Definition of Terms
Before proceeding with the discussion of the issues and solutions, there are three terms used in this paper that require definition. The first is regulatory burden. For the purpose of this effort, regulatory burden is defined as any aspect of Federal legislation, regulation, or policy, or Federal/research institution practices that could be made more efficient without diminishing the intended level of protections.
This definition recognizes that regulatory burden may arise from a variety of sources. It may be the result of restrictive Federal legislation, regulations, policies or practices that ultimately force requirements considered to be burdensome by the research community. More complexity is added when there are conflicting legislation, regulations, or policies administered by multiple Federal agencies, by Federal and State agencies, or by components of the same agency. Finally, burden may result from ineffective or inefficient practices by the research institution as it administers the requirements imposed by Federal agencies.
It is important to emphasize that the focus of this study is to identify potential streamlining solutions "without diminishing the intended level of protections." This approach does not challenge the legitimacy of the intended outcome. The purpose of this initiative is to identify potential opportunities to improve the efficiency and effectiveness of the administration of the regulations, not to lessen the protections that are being provided.
Two other terms are used that require definition. System of regulation is used in this paper to encompass the totality of the laws, regulations, and policies that have been promulgated for any one of the five specific areas that are the focus of this paper. Similarly, program of protection is used to encompass the broad set of activities taken by the research institution within the context of a system of regulations to provide and assure the intended protections.
The issues identified as candidates for reducing regulatory burden, and potential solutions, as they emerged from the workgroup discussions, are presented below in a summarized form. The detailed discussion of these issues and solutions is presented in sections III through VIII of this report. These individual sections should be consulted for the detailed information summarized in this section.
Issues and Potential Solutions
- Financial Conflict of Interest
The purpose of these regulations and policies is to ensure that standards exist so that there is a reasonable expectation that the design, conduct or reporting of research will be unbiased by any conflicting financial interest of the investigator. Regulations have been promulgated by NIH, on behalf of the Public Health Service (PHS) and a nearly identical set of requirements has been issued as a policy document by the NSF. The PHS regulations flow from enacted legislation, while the NSF policy has no legislative history. These were developed collaboratively by NIH and NSF but some differences remain. While relatively non-prescriptive, the NIH regulation and the NSF policy place primary responsibility on the research institution for identifying and managing potential conflicts of interest.
The workgroup generally concluded that these requirements, particularly when compared with others governing the conduct of research, constitute a relatively low burden; yet at the same time, opportunities for streamlining exist. The primary opportunity results from the fact that the PHS regulations significantly expand the requirements beyond those originally enacted in statute. This illustrates a phenomenon often pointed to by the research community - that regulations increase the restrictions beyond those enacted in the legislation, and policies then often place additional restrictions beyond the regulations. Research institutions often contribute further to the "burden creep" by establishing more conservative policies so as to avoid potential criticism by regulatory overseers.
With respect to financial conflict of interest, the PHS regulations require adherence to Federal standards by all institutions applying for research grants, contracts, or cooperative agreements and to each investigator participating in such research. The legislation, however, applies only to institutions and investigators using PHS funds to conduct clinical research. In addition to this issue, others were noted as follows:
- The equity interest disclosure thresholds of $10,000 or a 5% ownership interest often trigger the reporting of an excess number of financial disclosures for which there is no conflict that need be managed.
- A dialogue needs to take place between the institutions and NIH on several key terms, some of which are used in the regulations, that require better definition.
- Given the complexity of the issues that arise, regulations must provide flexibility to allow local management.
- The disclosure system must recognize the need to identify conflicts of interest that must be managed while pursuing the commercialization of research results as intended by the Bayh-Dole Act (see 37 CFR 401).
- Differences still remain between the PHS and NSF requirements that should be reconciled.
- Public institutions must deal with the differences that exist between State and Federal regulations.
Each of these issues is described in detail in section III, pp. 16-17.
As a result, the most significant solution proposed by members is to amend the Federal regulations to make them no more restrictive than the PHS legislation, and to allow institutions to tailor conflict of interest programs beyond those required by legislation to their individual needs and culture. A corollary suggestion is that the institution be given the flexibility to set the disclosure limits for conflict of interest programs required by law, or, at a minimum, have the Federal government adjust the limitation for inflation. Other solutions that emerged are for NIH to issue a policy statement affirming that conflict of interest protections and the Bayh-Dole Act complement each other; for NIH and NSF to reduce further the differences that remain between their respective systems of regulation; and for NIH to facilitate, through its conference grants program, educational workshops by the research community to identify and share best practice strategies. Each of these solutions is described in detail in section III, pp. 18-19.
