1 Traditionally, and in current regulations, those studied in experimental research are referred to as research subjects. This term accurately captures an important aspect of the relationship between an investigator and the individual being studied. However, the term subjectalso connotes society’s worst fears about research participation, rather than its aspirations. There are methods, such as obtaining voluntary informed consent, by which investigators can show respect for the human dignity of those involved in research. By securing consent, individuals become volunteers, not mere subjects, who are active participants in the research process. Therefore, this report uses the term human participantsto refer to those who are studied in research protocols. See Chapter 2 for a more extensive discussion of this topic.
2 To date, NBAC has issued five reports: Cloning Human Beings (NBAC 1997), Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity(NBAC 1998), Ethical Issues in Human Stem Cell Research(NBAC 1999a), Research Involving Human Biological Materials: Ethical Issues and Policy Guidance(NBAC 1999b), and Ethical and Policy Issues in International Research:
Clinical Trials in Developing Countries(NBAC 2001).
National Bioethics Advisory Commission
3 NBAC Meeting, 17 May, 1997. Arlington, Virginia.
4 Those who conduct research are usually referred to as either researchersor investigators. NBAC uses the terms interchangeably.
5 FDA “Warning Letter” from S.A. Masiello, FDA, to James M.
Wilson, University of Pennsylvania. March 3, 2000. Available at http://www.fda.gov/foi/warning.htm. Last accessed November 17, 2000.
6 Ibid.
7 Ibid.
8 Ibid.
9 OPRR letter from S.L. Crandall to G. Sarkar, Manhattan Eye, Ear, and Throat Hospital. May 8, 1998.
10 OHRP letter from M.A. Carome to G.R. Newkome, University of South Florida. September 28, 2000. Available at http://ohrp.osophs.dhhs.gov/detrm_letrs/sep00f.pdf. Last accessed May 21, 2001.
11 Ibid.
12 NIH Extramural Data and Trends. Available at http://grants.
nih.gov/grants/award/trends95/annotate.htm. Last accessed November 13, 2000.
13 Estimates of National Support for Health R&D by Source or Performer, 1986–1995. Available at http://grants.nih.gov/
grants/award/trends95/pdfdocs/fedtabl1.pdf. Last accessed November 13, 2000.
14 Pub. Law 33, 105th Congress.
15 See NBAC, “Federal Agency Survey on Policies and Procedures for the Protection of Human Subjects in Research.” This staff analysis is available in Volume II of this report.
16 See Heath, E., “The History, Function, and Future of
Independent Institutional Review Boards.” This background paper was prepared for NBAC and is available in Volume II of this report.
17 Ibid.
18 FDA, 1993, “Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation.” 22 July. 58 Fed. Reg.39406;
NIH, 1994, Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research. 28 March. 59 Fed. Reg.14508;
CDC, 1995, Policy on the Inclusion of Women and Racial and Ethnic Minorities in Externally Awarded Research. 15 September.
60 Fed. Reg.47947.
19 Pub. Law 115, 105th Congress.
20 White House, 2000, “Taking New Action to Encourage Participation in Clinical Trials.” [Press Release.] 7 June. Available at http://www.whitehouse.gov/WH/html/briefroom.html. Last accessed 12/10/00. See also Medicare Coverage Policy. Available at http://www.hcfa.gov/coverage/default.htm. Last accessed December 10, 2000.
21 A Multiple Project Assurance is an agreement between an institution and the federal government in which the institution pledges to comply with regulations.
22 Subpart B of 45 CFR 46 pertains to research involving fetuses, pregnant women, and human in vitrofertilization. Subpart C pertains to research involving prisoners. Subpart D pertains to research involving children.
23 48 Fed. Reg.9266.
24 Ibid.
25 Ibid.
26 Ibid.
27 HRSA Circular 96.05.
28 NBAC Town Meetings: February 9, 2000, Houston, Texas; April 5, 2000, Pittsburgh, Pennsylvania; May 3, 2000, Orlando, Florida;
June 7, 2000, Chicago, Illinois; August 14, 2000, Portland, Oregon.
29 Pub. Law 310, 106th Congress.
30 66 Fed. Reg.20589.
31 Porter, J., Testimony before NBAC. November 23, 1997.
Bethesda, Maryland. See McCarthy, C.R., “Reflections on the Organizational Locus of the Office for Protection from Research Risks.” This background paper was prepared for NBAC and is available in Volume II of this report.
