AAAS Policy Brief:
Human Research Subject Protections
Issue Summary | AAAS Resources
Introduction
With research in the biomedical sciences continuing to expand,
the number of people needed to participate in clinical research studies can
be expected to climb as well. Experimental therapeutics, such as gene therapy,
ultimately requires preliminary investigation in patients and other research
participants. Some perceive an increasing gap between the rapid proliferation
of clinical research and the set of regulations currently in place to protect
the human subjects of research. Back to top
Present Guidelines and Oversight
Currently, guidelines for the protection of human research subjects
vary depending upon the source of funding (federal or private) and the federal
agency sponsoring the research. The National Institutes of Health (NIH) and
the Food and Drug Administration (FDA) are the two agencies responsible for
managing the majority of federally funded clinical research. Each has a separate
section in the Code of Federal Regulations (CFR) containing guidelines for the
protection of human research subjects. Though similar, the NIH and FDA guidelines
are not identical, in part due to the agencies’ differing roles in supporting
research.
National Institutes of Health
The NIH serves as the nation’s primary source for basic medical
and behavioral research to improve human health. It conducts research within
its own laboratories and allocates resources for research in universities, hospitals,
and other institutions nationwide.
The NIH guidelines for the protection of human research subjects
fall under Title 45, Part 46 of the CFR, and are widely known as the "Common
Rule." Generally, the regulations include provisions for:
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Institutional Review Board (IRB) approval and oversight
of research protocols
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IRB membership and composition
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Requirements for informed consent documentation
The NIH currently maintains the Office of Human Subjects Research
(OHSR) to help intramural researchers understand and comply with the ethical
guidelines and regulations surrounding clinical research.
Food and Drug Administration
The FDA exists to promote and protect the public health by ensuring
that safe and effective products become available to the general public. But
unlike the NIH, whose total authority relates to human health and biomedicine,
the FDA has oversight authority for food and other products in addition to clinical
research. Biomedical products such as pharmaceuticals and medical devices are
developed primarily by researchers in the private sector, and must be approved
by the FDA before they can be used by doctors and patients.
The FDA regulations for human research subjects appear in Title
21, Parts 50, 312, 812 of the CFR. These provisions include:
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Requirements for informed consent documentation
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Exceptions from informed consent for emergency research
and for research conducted by the Department of Defense
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Protocol and oversight requirements for Investigational
New Drug and Investigational Device studies
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Assurance of IRB review
The FDA’s Office of Good Clinical Practice (OGCP) offers regulatory guidance
for scientists conducting FDA-supported clinical research.
Federal Oversight of Human Subjects Research
The Office of Human Research Protections (OHRP) within the Department
of Health and Human Services (HHS) has oversight responsibilities wherever HHS
funds are used to support research involving human subjects. In 2000, the OHRP
moved organizationally from within the NIH to HHS in order to better achieve
its role in the regulation of all federally funded clinical research. The OHRP
offers policy guidance and educational materials for investigators and patients
involved in human subjects research.
Private Industry
By contrast to the statutes and organizational offices in place
for the oversight of federally funded research, no regulations currently exist
to protect people participating in research that is privately funded. Furthermore,
no single federal entity exists to oversee human subjects research and facilitate
consistent practices throughout public and private research institutions. Back to top
Strengthening the Regulatory System
Recent events illustrate what some believe are flaws in the current
human subject protections policy. In 2001 OHRP suspended clinical research activities
at Johns Hopkins University after a healthy volunteer died during participation
in an asthma study at its School of Medicine. A committee conducting an internal
investigation of the incident concluded that the consent form did not adequately
describe the risks of the drug being tested in the study.
Conflicts of interest between research investigators, IRB members,
the institutions they serve, and corporate sources of funding can affect research
objectivity, undermine scientific integrity, and compromise the safety of research
volunteers. Presently, federal regulations do not require that potential conflict
of interest information be made available to research subjects.
