15 AUGUST 2000

Thank you, Stuart; and good morning, ladies and gentlemen. I echo the earlier welcomes from my colleagues, and I thank you for foregoing a couple of lazy days of summer to join in this important conference.

We meet today and tomorrow at the initiative of Secretary Shalala and, in part, as a consequence of several trains of events set into motion in Philadelphia last fall with the death of a patient in a gene transfer trial. The immediate aftermath of that tragedy featured intensified debate about the readiness of gene transfer for prime time and stepped up efforts by the National Institutes of Health and the Food and Drug Administration to oversee this emergent medical technology. Both the debate and the evolution of gene transfer oversight continue.

But, amidst our focus on gene transfer, a larger truth emerged — namely, that many of the issues raised by the events in Philadelphia were not unique to gene transfer research but rather were applicable to essentially all forms of human clinical investigation. This caused us to broaden our scope. In particular, we took account of the fact that clinical research in recent decades has grown ever more complex in terms of its goals, its substance, its financial underpinnings, and its associated ethical considerations. The overarching issue, therefore, became the adequacy of our rules and processes for the protection of human research subjects in the face of these ever more formidable challenges.

That phase of our efforts culminated in May of this year when Secretary Shalala announced the following five initiatives designed to enhance protection for human research subjects:

The last of this list obviously is the reason we gather today. As indicated in the advance materials for this conference, we are hopeful that the insights gained here will help us formulate new guidance for the research community and ourselves regarding what information about the financial interests of investigators and research institutions should be disclosed to prospective and enrolled research subjects and others.

The regulations to which I refer are three: first, the conflict of interest regulations applicable to research funded by agencies of the U.S. Public Health Service; second, the conflict of interest regulations promulgated by the Food and Drug Administration for sponsors and investigators engaged in development of new diagnostic, therapeutic, or prophylactic products; and, third, the regulations for protection of human research subjects — commonly known as the Common Rule as a result of their adoption by 17 different Departments and Independent Agencies of the federal government. As thoroughgoing as these rules are in many respects, they are not explicit as to what information, if any, about financial conflicts of interest of investigators and research institutions ought to be shared with prospective and enrolled human research subjects. Through this conference, we are seeking insights about what interpretive guidance might be offered the research community to make these current regulations more effective.

In the main, this conference marks the collision of tradition and change. For more than a half- century, beginning with the Nuremburg Code, the people of this nation and others have been almost unanimous regarding the importance of protecting human research subjects from undue and undisclosed harms. Informed consent has been -- and surely will continue to be -- the bedrock upon which our infrastructure of protections rests. Anything that threatens to erode or compromise informed consent is a threat to the entire system of human clinical investigation.

Financial conflicts of interest on the part of investigators or research institutions are cause for such concern.

Yet, now more than ever before, financial conflicts of interest — at least in appearance, if not in fact — seem to be an inescapable part of the modern clinical research scene. Legislation passed in the early 1980s to foster commercialization of research results emanating from universities and other traditionally non-commercial entities has spawned a host of new financial relationships that continue to evolve in scope and complexity with no end in sight. On the whole, these new financial relationships are making possible the kinds of knowledge and technology transfer that the legislative architects envisioned; and, in view of the stream of impressive new products entering the health care marketplace, the public clearly is better off as a result of these new relationships.

Our challenge, therefore, in my judgement, is not to arrest or reverse these trends that attend the commercialization of research results. Rather, our challenge is to understand and modulate these trends so that our traditional commitment to protection of human research subjects is continually reaffirmed in word and continually exercised in practice.

In taking up this challenge, we dare not forget that human clinical investigation almost always is the final common path for knowledge and technology on the way from the laboratory to the health care milieu. Without strong protections for human research subjects, enrollment in clinical studies inevitably will decline; and what is now a wide and heavily traversed passage will become a bottleneck instead. Moreover, the losses resulting from a diminished clinical research stream will be to the detriment of current patients as well as future ones — for, in many areas of medicine today, the interventions offered in the context of randomized controlled clinical trials often are the best health care available.

Thus, my colleagues and I accept the challenge of harmonizing the new financial realities with our longstanding commitment to effective informed consent. The fact that, by your attendance today, so many of you apparently stand ready to contribute your experience and insight is highly gratifying. Thank you for what you are about to do.