3a. Federal regulations

Society protects the welfare of individuals in many ways, but it did not specifically address the issue of the welfare of research subjects until after World War II. Following the War, widespread concerns about atrocities committed during the War in the name of research led to the formulation of a code for human subjects research known as the Nuremberg Code (1947). Although not binding on researchers, the Nuremberg Code and the later Declaration of Helsinki (1964; latest revision and clarification, 2002) provided the first explicit international guidelines for the ethicaltreatment of human subjects in research.

The Nuremberg Code and Declaration of Helsinki did not put an end to unethical human subjects research. During the Cold War, U.S. researchers tested the effects of radiation on hospital patients, children, and soldiers without obtaining informed consent or permission to do so. Through the 1950’s and 1960’s, well after antibiotics effective for the treatment of syphilis were discovered, scores of African-American males in a long-term syphilis study (conducted by the U.S. Public Health Service in Tuskegee, Alabama) were not offered treatment with the new drugs so that researchers could continue to track the course of the disease. These and other questionable practices raised serious public concern and led eventually to government regulation.

To prevent these and similar abuses from continuing,in 1974 Congress required the Department of Health, Education and Welfare (HEW, currently Health and Human Services—HHS) to clarify its rules for the use of human subjects in research. With this mandate in hand, HEW codified its procedures under Title 45 of the Code of Federal Regulations, Part 46 (45 CFR 46). (At roughly the same time, the FDA codified its rules for human subjects research under 21 CFR 50 and 56.)

Congress also called in 1974 for the creation of a National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. During the 4 years it met, the Commission issued a number of reports on the protection of research subjects and recommended principles for judging the ethics of human subjects research(discussed below).

In 1991 most Federal departments and agencies that conduct or support human subjects research adopted acommon set of regulations for the protection of humansubjects referred to as the “Common Rule” (45 CFR 46,Subpart A). Additional requirements on three sensitive research areas are also included in 45 CFR 46:

• Subpart B – Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research.
• Subpart C – Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisonersas Subjects.
• Subpart D – Additional Protections for Children Involved as Subjects in Research.

Together, 45 CFR 46, Subparts A-D, provide acomprehensive articulation of society’s expectations for the responsible use of human subjects in research.
Authority for enforcing the HHS regulations for the protection of human subjects who participate in research conducted or supported by HHS now rests with the Officefor Human Research Protections (OHRP) in the Office of Public Health and Science (OPHS). If you have specific questions about the Federal requirements for the protection of human subjects, contact your local institutional officials, OHRP (for research conducted or supported by HHS), or appropriate officials at the department or agency conducting or supporting the research.