understanding normal and abnormal physiological or Comment: "Intervention" includes both physical proce- All agencies that conduct or support research involving human subjects, according to the definitions supplied, were asked to provide the following information as well: (1) A description of the nature and extent of such research; (2) Copies of the regulations or guidelines that govern the conduct of such research; (3) An analysis of the extent to which their regulations or guidelines conform to those of the Department of Health, Education, and Welfare (codified at 45 CFR 46, as amended in 43 Federal Register 51559, November 3, 1978); (4) A description of their procedures for monitoring such research during the course of its conduct, and for assuring that the agency is informed of any untoward or unexpected events; 1 (5) A description of the nature and extent of any injuries or of any departures from approved protocols that have been reported or discovered, and the steps taken by their agency to investigate and resolve such problems; (6) The views of their department or agency regarding recently proposed modifications to the existing HEW regulations; and (7) Any action taken by their department or agency with respect to the proposed modifications enumerated above. Agencies Excluded from Further Review. The definition of research involving human subjects supplied to the Federal agencies was compatible with the scope of the then existing HHS regulations which applied to, among other things, the administration of surveys or questionnaires and the review of records. Those regulations were revised January 1981, however, and most research involving only the use of surveys and questionnaires or the review of records is now exempt from the regulations. Therefore, those Feder-. al agencies indicating that they sponsor only research exempt from review under the HHS regulations will be noted but not discussed further in this Report (see Table 2). Only those agencies that support, conduct or regulate biomedical or behavioral research of the type HHS now requires to be reviewed and approved in accordance with 45 CFR 46 are included in this analysis of Federal regulations and policies governing research with human subjects (see Table 3). Also excluded from independent analysis in this Report are the Nuclear Regulatory Commission (which, as a matter of policy, does not conduct research involving human subjects except through health agencies, such as HHS, which impose their own regulations), the Smithsonian Institution, which conducts research under grants from HHS and is subject to the regulations of that department, and the U.S. Postal Service and ACTION which permit access to their personnel and facilities by agencies of the Public Health Service (HHS) for research related to health and safety.4 Agencies Included in the National Commission Report That are Not Reviewed in This Report. A comparison of this Report with that of the National Commission will reveal various differences, some of them merely superficial.5 4 See letters to Barbara Mishkin from: Robert B. Minogue, Director, Office of Nuclear Regulatory Research (July 23, 1981); S. Dillon Ripley, Secretary, Smithsonian Institution (April 2, 1980); William F. Bolger, Postmaster General (April 4, 1980); and James B. Lancaster, Assistant Director for Administration and Finance, ACTION (April 11, 1980 and December 31, 1980). 5 Five Federal entities that appeared in the 1977 report of the National Commission appear under different names in this report For example, the Commission on Civil Rights no longer has an Office of Research, and the research responsibilities formerly undertaken by that office have not been reassigned; therefore, the Commission on Civil Rights no longer conducts or supports any research with human subjects. The National Oceanic and Atmospheric Administration (NOAA) of the Department of Commerce conducts only research involving deep sea diving and other underwater activities; the agency is not involved in research involving humans as subjects in the underwater environment.7 The Federal Railroad Administration, within the Department of Transportation, reports that it no longer conducts research with human subjects as described in the report of the National Commission.8 The National Academy of Sciences has been deleted from coverage in this Report, at its own request, because it is not a Federal agency and receives no appropriations from Congress. Rather, it is a private institution chartered by Congress as a non-profit organization to provide advice to the government on matters of science and technology. The Academy occasionally conducts or supports research with human subjects at the request of Federal agencies and requires that such research conform to the regulations of the Department of Health and Human Services.9 Somewhat differently situated is the Gorgas Memorial Institute of Tropical Diseases and Preventive Medicine, located in Panama. The Institute is a non-profit organization incorporated in Delaware, which receives a significant part due to reorganization. The Civil Service Commission is now the Office of Personnel Management; it conducts only surveys and questionnaires. The Agency for International Development (AID), formerly part of the Department of State, has become the International Development Cooperation Agency. The Education division of the Department of Health, Education, and Welfare became a separate Department of Education, and HEW became the Department of Health and Human Services. Finally, the Law Enforcement Assistance Administration (LEAA) is now part of the Office of Justice Assistance, Research, and Statistics-still within the Department of Justice. "Letter (March 25, 1980) from Louis Nunez, Staff Director, U.S. Commission on Civil Rights. "Letter (July 31, 1981) from Joseph C. Brown, Acting Director of Personnel, U.S. Department of Commerce. 