I am very pleased to be able to participate in this DHHS conference on conflict of interest in biomedical research. To begin, let me say that I am here today as an officer of the AAMC; but having spent my entire academic career at Stanford University (as many of you know), I bring to this discussion long leadership experience in an institution renowned for its biomedical research and faculty entrepreneurship and situated in the very heartland of biotechnology, venture capitalism, and aggressive technology transfer. This experience has shaped my remarks today. This conference has been organized by DHHS around six major questions, to which the AAMC has submitted a formal letter of response that is posted on our web site at www.aamc.org/research/coicomment.pdf. In this afternoon’s session, my colleague, Allan Shipp, will present the highlights of the letter to you, so I shall use my time to offer some personal observations about conflicts of interest and commitment that I hope will prove helpful in informing our discussions during the next day and a half.
I begin by reminding this audience of the existence of three very thoughtful and helpful monographs on the topic of conflict of interest and commitment in academic medical centers, which were published in the early 1990s by the AAMC and the AHC, respectively. In preparing for this meeting, I reviewed those documents and found them as insightful and compelling now as they were when first disseminated. So, I would argue that a sound framework of recommended institutional policies and procedures for managing and mitigating these kinds of conflict exists, and I commend them to you. The framework may well need some fine-tuning to bring it into conformity with the remarkable changes that have occurred in biomedical science and technology in the past decade, but I suggest that we do not have to start from scratch, and that should give all of us some comfort. .
Among the important points emphasized in the documents were several that bear repetition and reflection: First, conflicts of interest and commitment are ubiquitous in academic life (and indeed, in all professional life), and conflicting pressures inherent in the academic milieu, e.g., for faculty advancement, obtaining sponsored research funding, winning the acclaim of one’s professional peers, competing for prestigious research prizes, and yes, desiring to alleviate human pain and suffering, all may be more powerful in influencing faculty behavior than the prospect of material enrichment. These intellectual academic conflicts tend to be amorphous and are not of much concern to the public, but they are widely recognized within the academy, and institutional policies and procedures, as well as scientific review processes, have long been in place to manage them. In contrast, financial conflicts tend to be discrete and quantifiable, but are often unrecognized until specifically disclosed. Moreover, financial conflicts are very well understood by the public and for this reason pose a special vulnerability and risk to our enterprise that demand our attention.
Second, it follows that although these conflicting pressures are diverse in origin, and may be subtle, their oversight and management are primarily the responsibility of universities and academic medical centers. The federal government, which continues to be the major sponsor of basic research in this country, certainly has a legitimate interest in the issue, but that interest is circumscribed and should be limited to first, ensuring itself and the American public that research involving human subjects is performed in compliance with the requirements of 45CFR46; second, that federally supported biomedical research is conducted and reported with integrity; and third, that data that buttress decisions that affect the health of the public are sound and trustworthy. Accordingly, the federal involvement with conflict of interest should be proportionate and carefully tailored.
Third, it also follows that since these conflicts can never be eradicated from professional life, their existence must be accepted and not equated with professional misconduct. This last point is very important and bears repeating: the presence of conflict of interest does not equal scientific misconduct. Unfortunately, the history of Congressional and media interest in this issue derives from several well-publicized medical research scandals in the early and mid-1980s, in some of which scientific misconduct and blatant conflicts of financial interest appeared to be inextricably intermingled. Ever since, whenever the public has become aware of an allegation of scientific fraud or the occurrence of a major adverse event in clinical research, the search has immediately begun to ferret out even a whiff of financial conflict of interest on which to lay the blame. Indeed, it is the publicity about recent tragic deaths in gene transfer trials that aroused the Congress and is arguably responsible for the Department’s renewed attention to this issue and the convening of this conference. Fourth, I think a remarkable feature of U.S. science policy during much of the post-WW II era, especially given the extraordinary growth in support of biomedical research, has been the relatively light hand of federal oversight of the scientific process, the deference shown to scientific and academic self-governance, and implicit trust in the integrity of scientists. It has helped that the vast majority of federal funding for basic science has flowed through universities, which have benefited enormously from their public image as independent and disinterested producers and arbiters of knowledge. It is instructive to revisit a principle embodied in the 1915 Declaration of the
American Association of University Professors: “All true universities, whether public or private, are public trusts designed to advance knowledge by safeguarding the free inquiry of impartial teachers and scholars. Their independence is essential because the university provides knowledge not only to its students, but also to the public agency in need of expert guidance and the general society in need of greater knowledge; and…..these latter clients have a stake in disinterested professional opinion, stated without fear or favor, which the institution is morally required to respect.” I would only add, which both the institution and its faculty are morally required to respect. Today, I suggest, that image of academic virtue and the public’s willingness to trust may both be tottering as major research universities and academic medical centers struggle to meet the ineluctably contradictory demands from government and industry that they become “engines” responsible for regional economic development, while at the same time assiduously avoiding even the slightest suspicion that their growing financial entanglements with commerce might distort their conduct and reporting of research. Nowhere, in my opinion, is this dilemma and exposure greater than in academic medicine, in which the breadth, depth and intensity of commercial engagement have grown especially rapidly and visibly. I do not suggest that the commercial exploitation of faculty discovery is limited to biomedicine, far from it. But when faculty or institutional
conflicts of interest or commitment occur in computer science or micro-electronics, or in schools of business or law – as they do, they do not generate vivid front-page stories in the national media or headlines on the “6 o’clock news.” I suggest that neither our biomedical scientific professions nor our academic medical centers have yet stepped up to the challenges posed by this profoundly changing relationship between the academy and the world of commerce, nor have they devised mechanisms that would successfully enable them to meet these conflicting public imperatives while remaining free from suspicion and protecting their image of virtue from blemish. This failure is particularly dangerous when one considers that biomedical research has flourished in the past decades because of public trust in the “Good” of the enterprise. That trust is nowhere more evident or fragile than in medical research involving the participation of human subjects, where even the perception of faculty or institutional conflict of interest cannot be tolerated. I acknowledge that this sets a very high standard, more stringent than that faced by any other faculty, or, indeed, by most members of society. But the future of our enterprise demands that we meet it.
