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nent of the Public Health Service within HHS. The FDA regulates research, regardless of the source of funding, that is performed in support of applictions for approval of new drugs, biologicals, and medical devices to be sold in interstate commerce. Research of this type often presents the greatest need for protection of human subjects.

With the 1981 revisions, the FDA regulations on research involving human subjects have become almost identical to those of 45 CFR 46, with one important exception (and several minor ones). The FDA does not require prior agency approval of the composition and procedures of IRBs. Instead, FDA makes site visits ("inspections") to approximately 400 IRBS annually to monitor compliance with the requirements of its regulations. Routine inspections include initial inspections and subsequent inspections every 2-3 years for those IRBS found to be in full compliance, or within two years for IRBS found to have only minor deficiencies. Directed inspections are conducted within six months after a routine inspection reveals serious noncompliance with the regulations or when FDA receives information that calls into question the practices of a particular IRB. These site visits are built around the "paper trail" of studies of particular drugs and devices selected by the FDA inspectors. In other words, the performance of the institutions and its IRB are judged on the basis of its documentation of compliance with the regulatory requirements as applied to one or more investigational drugs or devices. (See Appendix B for further description.)

Thus, the FDA does not necessarily know whether an IRB is properly constituted (or even that it exists) unless or until a routine inspection is conducted or some problem arises that triggers an investigation "for cause."13 The site visits do provide FDA with a means of evaluating the performance of IRBS although, as described in Appendix F, both the quality of the inspections and the communications of findings to OPRR deserve further attention.

Other Federal Agencies. Outside HHS, of the 17 Federal agencies that have adopted the IRB (or similar committee) as a mechanism for assuring the protection of human subjects, 12 report that they rely entirely on an agency review of IRB membership and an assurance of compliance

13 In a case in which a criminal indictment was recently handed down in Pennsylvania, a scientist allegedly conducted drug research over a period of years without benefit of IRB review. It was only when an FDA reviewer questioned some of the data submitted that an investigation was initiated and it was discovered that the IRB which had purportedly reviewed the protocols had never existed. (United States v. Levine, No. 81-203, E.D.Pa., Indictment, July 9, 1981, Count 18(e) at 8).

similar to that required by HHS in its approval of institutional assurances (see Table 5). Indeed, six of these agencies require grantees and contractors to have an assurance approved by HHS: the CIA, Department of Commerce, Department of Education, National Highway Traffic Safety Administration (a component of the Department of Transportation), the Environmental Protection Agency, and the National Science Foundation. Eleven accept either an assurance approved by HHS or their own review of IRB composition and procedures. Of these, the Red Cross relies on a system of general assurances, but reports that many of its IRBs have been inspected by the FDA.

Six agencies monitor extramural IRBs via procedures that go beyond a review of IRB membership and acceptance of an institution's promises to comply with regulations. The CIA reports that it conducts site visits "where applicable" and that CIA program managers provide continuing review of the conduct of research projects. Within the Department of Justice, the Federal Bureau of Prisons conducts site visits at least once every two years to inspect both IRBS and ongoing research programs; and both the Law Enforcement Assistance Administration (LEAA) and the National Institute of Justice monitor research via weekly phone calls and periodic site visits. The Veterans Administration has a system of regular site visits through which the Research Advisory Committee in Washington monitors both IRB performance and the conduct of research at VA facilities, and through which IRBS (regional “Human Rights Committees") monitor the conduct of research in the cooperative study programs.

Finally, within the three components of the Department of Defense, intramural IRBs are responsive to a commander who approves all IRB proceedings, and IRBs at institutions receiving Defense Department contracts are subject to review by contracting headquarters. There is no mechanism, however, for systematic monitoring of either the conduct of extramural research or the performance of grantee or contractor IRBs except in the Army, whose Medical Research and Development Command conducts site visits to each contractor prior to approval of the contract. One of the site visitors must be qualified to perform technical review; the other must be qualified "to evaluate the contract as an advocate of the human subjects."

