Prepared by CIHR Ethics Office
June 2005
Acronyms
Abstract
Introduction
I. Welcome and Opening Remarks
II. Overview of ICOI Issues
Presentation of two Main Issues
I. Sponsorship of Health Research
II. Publication and Dissemination of Research Findings
Focus on Specific Strategies
I. Recommendations
II. Feedback on the Schedule to the Tri-Council MOU
III. Action plan for CIHR
Conclusion
Appendix A - Key ethical concerns and proposed concrete strategies
Appendix B - List of Participants
COI - Conflict of interest
ICOI - Institutional Conflict of Interest
REBs - Research Ethics Boards
MOU - Memorandum of Understanding
CIHR - Canadian Institutes of Health Research
SSHRC - Social Sciences and Humanities Research Council
NSERC - Natural Sciences and Engineering Research Council
SCE - Standing Committee on Ethics
DSMBs - Data And Safety Monitoring Boards
AAHRPP - Association for the Accreditation of Human Research Protection Programs
CMAJ - Canadian Medical Association Journal
PhRMA -Pharmaceutical Research and Manufacturers of America
Rx&D - Canada's Research-Based Pharmaceutical Companies
This report summarizes the discussions that took place at the national invitational meeting on Institutional Conflict of Interest (ICOI) hosted by the Canadian Institutes of Health Research (CIHR) on October 22 and 23, 2004 at the Château Cartier in Aylmer, Québec. The issue of institutional conflict of interest was identified as an emerging priority by CIHR's Standing Committee on Ethics (SCE). The SCE believes that CIHR has a role to play in promoting discussion in the health research community on how to manage ICOI, and through leading by example. The SCE suggested that CIHR invite representatives of the various interested parties to discuss these issues and identify solutions. Given the breadth of the issue of institutional conflict of interest, the planning committee chose to focus on two specific topics at this meeting: sponsorship of health research, and publication and dissemination of research findings.
Participants in the invitational meeting included public and private sponsors of research, researchers, research participants, research ethics board members, ethics and law experts, and journal editors.
The objectives of the meeting were to:
In addition, other desired outcomes of the invitational meeting included a suggested short-term action plan for CIHR and feed-back on the draft Tri-agency Memorandum of Understanding schedule on conflict of interest.
Christine Fitzgerald, Vice-President of Corporate Affairs, CIHR, welcomed participants to the workshop, and stressed the importance of the issue of conflict of interest (COI) for CIHR.
Susan Sherwin, Research Professor in philosophy at Dalhousie University and Chair of the Planning Committee, presented some of the reasons why the issue of conflict of interest is an important priority for CIHR. CIHR's mandate is to promote research, to ensure that research is ethical, and to facilitate commercialization. As a result, CIHR's position on conflict of interest needs to be clarified. A matter for concern involves potentially conflicting mandates of other institutions in the Canadian research scene, whether they are funding institutions or research institutions such as universities or hospitals. This situation arises from the current trend where government requires universities to more aggressively pursue research opportunities and private funding.
G. DuVal opened his remarks with a quote from Dr. Jonathan Quick: "If clinical trials become a commercial venture in which self-interest overrules public interest and desire overrules science, then the social contract which allows research on human subjects in return for medical advances is broken." He stressed the importance of keeping in mind the social contract to which Dr. Quick is referring.
G. DuVal noted that the potential for financial and other conflicts of interest to influence decision-making by researchers is a familiar problem, and that conflict of interest policies have become increasingly prevalent, particularly among academic research centres and professional and regulatory groups. He also noted, however, that there is increasing recognition that institutions themselves may also be subject to financial and non-financial pressures that may distort responsible institutional decision-making.
G. DuVal described various secondary interests of an institution - or of its decision-makers - that may threaten the organization's ability to meet its primary obligations. He outlined several situations where appropriate decision-making is compromised in institutions, and suggested ways of dealing with them which included focusing on policies and procedures, disclosing ICOI, and developing oversight mechanisms.
G. DuVal's presentation elicited a number of questions and comments. COI committees were discussed as well as the role of Research Ethics Boards (REBs). Other observations included reference to the current situation in Canada in comparison with that existing in the U.S., which has more experience in using specific measures to deal with ICOI issues. Possible creative solutions suggested included the creation, in universities and academic centres, of separate research institutes that isolate commercially-supported research from other forms of research.
