Chapter 7: Implications of This Report (Research Involving Human Participants V1)
Introduction
This report proposes an oversight system for research involving human participants that addresses the needs, interests, and responsibilities of all parties involved in the research enterprise. Adopting the recommendations in this report will lead to better protection of human participants while also promoting ethically sound research and reducing unnecessary bureaucratic burdens. Achieving these goals will, in turn, support the public's trust in research, enhance enthusiasm for all research involving human beings, and restore the respect of investigators for the oversight system. Ultimately, the needs of the American people will be better met through research that is both ethically sound and of the highest scientific quality.
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Resources
The recommendations made in this report will generate additional costs for institutions, sponsors, and the federal government (through the establishment of a new federal oversight office). The importance of identifying the needed resources to support a robust system of protection of research participants has long been a concern. In 1978, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (National Commission), concerned that Institutional Review Boards (IRBs) could not function without adequate resources, recommended that the oversight system be appropriately funded (National Commission 1978). In 1998, the Department of Health and Human Service (DHHS) Office of Inspector General called attention to the critical shortage of resources, including staff, office space, and information technology, and recommended that IRBs be given access to adequate resources (OIG 1998). The scarcity of resources for IRBs has been attributed to low levels of support from sponsors and institutions (GAO 1996).
In previous reports, the National Bioethics Advisory Commission (NBAC) recognized that research should not be thwarted because resources are not available to provide the necessary protections for human participants and that compliance would require additional resources (NBAC 1998; NBAC 1999). Sponsors of research, whether public or private, should work together with institutions conducting research to make the necessary resources available.
Limited information is available concerning the human and financial resources that federal agencies, other sponsors, and research institutions dedicate to oversight. In fact, the only information NBAC could obtain in this regard was for the federal agencies. However, it is clear that the current system relies on other sponsors and research institutions also contributing substantial resources to oversight. Thus, the information presented below is an incomplete picture of the current resources used to support the oversight system.
Human and financial resources that directly support human research protection activities are limited at the federal level.1 As shown in Table 7.1, of the 16 federal agencies responding to an NBAC survey, 5 have no dedicated administrative unit or staff. Even within DHHS, four agencies have no dedicated administrative units or staff. Most departments spend only 1 to 2 percent of their human research budget on protection activities. The National Institutes of Health (NIH) spent less than .05 percent of its human research budget directly on protection activities, even when the Office for Protection from Research Risks (OPRR) was administratively part of the agency.
Table 7.1: Federal Agency Support for Research Participant Protections for FY 1999
| Agency |
Dedicated Administrative Unit Human Research |
Budget for Dedicated Administrative Unit |
Human Research Budget |
| *Until June 2000, OPRR was the administrative unit within DHHS that provided assurances for all DHHS agencies as well as other federal departments. ***During FY 2000, VA planned to increase to 8 FTE, and in FY 2001 there will be 12 FTE in Headquarters. There are plans for five field offices to be established in FY 2000. Source: NBAC, Federal Agency Survey on Policies and Procedures for the Protection of Human Subjects in Research. This staff analysis is available in Volume II of this report. |
| Central Intelligence Agency |
Yes, Chief of Human Subjects Research Panel and Contracting Officer's Technical Representatives |
Classified |
Classified |
| Department of Commerce |
National Telecommunications and Information Administration - No |
None reported |
17,600,000 |
| National Institute of Standards and Technology (NIST)- personnel in Office of NIST Counsel and elsewhere |
41,024,000 |
| Census - No |
158,500,000 |
| Department of Defense |
60 full-time equivalents (FTEs) |
3,500,000 |
37,100,000 |
| Department of Education |
1.5 FTEs |
200,000 |
50,000,000 |
| Department of Energy |
2 FTEs |
425,000 |
27,000,000 |
| Department of Health and Human Services |
|
|
|
