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Statement on "Human Subjects Research: Are Individuals Protected?"

Mr. Chairman and members of the Subcommittee, I am David Korn, M.D., Senior Vice President for Biomedical and Health Sciences Research at the Association of American Medical Colleges (AAMC). The AAMC represents the 125 accredited U.S. medical schools; the 16 accredited Canadian medical schools; some 400 major teaching hospitals, including 74 Veterans Administration medical centers; 91 academic and professional societies representing over 100,000 faculty members; and the nation's 67,000 medical students and 102,000 residents. Our member institutions conduct a very large share of the biomedical and behavioral research performed in this country, and have been the source of many of the dramatic breakthroughs that have revolutionized biology and are transforming medicine. My testimony today will focus on how the AAMC, on behalf of our members, has undertaken significant new initiatives aimed at strengthening the protection of the many thousands of human volunteers who participate in medical research each year.

The AAMC commends the Subcommittee for convening this hearing to explore the issues surrounding the protection of human research participants. We recognize that academic medicine and the American public have forged a special relationship rooted in trust that is nowhere more evident - or more fragile - than in clinical research involving human participants. We are troubled by recent reports of lapses in the oversight of clinical research in some of our most prestigious members, reports that threaten public confidence in our nation's system for protecting research participants. And we are disturbed by allegations that the financial interests of faculty investigators or their institutions may have compromised their independence and credibility, and threatened the welfare of research participants as well as scientific integrity.

AAMC and its members are vitally concerned for the safety and well being of the patients and healthy individuals who volunteer to participate in our research programs. We believe that their protection can be most reliably achieved and effectively sustained in settings that place a high priority on, and devote significant attention to, research ethics, as well as compliance with legal and regulatory requirements. We agree with OHRP Director, Dr. Greg Koski, that the most effective programs of protection of human research participants will occur in institutions that go beyond compliance to foster "a culture of conscience and responsibility" that lodges not just in Institutional Review Boards (IRBs), but in every principal investigator and all of those who engage in clinical research. To assist our members to create and maintain such a desired culture of conscience and responsibility, and to achieve uniformly high standards of human research protections across the entire community of academic medicine, we have organized national research compliance conferences, and have worked jointly with the organization Public Responsibility in Medicine and Research (PRIM&R) to sponsor focused regional educational programs for IRB members and staff, faculty who conduct clinical research, and institutional officials responsible for its oversight in our member institutions. All of these efforts have also been enthusiastically received and over-subscribed. A year ago the AAMC created a compliance Web site to publicize and make accessible the most promising initiatives developed by our members to address the education and credentialing of clinical investigators. A number of attractive approaches were already in development by our members well before October 2000, when the NIH made such educational programs mandatory for its awardees. We predict that the credentialing of clinical investigators, an approach initiated by the University of Rochester Medical Center, will become more widespread. Visitors to the AAMC compliance site can locate a rich set of information related to federal regulations, model policies and procedures, and available educational resources.

The remainder of my testimony will emphasize two major new initiatives in which the AAMC is heavily engaged: one to establish a system of voluntary accreditation of institutional programs of human research participant protections, and the other, to address the concerns that have been raised about financial conflicts of interests in clinical research.

Accreditation

Despite the existence for more than 25 years of an evolving code of federal regulations (since 1991 commonly dubbed "the Common Rule") and policies to protect the rights and welfare of human research participants, there has been increasing concern in recent years that the system for protecting these participants needs improvement. These concerns were dramatically underscored by the recent wave of federal suspensions of research at various institutions around the country, which indicated to many that systemic improvements in human research protection programs are necessary. While acknowledging that researchers and IRB members are generally adhering to the federal requirements for protecting human research participants, the Inspector General of the Department of Health and Human Services observed that the national system for protecting research subjects is currently under strain and facing increasing pressure in a rapidly changing research environment.

