Ethical and Policy Issues in Research Involving Human Participants
Volume II Commissioned Papers and Staff Analysis Bethesda, Maryland August 2001 The National Bioethics Advisory Commission (NBAC) was established by Executive Order 12975, signed by President Clinton on October 3, 1995. NBAC’s functions are defined as follows: a) NBAC shall provide advice and make recommendations to the National Science and Technology Council and to other appropriate government entities regarding the following matters: 1) the appropriateness of departmental, agency, or other governmental programs, policies, assignments, missions, guidelines, and regulations as they relate to bioethical issues arising from research on human biology and behavior; and 2) applications, including the clinical applications, of that research. b) NBAC shall identify broad principles to govern the ethical conduct of research, citing specific projects only as illustrations for such principles. c) NBAC shall not be responsible for the review and approval of specific projects. d) In addition to responding to requests for advice and recommendations from the National Science and Technology Council, NBAC also may accept suggestions of issues for consideration from both the Congress and the public. NBAC also may identify other bioethical issues for the purpose of providing advice and recommendations, subject to the approval of the National Science and Technology Council.
National Bioethics Advisory Commission 6705 Rockledge Drive, Suite 700, Bethesda, Maryland 20892-7979 Telephone: 301-402-4242 • Fax: 301-480-6900 • Website: www.bioethics.gov
ISBN 1-931022-17-8 Ethical and Policy Issues in Research Involving Human Participants
Volume II Commissioned Papers and Staff Analysis Bethesda, Maryland August 2001
National Bioethics Advisory Commission
Harold T. Shapiro, Ph.D., Chair President Emeritus and Professor of Economics and Public Affairs The Woodrow Wilson School of Public and International Affairs Princeton University Princeton, New Jersey
Patricia Backlar Laurie M. Flynn* Research Associate Professor of Bioethics Senior Research and Policy Associate Department of Philosophy Department of Child and Adolescent Psychiatry Portland State University Columbia University Assistant Director New York, New York Center for Ethics in Health Care Oregon Health Sciences University Carol W. Greider, Ph.D. Portland, Oregon Professor of Molecular Biology and Genetics Department of Molecular Biology and Genetics Arturo Brito, M.D. Johns Hopkins University School of Medicine Assistant Professor of Clinical Pediatrics Baltimore, Maryland University of Miami School of Medicine Miami, Florida Steven H. Holtzman Chief Business Officer Millennium Pharmaceuticals, Inc. Alexander Morgan Capron, LL.B. Cambridge, Massachusetts Henry W. Bruce Professor of Law University Professor of Law and Medicine Bette O. Kramer Co-Director, Pacific Center for Health Policy and Ethics Founding President University of Southern California Richmond Bioethics Consortium Los Angeles, California Richmond, Virginia
Eric J. Cassell, M.D., M.A.C.P. Bernard Lo, M.D. Clinical Professor of Public Health Director Weill Medical College of Cornell University Program in Medical Ethics New York, New York Professor of Medicine University of California, San Francisco R. Alta Charo, J.D. San Francisco, California Professor of Law and Bioethics Law School and Medical School Lawrence H. Miike, M.D., J.D. University of Wisconsin Kaneohe, Hawaii Madison, Wisconsin Thomas H. Murray, Ph.D. James F. Childress, Ph.D. President Kyle Professor of Religious Studies The Hastings Center Professor of Medical Education Garrison, New York Director, Institute for Practical Ethics Department of Religious Studies William C. Oldaker, LL.B. University of Virginia Senior Partner Charlottesville, Virginia Oldaker & Harris, L.L.P. Washington, D.C. Co-Founder and General Counsel David R. Cox, M.D., Ph.D. NeuralStem Biopharmaceuticals Ltd. Scientific Director College Park, Maryland Perlegen Sciences Santa Clara, California Diane Scott-Jones, Ph.D. Professor Rhetaugh Graves Dumas, Ph.D., R.N. Psychology Department Vice Provost Emerita, Dean Emerita, and Boston College Lucille Cole Professor of Nursing Chestnut Hill, Massachusetts University of Michigan Ann Arbor, Michigan *Resigned on May 10, 2001.
CONTENTS
Research Ethics in Australia...... A-1 Donald Chalmers University of Tasmania
Location of the Office for Protection from Research Risks Within the National Institutes of Health: Problems of Status and Independent Authority...... B-1 John C. Fletcher University of Virginia
Privacy and Confidentiality in Health Research ...... C-1 Janlori Goldman and Angela Choy Georgetown University
An Examination of Issues Presented by Proposals to Unify and Expand Federal Oversight of Human Subject Research ...... D-1 C.K. Gunsalus University of Illinois at Urbana-Champaign
The History, Function, and Future of Independent Institutional Review Boards...... E-1 Erica Heath Independent Review Consulting, Inc.