| Administration for Children and Families |
No |
None reported |
30,000,000 |
| Agency for Healthcare Research and Quality |
No |
None reported |
109,411,000 |
| Centers for Disease Control and Prevention |
6 FTEs |
651,505 |
172,025,000 |
| Food and Drug Administration |
~200 FTEs |
~$37,000,000 |
11,329,000 |
| Health Care Financing Administration |
6 FTEs |
None reported |
15,000,000 |
| Health Resources and Services Administration |
No |
None reported |
75,908,000 |
| Indian Health Service |
4.7 FTEs |
1,000,000 |
22,400,000 |
| National Institutes of Health |
4 FTEs in Office of Human Subjects Research, another 10.73 in Institute's administrative units, 19 FTEs in OPRR* |
480,000 |
8,580,000,000 |
| 334,965 |
| 2,700,000 for OPRR |
| Substance Abuse and Mental Health Services Administration |
No |
None reported |
338,349,000 |
| Department of Housing and Urban Development |
No (Office of Lead Hazard Control conducts some oversight) |
None reported |
11,000,000 |
| Department of Justice |
2 part-time employees |
Not available |
110,705,000 |
| Department of Transportation |
No |
None reported |
Not reported |
| Department of Veterans Affairs (VA) |
3 units, 3 FTEs** |
None reported for FY 1999 |
175,600,000 |
| National Aeronautics and Space Administration |
5.9 FTEs |
625,000 |
20,000,000 |
| National Science Foundation |
Part-time employee |
Part-time employee |
150,360,000 |
| Social Security Administration |
No |
None reported |
40,000,000 |
| Agency for International Development |
Cognizant Human Subjects Officers |
None reported |
60,000,000 |
| Consumer Product Safety Commission |
No |
None reported |
<$100,000 |
| Environmental Protection Agency |
Environmental Protection Agency |
Environmental Protection Agency |
Environmental Protection Agency |
The lack of adequate resources also has been noted in site visits by the Office for Human Research Protections (OHRP), formerly OPRR, and in testimony presented to NBAC. For example, in a site visit by OPRR to Duke University, OPRR found that the university had assigned only 2.5 to 3 full-time staff members to the IRB, even though the university reviewed over 1,700 protocols annually.2 IRB administrators, in particular, who testified to NBAC described the need for resources and strongly encouraged NBAC to consider the issue of resources in its recommendations.3 A report commissioned by NIH, Reducing Regulatory Burden, noted that resources available to IRBs are decreasing despite increases in workload and recommended providing additional federal resources when adding to IRB duties (Mahoney 1999).
Data estimating the costs of institutional protection programs are nearly 20 years old (Brown et al. 1979; Cohen 1982). In 1982, it was estimated that the total cost (administrative plus meeting costs) of IRB review at universities without medical schools was $137 per protocol, $154 at universities with medical schools, and $207 at hospitals. Adjusting these cost estimates for inflation using the Consumer Price Index, the total cost of IRB review at universities without medical schools would currently be estimated at $245 per protocol, $275 per protocol at universities with medical schools, and $369 per protocol at hospitals. Based on these inflation-adjusted figures, the current cost of protecting human research participants at research institutions nationwide is estimated to be $32.12 million. It is difficult, however, to estimate IRBs' costs at academic institutions, because costs are not itemized separately in grant applications; rather they are part of the costs recovered, at least partly though the indirect cost mechanism (Goldman and Williams 2000).
Some information, however, is available about the prices (which may be higher or lower than costs) being charged for IRB review. One commentator reported that her independent IRB charged $1,000 for an initial review of a protocol and $275 for initial review of a research site.4 Another commentator estimated that the average fee for a protocol review was $1,000.5 The number of academic institutions charging for IRB review of research that is not federally funded has been increasing in the past few years, with fees ranging from $500 to $2,000 for initial review and an average fee of $1,130.6 In addition to the call for additional resources, academic institutions have expressed concerns about the costs of the IRB being billed through the indirect cost mechanism, because an administrative capitation prevents them from requesting additional resources (AAU 2000). Alternatives, such as a direct budget line for protection of research participants, have been suggested (AAU 2000).
Recommendation 7.1:
The proposed oversight system should have adequate resources to ensure its effectiveness and ultimate success in protecting research participants and promoting research:
- Funds should be appropriated to carry out the functions of the proposed federal oversight office as outlined in this report.