IRBs have a significant number of weighty responsibilities. Under the terms of the assurances their institutions provide to federal funding agencies, IRBs must make certain that the research they oversee is conducted in accordance with Federal policies and all applicable state and federal laws. To assure that the risks to human participants are minimized, IRBs must assess these risks in hundreds or even thousands of research protocols, while meeting exacting procedural requirements and maintaining detailed records. Moreover, even as the complexity of clinical research and the volume of research protocols are increasing, IRBS must respond to an ever-expanding array of federal and state requirements that, in the aggregate, have become procedurally onerous, and, some argue, distracting.

Given that within the academic community IRB members are almost always volunteers with major responsibilities in teaching, research, and often, patient care, it is not surprising that they are finding it difficult to accept progressively increasing new burdens of oversight, or finding the time and resources to undertake periodic self-assessment. The AAMC agrees with Dr. Koski that responsibility for ensuring the well being of human research participants in this rapidly changing environment of clinical research, can no longer be considered primarily to rest on IRBs, but must become the duty of all who are engaged in the enterprise. The British code of medical ethics speaks of a solemn "duty of care" that rests on every physician; the AAMC suggests that same ethical "duty of care" should rest on every physician-investigator who conducts research on human participants.

Universities, medical schools, and teaching hospitals must work to instill across their campuses, in all who engage in human participant research, a new sense of shared obligation and a new culture of individual responsibility. The AAMC believes, based on its long experience with many different kinds of academic accreditation programs, that establishing a mechanism of voluntary accreditation of human research protection programs would be very helpful to our members, as well as the broader academic community, in accomplishing the changes in faculty attitude and institutional culture that are necessary. The idea of creating such an accreditation mechanism had been debated within PRIM&R circles for several years. In May 1999 PRIM&R announced that it would develop a program of accreditation for human research protection programs, which it dubbed AAHRPP (Association for the Accreditation of Human Research Protection Programs), and formed a committee to begin to draft accreditation standards. Since that time, as I will describe, the AAMC has partnered with PRIM&R to bring this concept into existence in a way that is consonant with our traditional and uniquely American model of voluntary, peer-driven, educationally focused accreditation of academic institutions and their components. The accreditation model, while necessarily conforming to all applicable statutory and regulatory requirements, is importantly different from the regulatory model, common in other countries, which focuses purely upon regulatory compliance. Accreditation fosters a process of self-examination and a culture of self-improvement that is stimulated and nurtured by the accreditation process itself. AAMC shares with PRIM&R the belief that such an accreditation process for human subjects protection programs should combine objective, outcome-oriented performance standards with on-site reviews involving collegial dialogue and education. An approach that is collaborative yet based upon clearly defined standards will encourage institutions to strive for ever higher levels of performance beyond the threshold of compliance. The ultimate objective of accreditation will be to foster a commitment to continuing quality improvement within each institution's system for the protection of human research participants.

The AAMC conceived of AAHRPP as a nonprofit Member corporation, in which the Members would be the large Washington-based associations representing America's universities (AAU and NASULGC), medical schools and teaching hospitals (AAMC), biomedical scientists (FASEB), behavioral and social scientists (COSSA), patient advocacy organizations (NHC), and IRB experts (the Boston based PRIM&R). AAMC took the lead in forging this alliance, securing funding, and bringing AAHRPP into existence; AAHRPP was incorporated in the state of Maryland on April 23. AAHRPP's mission is to provide a process of voluntary, peer-driven, educationally focused accreditation and continuing quality improvement for academic institutions and other organizations concerned with research involving human participants. AAHRPP's goal is to create and administer a highly respected program of accreditation that is viewed by the larger research enterprise, the federal government, and the public as safeguarding and improving the protection of human research participants.

AAHRPP will be governed by a 21 member Board of Directors that will include 5 public representatives and has full authority over the organization and its accreditation programs and activities. The founding Members will serve in a Trustee role, with strictly circumscribed fiduciary responsibilities; the Members will have no role whatever in the operations of AAHRPP or its decision-making processes. The CEO of AAHRPP will be an Executive Director, for which recruitment is well underway. In addition to the sundry committees that are required by an accrediting body, AAHRPP will establish an Advisory Committee in which the stakeholders in human research are broadly represented to ensure that there will be continuing patient and other public input into its deliberations and processes. The AAMC is very pleased to have been able to play a major role in the creation of AAHRPP and is prepared to continue to do whatever it may be asked to ensure its success. We believe that AAHRPP will contribute in important ways to the change in culture of human participant research, which Dr. Koski has repeatedly called for, and to which our members and we unequivocally subscribe.

