des nouveaux membres du Groupe consultatif interagences en éthique de la recherche
Date: Tuesday, July 22, 2003 2:38 PM

(la version française suit la version anglaise)

Announcement of New Members To the Interagency Advisory Panel on Research Ethics

The Presidents of Canada's three federal Granting Agencies, Dr. Alan
Bernstein of the Canadian Institutes of Health Research (CIHR), Dr. Tom
Brzustowski of the Natural Sciences and Engineering Research Council
(NSERC), and Dr. Marc Renaud of the Social Sciences and Humanities Research
Council (SSHRC), are pleased to announce the appointment of three new
members to the Interagency Advisory Panel on Research Ethics (PRE).

- Marlene Brant Castellano - Trent University, ON

- Ian Mitchell - University of Calgary, AB

- Florence Piron - Université Laval, QC

The new members complement and strengthen the current experience and
expertise on PRE, while enriching its diversity and perspectives. With the
addition of new expertise, PRE is now composed of 12 members (previously 11)
drawn from across the country to represent a wide spectrum of expertise and
experience in the ethics of human research, such as research involving
Aboriginal peoples, ethics and ethics review, research administration;
research in the health, natural and social sciences; humanities and
engineering, law, as well as a lay perspective. PRE members are typically
appointed for two years to ensure a dynamic and continuous membership.

Biographical information on the members can be found on PRE's website at:

The Interagency Advisory Panel on Research Ethics and the Secretariat on
Research Ethics are part of the governance structure put in place by CIHR.
NSERC, and SSHRC, for the development, evolution, interpretation, and
implementation of the Tri-Council Policy Statement: Ethical Conduct for
Research involving Humans (TCPS).