- Federal appropriations for research programs should include a separate allocation for oversight activities related to the protection of human participants.
- Institutions should be permitted to request funding for Institutional Review Boards and other oversight activities.
- Federal agencies, other sponsors, and institutions should make additional funds available for oversight activities.
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Future Research
This report has raised many questions about ethical issues that could not be answered because of insufficient or nonexistent empirical evidence. Little research has been conducted on the actual conduct of research, although some studies are under way.7 Current thinking about ethical issues in research - including the importance of conducting analyses of risks and potential benefits, obtaining informed consent, protecting privacy and confidentiality, and protecting those who are vulnerable - would greatly benefit from research designed to address these specific issues. For example, approaches for assessing cognitive competency, evaluating what participants want to know about research, and ascertaining best practices for seeking informed consent are deserving of more study. Clearer guidance could be developed from a stronger knowledge base.
In addition, although a good deal of ethical analysis has been conducted on many research issues, some (e.g., ethical standards for informed consent) have received more attention from ethicists than others (e.g., understanding what constitutes undue inducement or exploitation in research). In general, increased interdisciplinary discussion that includes biomedical and social scientists, lawyers, and historians would advance understanding of the ethical conduct of research.
Recommendation 7.2:
The federal government, in partnership with academic institutions and professional societies, should facilitate discussion about emerging human research protection issues and develop a research agenda that addresses issues related to research ethics.
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The New System as a Dynamic and Responsive Structure
Research is an ever-evolving enterprise, responding to scientific interests, the biological and social condition of humans, the practicalities of resource availability, and competing demands on academic institutions and others involved in sponsoring or conducting research. Thus, the oversight system also must be dynamic and should be enhanced in order to ensure that sound ethical principles and standards are followed, while interpretation and application of those principles and standards accommodate and remain relevant to new discoveries, influences, and ethical challenges. The system should provide both the stable foundation and the flexibility necessary to respond to the changing research enterprise.
The proposed oversight system reflects a rethinking of the entire structure for protecting research participants, taking into account the roles of various parties, including participants, investigators, institutions, IRBs, sponsors, and other entities, such as professional societies, a federal oversight office, state regulators, Congress, and the public. Articulating the roles of each of these parties serves several purposes. It encourages a range of individuals, organizations, and communities to take more seriously their roles in the protection of research participants and holds them accountable for their actions. Distributing roles and responsibilities among more parties in the oversight system also reduces the burden placed on any one entity, such as IRBs. In articulating roles in various areas, such as monitoring and education, responsibility should be delegated to one or more parties, such as a central IRB, a local IRB, another entity within an institution, a Data and Safety Monitoring Board, or the research sponsor. It is critical that all parties understand their responsibilities and those of others in the system.
Once these roles have been articulated, it becomes clear that the oversight system must be more than a federal structure. Outside parties play a crucial role. Indeed, the system functions in large part because of the goodwill of the thousands of people who aspire to meet their obligations to conduct research ethically. Although attention is often focused on those who do not take their ethical obligations seriously, a majority of those involved in research are committed to ethical behavior. However, the awareness of and commitment to ethically sound research can be strengthened and enriched by educational institutions, credentialing and professional organizations, editors and publishers, and advocacy groups, organizations that have tremendous influence over their constituencies and that are in an excellent position to harness the energy of their members to support an efficient and effective oversight system.
Six distinct functions or responsibilities of a consolidated oversight system are recommended: policy development through regulations and guidance; educational programs aimed at the responsibilities of all parties; ethical review of proposed research; monitoring of ongoing research; enforcement of the requirements; and accountability for all those involved in the review and conduct of research. By focusing attention and resources on these functions, the system will provide the necessary infrastructure for protecting research participants and promoting research. To ignore any one of them is to have a system that functions less than optimally.
The functions of the system are, and should be, interconnected, with changes in one function affecting outcomes in another. For example, the creation of a single set of regulations and a single office to promulgate them makes it possible to implement specific regulatory changes without amending the regulations of each of the agencies, as is now required. Creation of a single, independent oversight office would also facilitate issuance of regulatory guidance, because direction from that office would apply to all parties conducting research involving human participants.