Conflicts of Interest

Following last year's reports of several tragic events that occurred in gene transfer experiments in which both faculty and their sponsoring institutions were perceived to have significant financial interests, the Administration, the Congress, and the media began to question the sufficiency of current federal conflict of interest guidelines, the credibility of institutional conflict of interest policies, and the dependability of academic institutions in complying with their own policies. Driving this concern was the fear that financial conflicts of interest may jeopardize the safety of research participants and the integrity of research data. This topic had last captured public attention in the 1980s, when congressional hearings cast a harsh light on several instances in which financial conflicts of interest seemed linked to scientific misconduct in clinical research.

More than a decade ago, the AAMC developed and published guidelines to aid its membership in addressing faculty conflicts of interest in research. These guidelines were a necessary response to the emerging paradigm of university/industry collaboration spurred by the Bayh-Dole Act, which in 1980 gave universities title to inventions arising from federally sponsored research. Bayh-Dole created fertile ground for nurturing the transfer of basic research findings to the developers of beneficial products, but also gave rise to new incentives for investigators and their institutions to pursue financial interests in the course of scientific research. Although the AAMC guidelines have served as a useful model for conflict of interest policies developed by individual medical schools and teaching hospitals, recent studies have indicated that across the academic community approaches to identifying and managing individual financial conflicts of interest vary widely. Of particular concern is the absence of consensus regarding the proper management of related financial interests in clinical research that involves human participants. Moreover, neither the AAMC guidelines nor most institutional policies address the conflicts that may arise from the financial interests of the institutions themselves, which have increased substantially in the past decade from both royalty streams and equity holdings. Although conflicts of interest are ubiquitous and inevitable in academic life, as they are in all professions, the existence of related financial interests of either individual investigators or their institutions in research involving human participants raises special concerns. Yet, such interests have become particularly widespread in academic medicine, which has spawned a flourishing biotechnology industry, generated an insatiable public appetite and impatience for ever more wondrous treatments, and contributed importantly to the intense public and political interest in universities as sources of regional economic prosperity.

Our collective experience with the increasingly commercial nature of academic research and our obligation to be responsible compel a thorough reexamination of how the academic medical community manages financial interests in research involving human participants. The AAMC believes it imperative that our community take the initiative in reassuring the public and policy makers that neither institutional nor faculty financial interests will be permitted to compromise the safety of human participants or the integrity of biomedical research. AAMC President Jordan Cohen, M.D., made financial conflicts of interest the theme of his address at the AAMC 2000 Annual Meeting, where he announced the formation of a high level Task Force on Financial Conflicts of Interest in Clinical Research. The Association has chosen to focus the efforts of the Task Force upon financial conflicts of interest involving human participants, in part because we perceive an urgent need to rethink and revise our guidance in this area, and in part to complement the activities of an AAU Task Force on the Responsible Conduct of Research, which is examining some of these same issues from the campus-wide perspective of university presidents. In composing our Task Force and developing its charge, we have been particularly sensitive to the special relationship of trust that academic medicine enjoys with the American public. The work of the Task Force will be guided by our commitment to sustain that trust in the context of the new, extraordinarily promising, and far more entrepreneurial environment in which we now conduct research.

The Task Force roster is contained in the AAMC's brief press announcement of its creation, which is appended to this testimony. We request that this material be entered into the record of this hearing. Among the 28 members of the AAMC Task Force on Financial Conflicts of Interest in Clinical Research are prominent representatives from the fields of academic medicine, law, industry, bioethics, patient advocacy, the media and politics. Chaired by William Danforth, M.D., chancellor emeritus of Washington University, the task force anticipates completing its work within the next 12-18 months.

