AAAS Policy Brief:
Human Research Subject Protections

Issue Summary | AAAS Resources

• Introduction
• Present Guidelines and Oversight
• Strengthening the Regulatory System
• Policy Recommendations
• Congress Responds

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.

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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:

• Institutional Review Board (IRB) approval and oversight of research protocols
• IRB membership and composition
• 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:

• Requirements for informed consent documentation
• Exceptions from informed consent for emergency research and for research conducted by the Department of Defense
• Protocol and oversight requirements for Investigational New Drug and Investigational Device studies
• Assurance of IRB review

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.

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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.

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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.

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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