Henry B. Dinsdale, MD, President, NCBHR, Professor Emeritus, Queen’s University
My congratulations to the organizers for choosing the subject of research ethics board (REBs) as the topic of this conference. Not many other organizations are addressing this issue.
The research environment has changed markedly in recent years. About 20 years ago, I was part of a small group of investigators that developed a protocol with a major drug company. That study demonstrated that aspirin was more useful than the company’s product in preventing stroke. The inter-relationship between the clinical researchers and the company was easy with both groups represented equally on the committee drawing up the research protocol.
Many factors, about which REBs need to become knowledgeable, now serve to complicate those relationships. Relative risk, informed consent, confidentiality clauses, dispute resolution procedures, limitations on publication, monitoring, placebos and conflict of interest are some of the items on the list. The increasing involvement of academics in commercial enterprises also brings a new set of considerations.
My topic is the composition of REBs. I will address that topic by reviewing briefly the Medical Research Council of Canada Guidelines and the context in which they operate. Comparisons will be made with guidelines from some other jurisdictions. I will review what we know about the composition of REBs in Canada. This will be followed by comments on some operational issues. I will end by identifying some current and future challenges facing REBs in Canada. Other speakers will deal with issues of commercial REBs, conflict of interest, REB accountability and accreditation.
Ethics review has evolved from a period of benevolent paternalism, through the Helsinki modifications to the present era of guidelines from a variety of international and national organizations such as the Canadian MRC. The MRC Guidelines of 1987 contain reference to the difficulty of achieving nationwide standards under Canadian constitutional provisions. The criminal code provides access for the federal government into provincial jurisdictions such as health. Heavy-handed statutes requiring proof of wrongful intent before sanctions can be imposed thereby accompany Federal intervention. The complexities of federalism may be one reason that we often seek methods for voluntary compliance to national standards.
There is always a tension between ethics and the law. The MRC 1987 report states: "Guidelines can accommodate more easily than law the shifting social evaluations that affect research" and "The truly ethical quality of the assessments to be made may atrophy when judgments are directed by the law."
The MRC guidelines also noted that "the committee believes that researchers and institutions should bear the cost, including that of day-to-day monitoring".
What should be the composition of REBs? According to MRC guidelines there should be community representation, ideally by an individual not affiliated with the institution. There should be relevant specialists, who could be permanent or ad hoc members, depending upon the nature of the protocols under review. A nurse, bioethicist, philosopher, theologian and lawyer are desirable members. Specifications were not stated concerning the number of people on the committee.
What about other jurisdictions? U.S. recommendations suggest that REBs should have five or more members, including at least one scientist, one non-scientist and one person not affiliated with the institution. The REB should include people knowledgeable in the law and standards of practice and professional conduct. Special memberships are advocated for handicapped or disabled concerns, if required by the protocol under review.
The European Forum for Good Clinical Practice (EFGCP) suggests that REBs include two practicing physicians who share experience in biomedical research and are independent from the institution where the research is conducted; one lay person; one lawyer; and one paramedical professional, e.g. nurse or pharmacist. They recommend that a quorum include both sexes from a wide age range and reflect the cultural make-up of the local community.
The 1996 Australian Health Ethics Committee recommendations were entitled, "Membership Generally of Institutional Ethics Committees". They suggest a chairperson be preferably someone not employed or otherwise connected with the institution. Members should include a person with knowledge and experience in professional care, counselling or treatment of humans; a minister of religion or equivalent, e.g. Aboriginal elder; a layman; a laywoman; a lawyer and, in the case of a hospital-based ethics committee, a nurse.
Recommendations about REB composition appear similar worldwide. But how do you find these people? How are they recruited? What are ideal generic skills and attitudes?
Who should select the committee? In Canada, the guidelines say that the president, principal, or CEO of the hospital should control the selection process. In the U.S. it is the CEO of the institution. In Australia, "an institution" may appoint the members. EFGCP guidelines state that REB members should not be appointed by those with a vested interest in the research outcome.