8 Memorandum from Acting Associate Administrator for Research and Development, included as attachment to letter (May 27, 1980) from Martin Convisser, Director, Office of Environment and Safety, Office of the Secretary, DOT. 'Letter (April 28, 1980) from Robert W. White, Administrator, National Research Council, National Academy of Sciences. of its operating budget from direct Congressional appropriations. 10 In Fiscal 1980, $1.7 million of a $2.5 million budget came from Congress. Most of the Federal money pays administrative costs such as salaries, field work, maintenance of the plant and equipment, and publications. In FY 1980, the Institute received an additional $952,000 in research grants from NIH, the World Health Organization, the Army, the Navy, and the Pan American Health Organization. Most of the Institute's research is related to tropical diseases; however, the Institute currently has a special assurance on file at NIH's Office for Protection from Research Risks (OPRR) for a grant from the National Cancer Institute to conduct research on cervical cancer. Except for conditions attached to grants from the NIH and the Army, however, there is no specific legal or regulatory provision requiring research involving human subjects conducted by the Gorgas Memorial Institute to undergo IRB review or to comply with provisions for informed consent. Although the direct appropriations from Congress are administered by the Fogarty International Center at NIH, the Center has no authority to attach conditions to such funds.11 Scope of This Report. As a result of the foregoing deletions, reorganizations, and modifications, 17 Federal departments or agencies have been identified that currently conduct or support biomedical or behavioral research with human subjects that comes within the definition provided by 45 CFR 46. Three of those agencies have separate subsidiary components that operate under their own policies or regulations for the protection of human subjects: the Department of Defense (the Army, the Navy, and the Air Force); the Department of Justice (the Bureau of Prisons, and the Office of Justice Assistance, Research, and Statistics); and the Department of Transportation (the U.S. Coast Guard, the Federal Aviation Administration, the Federal Highway Administration, and the National Highway Traffic Safety Administration). Thus, there are a total of 23 separate Federal entities that conduct or support biomedical or behavioral research with human subjects whose rules and procedures are scrutinized in this Report. The Commission has also chosen to review the rules and procedures of the Food and Drug Administration (FDA), within the Department of Health and Human Services. Under the Federal Food, Drug and Cosmetic Act, the FDA regulates research on new drugs, biologicals, and medical devices. Its basic regulatory scheme was brought into 1022 USC 278, 45 Stat. 491 (1928) as subsequently revised. 11 Personal communication (October 2, 1981) with William Doak, Executive Officer, Fogarty International Center. conformity with the regulations governing research conducted and supported by the new rules issued simultaneously with the 1981 HHS revisions. The FDA's method of implementation and monitoring differs from that applicable to grant and contract aspects of HHS, as noted in Chapter Three. Draft summaries of the regulations and policies of each of these Federal entities were sent to the head of the appropriate departments or agencies in June 1981 for review. Agency heads were asked to confirm the accuracy of the summaries or to indicate necessary modifications. (Agency heads were also asked to provide a description of their procedures for monitoring the implementation of the regulations and investigating and resolving complaints. That material is discussed in Chapter Three of this Report.) The agencies were also asked for documentation to justify significant changes. The material provides the basis for the description and analysis of this chapter. The Regulatory System Governing Research Since 1966, when the Surgeon General issued an order requiring institutional review to assure ethical acceptability of research with human subjects supported by the Public Health Service (PHS), the PHS policies and procedures have served as a model for other Federal agencies. The history and development of those policies (now embodied in HHS regulations) have been amply chronicled before in the National Commission's report on IRBS and elsewhere,12 and need not be repeated here. 12 Briefly summarized, the HHS regulations derive from Public Health Service review requirements initiated in 1966 by the Surgeon General. These were expanded and elaborated in the 1971 Institutional Guide to DHEW Policy on Protection of Human Subjects, a description of the grants administration policy which required initial review of proposed research by committees at each institution to assure that the risks were justified by the anticipated benefits or the importance of the knowledge to be gained, and that informed consent would be obtained by methods that are adequate and appropriate. (The required elements of informed consent were defined and explained.) Continuing review of ongoing projects was also required. Proposed regulations were published in 1973 and final rules were issued in 1974 which converted the earlier grants administration policies into regulations applicable to all research conducted or supported by HEW. An important difference between the new regulations and the old policy was that whereas formerly |