Chair: Daryl Pullman, Associate Professor of Medical Ethics, Faculty of Medicine, University of Newfoundland
Position Statement
Michael McDonald, Bio-ethicist, Director of W. Maurice Young Centre for Applied Ethics, University of British Columbia
M. McDonald, SCE member and member of the Planning Committee, presented his views on institutional conflict of interest. He described a conflict of interest situation as one where there is good reason to believe that the independent judgment necessary to fulfill a fiduciary responsibility may be compromised. In such situations, the conflict should be avoided, declared or otherwise appropriately managed. M. McDonald also commented on the relationship between industry and universities and on the fundamental tensions inherent in the various roles that public institutions play. He also stressed the importance of determining who should bear the responsibility within an institution to deal with ICOI issues. He closed his presentation with a list of ten suggestions of practical solutions for addressing institutional conflicts of interest, and some thoughts on the implementation of the proposed measures. He recommended taking a concerted approach, and that there be as much transparency, public accountability and public participation in the process as possible. The list of recommendations discussed by the participants as a group is included in the "Focus on specific strategies section" of this report.
Response from the Perspective of a Research Institution
Bill McBlain, Senior Associate Vice-President (Research), University of Alberta
B. McBlain discussed institutional barriers that interfere with the ability of research institutions to address ICOI. He agreed with M. McDonald's suggestion that the onus in dealing with ICOI is on institutions, not on the public or the media. B. McBlain endorsed the idea of disclosure as a way to manage some institutional conflicts of interest, adding the importance of having consistency and country-wide ground rules for transparency for all universities in Canada. He added that some resistance can be expected where disclosure runs against the grain of university culture and notions of academic independence. He stressed the need for education to 1) recognize the complexity of the situation in universities; 2) acknowledge the importance of dealing with the perception of conflict of interest as much as its reality; and 3) move forward with practical solutions such as those suggested by M. McDonald.
Response from the Perspective of a Research Sponsor
Koenraad Blot, Director, Clinical Research Operations, Pfizer Canada Inc.
K. Blot discussed the importance of distinguishing between sponsors that are not necessarily responsible for the conduct of research and do not necessarily have an interest in the results of research, such as granting agencies, and those that, under the regulatory definition, bear some level of responsibility towards regulators and have a stake in the outcome of research. He agreed that all research sponsors have potential conflicts of interest and that the pharmaceutical industry has been developing and implementing stringent standards and operating procedures derived from the US, Canada and EU regulations. They emphasize the importance of training, as well as documenting, monitoring, validating, and auditing in regard to these COI issues. K. Blot also made a few remarks regarding the informed consent process, indicating that even though it is the most critical juncture for patients involved in research, sponsors are usually not aware of how patient consent is obtained. He suggested that the consent process be administered by a neutral party.
Response from the Perspective of a Researcher
John Cairns, Project Leader, Clinical Research, Cross-Cutting Initiatives, CIHR
J. Cairns compared the significant progress made in Canada on individual COI with the much slower pace on ICOI. He strongly agreed that COI may threaten the institutional research agenda, trainees, human subjects and the integrity of the research itself, and affirmed that clear, transparent and well-communicated institutional policies are essential in dealing with these issues. Once such policies are developed, they must be closely enforced to ensure effectiveness. He suggested leveraging the successes achieved in the area of individual COI to deal with ICOI. J. Cairns expressed support for COI committees while highlighting potential issues in ensuring independence of their members. He also stressed the importance of a top-down approach to this issue and of ensuring that faculty members and university officers are educated about COI and ICOI policies. He emphasized that giving exclusive contract signing powers to designated university officers would reduce misunderstanding and mitigate liabilities. J. Cairns added that the issue of ICOI should also include a discussion about the CIHR commercialization agenda and the real potential conflicts that may arise.
Questions and Answers
Participants were invited to briefly discuss the presentations. While all agreed on the urgent need for coherent national standards, several questions were raised about how to ensure consistency of institutional policies across the country, who should be responsible for the monitoring and the enforcement role of such standards, how the independence of REBs or ICOI committees can be achieved, whether having regional committees could be a viable option in dealing with ICOI issues, whether a risk management approach to the management of ICOI would be possible, and what parameters should be used when partnering (e.g., is partnering with tobacco companies acceptable?). Comments were made on the danger of over-regulating which could create disincentives to do research, and on the importance of broadening the scope of such requirements to make sure that all health research is covered.