The National Council on Bioethics in Human Research (NCBHR) carried out a survey and site visit to the REBs of the 16 Canadian medical schools. That survey revealed that the chair of the REB usually selected committee members. Sometimes the dean of the faculty, a nominating committee from the hospital or university, or the hospital administrator controlled the process. The latter option may be of concern in view of a case presently before the Quebec courts in which a hospital administrator overturned the ruling of its REB.
Of the 47 REBs surveyed by the NCBHR between 1990 and 1993, only five met MRC and NIH guidelines. The most frequent transgressions were that committees were department-based and did not have the composition suggested by MRC guidelines. Only 50% of the REBs had outside members. Frequently, there were problems recruiting individuals with expertise in ethics. It is to be hoped that the availability of individuals with knowledge of ethics will increase as teaching of ethics becomes increasingly part of undergraduate and graduate education.
The majority of REBs felt that adequate scientific expertise was available. Did REBs conduct ongoing reviews or audits of research in progress? The answer was almost universally "No". Some considered such review not part of their mandate. Others stated they had neither time nor resources to review or monitor.
REBs were asked to state what they considered to be the major weaknesses of the review process. The majority replied that their workload was too heavy. Most committees met once a month. The average meeting lasted 3 hours. The chairperson spent about 10 hours a month on REB activity. That workload has probably increased during the time since the NCBHR study.
Concerns were voiced about the legal liability of REB members. Most members assumed they were covered by the institution’s legal liability insurance. In some instances, individuals who were not employees of the institution were not covered. Information about liability insurance practices across Canada was fragmentary.
Guidelines recommend written policies on record keeping. Many REBs did not have such policies. Documents should be accessible to applicants and others. Concerns were raised about confidentiality and storage.
What qualities should one seek in lay committee members? This question arose last week at a conference on xenotransplantation. If a national committee was established to provide advice to local REBs who should serve on that committee? The ideal REB lay member is without a vested interest, has good judgment, interested and able to listen to both sides of an argument.
Is a lawyer always necessary? Smaller institutions in particular are concerned about being able to attract the voluntary services of a lawyer. Will it be particularly difficult to attract a lawyer at universities without law faculties?
Will the forthcoming Tri-Council Policy Statement change the composition of REBs? The last version stated that the minimum acceptable number for membership is five, both men and women. Of these, at least two must be experienced in relevant research, one knowledgeable in the discipline of ethics, one lawyer and one without other affiliation with the institution. The institution’s legal counsel must not be a member.
Scientific expertise in members may become an increasing issue. Federal plans to off-load aspects of Phase 1 drug testing will create challenges for the average REB. Some REBs are comfortable with the prospect of change in that area. Others are apprehensive. Xenotransplantation and the transplantation of cells or organs between species create special needs in scientific expertise. Can local REBs cope?
REBs should increasingly ask investigators "Is this the best drug to test for this disease? Are the investigators organized into responsible consortia with scientific subcommittees that reach impartial decisions about which one of a number of new agents from various companies is most meritorious of evaluation?" Such consortia develop only if investigators are not already allied with a specific company. They must be able to function in a collegial manner with other investigators in the same specialty. This process often requires considerable ego suppression. There are important examples of such consortia of investigators able to make wise choices about drugs to be studied. This avoids centres being "cherry-picked" by companies to test every compound that comes along. We owe it to our patients to ensure such credibility of protocol development.
NCBHR is developing a registry of Canadian REBs. We also need a study of the human and financial resources needed for a nation-wide REB review process, particularly in view of forthcoming Tri-Council Policy Statement requirements.
The quality of local REB work depends to an inordinate degree on the conscience and commitment of committee members. National and international committees with special expertise will be required to deal with singular developments, such as recombinant DNA and xenotransplantation. Such committees should have the resources to stay abreast of research methods and issues. They would be able to publicize the significant questions and provides material for guidance to local REBs.
REBs are under increasing pressure to perform more work with limited resources. Those in control of institutional budgets must become more aware and supportive of the work done by REBs. Conferences such as this can only help in that process.