During the course of its deliberations the Task Force is charged with examining the appropriate limits of financial interests for faculty, students, and staff involved in the conduct of research with human participants, and whether certain types of financial interests should be prohibited. The Task Force shall consider the most effective means by which significant related financial interests in research involving human participants should be disclosed to the institution, the research participants, and to the public, and under what circumstances, if any, it is acceptable for institutions to invest in and sponsor faculty entrepreneurial activities involving human participants. For those circumstances that may be deemed acceptable, the Task Force shall propose mechanisms to ensure that institutional oversight of faculty activities is responsible and credible.

At the first Task Force meeting, on May 14th, 2001, members agreed that the academic medical community must undertake an unprecedented re-examination of the values that animate and sustain the clinical research enterprise, to ensure that the welfare of participants is never subordinated to the financial pressures that confront individual faculty or research institutions. At the same time, some members cautioned that the unintended consequence of blanket prohibitions on financial relationships might well be to slow medical advances or to drive gifted scientists out of the academic setting. Notwithstanding these concerns, all members shared the view that studies involving human participants require special safeguards above and beyond those applicable to other forms of research. Most members appeared to agree that these safeguards should include disclosure of related financial interests and restrictions or outright prohibitions where those interests pose an untenable conflict between personal gain and participant welfare.

During the summer months, the Task Force will work diligently to develop a policy document that will offer our members specific and detailed guidance for the oversight of individual financial conflicts of interest. Simultaneously, Task Force members will begin to consider the entirely new and complicated question of institutional financial interests in research. The AAMC respectfully urges the Subcommittee to afford academic medicine the opportunity to demonstrate that we can - and will - take the actions necessary to sustain the public trust in our institutions, our investigators, and the integrity of biomedical research, while continuing to play a seminal role in translating the remarkable fruits of the "Golden Age of Biology" into public benefit.

To conclude, the AAMC and its members are firmly committed to the protection of the rights and welfare of every individual who elects to participate in human research, and we look forward to continue working with the members of this Subcommittee to achieve this goal.

Appendix

Testimony of David Korn, M.D.
Sr. Vice President for Biomedical and Health Sciences Research
Association of American Medical Colleges
Before the Senate Health, Education, Labor and Pensions Committee
Subcommittee on Public Health
Senator Bill Frist (R-Tenn.), Chairman
Hearing on Human Subjects Protection
Wednesday, May 23, 2001

The AAMC Task Force on Financial Conflicts of Interest in Clinical Research

With the goal of assembling many of the stakeholders in clinical research - including investigators, patient representatives, medical school, teaching hospital and university leaders, and those from industry, law and the media- the Association of American Medical Colleges (AAMC) has named 28 members to its Task Force on Financial Conflicts of Interest in Clinical Research. The panel is charged with assessing current AAMC guidelines on conflict of interest, and with formulating new principles that address financial interests in research held by both individual investigators and institutions. The Task Force met for the first time on May 14th, 2001 in Washington, D.C.

AAMC President Jordan J. Cohen, M.D., announced the formation of the Task Force last November at the AAMC Annual Meeting in Chicago. Following the subsequent announcement of the composition of the panel he said, "This new Task Force addresses one of the most significant issues the Association and its members face - sustaining public trust in research in which both the investigators and their institutions may hold financial interests. We have lots of ground to cover and the stakes are high; the public's support for medical research may turn on the ability of the academic community to police itself in ways that are credible."

The Task Force Chair is William Danforth, M.D., chancellor emeritus of Washington University. "We have an excellent group with members who bring diverse perspectives to the task," said Dr. Danforth. "Our work is timely and important, especially because of the increased cooperation between business and academia, which brings with it new forms of financial rewards."

A significant feature of this AAMC Task Force is the inclusion of national leaders from patient groups. Martin Delaney, Task Force member and Founding Director of Project Inform, a San Francisco-based HIV/AIDS information and advocacy organization, said, "Putting patients' interests first-ahead of financial and product sponsors of clinical trials-is one of the most basic goals of patient activism. I worry that people with life threatening illnesses, who often lack the support of organized activism so common in the AIDS community, are left to fend for themselves in an environment heavily influenced by corporate and academic goals. I'm very grateful for the opportunity to address these concerns through this Task Force."

