Frederick Lowy, MD, Rector & Vice-Chancellor, Concordia University
As biomedical investigators become more involved in industry/academic relationships, they and their institutions are confronting different ethical problems. While investigators have always had to confront the issue of conflict of interest. Only relatively recently has that focus shifted to the institutions, although it is clear, even on cursory reflection, that institutions are as vulnerable as individuals to this problem.
A shift in my personal activities moved me from the Tri-Council Working Group to the presidency of an academic institution. I found that my colleagues among Canadian university presidents disagree with the working group"s philosophy. I have spent a fair amount of time with them debating issues that are taken for granted in the ethics community. Many presidents of Canadian universities have never been involved in biomedical research. They are highly influenced by their vice-presidents or deans of research. Their general attitude seems to be that the proposed Tri-Council code is unduly restrictive, that it will slow or, in some instances, block research, and that it is generally not in the interest of Canada's academic community. Some university presidents are pressuring the three granting councils to water down or possibly even block their approval of the Tri-Council Working Group's code.
An example of institutional conflict of interest exists here in full sight. Our academic institutions are supported by public and private funds, but they are expected primarily to serve public interest. The public expects health-care institutions to be committed to the pursuit of truth, advancement of learning, and dissemination of research results. In recent years, they have also expected these activities to be conducted in an ethical fashion.
Scientists, university administrators, and the public subscribe to this in principle: No conflicts of interest will exist between the academic institutions, including their research ethics boards (REBs), and those who conduct research; academic institutions will enter agreements with private granting agencies only when such agreements advance public interest by funding potentially beneficial research that would not otherwise occur.
These statements define the official responsibilities of academic institutions. Indeed, the mission statement of Canadians for Health Research (CHR) explicitly relates the research enterprise to the public good, specifically to the health of Canadians and, as its first principle of process, lists the word integrity.
Yet, given the complexity of human interactions and motivations, conflicts of interest are ubiquitous and these principles are not always reflected in operational decisions.
Webster defines conflict of interest very simply: "A conflict between the private interests and the official responsibilities of a person or institution in a position of trust." Conflicts of interest are inherently neither bad nor good, neither ethical nor unethical. It is how one deals with conflicts that is either bad or good, ethical or unethical. The existence of conflict per se does not equal impropriety. But people with conflicting interests are more vulnerable to impropriety and the perception or suspicion of impropriety.
Everyone recognizes that it is preferable to avoid conflicts of interest. If conflicts are unavoidable, which is often the case, then people can resort to various strategies, e.g., full disclosure, prohibition of certain activities, etc. However, to believe that conflicts of interest can be totally avoided is naive.
People conduct research for many reasons. Most researchers are well-meaning, but both they and institutions are motivated by various factors. If we want to understand the conflicts that confront institutions, we should examine their private interests. Since Canadian academic institutions' operating budgets are under tremendous pressure, they look to researchers to attract funds to support laboratories, technicians, graduate students, post-doctoral students, etc. Every academic institution in Canada, including teaching hospitals, affiliated research institutes, and university departments, is attempting to maximize the volume of externally funded research at that institution to survive difficult funding situations.
Not-for-profit funding agencies in this country, particularly federal granting councils, have been cut back considerably in recent years. Although a new era of optimism has been created by the establishment of the Canada Foundation for Innovation and rosy forecast of a bountiful post-deficit federal budget, a very considerable discrepancy still separates the amount of available funding and number of excellent research projects waiting to be done.
There are powerful reasons for universities to welcome associations with commercial enterprise, including health-related industries. I am convinced that powerful, positive, scientific reasons exist for industry-university technology- and information-sharing. There is no doubt that public interest is well-served by such relationships, but the wide-scale introduction of for-profit companies as a fourth partner in the Canadian research enterprise greatly expands the potential for conflicts of interest, which is already present in more traditional relationships among researchers, academic institutions, and not-for-profit granting agencies.