Chair: Susan Zimmerman, Associate, Borden Ladner Gervais
Position Statement
Timothy Caulfield, Research Director, Health Law Institute, University of Alberta
T. Caulfield addressed dissemination of research findings, taken in the broad sense to mean how results are transmitted to the public, and not just publications in peer-review journals. He first presented various sources of ICOI in dissemination of research, then discussed the various adverse impacts on the research environment and for the public perception of science.
On the topic of research and the economic agenda, T. Caulfield noted the increasing commercial ties of universities, and the legislated commercialization mandate of organizations like CIHR and Genome Canada. He used a concept called the "cycle of hype" to illustrate the tendency to publish overly positive messages regarding research and research results, and the increased risk of losing public trust.
T. Caulfield closed his presentation by proposing a number of recommendations to address issues of ICOI in the publication and dissemination of research findings. A list of the recommendations that were discussed by the participants as a group is included in the "Focus on specific strategies section" of this report.
Response from the perspective of a Research Institution
Sandra Crocker, Associate Vice-Principal (Research), Queen's University
Ms. Crocker discussed the difficulties of introducing changes to COI and ethics policies in the university environment, particularly when new policies show some departure from existing provisions of faculty collective agreements. She suggested that while COI may not be eliminated, the way we respond to COI (both individual and institutional) can be improved.
She indicated that it is not practical to compel REBs to review contracts for appropriate publication and confidentiality provisions as this would take them away from their principal mandate that involves the protection of human subjects. Rather, a mechanism should be in place to assure the REB that contracts are being reviewed with COI in mind. For instance, Ms. Crocker described the approach of Queen's University, which is to have a legal counsel assume responsibility for reviewing contracts, and report any issues or concerns to the ethics board. She also stressed the importance of making appropriate arrangements with companies in which universities hold equity, and spoke of the measures taken by Queen's University to address this issue.
Response from the perspective of a Research Sponsor
Marianne Vanderwel, Associate Director, Corporate Pharmaceutical Regulatory Monitoring, Pfizer Inc.
Mrs. Vanderwel introduced the Principles of Conduct of Clinical Trials and Communication of Clinical Trial Results that were issued by the US pharmaceutical industry trade association, PhRMA. These principles support the timely communication of meaningful study results of marketed products, regardless of outcome. Recent proposals regarding registration of clinical trials were discussed as well as the initial responses of PhRMA and various pharmaceutical companies indicating a commitment to better communicate the results of clinical studies of marketed drugs. She expressed a concern about the disclosure of results of early developmental trials with investigational products due to the need to protect intellectual property. Finally, she suggested alternative ways to improve public trust in the research process by establishing, for instance, a Canadian system of accreditation for human research protection programs.
Response from the perspective of a Researcher
Glenville Jones, Craine Professor, Head of Biochemistry & Professor of Medicine, Queen's University
G. Jones first remarked on the gap that usually exists in research institutions, between people knowledgeable in ethics and researchers. He commented that the lack of communication between them is an issue, and also that researchers in general do not give the issue of ICOI as much attention as they should.
G. Jones then described his involvement in the creation of a spin-off company, and shared some observations and lessons learned based on his experience. He identified instances in which publication is affected by commercialization, and where pressures not to publish come into play. He suggested the need to maintain a balance and a separation between spin-off activities and ongoing basic science research.
G. Jones recommended that CIHR and universities make greater efforts to understand the publication pressures put on researchers and that basic research contracts should be reviewed by REBs.
Response from the perspective of a Journal Editor
John Hoey, Editor in Chief, Canadian Medical Association Journal (CMAJ)
J. Hoey presented his perspective as an editor and as a member of the International Committee of Medical Journal Editors. He described the various levels of COI using a pyramid diagram, with financial COI at the top, as the small, visible portion that might damage public trust. At the level below are the personal, social and institutional biases from universities, sponsors, and disease-specific foundations, pushing for positive results. In the third band is some researchers' incompetence which often results in badly-conceived manuscripts, and the bottom tier is due to carelessness, or small errors that get picked up through the editing process. The last two tiers are seldom discussed and are the responsibility of universities.