The Danish Research Ethics Committee System—Overview and Critical Assessment ...... F-1 Søren Holm University of Manchester
Vulnerability in Research Subjects: A Bioethical Taxonomy ...... G-1 Kenneth Kipnis University of Hawaii at Manoa
Reflections on the Organizational Locus of the Office for Protection from Research Risks ...... H-1 Charles R. McCarthy
Protectionism in Research Involving Human Subjects...... I-1 Jonathan D. Moreno University of Virginia
Federal Agency Survey on Policies and Procedures for the Protection of Human Subjects in Research...... J-1 National Bioethics Advisory Commission
Local Institutional Review Boards...... K-1 Steven Peckman University of California-Los Angeles
Institutional Review Board Assessment of Risks and Benefits Associated with Research ...... L-1 Ernest D. Prentice and Bruce G. Gordon University of Nebraska Medical Center
Oversight of Human Subject Research: The Role of the States...... M-1 Jack Schwartz Office of the Maryland Attorney General
v Privacy and Confidentiality: As Related to Human Research in Social and Behavioral Science ...... N-1 Joan E. Sieber California State University, Hayward
Unfulfilled Promise: How the Belmont Report Can Amend the Code of Federal Regulations Title 45 Part 46—Protection of Human Subjects...... O-1 Harold Y. Vanderpool University of Texas Medical Branch, Galveston
The Ethical Analysis of Risks and Potential Benefits in Human Subjects Research: History, Theory, and Implications for U.S. Regulation ...... P-1 Charles Weijer Dalhousie University
Charles Weijer of Dalhousie University, Halifax, Nova Scotia, Canada, prepared a paper for NBAC on the topic of protecting communities in research. That paper was published in 1999 in the journal Cambridge Quarterly of Healthcare Ethics. The reader can find the article at the following citation:
Weijer C. 1999. Protecting Communities in Research: Philosophical and Pragmatic Challenges. Cambridge Quarterly of Healthcare Ethics 8:501–513.
The papers included in this volume were edited to conform to minimal stylistic consistency. The content and accuracy of the papers are the responsibility of the authors, not the National Bioethics Advisory Commission.
vi RESEARCH ETHICS IN AUSTRALIA
Commissioned Paper Donald Chalmers University of Tasmania
A-1
Preface ustralia has had a comparatively creditable record of ethical research involving humans. The litany of Acriticism about shoddy medical research documented in the epochal article by Professor Beecher (Beecher 1966, 1968; Levine 1986) has not occurred in this country. Comparatively fine as the Australian record may be, that record is not unblemished. A report commissioned by the Commonwealth Government in 1994 by Professor Margaret Allars into unsatisfactory aspects of the collection, manufacture, and injection of human growth hormone (Allars 1994) recommended that aspects of the research structure had to be reassessed. In particular, the Allars Report recommended a review of the National Health and Medical Research Council (NHMRC) Statement on Human Experimentation and the Supplementary Note on Reproductive Technology Procedures. Similarly, the Commonwealth Minister for Health (now called the Commonwealth Minister for Health and Aged Care) referred ethical concerns about two postwar procedures and one multi- center clinical trial in the 1990s to the Australian Health Ethics Committee (AHEC). The two postwar procedures involved first, the inclusion of orphans and State wards in vaccine trials conducted in the postwar years and, second the experimental use of estrogen to reduce the height of “tall girls” in the 1950s. The multicenter trial involved the so-called “morning after pill” (RU486). Research and experimentation has been a major issue, at least for the research community, in the last two decades in Australia. This “age of skepticism” (pace Eric Hobsbawn) has seen continuing demands for open government and greater public accountability, demands for expanded civil liberties, and demands for privacy protection rights. This wide debate has translated into debate about the protection of subjects in medical research (Laufer 1990; Darvall 1993), its major focus being the maintenance and improvement of ethical standards. This focus of concern is reflected in much of the work of the peak national health ethics body, the AHEC. In particular, the AHEC has conducted two series of National Workshops for Institutional Ethics Committees, a major review of the ethics review system in Australia (Chalmers 1996), and a major revision of the guidelines on research ethics published as the National Statement on Ethical Conduct in Research Involving Humans in mid 1999 (National Statement 1999). Ethical standards in human research and experimentation have not been static. The Australian research ethics community conducted a debate on improving and professionalizing the ethics review system during the late 1980s and 1990s. Researchers, institutions, trial sponsors, academic and professional critics, and changing attitudes to accountability have all contributed to an improvement in the practices and culture of research involving humans in this country. The AHEC has come far since the Finn Report amalgamated the National Bioethics Consultative Committee (NBCC) and the Medical Research Advisory Committee to form the AHEC. Professor Finn stated in his report that “until the HEC (AHEC) concept is more fully developed and particularized, until the Council addresses more directly the burden of the ethics function...one cannot surmise with any confidence as to the extent to which those differences between the two bodies in their areas of mutual interest are likely to recede or be perpetuated” (Finn 1990 at 14). Considerable advances were made in the first three triennia toward this “evolutionary” change. The Australian research ethics review system continues to evolve. The system could be described as a hybrid or intermediate system in contradistinction to entirely legislatively regulated systems or voluntary self-regulated models. There is no Australian equivalent of the National Research Act 1974. However, there is greater regula- tion of the system since the pre-1982 Australian voluntary system. Human Research Ethics Committees (HRECs), which conduct ethics review are not established by specific Commonwealth legislation, but they are recognized within the NHMRC Act 1992. In this major respect, research ethics review in Australia is not a voluntary system; it is better classified now as a regulated system.