The Task Force anticipates completing its work within two years. It is charged with reviewing and updating the AAMC's 1990 guidelines on faculty conflicts of interest, and with developing a new set of principles for addressing institutional financial conflicts of interest in clinical research. As a starting point for its deliberations, the Task Force will consider the principles and guidelines recently developed by a group of prominent medical school leaders convened by Harvard Medical School Dean Joseph B. Martin, M.D.

A list of the members of the Task Force on Financial Conflicts of Interest in Clinical Research follows.

Chair
William Danforth, M.D., Chancellor Emeritus and Vice-Chairman Board of Trust, Washington University

Academic Leadership
Russel E. Kaufman, M.D., Vice Dean, Education and Academic Affairs, Duke University School of Medicine
Robert P. Kelch, M.D. Dean, University of Iowa College of Medicine
Mark R. Laret, Chief Executive Officer, University of California, San Francisco, Medical Center
Joseph B. Martin, M.D., Ph.D., Dean, Faculty of Medicine, Harvard Medical School
Edward D. Miller, M.D., Dean, Johns Hopkins School of Medicine, CEO, Johns Hopkins Medicine
Paul G. Ramsey, M.D., Vice President, Medical Affairs, Dean, School of Medicine, University of Washington

Researchers
John Thomas Bigger, M.D., Professor of Medicine and Pharmacology, Columbia University
Ronald Levy, M.D., Professor, School of Medicine, Stanford University
Charles P. O'Brien, M.D., Ph.D., Chief of Psychiatry, Philadelphia VA Medical Center, Vice Chair of Psychiatry, University of Pennsylvania
Savio Woo, Ph.D., Director and Professor, Institute for Gene Therapy, Mount Sinai School of Medicine
Alastair J.J. Wood, M.D., Assistant Vice Chancellor for Research, Professor of Medicine, Professor of Pharmacology, Division of Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine

Attorneys
Susan H. Ehringhaus, Esq.,Vice Chancellor and General Counsel, University of North Carolina at Chapel Hill
Joan S. Leonard, Esq., Vice President and General Counsel, Howard Hughes Medical Institute
Dorothy K. Robinson, Esq., Vice President and General Counsel, Yale University

Ethicists
Jeffrey Kahn, Ph.D., M.P.H., Director, Center for Bioethics, University of Minnesota
Thomas H. Murray, Ph.D., President and Chief Executive Officer, The Hastings Center

Industry
Ginger Graham, Group Chairman, Guidant Corporation Susan Hellmann, M.D. M.P.H., Chief Medical Officer, Genentech
Roger Porter, M.D., Vice President Clinical Research and Development, Wyeth-Ayerst Research

Journalists/Media
Frank Davidoff, M.D., Editor, Annals of Internal Medicine
Susan Dentzer, NewsHour with Jim Lehrer
Marvin Kalb, Lecturer in Public Policy, Executive Director, Washington Office, Joan Shorenstein Center for the Press, Politics and Public Policy, Trustees for Harvard University
Hedrick Smith, President, Hedrick Smith Productions, Inc.

Public/Patient Representatives
Martin J. Delaney, Founding Director, Project Inform
Constance E. Lieber, President, National Alliance for Research on Schizophrenia and Depression
Hon. John E. Porter, Esq., Partner, Hogan and Hartson, LLP
Frances M. Visco, Esq., President, The National Breast Cancer Coalition

Staff
David Korn, M.D., Senior Vice President, AAMC Division of Biomedical and Health Sciences Research
Jennifer Kulynych, J.D., Ph.D., Director, AAMC Division of Biomedical and Health Sciences Research
Justin E. Bekelman, Visiting Research Fellow, Student, Yale Medical School

Association of American Universities Liaison
Richard J. Turman, Director of Federal Relations, Association of American Universities

The Association of American Medical Colleges represents the 125 accredited U.S. medical schools; the 16 accredited Canadian medical schools; some 400 major teaching hospitals, including 74 Veterans Administration medical centers; 91 academic and professional societies representing nearly 88,000 faculty members; and the nation's 67,000 medical students and 102,000 residents.