J. Hoey also underlined the importance of the basic science funnel, which is heavily funded with venture capital funds. He expressed concern that increased targeting of research has a selection effect on basic science and might result in much larger numbers of "orphan diseases" that get ignored. This is because those who fund basic research will not be interested in pursuing certain types of research.
Table Discussions and Plenary Debrief
Following the panel discussion, Ms. Zimmerman facilitated an open discussion on the topic.
An animated debate took place about the registry of clinical trials. Some participants challenged the reluctance of industry representatives to publish trial results. The question of how much information should be included in the registry was also raised and a suggestion was made that patients should be advised before they participate when disclosure of research results will not take place. It was also suggested that the need for transparency be balanced with the business constraints of companies.
The question of public trust was discussed, as was the need to provide additional information to participants in clinical trials to ensure truly informed consent.
The recommendations M. McDonald and T. Caulfield developed in their respective position papers were discussed by the participants. The following recommendations received the general support of participants.
Sponsorship of Health Research
Publication and Dissemination of Research Findings
Additional recommendations were suggested by participants. They refer to measures that could be taken nationally:
Suggestions for Research Topics. Participants offered many valuable suggestions concerning potential research questions related to ICOI. These questions have been clustered into the following general categories:
Participants were asked to provide feedback on the current draft schedule on COI developed by the three funding agencies (CIHR, NSERC, SSHRC) which is intended to form part of the Memorandum of Understanding regarding the roles and responsibilities of research institutions and funding agencies in the management of federal funds. The following feedback was provided by participants:
Participants made recommendations to CIHR on an action plan in the coming year. The following suggestions were made:
S. Susan Sherwin closed the meeting by thanking participants for their presence and engagement in the discussions. She indicated that the Planning Committee would be reporting back to the SCE on the results of the workshop.
Groups were invited to discuss two case studies to identify key ethical concerns inherent in ICOI and propose concrete strategies to address them.
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Case Study # 1 A brilliant young scientist working at a large hospital-based research centre has developed a molecule that holds promise as a revolutionary new treatment for Alzheimer's disease. However, bringing this potential drug even to the early clinical trial stage would be very expensive. So, the hospital negotiates with venture capital investors to provide the bulk of the funding required for drug development and the hospital would contribute its facilities and the scientific expertise and work to date of the inventor and his research team. A corporation is to be established that would own, develop and market the technology, and manage the research. Under the terms of the Agreement, the hospital would receive equity in the new company and would share evenly in the earnings derived from the technology, after the venture capital sums have been re-paid. The hospital is also entitled to appoint three persons to the new company's Board of Directors, and the plan is to appoint members of the hospital's Board of Trustees or senior management personnel. Corporate Board members would be paid a modest stipend but would receive also options to purchase shares that may become extremely valuable if the new drug is brought to market or licensed or sold to a large drug company. The hospital scientist would be appointed to a senior position in the new company and would be paid a salary and also be offered shares or options. |
Key ethical concerns identified:
Responsibilities of research institutions in dealing with ICOI issues:
Elements of an effective management of ICOI:
Questions and Answers:
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Case Study # 2 Dr. Productive is the Chair of a large general hospital REB. She is also a senior researcher and is the Principal Investigator for a range of industry-funded clinical trials, primarily, but not exclusively, investigator-driven. She also has close ties to a number of pharmaceutical and biotechnology companies. She serves as a consultant and is a member of several speakers' bureaus for industry. Her studies are submitted for approval to her own hospital REB, but she takes no part in the voting with respect to her studies. |
Key ethical concerns identified:
Responsibilities of research institutions in dealing with ICOI issues:
Elements of an effective management of ICOI:
Questions and Answers:
Dr. Janet Atkinson-Grosjean
W. Maurice Young Centre for Applied Ethics
University of British Columbia
Mr. David Bell
Manager
Health Sciences Policy Division, PPPD/HPB
Health Canada
Dr. David Brener
Director, Research Translation Programs
Research Portfolio
Canadian Institutes of Health Research (CIHR)
Dr. Richard Carpentier
Executive Director
National Council on Ethics in Human Research (NCEHR)
Dr. An-Wen Chan
Research Advisor & Physician
University of Toronto
Dr. Denis Cournoyer
Associate Professor
Research Ethics Office
McGill University Health Centre
Ms. Barbara Cox
Director
Office of Research Administration
Memorial University of Newfoundland
Dr. Henry Dinsdale
Professor Emeritus
Queen's University
Prof. John B. Dossetor
Prof. Emeritus (Medicine/Bioethics)
University of Alberta
Ms. Martine Dupré
Corporate Secretary
Council Secretariat
Natural Sciences and Engineering Research Council of Canada
Dr. Diane T. Finegood
Scientific Director
CIHR Institute of Nutrition, Metabolism and Diabetes
Dr. Norman Frohlich
Professor
Dept of Business Administration,
I.H Asper School of Business
University of Manitoba
Dr. Brenda L. Gallie
Head, Cancer Informatics Division
University Health Network - Princess Margaret Hospital
Ontario Cancer Institute
Dr. Gordon R. Gray
Professor
Dept of Plant Sciences
University of Saskatchewan
Dr. Ronald Heslegrave
Chair, Research Ethics Board
University Health Network - Mount Sinai Hospital
Ontario Cancer Research Ethics Board
Mr. Derek J. Jones
Executive Director
Secretariat on Research Ethics
Interagency Advisory Panel on Research Ethics (PRE)
Dr. Lyne Létourneau
Professeure sous octroi
Centre de recherche en biologie de la reproduction
Département des sciences animales, Université Laval
Mr. Benoît Lussier
Assistant Director
CIHR Institute of Cancer Research
Dr. Jean Marion
Director, Scientific Affairs
Rx&D
Dr. Barbara McGillivray
President
National Council on Ethics in Human Research (NCEHR)
Mr. Gilles Morier
Director
Research Grants and Ethics
Ottawa University
Dr. Daryl Pullman
Associate Professor
Medical Ethics
Memorial University of Newfoundland
Ms. Stephanie Robertson
Assistant Director
CIHR Institute of Genetics
Dr. Francis Rolleston
Chair, NRC Ottawa REB
Dr. Noralou P. Roos
Professor
Community Health Sciences
University of Manitoba
Dr. Wayne S. Rosen
Clinical lecturer
Dept of Surgery
Office of Medical Bioethics, University of Calgary
Mr. Charles A. Shields, Jr.
Director, External Relations
Canadian Institutes of Health Research (CIHR)
Ms. Susan V. Zimmerman
Associate
Borden Ladner Gervais
CIHR ETHICS OFFICE STAFF
Ms. Patricia Kosseim
Acting Director, Ethics Office
Canadian Institutes of Health Research (CIHR)
Dr. Geneviève Dubois-Flynn
Senior Ethics Policy Officer, Ethics Office
Canadian Institutes of Health Research (CIHR)
FACILITATORS
Dr. Kathleen Oberle
Associate Professor
Faculty of Nursing
University of Calgary
Ms. Lise Hebabi
Groupe Intersol
SPEAKERS
Dr. Koenraad Blot
Director
Medical Operations
Pfizer Canada Inc.
Dr. John A. Cairns
Professor of Medicine
University of British Columbia, and
Project Lead on CIHR Clinical Research Initiative
Dr. Timothy Caulfield
Professor and Canada Research Chair in Health Law and Policy, Faculty of Law and Faculty of Medicine and Dentistry,
Research Director, Health Law Institute
University of Alberta
Ms. Sandra Crocker
Associate Vice-Principal (Research)
Queen's University
Dr. Gordon DuVal
Bioethicist
Joint Centre for Bioethics
University of Toronto
Dr. John Hoey
Editor-in-Chief
CMAJ
Dr. Glenville Jones
Craine Professor and Head, Department of Biochemistry
Professor, Dept of Medicine
Queen's University
Dr. William A. McBlain
Senior Associate Vice-President (Research)
Research Services Office
University of Alberta
Dr. Michael McDonald
Director
W. Maurice Young Centre for Applied Ethics
University of British Columbia
Dr. Susan Sherwin
Professor
Department of Philosophy
Dalhousie University
Ms. Marianne Vanderwel
Associate Director
Corporate Pharmaceutical Regulatory Monitoring
Pfizer Canada Inc.