Do private interests conflict with official responsibilities? The private sector, e.g., pharmaceutical, agricultural, or medical-device industries, tends to have an up-front, straightforward position in this regard. Companies are responsible to their stockholders or owners to maximize profits, while adhering to ethical standards with regard to safety, efficacy of products, and avoidance of deception. Like all citizens, those who direct these firms rejoice when their products improve the human condition, but they measure their employees' performance and distribute rewards according to customary business success criteria, e.g., market sharer, sales, profits. Since they operate in a competitive environment, they want sweeping patent protection for as long as possible. They try to maintain the tightest possible security for their products, until they are certain of patent protection. These practices are consistent with their business mandate and public declarations of intent.
Scientists in publicly supported, not-for-profit academic institutions are in quite a different situation. Their stated objective is the pursuit of truth, advancement of learning, and dissemination of knowledge. As health professionals, they have an additional, overriding obligation to provide their patients with the best possible health care and advice. As professionals, they profess that they will employ their skills, knowledge, and experience primarily on behalf of their patients. If their duty to patients conflicts with other interests, particularly their private interests, they are expected to practice a high degree of self-effacement. Are they entitled to use cell lines derived from patients' bodies, as in the Moore case in California, to benefit for-profit operations in which they have interests? Are they entitled to use tax-supported public university and hospital facilities to generate financial gain for themselves or for private sector sponsors of research?
What of academic institutions? Historically, they are, par excellence, the societal embodiment of the search for truth. Research is meant to be a means to this end. But academic institutions have responsibilities to their students, faculty, staff, and public communities. They are under considerable pressure to survive in a competitive environment. In this environment, there is a tremendous pressure to facilitate and expedite research. It is therefore not surprising that conflicts of interest arise that are not satisfactorily dealt with, often to the institution's embarrassment, destruction of scientific careers, and the disillusionment of those who support research.
Two years ago in the New England Journal of Medicine (332:262-267, 1995), Ezekiel Emanuel and Daniel Steiner analysed a publicly disclosed case at Harvard University, in which the institution and investigators held equities in companies that exploited their research findings. They analysed the case along four dimensions:
- the conflicts between raising funds to support the institution's activities vs. its primary missions of patient care, teaching, research;
- the size of financial interests in question;
- the degree of direct or indirect institutional pressure on clinical investigators;
- the potential harm from conflicts of interest.
A few years earlier, an entire section of Science (Vol. 257, 31 July 1992), entitled "Confusion on the Cutting Edge", was devoted to emerging conflicts of interest in leading fields of clinical research.
Today, with the explosion of molecular biology and biotechnology, it is rare to find a university that does not have some kind of involvement, either direct or indirect, in biotechnology companies.
Where do REBs fit into this environment? In many ways, they have become the moral conscience of institutions. This role has brought them, at times, into conflict with scientists and university administrations. Examples abound. One, from the field of psychiatry, both in Canada and the USA, concerns the propriety of conducting randomized clinical drug trials with a placebo arm in seriously ill, depressed, and schizophrenic patients. Many industry-sponsored multicentre trials call for this research strategy. The benefits of drugs are easier to identify when they are measured against placebos rather than other effective drugs. This strategy greatly facilitates the Canadian HPB or U.S. FDA drug approval. But should suffering, psychotic patients be denied the best currently available therapy to accelerate the development of better drugs that will benefit future patients? Many REBs have said no, thereby blocking studies of high interest to research colleagues that are potentially lucrative to the institution. To their credit, most university administrations have supported the REB decisions.
This brief foray has explored a problem that requires far deeper consideration than time permits. Some years ago, I began to hold firmly to the notion that, in Canada, we are better off with guidelines than regulations. That is the Canadian way of doing things. But as time goes on and particularly in light of opposition even to the watered-down codes of ethics that have been proposed, perhaps we do need regulations.
Dr. Joly and his colleagues ought to be congratulated for their final product, because it already exerts moral force. I was happy to learn this morning that merged hospitals in Halifax are already using the code as their guideline. I have no doubt that, whatever happens, the existence of this code and its publication will set a moral ground to which many institutions will aspire.