• Terms of Reference
• Investigator Procedures for Submission of a Research Proposal
• Committee Guidelines for the review of a Research Proposal
• Decision of the Research Ethics Board
• Report of the Research Ethics Board
In November of 1987, the Standing Committee on Ethics in Experimentation of the Medical Research Council (MRC) of Canada released its Guidelines on Research Involving Human Subjects. These guidelines, accepted by the MRC, were established out of concern that research on humans always be accomplished in an ethically acceptable manner; history tells us this has not always been the case.
The Committee has chosen "Research Ethics Board" (hereafter referred to as REB) as the name to be given to the institutional review boards to which each protocol involving human subject be submitted to ensure that it complies with these principles. The REB will have to determine whether the scientific question or hypothesis is significant enough to warrant the use of human subjects. Clearly, to be ethically permissible, a protocol must be scientifically acceptable. The REB will, in many situations, rely on peer-review granting agencies for scientific review. In others, however, it may be necessary to request the assistance of external reviewers from the Queen's community on the scientific validity of eve ethically sound research must adhere. The criteria are respect for life, respect for self determination, beneficence and justice.
protocols.The Standing Committee identified four principles to which they beli
Stemming from these principles is the necessity of any review to consider, among others:
• An evaluation of Risk and Benefit
• Special Types of Research
• Principles of Consent
Historically, Queen's University's Health Sciences has reviewed each protocol involving human subjects, using available guidelines, through departmental committees. It was believed that the new guidelines of the MRC could best be implemented through the establishment of a Research Ethics Board, as set out in the Guidelines on Research Involving Human Subjects, 1987. The Board was instituted as a committee of the University by the Principal, Dr. David C. Smith, in June of 1992. With the agreement of the Joint Liaison Committee (Queen's University, Kingston General Hospital, Hotel Dieu Hospital, St. Mary's of the Lake Hospital, Kingston Frontenac Lennox & Addington Health Unit), the REB will review all research protocols involving human subjects for the Faculty of Medicine and the three teaching hospitals. Since then it has been agreed that protocols from the School of Nursing (January 1, 1993) and Kingston Psychiatric Hospital (April, 1993) will also be reviewed by the REB. It is anticipated that procedures will evolve with assessment of the REB workload.
The Queen's University and Affiliated Teaching Hospitals Health Sciences Human Research Ethics Board (REB) is responsible to the Principal, Queen's University, with appropriate consultation and interactions with the hospitals through the Joint Liaison Committee Executive for:
• developing policies regarding ethical issues relating to the use of human subjects in research and experimental teaching protocols;
• developing a process for reviewing research protocols that require the participation of human subjects;
• reviewing all protocols requiring the participation of human subjects for ethical approval;
• reviewing annually all policies regarding ethical issues relating to the use of human subjects in research projects to ensure that policies remain current;
• dealing with other matters concerned with human-based research including those referred to the Board. The latter may be referred to the Bioethics Committees of the affiliated teaching hospitals;
• preparing an annual report for submission to the hospital boards and the University.
The policies developed by the REB will take into consideration the published guidelines of The Medical Research Council of Canada, guidelines suggested by the National Bioethics Board, policies of Queen's University, and the mission statements and policies of the hospitals in which the research will be performed.
The REB shall comprise a minimum of 10 members, including at least:
• 2 active researchers with broad interests in biomedical research, at least one of whom shall be a physician
• 1 community representative
• 1 nurse involved in research
• 1 clinical psychologist or other mental-health expert
• 1 scientist with expertise in research design
• 1 lawyer
• 1 bioethicist, philosopher or theologian
Board members shall serve for three year terms which may be renewed once. Initially, appointments shall range from one to three years to allow for continuity of membership when members are being changed.
The REB membership shall be the responsibility of the Principal, Queen's University, who shall seek nominations from hospital presidents or delegates, appropriate department heads, the Vice-Principal (Health Sciences), the Vice-Principal (Research and Graduate Studies), the Dean (School of Nursing), and others, prior to making appointments to the Board. Members will be selected on the basis of experience with or an interest in the ethics of human experimentation. All nominations will be subject to the approval of the Joint Liaison Committee Executive. The chairperson of the REB will be appointed by the Principal, on the recommendation of the JLC.
The REB shall meet regularly and shall review all protocols requiring the participation of human subjects. The Board shall review all protocols for the Faculty of Medicine, including the School of Rehabilitation Therapy, and the School of Nursing. The Board review process replaces departmentally/school based reviews. All applications and experimental protocols of Health Sciences University faculty are required to go through the Board review process.
