The Human Radiation Interagency Working Group (IAWG) is a temporary collaboration among several Federal agencies. The IAWG has worked to support ACHRE and to respond to its recommenda-tions. The policies in this report seek to ensure appropriate follow-up on ACHRE recommendations by more permanent bodies.

[H]uman research involving radioisotopes is currently subjected to more safeguards and levels of review than most other areas of research involving human subjects. The Advisory Committee further finds that there are no apparent differences between the treatment of human subjects of radiation research and human subjects of other biomedical research. (Finding 20)

[T]oday research involving human subjects sponsored by the government may be classified and conducted in secret, but it must comply with the provisions of the Common Rule. (Finding 21)

[I]n comparison with the practices and policies of the 1940s and 1950s, there have been significant advances in the protection of the rights and interests of human subjects of biomedical research. However, we also find that there is evidence of serious defi-ciencies in some parts of the current system for the protection of the rights and interests of human subjects. (Finding 22)

National Bioethics Advisory Commission
The National Bioethics Advisory Commission (NBAC), a national deliberative body of private citizens, was established by the

President to provide guidance to all Federal agencies on the ethical conduct of human behavioral and clinical research, and the applications of that research. NBAC was established, in part, to respond to ACHRE, and the Administration expects NBAC will choose to address the key issues identified in ACHRE's recommendations. NBAC will not be able to review all issues raised by ACHRE. The Administration has been careful to ensure that issues not taken up by NBAC will be addressed elsewhere.

As a first priority, NBAC will seek to improve protection of the rights and welfare of human research subjects. The Executive Order establishing NBAC, required each agency to review its current human subjects research in light of the Advisory Committee recom-mendations and report the results to NBAC. NBAC is currently reviewing these documents. Appendix C details specific activities currently being carried out by the agencies as a result of their reviews.

Education
ACHRE's report made clear that a key to preventing the repetition of past mistakes is thorough and continuing education about ethics and how they apply to current human subjects research. The Administration is responding to ACHRE's specific recommendations by co-sponsoring educational programs with external groups such as medical schools, universities, and scientific societies. The goals of these educational efforts are to strengthen human subjects protection, to provide a forum for addressing ongoing as well as emerging issues in human subjects research, and to familiarize professionals engaged in non-federally funded human subjects research with relevant ethical considerations. Part of the ongoing educational process is a reinforcement of the importance of Institutional Review Boards (IRBs) at institutions conducting federally funded research. These IRBs are local groups whose membership and responsibilities are regulated by the Federal government. They are responsible for reviewing and approving the ethical content of all proposed human subjects research projects. IRBs are a linchpin in the protection of human subjects, and their credibility and effectiveness depend on adequate awareness of basic ethical topics.

Similarly, educational programs are also being targeted at government-regulated research that is not government-funded (e. g., FDA-regulated research sponsored by the pharmaceutical industry). In September of 1996, the FDA sponsored its first nationwide conference on human subjects protection. Government employees who have responsibility for supporting or overseeing human subjects research are also targeted for educational programs. Thus, Federal agencies are implementing training programs to educate senior level officials on regulations and policies governing this research. For example, NASA is working with international research partners to develop common ethical principles that ensure the protection of human subjects. DOE educational efforts target laboratory staff, field office personnel, and program officials.

In addition, Departments have pooled resources to sponsor research on the informed consent process. The informed consent process is intended to help each potential research subject decide whether to participate in research by providing advance information about the research. Information includes a description of the nature of the research, the subject's role and potential risks, and the subject's rights and responsibilities. Despite the vigor with which all parties embrace the informed consent process, it is not well understood. Much of the Advisory Committee's commentary on current human subjects research was centered on informed consent. The National Institutes of Health (NIH), VA, and DOE are committed to support-ing research that will more fully illuminate the informed consent process. A Request for Applications (RFA) to conduct research on this issue was published in the fall of 1996, and Fiscal Year 1997 monies are earmarked to support this RFA.

1. mechanisms to ensure a stronger focus on studies that pose more than minimal risk to subjects;
2. better means of explaining to potential subjects the distinction between research and treatment, the realistic likelihood of medical benefit to the subject from participation, and the potential for discomfort and pain;
3. ensuring that potential subjects fully understand the sponsors and purposes of the research;
4. ensuring that potential subjects fully understand the financial implications of participation; and
5. recognition that the IRBs must decide if the quality of the science justifies the risk to the subjects.

In the interim, agencies are informing IRBs of ACHRE's recommen-dations and are working to improve IRBs. The Office for Protection from Research Risks (OPRR), part of NIH, is undertaking a national effort to educate the research community about ACHRE's recommendations. OPRR and FDA support an annual public meeting for individuals interested in the governance of human subjects research. In addition, OPRR, in cooperation with FDA and local academic institutions, has held discussions of the recommendations at national workshops in Atlanta, Oklahoma City, Honolulu, Peoria, Houston, and San Diego.

OPRR and the FDA make extensive use of public meetings, forums, hearings, and electronic media to address evolving issues on human subject protection. OPRR and FDA also regularly mail information directly to IRBs and other interested parties. FDA seeks public input through the Federal Register and by mailing proposals to the IRB and clinical investigator communities. In October 1995, FDA issued a major revision of its "Information Sheets for Institutional Review Boards and Clinical Investigators," to take into account the latest thinking and to provide guidance to IRBs. This information is available on the Internet (http://www.fda.gov/cder/about/smallbiz/clinical_investigator.htm).

As noted above, ACHRE recommended that IRBs focus the bulk of their time on studies that present more than minimal risk to subjects. To educate the research community about the importance of this recommendation, OPRR sent information to 5,500 addressees worldwide. The information highlighted regulatory provisions for (1) exemption from IRB review of 6 categories of low-risk research, and (2) expedited IRB review of 10 other kinds of research when it is judged by IRBs to be of minimal risk. Proper use of these time-saving mechanisms permits IRBs to devote greater effort to the areas of concern to ACHRE.

The Administration anticipates specific recommendations from NBAC regarding reform of IRBs, including recommendations that address ACHRE's concerns.

Response

The Administration also agrees that there is a need for a mechanism to interpret the existing rules that apply to government-sponsored research. The Department of Health and Human Services (HHS), particularly OPRR and FDA, provides information and interpretations of the regulations for protection of human subjects. OPRR also maintains an Information-by-FAX service (301-594-0464) and a World Wide Web site (nih.gov:80/grants/oprr/oprr.htm) to distribute information, and responds to inquiries by mail. FDA provides these functions for FDA- regulated research and OPRR provides them for other federally supported research.

Individual agencies are also promoting public discussion of current ethical issues. For example, DOE's Ethical, Legal, and Social Issues (ELSI) program sponsors a wide variety of educational programs, including meetings and seminars. DOE has recently sponsored two highly acclaimed public television programs on the human genome program. DOE has also sponsored a workshop for trial judges to receive information about, and discuss the use of, DNA evidence in the courtroom. The genome program has also sponsored conferences to discuss genetics in light of religion, discrimination, and other ethical issues.

These projects are good examples of public and private entities working together to promote civil discourse over ethical issues. The Administration will seek additional opportunities to support this kind of effort.

The military setting, with its strict hierarchical authority structure and pervasive presence in the lives of its members, poses special problems for ensuring the voluntariness of participation in research activities. Thus, although the DOD has adopted and implemented the consent requirements of the Common Rule, additional procedural safeguards and educational activities for officers may be warranted to counteract the generalized deference to authority inherent in military culture. Also, because the opportunity to serve the nation as subjects in defense-oriented research projects is closely akin to the demands placed on members of the military in their routine duties, it is desirable to emphasize the distinction between research and course-of duty risks both in consent procedures and in officer training programs.

ACHRE recommended that the military better ensure the protection of rights and interests of military personnel who are involved in human subjects research by reviewing general policies and procedures, educating officers and investigators, implementing policies and practices that make certain participation is genuinely voluntary, and maintaining a registry of volunteers. (Recommendation 12)

ACHRE found that sanctions may be inadequate for violations of human subjects research protections. For example failure to obtain consent from subjects (who are not physically injured) is generally punishable only by the withdrawal of research funding.

ACHRE also found that "there is a need to assess the level of research performed outside [the Common Rule] and to consider action to ensure that all subjects are afforded the protections it offers." ACHRE recommended the improvement of three parts of the current Federal system for human research subject protection: oversight of the research process; sanctions for violations of human subjects protections; and protections for subjects of non-federally funded research. (Recommendation 13)

In addition to exploring legislation, Federal agencies are undertak-ing specific activities to strengthen oversight, some of which are described in Appendix C. The Administration expects that NBAC will recommend additional actions to improve oversight of Federal research, and will identify the highest priority steps.

The Administration does, however, view the debate over the extent and effectiveness of our current human subject protections to encompass this issue. The Administration would be open to considering any recommendations from NBAC or legislation from Congress that seek to address this issue. The desire to spread the cost of research injury is a reason to consider a compensation scheme. The current tort system, though imperfect, provides one mechanism to seek compensation for injuries that arise from research. In addition, the tort system provides a powerful incentive to researchers to observe appropriate standards of care in conducting the research. These standards generally include providing for informed consent and exercising care in the conduct of research.

• obtain informed consent from all human subjects;
• inform subjects of the identity of the sponsoring agency;
• inform subjects that the project involves classified research; ° establish permanent records; and
• be approved by an "independent panel of nongovernmental experts and citizen representatives, all with the necessary security clearances."

The Administration agrees with the first four recommendations. The President is issuing a memorandum directing Federal agencies to jointly propose modifications to the Federal Policy for the Protection of Human Subjects (Common Rule) as it applies to classified research in order to implement these changes. Further, subjects will be informed of the sponsoring agency, except in limited, minimal-risk cases. In all secret studies, researchers will obtain informed consent, disclose that the project involves classified research, and keep permanent records.

The Administration is taking two additional steps to ensure that classified human subjects research remains rare. The President is directing the heads of Federal agencies to disclose annually the number of secret human research projects undertaken by the agency and the number of human subjects participating in each project.

These steps will preserve the government's ability to conduct any necessary classified research involving human subjects while ensuring adequate protection of research participants. (See Appendix E for the directive from the President regarding classified research.)

The Advisory Committee further noted that, today the law provides that environmental reviews may be conducted in part or even in whole in secret, thereby eliminating provision for public notice and comment. In classified programs, the government must still comply with environmental standards, and the Environmental Protection Agency must oversee and review environmental compliance. However, the EPA has not maintained records of environmental releases where the reviews were conducted in whole or in part in secret. (Finding 23)

The Advisory Committee recommended that (a) there be review by an independent panel of any planned environmental release where any aspect involves secrecy; and that (b) environmental oversight of classified programs, now done by the Environmental Protection Agency (EPA), should include keeping review records permanently and reporting to Congress. (Recommendation 16)

EPA, in conjunction with Federal agencies conducting classified programs, is taking steps to improve environmental oversight and enforcement capability over all classified activities. These steps include formal agreements between EPA and other Federal agencies to streamline the process of providing information about environmental compliance related to classified activities. This effort will give environmental enforcement authorities the information they need to appropriately review secret environmental releases. It would be difficult, if not impossible, to create similar enforcement capabilities in a new regulatory entity, such as an independent review panel, that focuses only on these extremely rare occurrences. In addition, a new entity would add to the bureaucratic complexities of ensuring environmental safety and would not necessarily increase public protection.

EPA will establish and maintain a permanent file to document EPA's classified reviews under the National Environmental Policy Act (NEPA). The EPA policy establishing this permanent file will address transport, storage, review, and permanent recordkeeping of classified NEPA documents and EPA review comments. EPA will notify all Federal agencies of its new classified filing and review procedures and will provide Congress with information on request.