The greater flexibility proposed for IRBs in deciding what information must be provided to participants and in determining frequency of continuing review demands a higher level of competency among IRBs. Certification of IRB members and staff and accreditation of institutions can validate such competency. Higher and consistent standards for IRB members will ensure more effective assessments of risks and potential benefits as well as determinations of vulnerability. Similarly, certification of investigators allows for flexibility in implementing the recommended informed consent process. More education should make certification of investigators easier to achieve, because investigators will receive the knowledge and skills necessary for certification as part of their professional training. The recommendations regarding verification, adverse event monitoring, and accreditation of research institutions all make single review of multi-site research more feasible.
Thus, just as the oversight functions are interconnected, so too are the recommendations for improving them, and, therefore, consideration should be given to adopting them more or less in total, for to do otherwise may result in diminished success in implementing many of the recommendations in this report. For example, a crucial component of the proposed system is the creation of a new independent oversight office. If this new office were not created, it would be imperative to find an alternative mechanism that would allow the Common Rule to be modified more easily.
Now is the time for strategic change. With more than 20 years of experience with much of the current regulatory language and 10 years of experience with the Common Rule structure, all parties understand the strengths and weaknesses of the current oversight system, and it is evident that making minor tactical changes to it will not result in the corrections that are needed. However, the proposed changes should be implemented in a planned, phased-in fashion, to avoid creating major disruptions that could compromise the protection of research participants or the conduct of ethical research.
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General Themes in the Recommendations
Three general themes are found in this report. First, the recommendations related to policy generally suggest that there should be fewer regulations and more guidance, which clarifies regulatory responsibilities, suggests ways of fulfilling those responsibilities, and assists institutions in formulating institution-specific policies - improving consistency across institutions. At the same time, guidance permits reasoned deviations from the regulations.
Second, the recommendations generally focus attention on research in which participants need the most protection, striving to make the level of protection commensurate with the level of risk. This theme is strongest in the recommendations regarding continuing review, verification, reporting of adverse events, informed consent, review of minimal risk research, and additional scrutiny for research involving a high level of risk.
Third, the recommendations somewhat increase the scope of regulated research while streamlining the process of regulatory compliance. The recommendations regarding privately funded research and the removal of exemptions close some gaps in the current system and thus increase the amount of research subject to regulation. However, it is also recommended that requirements for initial and continuing review of all minimal risk research be reduced. Thus, although the scope of the oversight system is broadened, changes are proposed that will streamline the system and attenuate the need for additional resources by increasing efficiency, making it safer and more productive.
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What This Report Means to Those Who Use the System
One unified and comprehensive federal policy embodied in a single set of regulations and guidance should govern all research with human participants. Furthermore, one office should have the authority to promulgate those regulations and issue appropriate guidance (see Recommendations 2.1 - 2.3). At the same time, there is a continuing role for the various federal departments and agencies that conduct and fund research with human participants - a role focused particularly on education, monitoring, and enforcement (see Chapter 2). Nonfederal accreditation and certification bodies should be created to improve the quality and accountability of institutions and bodies responsible for the review and conduct of research (see Recommendations 3.3 and 3.4). In addition, it is time to encourage and foster the participation of groups often overlooked in the protection of research participants, including professional organizations, journal editors, and patient advocacy groups (see Chapters 2 and 3).
As a whole, these recommendations strengthen oversight by dispersing responsibilities more widely. However, although a new federal oversight office will provide much needed leadership and uniformity in the system, the research community must move to implement self-regulation through nonfederal credentialing organizations. The desired outcome of these reforms would be a system that emphasizes education as a means for improving protections and avoiding the need for large-scale federal enforcement actions.