In 1999, an 18 year-old participant in a gene therapy study at
the University of Pennsylvania died due to an exaggerated immune response to
the DNA vector used in the study. A thread of financial interest was uncovered
connecting the lead investigator of the gene therapy study, a biotech company
co-founded by the lead investigator, and the university. In this case, the patient
was not informed of these ties before participating in the study. Biomedical
research is often safely and successfully conducted as a collaboration between
academic, private industry, and/or government institutions. However, some worry
that scientists disproportionately motivated by financial or scientific gain
may design studies that put subjects at greater risk in order to produce desired
results.
Sparked by these and other incidents, policy groups have suggested
measures to strengthen protections for human research subjects. Back to top
Policy Recommendations
National Bioethics Advisory Commission
The National Bioethics Advisory Commission (NBAC), a commission
created under the Clinton Administration, published an August 2001 report entitled
"Ethical and Policy Issues in Research Involving Human Participants." After
studying the evolving problem of human subjects protections over a period of
five years, this report summarized the NBAC’s overall conclusions and recommendations.
Briefly, the NBAC recommended the following: 1) designating a new federal oversight
office to coordinate research involving human subjects across all government
agencies, academia, and the private sector; 2) establishing uniform regulations
under federal policy ensuring the protection of all human research participants;
and 3) outlining federal standards for IRB composition and member selection.
Association of American Universities
In June 2000, the Association of American Universities (AAU)
Task Force on Research Accountability issued a report on university protections
of human research subjects. To ensure the highest level of protection for participants
in university research, they recommend increases in oversight by senior university
management; increased training for IRB members and for all staff contributing
to clinical research; voluntary accreditation for conducting human subjects
research; and increased public information about human subjects research to
ensure university accountability.
The same AAU Task Force released a report on financial conflict
of interest in October 2001. This report distinguishes between conflicts of
interest at the level of the individual investigator and at the institutional
level, and discusses different methods of addressing each problem. The Task
Force concludes that generally, universities must develop stronger systems for
disclosing and managing financial conflicts of interest in all areas of research.
In the case of human subjects research, however, it recommends that university
researchers simply not have any financial interests unless justified by "compelling
circumstances."
Association of American Medical Colleges
In January 2001, the Association of American Medical Colleges
(AAMC) released a comment letter to the NBAC. Although the AAMC agrees that
Common Rule protections should be extended to all human research subjects, they
do not believe that creating a new federal office is necessary. They feel that
the Office of Science and Technology Policy and the National Science and Technology
Council within the Executive Branch already have sufficient capabilities to
coordinate and oversee national human subjects protections activities.
The AAMC Task Force on Financial Conflicts of Interest in Clinical
Research produced a policy report on individual conflicts of interest. Like
the AAU, the AAMC Task Force recommends that individuals with significant financial
interest in a human research study should not conduct such research. Furthermore,
institutions should require full disclosure of an individual’s potentially biasing
financial interests prior to approval of research protocols. Back to top
Congress Responds
In April 2002, the Senate Committee on Health, Education, Labor,
and Pensions held a hearing to evaluate the adequacy of current human subject
protections. While most witnesses testified in support of strengthening and
expanding the scope of human subject protections, a representative of the biotechnology
industry cautioned that the increase of protections should not bring with it
added and conflicting layers of bureaucracy.
Rep. DeGette (D-CO) introduced the Human Research Subject Protections
Act of 2002 (H.R. 4697) in May. This legislation would amend the Public Health
Service Act to require that all human subject research, at both public and private
institutions, be conducted in accordance with the Common Rule. It provides for
the creation of an Office of Human Research Protections within the HHS Office
of the Secretary to coordinate federal oversight of human research activities.
It further specifies informed consent and IRB membership requirements. This
bill has been referred to the House Committee on Energy and Commerce, Subcommittee
on Health.
A similar bill is expected to be introduced in the Senate.
Updated August 29, 2002
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