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Regulations Governing Human Research

From the US Dept. of Health and Human Service's Website:

HHS Regulations

Basic regulations governing the protection of human subjects in research supported or conducted by the Department of Health and Human Services (HHS, then the Department of Health, Education and Welfare) were first published at 45 CFR part 46 in 1974. In the United States, a series of highly publicized abuses in research led to the enactment of the 1974 National Research Act (Public Law 93-348), which created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. One of the charges to the National Commission was to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines to assure that such research is conducted in accordance with those principles. In 1978, the Commission published “Ethical Principles and Guidelines for the Protection of Human Subjects of Research,” also known as the Belmont Report, named after the Belmont Conference Center where the Commission met when drafting the report. The Belmont Report identifies three fundamental ethical principles for all human subjects research: respect for persons, beneficence, and justice.

Based on the Belmont Report and other work of the National Commission, HHS revised and expanded its regulations  in the late 1970s and early 1980s, requiring basic protections to human subjects involved in both biomedical and behavioral research conducted or supported by HHS.  The statutory authority for the HHS regulations derives from 5 U.S.C. 301; 42 U.S.C. 300v-1(b); and 42 U.S.C. 289.

The current version of the regulations includes five subparts.

Subpart A is the basic set of protections for all human subjects of research conducted or supported by HHS, and was revised in 1981 and 1991, with technical amendments made in 2005.

Three of the other subparts provide added protections for specific vulnerable groups of subjects.

  • Subpart B, issued in1975, and most recently revised in 2001, provides additional protections for pregnant women, human fetuses, and neonates involved in research.
  • Subpart C, issued in 1978, provides additional protections pertaining to biomedical and behavioral research involving prisoners as subjects.
  • Subpart D, issued in 1983, provides additional protections for children involved as subjects in research.

Subpart E, issued in 2009, requires registration of institutional review boards (IRBs) which conduct review of human research studies conducted or supported by HHS.

OHRP publishes a booklet that includes the text of the human subject protection regulations, the categories of research that an IRB may review through an expedited review procedure, the statutory basis  for the regulations, and the departments and agencies that have published or follow the Common Rule.  For the current version of the  booklet issued in 2009 click here.

FDA Regulations

The Food and Drug Administration (FDA) is an HHS agency that regulates clinical investigations of products under its jurisdiction, such as drugs, biological products, and medical devices. FDA regulations are published in title 21 of the CFR. FDA’s human subject protection regulations include:

21 CFR part 50, Protection of Human Subjects
21 CFR part 56,  Institutional Review Boards
21 CFR part 312, Investigational New Drug Application
21 CFR part 812, Investigational Device Exemptions

21 CFR part 50 “Protection of human subjects,” issued in 1980, amended in 1981, 1989,  1990, 1991, 1996, 1997, 1999, 2006, and 2011,  applies to informed consent by research subjects. Subpart D was added to 21 CFR part 50 in 2001 and provides additional protections for children involved in clinical investigations.

21 CFR part 56, issued in 1981 and amended in  1989, 1991, 1996, 1999 , 2000, 2001, 2002, and 2009, applies to IRBs.

Other FDA regulations that apply to clinical investigations include 21 CFR part 54, Financial  Disclosure by Clinical  Investigators.

The Common Rule

In 1991, the “Federal Policy for the Protection of Human Research Subjects,” informally known as the “Common Rule” was issued by 15 federal departments and agencies. The Common Rule was based on the HHS 45 CFR part 46 subpart A, and includes identical language in the separate regulations of those departments and agencies. Technical amendments were made to the Common Rule in 2005. 

Three departments and agencies have not issued the Common Rule but apply all parts of 45 CFR part 46: The Central Intelligence Agency, the Social Security Administration, and the Department of Homeland Security. 

Other departments and agencies have adopted one or more of the other HHS subparts and some have their own additional human subject protection regulations.


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