the department. If the rules are sufficiently flexible, they can be applied to all modalities of research (e.g., biomedical, behavioral, surveys, questionnaires, record reviews, and so forth). Therefore, the Commission sees no justification for differentiating among funding mechanisms or individual departmental components. This recommendation is made, as a formal matter, under §1802(b) of the Commission's enabling statute (42 USC §300v-1(b)) to the Secretaries of Defense, Education, Health and Human Services, Justice and Transportation, and to the Administrator of NASA, for action within the specified time periods.

4. All Federal departments and agencies that conduct or support research with human subjects should require principal investigators to submit, as part of their annual reports to the IRB and the funding agency, information regarding the number of subjects who participated in each research project as well as the nature and frequency of adverse effects.

Comment: This recommendation, like the preceeding one, is intended for implementation whether or not the full uniformity and centralization of Recommendations 1 and 2 are achieved. In any event, the Commission suggests the reporting requirements recommended here be uniform so that comparable data are available on a government-wide basis. (The timetable established by §1802(b) of the Commission's authorizing statute applies to this recommendation unless the government-wide task force proposed under Recommendation 1 is at work within 60 days on a uniform set of rules and has published such rules within 180 days thereafter.)

In preparing its report on Compensating for Research Injuries, the Commission was disappointed to discover that data on the number of human subjects who participate in Federally funded research are not routinely and systematically compiled. Data regarding the incidence and severity of injuries that occur in such research are also not collected. The inability to obtain such information was one of the most frustrating aspects of the Commission's attempt to determine whether a program to compensate individuals for injuries resulting from their participation in research is needed. Federally funded investigators are already required (under the terms of their grants and contracts) to report on their projects at least once a year. A requirement that they note in such reports the numbers of subjects and of injuries during the period in question would add only a trivial burden while yielding a large benefit.

The Commission recommends that copies of such reports be collected and reviewed by the IRB at the institution in which the research is conducted and then forwarded to a

specified office within the funding agency to be collated. Those with oversight responsibility for human research-at Congressional, Presidential or Departmental level-will then be able to obtain information about the number of human subjects and the number of injuries from each Federal agency supporting research with human subjects as well as from each institution conducting such research with Federal funds. This information seems the minimum necessary for public accountability regarding such an important and sensitive enterprise as collectively supported research with human beings.

The Commission is aware of the difficulty of defining injuries or adverse effects in a way that will avoid massive reporting of trivia but at the same time encourage the reporting of significant problems. The Commission notes, however, that several institutions with insurance programs have found means of categorizing harmful effects and that the Veterans Administration has recently implemented a reporting requirement along the lines recommended here. Its initial experience points to some administrative difficulties needing further attention, both by the VA and by other Federal entities implementing this recommendation. Concurrent with such implementation, the Commission suggests that the agencies (ideally, with coordination by the designated "lead office") work together to resolve any remaining definitional problems (e.g., determining whether under- or over-reporting occurs if transient effects such as mild to moderate headache, nausea, and the like are not reported unless they persist so long as to interfere with the subject's normal activities; determining the extent to which injuries caused by the research process can be distinguished from those caused by the treatment being tested or by the subject's disease or condition; etc.). A certain amount of trial and error may be necessary before the optimal definition is developed; nevertheless, refinements and adjustments can be made over time. It is important to make a beginning.

5. The Department of Health and Human Services and all other relevant Federal departments and agencies should proceed promptly to take action on the National Commission's recommendations concerning research involving children and research involving those institutionalized as mentally disabled, and other Federal agencies should also act on the final regulations of HHS governing such research.

Comment: It is now four years since the National Commission for the Protection of Human Subjects transmitted to the Secretary, HEW, its recommendations concerning research involving children and research involving those

institutionalized as mentally disabled.4 Those recommendations address a very complex and sensitive topic: research with subjects who are unable to give legally valid consent to their own participation. The subject is complicated because state law on "proxy consent" is not well developed or clear. The procedures and standards recommended by the National Commission were intended to provide greater protection for children and the mentally disabled than exists under the basic HHS rules. Under current regulations, children and the mentally disabled may be enrolled in research even over their express objections on the basis of parental or guardian consent. Ironically, since the National Commission's recommendations would erect special protections, their adoption might actually facilitate research, since scrupulous compliance with their terms might lay to rest concerns over the status of "proxy consent" in research under the common law.

The legislation that created that Commission required the Secretary to publish those recommendations within 60 days of receipt, and to publish the Department's response (in the form of proposed rulemaking) within the next 180 days. Although no deadline for implementation of final

"National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Report and Recommendations: Research Involving Children, U.S. Government Printing Office, Washington (1977); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Report and Recommendations: Research Involving Those Institutionalized as Mentally Infirm, U.S. Government Printing Office, Washington (1978).