A-3 Comparisons between HRECs in Australia and Ethics Committees in the United States are misleading. Some HRECs in Australia may perform some of the functions of Ethics Committees, but the comparable institution in the United States is an Institutional Review Board (IRB). As well as the infamous Tuskegee Study (Furrow et al 1995 at 548–550), a number of questionable human experiments were disclosed before the U.S. Congress in the early 1970s. Disclosures were made particularly about dubious research conducted in prisons and mental hospitals and on human fetuses. Following these events, the National Research Act 1974 was introduced which required each institution conducting federally supported research involving human subjects to establish an IRB. These IRBs are required to review the ethical aspects of all research protocols within the institution. The general standards for the composition, operation, and responsibility of IRBs are contained in federal regulations (Code of Federal Regulations 1992). In order to fulfill the requirements of the federal regulations, each IRB is required to follow written proce- dures for the conduct of initial and continuing review of research and for reporting findings and actions to the investigator and the institution. An IRB determines which projects require review more often than annually and which projects need verification from sources other than the investigator. Changes in approved research may not be initiated without IRB review and approval, except where there are apparent immediate hazards to the human subjects. In addition to reporting to the IRB, there are other safeguards in the system. Both institutional officials and the Food and Drug Administration (FDA) must be told of any unanticipated problems involving risks to human subjects or others. Similarly, any instance of serious or continuing noncompliance with federal regulations or the decisions of the IRB (or any suspension or termination of IRB approval) must be reported to the institution or FDA. There are IRB procedural requirements aimed at ensuring proper consideration of the research. Except when an expedited review procedure is used, a research proposal must be reviewed by a majority of the members of the IRB. On review, at least one of the IRB members must be primarily concerned with nonscientific areas, and the proposal must receive the approval of a majority of those members present at the meeting. American Ethics Committees continue to evolve and are not settled in their functions (Annas 1984; In Re Quinlan 1976; President’s Commission 1983). Ethics Committees in the USA include the following roles: Advising doctors and family on decisions about withdrawing life support treatment; Providing advice on withholding treatment from newborn infants with birth defects; Making policy through drafting guidelines for hospital personnel on controversial areas of medical practice; Providing education through the organization of seminars on areas of controversy; and Providing advice on specific ethical dilemmas in the treatment of specific patients. In effect, American Ethics Committees are patient care committees and are often referred to by this title. Some Australian hospital HRECs may perform some of the same functions as American Ethics Committees. Comparisons are also sometimes made with Research Ethics Committees in the United Kingdom, but, again, their functions do not compare precisely with those of Australian HRECs. The United Kingdom Research Ethics Committees are diverse in their functions and do not directly relate to Australian HRECs in that they operate within the National Health Service. A United Kingdom Department of Health circular of 1989 (HSC (IS) 153) requires that each district health authority appoint a “...properly constituted Local Research Ethics Committee (LREC), which meets regularly, to register, review and approve (or not approve) the research conducted by its staff, or using its premises or facilities, including access to personal health information held by the authority (and research undertaken by general practitioners within its boundaries).” Research Ethics Committees in the United Kingdom are locally established and formally constituted as subcommittees within the health authority system. It has been noted that an “Ethics Committee acts for and on behalf of the Authority” (Brazier 1990).
A-4 The growth of ethics committees has followed diverse paths, and a number of other ethics committees have been established beyond the terms of the Department of Health Circular Guidelines (Rawbone 2000). Brazier particularly notes that a number of fertility units have established advisory committees to assist practitioners in making decisions about the admission of individual patients to the program (Brazier 1990). This report presents background information on the ethics review system in this country, defines the current ethical system, and provides some background information on the new National Statement on Ethical Conduct in Research Involving Humans. This paper considers the current operation of the AHEC and the system of ethical review of research involving humans by HRECs in Australia. The paper also addresses some specific questions posed by the National Bioethics Advisory Commission (NBAC), namely the following: 1. What are the strengths and weaknesses of nonregulatory systems of protection? 2. What features of these systems, if any, should be incorporated in the U.S. system? 3. What are the strengths and weaknesses of models that are comprehensive, those that encompass private and government sectors, and nonbiomedical and biomedical research?