In my remaining time, let me make just a few comments about the substance of today’s agenda. The oversight of financial conflicts of interest in federally sponsored research has been accomplished by federal guidance rather than prescription, through the mechanism of institutional assurance. I remind you that in 1990, when the first proposed regulation of conflict was published for comment by DHHS in response to its new Congressional mandate, it was roundly denounced by the scientific community, academic medical centers, and universities for being over-reaching, unacceptably prescriptive, and intolerably intrusive into matters that traditionally were reserved to academic self-governance. In the face of this outburst, Secretary Louis Sullivan chose to hastily withdraw the proposed rule. Subsequently, the Department issued the more general guidance in place today, in which management of conflict was to be based on disclosure, and the most prescriptive element was the setting of a threshold to define “significant financial interest.” All responsibility for oversight and management was deferred to the institutions. Today, I think it is legitimate to ask whether, given the growing entanglement of academic medicine with industry, and the sometimes very large financial interests held by investigator faculty and their institutions in start-up ventures founded on those investigators’ inventions, is disclosure alone still sufficient to protect public trust? I would like to offer two lines of consideration with respect to this question. First, if we agree that disclosure is necessary, to whom should that disclosure be made, and in what detail? To IRBs only? To prospective research subjects in the informed consent process? Yet to others? In deliberating on these questions, we should keep in mind that there is a research literature on the informed consent process itself that calls attention to some of its limitations. One such limit is the amount of information a prospective subject can integrate and understand, especially when that subject is also an anxious patient. We must take care that we not burden the process with information overload that may, as Yale Professor Robert Levine once so aptly put it, subvert a process designed to elicit informed consent into one that elicits uninformed denial. With respect to this point, I would note that way back in
1982-83, a select committee of faculty at Stanford Medical School recommended, and the University adopted, changes in both the grant routing sheet, the protocol for requesting IRB approval, and the informed consent protocol, which required disclosure of consulting arrangements, line management responsibilities, or substantial equity holdings in the proposed sponsor, vendors, or subcontractors. The detail to be submitted to the IRB was extensive, and full disclosure of consultative or financial relationships was required in the informed consent process, as well. To the best of my knowledge, these requirements have not impeded the growth or vigor of biomedical research at Stanford over the ensuing 17 years. Second, I would suggest that disclosure alone may no longer be sufficient, and argue that some forms of financial conflict that have come to public attention go beyond the pale of acceptability and should be forbidden. To this point, I commend the recent decision by Harvard Medical School Dean, Joseph Martin, to reaffirm his institution’s policy on financial conflicts of interest, which is arguably one of the most stringent in academic medicine. Under Harvard’s policy, financial conflicts of faculty are stratified into three groups based on the magnitude of faculty members’ financial interests, and a limit is defined – a rather conservative limit in today’s world - above which a proposal is deemed to be unacceptable.
We must recognize that the stringency of financial conflict of interest policies varies substantially across academic medical centers, and to an extent that I believe is worrisome and may be dangerous. Aside from this variation in policies, it is also fair to ask how diligently are institutions enforcing their policies on the oversight and management of financial conflicts of interest? I don’t have any data that bear on this issue, but I do think, once again from the public record, that there may be dangerous inconsistency here as well, and some of the reported lapses in insitutional oversight – or better, in institutional judgment - are difficult to understand. Finally, I note that following their loud protestations in 1990, our professional societies have become curiously silent on this issue, which I think is regretable. Here I wish to recognize the position statement recently issued by the American Society of Gene Therapy, which states plainly that certain financial arrangements are unacceptable for a principle investigator and other major participants on a research team engaged in gene therapy trials. Whether one agrees with the details of this proscription is not the point; what is the point that the society has taken an unambiguous and courageous stand. Would that others would follow its example! I conclude by suggesting that if our leading academic medical centers and professional societies can not come to reasonable agreement in defining the kinds and limits of financial interest that are prima facie acceptable in research involving human subjects, and cannot convince the government and the public that they are being diligent in meeting their responsibilities in this area, we are inviting the cognizant federal agencies, as well as the Congress, to step in and prescribe those limits for us. I hope these comments have been helpful in setting a constructive framework for this conference. Thank you very much for giving me this opportunity to address you.