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How This Report Will Affect IRBs, Investigators, and Institutions
Almost all of the recommendations in this report directly or indirectly affect investigators, IRBs, and institutions by increasing their responsibilities. For example, it is recommended that the scope of regulated research be expanded (see Recommendations 2.1 and 2.4); that risky research be more closely monitored (see Recommendations 6.1 - 6.4); and that additional educational and credentialing requirements be imposed on those who conduct and review human research (see Recommendations 3.1 - 3.4). Although these increased responsibilities are significant, numerous changes are proposed that would reduce the regulatory burden on IRBs, investigators, and institutions. Under the recommendations, these groups would be required to follow only one set of rules (see Recommendation 2.3), would have one office providing authoritative interpretation (see Recommendation 2.2), and would be given more guidance on issues not requiring a regulatory response (see Recommendations 4.1 - 4.3 and 5.1 - 5.4). Specifically, investigators, IRBs, and institutions would have greater flexibility to:
- create arrangements in which multi-site studies are reviewed by only one IRB (see Recommendation 6.5);
- approve minimal risk studies through procedures other than full IRB review (see Recommendations 2.5 and 4.2);
- use a range of means to communicate information to prospective research participants and document informed consent (see Recommendations 5.1 and 5.3);
- waive the requirement of informed consent when appropriate (see Recommendation 5.2);
- conduct continuing review of research as appropriate (see Recommendation 6.2).
These changes, as well as the recommendation that the distribution of IRB members with relevant expertise and experience should be commensurate with the types of research reviewed by the IRB (see Recommendation 3.9), should make the oversight system more applicable to research in the social sciences and humanities.
Overall, the recommendations suggest three broad changes for IRBs, investigators, and institutions. First, they shift requirements away from procedure and toward competence. That is, although investigators and IRB members are given greater discretion, they are also required to demonstrate appropriate levels of competence in the protection of research participants. Second, the recommendations encourage more strategic use of IRB review, with IRBs reviewing more protocols, but doing so using mechanisms that would allow them to focus on riskier research. Third, the recommendations propose a more strategic use of monitoring by increasing the focus primarily and more intensely on risky research and by reducing the monitoring requirements for less risky research.
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How This Report Will Affect Research Participants
Although the recommendations in this report aim to improve the operation of the oversight system, they are not intended simply to reduce inefficiency and needless regulatory burden. Rather, they seek to effect real change in the protections offered to research participants. Under the proposed system, with one oversight office providing enforcement authority and accountability for the oversight of all research:
- Research participants would be protected in all types of research regardless of funding source. Gaps that currently leave participants in some research unprotected would be eliminated (see Recommendations 2.1, 2.2, and 2.4).
- Individuals and institutions conducting and reviewing research would be appropriately credentialed (see Recommendations 3.3 and 3.4).
- The information on which potential participants rely to decide whether to enroll in a research study would be improved. By focusing federal policy on the process of informed consent (see Recommendation 5.1) and requiring education for investigators (see Recommendations 3.1 and 3.3), participants would better understand the nature of research and have an opportunity to ask questions before deciding whether to enroll in research, rather than simply sign an often long and confusing consent form.
- Because research involves risk, a system for compensating participants for research-related injuries would receive further analysis (see Recommendation 6.6).
- Changes would be made to improve protections for vulnerable research participants, while at the same time ensuring that vulnerability does not become an excuse for arbitrarily excluding some people from research (see Recommendation 4.3).
- A model is proposed for use in assessing risks (see Recommendation 4.1), and methods are suggested that would improve protections related to privacy and confidentiality (see Recommendation 5.4).
- Finally, one location would be established to which participants and others could report problems (see Recommendation 2.2).
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Summary
This report proposes 30 recommendations for changing the oversight system. These changes are proposed at both the national and local levels and are directed at all who are involved in the research enterprise. The time is right for changes of such magnitude and breadth, because only such across-the-board modifications will reform the oversight system so that it is capable of adequately protecting the rights and welfare of research participants while promoting ethically sound research.
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Footnotes
Cite this page:
"Chapter 7: Implications of This Report (Research Involving Human Participants V1)"
Online Ethics Center for Engineering
5/21/2007
National Academy of Engineering
Accessed: Wednesday, February 08, 2012
<www.onlineethics.org/Topics/RespResearch/ResResources/nbacindex/nbachindex/hchapter7.aspx>