Specifically, both children (age 7 and over) and the mentally disabled would be given an explanation of the proposed procedures geared to their level of understanding and, if the research presented no likelihood of benefit to them, would have an opportunity to assent or refuse to participate. In addition, research presenting more than minimal risk and no likelihood of benefit to the subjects would be permitted to involve children or the mentally disabled if: (a) the risk is no more than a minor increase over minimal; (b) the research is relevant to the subjects' condition; and (c) the research holds out the promise of significant benefit in the future to either the subject or others with similar disorders or conditions. Finally, the National Commission recommended review at a national level (with opportunity for public participation) of proposed research that would present more than a minor increment of risk and no anticipated benefit to children or the mentally disabled but may be of major significance to the solution of a serious health problem affecting persons similarly situated. As noted earlier, action on these recommendations might clear the way for important research on severely disabling conditions such as senile dementia of the Alzheimer's type.

5 National Research Act, Pub. Law 93348, §205 (1974).

regulations was set forth in the National Commission's enabling legislation, the President's Commission is certain that Congress anticipated an orderly and expenditious proceeding. Surely, it did not contemplate that the Department would prolong its rulemaking over a period of years.

The President's Commission agrees with the National Commission about the importance of pediatric research and of research to prevent or alleviate serious cognitive and emotional disorders. This Commission also shares the concerns of the National Commission that the subjects of such research be properly protected. The Commission concludes, therefore, that the time is long past for action, either by adoption, rejection or modification of the National Commission's recommendations. This recommendation, like Recommendations 3 and 4, is made pursuant to §1802(b) of the President's Commission's authorizing legislation, to the Secretary of Health and Human Services, and to the heads of all other Federal entities that conduct or support research with children or institutionalized mental patients. Within 60 days, this recommendation shall be published by each agency, and each agency is then obliged within 180 days to act upon the recommendation, favorably or unfavorably, and to announce its disposition and reasons. The President's Commission would regard this requirement to be met by a single publication in the Federal Register if the government-wide task force proposed under Recommendation 1 is at work on establishing a uniform set of rules and regulations by 60 days from the date of this Report and has published proposed uniform regulations within 180 days thereafter. Plainly, such unified action would avoid adding to the needless duplication that already characterizes regulations in this field.

6. Congress should attach the following condition to any direct appropriations for "private" research entities: "No funds appropriated under this Act may be used, directly or indirectly, to support research involving human subjects unless such research is reviewed and conducted in compliance with either (1) appropriate regulations of [the disbursing agency] or (2) the regulations of the Department of Health and Human Services (45 CFR 46)."

Comment: It has come to the Commission's attention that Federal monies are appropriated to organizations that are established as private, non-profit corporations. In the case of the Gorgas Memorial Institute of Tropical and Preventive Medicine, Inc., which conducts research on tropical and other diseases in Panama, the funds are disbursed through the Fogarty International Center at the NIH, but the Fogarty Center lacks authority to require the Gorgas Institute to follow the rules on the protection of human subjects that attach to other research that receives funds from NIH.

In the absence of specific legislation, such recipients of direct appropriations are not required to comply with any regulations governing research with human subjects.

The Commission recommends that Congress attach conditions to its appropriations that would require compliance with regulations for the protection of human subjects participating in research supported by those funds. As noted above, the Commission would prefer to see a uniform standard applied to all research supported by Federal monies; if this is to be accomplished, private organizations receiving "line item" appropriations should have to comply with the designated standard. Even if uniformity of regulations among agencies is not achieved, however, the Commission recommends as an alternative that Congress require such entities to comply with the regulations of either HHS or of the disbursing agency, if other than HHS.

Recommendations for Improving

Institutional and Federal Oversight of Research and the Response to Reports of Misconduct.

As discussed in Chapters One and Three of this Biennial Report, the Commission has concentrated its efforts regarding Federal regulations for the protection of human subjects on scrutinizing the adequacy of Federal oversight and the implementation of the regulations. Several recommendations on implementation and Federal compliance activities are made in this Report pursuant to §1802(b) of the Commission's statute; the process of review is ongoing and further recommendations may be forthcoming in the next Biennial Report.

Examining the implementation of the present regulations has, moreover, revealed certain problems with those regulations themselves. These problems emerged through the Commission's hearings on, and studies of, instances of alleged fraud or abuse in research involving human subjects. The few cases of alleged misconduct examined by the Commission should not be regarded as grounds for indicting the research enterprise in general or the IRB system in particular. Rather, the cases demonstrate the need for an oversight process that would provide the systematic data necessary to place the "problem cases" in context and to justify the confidence generally expressed regarding the present system. Furthermore, the cases bring to the fore basic questions about the role and functions of IRBs, questions that will be the subject of further study by the President's Commission during the preparation of its next Biennial Report.

For the moment, the Commission has identified several aspects of institutional responsibility in need of clarifica