A modest check on IRB performance is provided in some agencies through review of consent forms. At the Consumer Product Safety Commission, consent forms must be approved by the agency prior to initiating research and all signed consent forms are reviewed-and retained-by the agency. Within the Public Health Service, by contrast, routine submission of consent forms to be used in proposed re

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search activities is generally not required. The study sections do not routinely examine consent forms, and OPRR reports that, given the volume of research projects flowing through that Office, it cannot undertake this added function. At one time ADAMHA reviewed all consent forms for research it supported, but this practice has now been curtailed. The lone present exception in HHS arises when the government (most usually, the National Cancer Institute) is acting as a "sponsor" of a drug or device being tested, since the FDA requires all sponsors to review consent forms.

Are IRBS Able to Understand

and Fulfill Their Obligations?

This is plainly a time of transition for the IRB system. The National Commission for the Protection of Human Subjects gave careful consideration to the institutional review system and issued recommendations supportive of the basic elements of that system while at the same time seeking to strengthen certain of its important facets. The new regulations, issued by HHS early in 1981, are based substantially on the National Commission's recommendations, and institutions are now at various stages in revising their procedures and negotiating with HHS to accept their assurances of compliance with the regulations. Moreover, HHS is in the process of developing educational materials and conferences to assist IRBs in understanding their responsibilities under the new regulations. Thus, while a new general assessment of the basic institutional review system would be premature, it is appropriate to examine particular problem areas which arose prior to 1981 and appear to be incompletely resolved by the new regulations. Two requirements that seem to pose the greatest difficulty are: (1) continuing review by an IRB of projects it has approved and (2) IRB reporting of adverse affects of serious and continuing noncompliance.

Initial Review. The IRB study undertaken by the National Commission for the Protection of Human Subjects suggested that IRBs had a fairly good understanding of most of their responsibilities for initial review of research involving human subjects, although 25% of IRB members felt that they, and researchers, needed more information (i.e., better definitions and clearer guidelines) from the Department.14 The recent revisions in the HHS regulations provide more explicit guidance than previously offered as to what constitutes research with human subjects and what categories of such research must be reviewed or, alternatively, need not be reviewed. It remains to be seen how well the new regulations and the planned educational

14 IRB Report, supra note 1, Appendix at I-263 (Table XVII–10).

programs will meet the IRBs' needs for further guidance. Many of the most important decisions made by IRBS are matters of interpretation and judgment. These are best left to the IRB, as they are not likely to be improved by ever more detailed regulations.

Continuing Review. In contrast to the IRB's role in initial review, available information strongly suggests that many IRBs do not understand what is expected in the way of "continuing review" of projects that the IRB has approved. Although continuing review has been required since 1971,15 the survey conducted for the National Commission between July 1, 1974, and June 30, 1975, found that only 20% of IRBs routinely designated members or other representatives to observe the manner in which a research project was being conducted; 63% reported that they never did, and 17% said that they did under certain circumstances. Moreover, 38% of the IRBS reported that in few or none of the proposals they reviewed was there even an understanding that the project would be reviewed again after a specified period of time and 47% seldom or never received copies of interim reports. 16

The problems manifested in these statistics clearly need attention. Some improvement might even occur as part of the current process of negotiating assurances with research institutions, if certain definitional difficulties were overcome. For example, "continuing review" and "annual review" appear in the HHS regulations to refer to separate functions (with distinct purposes and justifications). Yet the regulations do not make clear the meaning of the two terms nor the resulting expectations for institutional behavior. 17

Moreover, anecdotal information received by Commission staff at IRB conferences, and testimony presented to the Commission at hearings in Boston and Los Angeles, indicate the need for better guidance as to the Department's expectations. It appears that few IRBS perform ongoing re

15 Department of Health, Education and Welfare, Public Health Service, NIH, The Institutional Guide to DHEW Policy on Protection of Human Subjects, U.S. Government Printing Office, Washington (December 1, 1971) at 8.

16 IRB Report, supra note 1, Appendix at I-207 and at I-44. In fact, 60% of IRBs never received a copy of final reports. 1745 CFR §46.103(b)(4) sets forth in separate subsections that an institution's assurance must contain the "written procedures which the IRB will follow" for "conducting its... continuing review of research. . ." and for "determining which projects require review more often than annually..." 45 CFR §46.109(e) states that an IRB "shall conduct continuing review of research covered by these regulations at intervals appropriate to the degree of risk, but not less than once per year. . ."

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