1. Introduction 1.1 Three Tiers: Researcher Ethics Committee and National Body A three-tier system of ethics review operates within Australia: The researcher The HREC The AHEC At the first level, the researcher continues to carry ethical responsibilities toward research participants. The National Statement begins with a reference to the researcher and states that the “…guiding value for researchers is integrity…” (National Statement 1999, Principle 1.1 at 11). The National Statement continues that “the guid- ing ethical principle for researchers is respect for persons…” (Principle 1.2) and that “… the ethical principle of beneficence is expressed in researchers’ responsibility to minimize risks of harm or discomfort to participants in research projects” (Principle 1.3). Researchers are also required to design their protocols to ensure respect for the dignity and well-being of the participants (Principle 1.4). Researchers should not discriminate in the distribution of benefits and burdens of participation in research or in the selection of research participants (Principle 1.5). Researchers have great responsibility in ensuring participant consent is obtained (Principles 1.7–1.12). Researchers must conduct research that has merit and balance the risks and likely benefits to be gained. Only people with the required experience, qualifications, and competence should conduct the research (Principles 1.13–1.15). These General Principles are bolstered throughout the National Statement with specific contextual duties of researchers to research participants in relation to the project. For example, in a clinical trial the researcher must declare any conflicts of interest through involvement in business or other similar association (Principle 12.5 at 36). It was a deliberate policy in drafting the National Statement to recognize and reinforce the ethical responsibilities of researchers. HRECs, which, until 1999 were referred to as Institutional Ethics Committees (IECs), conduct the second level of ethical review. The Australia HRECs compare closely with the U.S. IRBs established under federal regu- lations. Some HRECs were already operating before the system was formally established in 1982 by amend- ments to the Statement on Human Experimentation. The NHMRC issued the Statement on Human Experimentation, which was the predecessor to the current National Statement on Ethical Conduct in Research Involving Humans,
A-5 promulgated in 1999. The NHMRC was a nonstatutory body until 1992. In that year the NHMRC became a statutory authority when the Commonwealth Parliament passed the National Health and Medical Research Council Act, 1992 (Cth.). Although HRECs are not statutory bodies, institutions cannot receive research fund- ing from public bodies unless consideration had been given to the research proposal by a properly constituted HREC. Originally, HRECs only considered medical and health research projects. Later, the Australian Research Council (ARC) (the major funding agency for nonmedical research) introduced a similar requirement that, in effect, expanded the jurisdiction of HRECs to all research involving humans. The third level in the system is the AHEC. This body is established under § 35 and § 36 of the National Health and Medical Research Council Act 1992 (Cth.). The AHEC is required to oversee the operation of the HREC system and receives annual Compliance Reports from every registered HREC (National Statement 1999 Principles 2.46–2.48). In addition, the AHEC has the sole authority to publish medical research guidelines. In so doing, the AHEC is required to follow § 11–14 of the National Health and Medical Research Council Act 1992, which provides a unique procedure of two stages of public consultation before such guidelines may be issued.
1.2 The National Statement: Changes in the Research Environment The National Statement reflects a number of significant changes in the ethics of human research. First, the National Statement includes a wider and more comprehensive view about research involving humans, going beyond medical experimentation and extending to all research involving humans. The first Australian guide- lines in relation to research, the Statement on Human Experimentation, followed the Declaration of Helsinki and applied ethical standards to medical research involving human subjects. Gradually, the Statement on Human Experimentation was applied not only to medical research but other research involving humans particularly in the social and behavioral sciences. The new National Statement recognizes this evolution. Second, the National Statement recognizes the evolution of community and research community acceptance that now “…all kinds of research involving or impacting upon humans should conform to the highest standards academic integrity and ethical practice” (National Statement 1999 at 2). Third, legislation is now more common place in the once self-regulated area of research ethics. Increasingly, Commonwealth and State legislation is impacting on and becoming more relevant to any consideration of research ethics. The regulation of Australian research is no longer a voluntary regulatory system of protection for research participants. Many Commonwealth and State Acts apply directly or indirectly to research. In particular, the NHMRC was brought under a statutory framework with the enactment of the National Health and Medical Research Council Act by the Commonwealth Parliament in 1992. Fourth, in a number of countries there have been efforts to identify a better definitional understanding of what is meant by research. The National Statement notes that: There are many definitions of research. These include a systematic investigation to establish facts, principles or knowledge a study of some matter with the objective of obtaining and confirming knowledge. A defining feature of research is the validity of its results…. An alternative approach to finding a definition of research is to list examples for what constitutes research, such as: