Food, Drug, and Cosmetic Act
Public Health Service Act
DHHS 16 Departments and
Agencies FEDERALLY FUNDED
Food and Drug Administration
Not federally funded and not subject to FDA
• Some colleges and universities not receiving federal research funds
• Some in vitro fertilization clinics
• Some weight-loss or diet clinics
• Some physician offices, some dentist offices, and some psychotherapist offices
• Some legal services clinics
• Some corporate and industrial health, safety, and fitness programs
• Some developers of genetic tests
• Some Websites Not federally funded and not subject to FDA
• Assured institutions that do not voluntarily pledge all activity to 45 CFR Part 46
Source: Office for Protection from Research Risks
Federally funded and not subject to FDA
• Some Department of Labor
• Some Nuclear Regulatory Commission
• Some National Endowment for the Humanities Informed consent
Institutional Review Boards
IRB inspections
1991 Federal Policy
for the Protection of Human Subjects 45 CFR Part 46
Subpart A
Institutional Assurances Informed consent Institutional Review Boards
Subpart B Pregnant women; fetuses Subpart C Prisoners
Subpart D Children
Site visits
“COMMON RULE”
=
to lead and coordinate the oversight system.
This office should be responsible for policy development, regulatory reform (see
Recommendation 2.3), research review and monitoring, research ethics education, and enforcement.
Recommendation 2.3:A unified, comprehensive federal policy embodied in a single set of regula-tions and guidance should be created that would apply to all types of research involving human participants (see Recommendation 2.2).
If these particular recommendations are not imple-mented, the federal government should find alternative approaches for realizing the intention of these and subse-quent recommendations in this report.
Advantages and Disadvantages of a Single, Independent Office
Advantages
Elevating the government entity that oversees research involving human participants to agency status with government-wide authority gives the federal commitment to protect research participants high public visibility.
Empowered with the authorities mentioned above, the office would be more likely to achieve the desired outcomes. Clear, consistent regulations and guidance tailored to various types of research would be developed and modified when needed. Most important, the office would be capable of prompt, decisive action in response to new research issues. NBAC envisions the office imple-menting a dynamic, evolving, and flexible system of oversight. Even on its first day of operation, the new office would be an improvement over the current sys-tem, because it will provide a focal point for oversight and a source for information that does not now exist. It also could begin promptly to develop policy, both regu-lation and guidance.
NOHRO would also eliminate the inertia that occurs in the current system because of the lack of a lead office with authority to direct federal agencies to carry out a task. One way in which NOHRO could facilitate both protection of research participants and the promotion of research is by introducing mechanisms for review of
research that involves complex ethical issues. These mechanisms might include requesting a federal agency to set up a special review body or working with local institutions in conjunction with a federal agency that is sponsoring a particular research program.
If the proposed office were located within a depart-ment rather than given agency status, special provision would need to be made to force other departments and agencies to follow the policies set by that lead agency.
Empowering such a lead agency within one department with authority over operations of other departments at the same administrative level presents a difficult arrange-ment at best. For example, staff of the other agencies may be subject to competing expectations and demands from their own agencies as well as the proposed office.
Another concern of locating NOHRO within a single department is that it could be perceived both externally and within the department as responsive primarily to that department’s interests, views, and the type of research it sponsors or conducts, to the exclusion of other types of research carried out primarily by other departments. For example, OHRP, located in DHHS, has interpreted regula-tions and developed policy generally in response to the conduct of biomedical research. Furthermore, housing an oversight office within a department that conducts or sup-ports human research could create a conflict of interest.
Such a potential conflict provided at least part of the reason for the recommendation to relocate the Office for Protection from Research Risks from NIH to the DHHS Office of the Secretary (OPRR Review Panel 1999). But this degree of separation may still be insufficient, because NIH is part of DHHS, and the new office is still regulating an organization on which it relies for budgetary and other support. The potential conflict of interest is thus attenu-ated, but not eliminated.9,10 The ability to act without approval from the agencies it regulates is essential to both the perception and reality of NOHRO’s effectiveness.
Disadvantages
Establishing an independent office might have disad-vantages. Most notably, an independent office would necessarily be smaller than the departments and agencies affected by the policies it develops and thus might lack some of the political support it would need to be effective.11
National Bioethics Advisory Commission
Creating an independent office could also lead to increased bureaucracy by adding another layer of over-sight. NBAC opposes the creation of another office that merely adds regulations that do not provide additional important protections. However, the new office should reduce unnecessary bureaucratic burden by eliminating some duplicative procedures currently existing under the Common Rule. For example, issuing assurances of com-pliance and registering IRBs should be centralized in the new office (see Chapter 4). The use of such centralizing rulemaking procedures eliminates the requirement that every federal agency bound to the Common Rule institute its own rulemaking procedures in order to revise the Common Rule or make new regulations.
The scarce resources that are currently available to support the oversight system would be insufficient to create and operate the new office. As discussed in Chapter 7, new funds should be appropriated to support the office. Although there might be short-term costs, in the long run, the investment in oversight could ultimately make more funds available for research by reducing the duplication in the current oversight system and stream-lining a number of functions.
Another potential disadvantage of an independent office is that its staff may be isolated from those who are involved in the daily conduct of research. However, mechanisms could be established that would make an independent office accountable to the research community, including the IRB community, participants, and the public. First, the office should establish a standing advisory committee to assist in policy development and interpre-tation with represeninterpre-tation from the appropriate federal agencies; the private sector; the research community, including all the major disciplines (e.g., clinical, public health, social sciences, humanities) that conduct such research; the IRB and ethics communities; and the public.
Ad hoc advisory committees should be established to deal with specific issues of ethics and review of research.
Interacting with the research community will help the office understand and appreciate the nuances in con-ducting research and deal effectively with emerging ethical issues. At the same time, this office should be closely tied to the IRB community so that it can address issues, problems, or challenges facing IRBs. NOHRO also
should develop mechanisms for public input, not only into rulemaking procedures, but also into guidance development procedures. This might include establishing a process for seeking input into decisions involving interpretations of regulations or guidance. The office should also be required to make annual reports to Congress on the status of oversight for research involving human participants.
Two examples of this model of independent, government-wide regulatory bodies, both of which were formerly located within agencies performing the activities they regulated, are the Office of Government Ethics (OGE) and the Nuclear Regulatory Commission (NRC).
OGE was formerly part of the Office of Personnel Management and has authority over all federal agencies.
NRC was part of the Department of Energy and has authority over both the public and private sector. The creation of OGE and NRC corrected some problems that NBAC has also observed occurring in the current oversight system for research.12These offices act independently and are free from the interests of other agencies. They are able to make rules and promulgate guidance, visit and audit those they oversee, govern pertinent activity within other federal departments and agencies, and operate with adequate resources, including staff.13
Operating Mode of NOHRO
A lead federal office should not carry out the day-to-day work of protecting research participants. Once cre-ated, it would be imperative for the office to review with all federal agencies their current responsibilities and tasks so that overlapping activities could be avoided or harmo-nized. Individual federal offices would be responsible for interacting with the lead office and for implementing the oversight system within their departments or agencies.
When appropriate, the office should delegate authority to departments or agencies, especially when the imple-mentation of the function will vary by department. For example, departments must have authority to manage the implementation of the human research oversight system in their extramural programs. OHRP should con-tinue to monitor compliance and investigate allegations of noncompliance, provide education, and work with the DHHS agencies in administering their extramural
research programs. In fact, OHRP should be able to expand its activities to cover the 11 agencies within DHHS in which they have not had much of a presence.
Generally, NOHRO should be directly responsible for policy development and interpretation through regu-lation and guidance. Rulemaking and guidance develop-ment should occur with input from federal departdevelop-ments, the private sector, academic and research institutions, IRBs, and the public. Education is a shared function, best carried out by other parties in the oversight system, such as academic and other research institutions, public and private sponsors, and professional societies. However, NOHRO should serve a coordinating role, ensuring con-sistency in educational standards and acting as a catalyst for educational program development.
NOHRO would not only ensure that review of research continues to occur through IRBs, but would also provide the leadership and policy needed to ensure con-sistency across IRBs. Its role in this function would be to 1) register those institutions and IRBs authorized to review and conduct research using human participants and work with credentialing bodies to develop mecha-nisms to accredit institutions and certify investigators, IRB members, and IRB staff and 2) coordinate reviews by specially accredited IRBs or specially created regional or national review bodies.
Other responsibilities would include the following:
■ defining the criteria of research studies that should receive additional review;
■ defining the criteria for when review should be con-ducted by a specially accredited IRB or a specially created regional or national review body versus review by a local IRB;
■ determining the mechanism for communication between local IRBs and the additional review body so that the latter is informed about locally relevant information and the former about deliberations of the additional review body; and
■ exploring whether there is a need to serve a mediation or arbitration function when IRBs disagree over the review of the same research study.
Monitoring is another shared function that is best carried out by those entities closest to the conduct of research, such as sponsors and institutions or accrediting
bodies. NOHRO’s role should be to set policy and insti-tute procedures for monitoring the federal agencies that sponsor research.
Although the lead office should have final authority for enforcement, this function should be shared with federal departments, institutions, and accrediting bodies.
NOHRO should set policy describing the types of non-compliance, types of sanctions, and use of various types of sanctions to address noncompliance. It should have the authority to conduct investigations to detect regula-tory noncompliance and should delegate authority to federal agencies to investigate allegations of noncompli-ance. Federal agencies, accrediting bodies, and institutions should be held accountable to report violations to NOHRO, which should investigate serious violations and repeat offenders.
Regulation of Research Involving Human