32 There has been a change in the categories of research that IRBs may review through an expedited procedure (63 Fed. Reg.60364).
However, this change did not require amendment of the Common Rule. The Common Rule does not contain the list of categories, but rather refers to such a list, to be periodically revised and published by the Secretary, DHHS. There are no similar provisions for modifi-cation elsewhere in the Common Rule.
33 Russell-Einhorn, M., Testimony before NBAC. March 1, 2000.
Herndon, Virginia.
34 See Gunsalus, C.K., “An Examination of Issues Presented by Proposals to Unify and Expand Federal Oversight of Human Subject Research.” This background paper was prepared for NBAC and is available in Volume II of this report.
35 21 CFR 56.120–121; 21 CFR 312.70; 21 CFR 812.119; Lepay, D., Testimony before NBAC, September 13, 2000. Washington, D.C.
36 See NBAC, “Federal Agency Survey on Policies and Procedures for the Protection of Human Subjects in Research.” This staff analysis is available in Volume II of this report.
37 NBAC Town Meetings: February 9, 2000, Houston, Texas; April 5, 2000, Pittsburgh, Pennsylvania; May 3, 2000, Orlando, Florida;
June 7, 2000, Chicago, Illinois; August 14, 2000, Portland, Oregon.
38 Ibid.
39 Stinson, R., Testimony before NBAC. July 11, 2000. Bethesda, Maryland.
40 Letter from E. Gislason, University of Illinois at Chicago to M. Carome, OPRR, and C. Weil, OPRR. September 30, 1999.
Available at http://www.uic.edu/depts/ovcr/oprr/nih09-30-99.html.
Last accessed December 5, 2000.
41 Spilker, B., Testimony before NBAC. April 7, 2000.
Washington, D.C.
42 For example, National Organization for Rare Disorders, Inc., Policy Position: Patient Protection in Clinical Trials. Available at http://www.rarediseases.org/new/patpro.htm. Last accessed August 22, 2000.
43 65 Fed. Reg.37136–37137.
44 Consortium of Social Science Associations, Public comment submitted to NBAC. Received February 16, 2001.
45 American Sociological Association, Public comment submitted to NBAC. Received February 20, 2001.
46 Shopes, L., Public comment submitted to NBAC. Received February 17, 2001.
47 American Psychological Association, Public comment submitted to NBAC. Received February 16, 2001.
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Introduction
T
his chapter proposes an enhanced system of U.S.oversight of research involving human participants, specifically addressing its purpose and functions, the parties involved, and its scope and structure. The chapter also focuses on the definitions of research and human participant, terms that are crucial to delineating the scope of the oversight system. Although some of the components of the proposed system already exist in total or in part within the current system, certain alterations and additions are required. Specifically, what is needed is a more effectively coordinated system:
■ in which coverage, in terms of protections, is not dependent on source of funding;
■ that can propose and implement reforms in a timely manner;
■ that can issue uniform interpretations of regulations, across the government and the private sector, and that can make the rules work both for medical and non-medical research;
■ that relies on certification and education to better ensure ethical research and that promotes guidance in lieu of regulation;
■ that streamlines review in a manner commensurate with research risks;
■ that better reflects the ways in which participants may become vulnerable and the ways this can be avoided;
■ that can facilitate multi-site review efforts and special-ized review mechanisms;
■ that continues to rely on decentralized review and monitoring, overseen by a more coordinated collection of adverse event reporting;
■ that has a wide array of enforcement tools that can be tailored more effectively to the nature of the problems encountered; and
■ that facilitates studying compensation possibilities for those injured in the course of research.
Discussion and recommendations pertaining to each of these criteria are found in this and subsequent chapters of this report. The most significant change proposed is that of consolidation—that is, where there are now multi-ple sets of overlapping regulations, the National Bioethics Advisory Commission (NBAC) suggests a unified com-prehensive policy in the form of a single set of regulations and a single source of guidance and interpretation. This consolidated structure would allow for much needed regulatory flexibility and, in certain areas, a greater use of guidance with less regulation. Of course, an effective oversight system consists of more than governmental regulation. Indeed, it should be devoid of excessive reg-ulation, relying, when appropriate, on the ethical behav-ior and commitments of all individuals and entities—
federal and nonfederal—engaged in research involving human participants.