The REB shall, with the written agreement of the hospitals through the Joint Liaison Committee, undertake ethics reviews for hospital researchers who do not hold University appointments.
The basic operating rule shall be that any use of human subjects for research or teaching purposes should be submitted for REB review. The investigator or instructor should consult the REB Chairperson for advice if there are any questions about whether a REB review is required.
For continuing projects without significant changes there will be a detailed review every three years. All protocols must be reviewed annually. There is a special form for annual renewals. For the annual renewal, the investigator should briefly indicate progress including the number of subjects or informants recruited. The investigator/instructor shall be reminded by the REB of the requirement for the annual review.
SUBMISSION OF AMENDMENTS
Many projects will have formal amendments made during their lifetime which will require REB review. "Amendment" is used in this context to mean a substantive change in the design, methods, or population under study. It does not refer to revisions of text or clarifications in wording which do not result in such changes. Some amendments will be "conservative" ie: function to make the study less risky to subjects and most would agree that amendments of this sort while requiring review should probably be implemented immediately (ie before the review takes place). Other amendments which result in a change in design, methods, or population which might result in increasing risk must not be implemented until the review has taken place. This differentiation is the same as the one used by the Health Protection Branch and the FDA in review of protocol amendments.
For all the instances listed above there will need to be a common submission process. The REB will meet monthly at a minimum. A list of scheduled meeting dates will be distributed with the requirement for submissions to be 2 weeks prior to the meeting date. This is required for agenda preparation and for distribution of materials to REB members allowing them sufficient time to prepare for the meeting.
SERIOUS ADVERSE EVENTS
In compliance with regulatory guidelines, the REB must be informed of serious or unexpected adverse events occurring during the trial, likely to affect the safety of the subjects or the conduct of the trial. The REB may re-evaluate the ethical aspects of the trial, as appropri
COMMITTEE GUIDELINES FOR REVIEW OF RESEARCH PROPOSALS
Preparation: Seven days (minimum) prior to the next scheduled meeting all committee members will receive copies of the submission form and consent form for each proposal to be discussed at that meeting. For each research proposal, two committee members will serve as "primary reviewers" and each will receive a full copy of the proposal/protocol. An external reviewer may also be sent the full documentation should the REB chair decide that the appropriate expertise is not to be found within the committee membership.
Presentation of the proposal: At the meeting of the committee the primary reviewers will present a summary of the proposal and their assessment of it using as a guide a check list review form - Committee Review Form (see Appendix IV). In the case of an external reviewer, he/she may respond in writing or come to the relevant portion of the meeting.
Criteria for REB Approval of Research:
In order to approve research the REB shall determine that all of the following requirements are satisfied:
• Risks to subjects are minimized. (For the purposes of the REB, risks will include not only physical injury but also loss of dignity and self-esteem, guilt and remorse, or feelings of exploitation and degradation.)
(i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and
(ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.
• Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the REB will consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The REB will not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.
• Selection of subjects is equitable. In making this assessment, the REB will take into account the purposes, aims and setting of the research; in particular,
(i) the research, where practicable, should strive to achieve a demographically representative sampling, subject to the specific constraints of the research hypothesis;
(ii) if the proposed research involves subjects who are vulnerable because they are not competent to give a legally or ethically valid consent, the research must never intentionally or inadvertently, increase or exploit this vulnerability;
(iii) if the proposed research involves subjects who are vulnerable because of their relative social or economic powerlessness, the research must never, intentionally or inadvertently, exploit this vulnerability;
(iv) whenever vulnerable people are proposed as subjects for research, the REB will determine whether other, non-vulnerable subjects would be more, or equally scientifically suitable: vulnerability must never be exploited for expediency.
• Informed consent will be sought and obtained from each prospective subject. The consent form must contain the elements listed in Appendix VI and be written in a comprehensive manner, intelligible to a lay person, and in a language in which the subject is fluent; in particular,
(i) for prospective subjects who were once competent to give consent, but who are no longer capable of being informed, or of freely exercising their consent, the protocol must take into account advance directives with regard to participation in research,, make provision for obtaining substitute consent from the legally recognized substitute decision-maker, and establish a procedure for consulting with the subject should he or she become competent later;
(ii) for prospective subjects who are children, every constructive attempt should be made to seek the consent of the child and to ensure, to the fullest extent possible, that the child understands what is to be done; and in addition, where the child is not legally competent to give consent, the protocol must make provision for obtaining substitute consent from the legally recognized substitute decision-maker;
(iii) for prospective subjects who have always been, and will likely continue to be incompetent to give consent, every constructive attempt should be made to seek the consent of the person and to ensure, to the fullest extent possible, that the individual understands what is to be done; and in addition, the protocol should make provision for obtaining substitute consent from the legally recognized substitute decision--maker and, where necessary, from the individual's advocate as well;
(iv) in those instances in which prospective subjects will not themselves be giving legally competent consent, the protocol must provide a consent form that is suitably addressed to the substitute decision-maker.
• Induced Consent and Payment. An over-riding principle in obtaining subjects for research studies is that the subjects have complete freedom of choice in deciding whether or not to participate in the study. Pressured consent is unacceptable. These facts must be considered when an investigator is recruiting subjects, whether they be patients, "normal" or control subjects.
Clinicians must be particularly sensitive to the "freedom of choice" principle if they are recruiting their own patients to a study. It is important, if at all possible, to have another person ask the patients for their decision. In certain situations, laboratory staff, students, or other employees may be "captive" audiences and find it awkward to decline to volunteer for a study. Such groups are very accessible and may be asked repeatedly to volunteer in studies.
Paying subjects for participation in a study is appropriate and ethically acceptable when payment is limited to compensation for incurred expenses, e.g. travel, parking, and meals (that would normally be had at home), etc.. Payments for time and inconvenience at the rate of minimum wage are acceptable. Remuneration should clearly not distort or influence the freedom of choice. Excessive remuneration or the offering of other or extra inducements is not acceptable.
When investigators are offering payment or any other form of remuneration, they must explain in the protocol how they arrived at the amount being offered. It must be clear that expenses are being covered.
• Informed consent will be appropriately documented. Written consent will be obtained (see Appendix VI).
• The research plan makes provision for monitoring the data collected to ensure the safety of subjects. The results of this monitoring should be included in the annual renewal form and in the reporting of adverse events.
• There are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
• Deception: In general, deception is not acceptable. Under certain circumstances it may be justified (see Appendix V).
DECISION OF THE RESEARCH ETHICS BOARD
The decision on each protocol will be categorized as follows:
Categories of Approval
(a) Category I Approved
(b) Category II Some concern must be addressed before approval is given. The Board endorses protocol with some changes and mandates the chair to grant approval when the concerns have been satisfactorily addressed.
(c) Category III Decision deferred. Based on the documentation provided, the REB is unable to make a decision. The decision is deferred pending receipt of supplementary information or documentation as specified by the REB. The Board will re-review the material.
(d) Category IV Not approved. The reasons will be provided.
REPORT OF THE RESEARCH ETHICS BOARD
In the case of Category I approval, an appropriate approval form (Appendix VII), signed by the chair, shall be sent to the principal investigator. In the case of Category I, II, and III decisions, the chair shall inform the principal investigator of the REB's concerns by memo or letter.
The chair shall make regular reports to the REB on annual renewals received. Those submissions not requiring full review will be signed at the discretion of the chair. An appropriate form (Appendix VIII) will be provided.
The chair has some discretionary ability to approve minor amendments without full committee review and will report these approvals to the committee at the next scheduled meeting. Other amendments will require full review and should be handled by the same process as Initial Review.
To assure that proposals which are rejected (Category IV) have received a full review, this will be a two step process. If one or both primary reviewers recommend rejection, the proposal will be reevaluated at the next meeting with review by two more reviewers (at least 1 external). If at this point the committee recommends rejection, the decision will be final.
In the event that an appeal is requested on the grounds that there was an error in process, an ad hoc committee of three will be appointed by the Vice-Principal (Health Sciences) to review the request. Their report and recommendations will be made directly to the Vice-Principal (Health Sciences)
Appendix I: Submission form for Initial Review:
Ethics Submission Form For Research Involving Human Subjects or Informants
Appendix II: Submission form for Annual Renewal or Amendments:
Annual Renewal and Amendment Form for Approved Studies
Appendix III: Committee Reviewer Sheet
Appendix IV: Committee Review Form
Appendix V: Deception in Human Research
Appendix VI: An Aid to Constructing a Consent Form and Checklist
Appendix VII: Sample Review Approval Form
Appendix VIII: Sample Renewal Approval Form