The purpose of these regulations is to define scientific misconduct and to outline the roles of both the research institution and the Federal government in assuring research integrity. Similar regulations were promulgated, and are administered, both by the PHS and the NSF. The PHS regulations flow from enacted legislation, while the NSF regulations have no legislative history.
The PHS regulations are administered by the Office of Research Integrity (ORI) within the Department of Health and Human Services (DHHS). These regulations are quite prescriptive in specifying how an institution should proceed, should there be an allegation of misconduct. Particularly at issue is that while the regulations state that the institution has the primary responsibility for conducting inquiries and investigations, they further state that "…the Department reserves the right to perform its own investigation at any time prior to, during, or following an institution's investigation." The institution's primary responsibility is further compromised by an appeal process that allows any individual found to have engaged in scientific misconduct by ORI, either through its own investigation or by concurring with an institution's finding, to appeal directly to DHHS's Departmental Appeals Board, a minority of whom are scientists. At this proceeding, ORI must defend the finding. The duplication of effort and "second guessing" of the institution's efforts by ORI is the cause of much of the regulatory burden that exists.
The workgroup generally concluded that aspects of these regulations and policies constitute a significant burden for those institutions unfortunate enough to be involved in investigations of alleged scientific misconduct by and against members of their faculty or staff. Several issues were identified by the workgroup that contribute to regulatory burden.
- As noted above, the regulations, as currently written, effectively require a duplication of effort on the part of the institution and ORI and compromise the legitimate role of the institution to have the primary responsibility for investigating and adjudicating allegations of scientific misconduct.
- The prescriptive nature of the regulations requires a defined series of phases for the investigative process that limits the flexibility of the institution to adapt the investigation to the individual circumstances of the case.
- Certain legal mechanisms paradoxically act as a disincentive to thorough institutional investigations of misconduct by exposing individuals serving on the institution's committees that investigate allegations of misconduct, or the institution itself, to legal liability.
- Insufficient effort is being devoted at both the Federal and institutional levels to conducting formal education programs in research integrity.
- A better dialogue must be established between institutions and ORI in order to develop a sense of trust that does not currently exist, primarily because of past tensions between the Office and the research community.
Each of these issues is described in detail in section IV, pp. 23-25.
A solution is proposed to fundamentally restructure the role of ORI, and to amend the regulations, so that the primary responsibility for responding to allegations of misconduct would reside unambiguously with the research institutions. ORI's primary role would focus on promoting and conducting education and training in practices supporting research integrity. Other solutions include amending the regulations to allow institutions the flexibility to adapt their investigations to the circumstances of the case; establishing an Advisory Committee to the ORI consisting of institutional representatives to assist in the development of a more collaborative relationship between both parties; taking appropriate action to assure that the legal system does not present a barrier to the investigations of allegations of misconduct; and initiating a program of continuing evaluation of the research integrity program. Each of these solutions is described in detail in section IV, pp. 25-28.
Human Subjects Protections
The Federal Government, through the Office of Protection from Research Risks (OPRR), within the NIH and DHHS, has promulgated regulations and policies which govern the protections for human subjects who participate in Federally-supported research. The DHHS regulations flow from the Public Health Service Act as amended. Subpart A of these regulations governs the programs of 17 Federal agencies that support research using human subjects and is referred to as the "Common Rule." Subparts B-D of the regulations apply only to research supported by DHHS. Further, policy guidance is provided in Protecting Human Research Subjects, Institutional Review Board Guidebook (1993) and periodic "Dear Colleague" letters that are promulgated by the OPRR, which administers these regulations on behalf of DHHS.
The Federal government also has promulgated regulations governing human subjects protections through the FDA. Unlike the DHHS regulations, Federal support is not necessary for the FDA regulations to be applicable as they apply to any FDA-regulated article. The FDA regulations apply to requirements of informed consent and Institutional Review Boards (IRB), the boards at research institutions that oversee research protocols to assure the protection of human subjects participating in research. In addition, FDA has promulgated regulations which govern research related to Investigational New Drug (IND) applications and Investigational Device Exemptions (IDE). These regulations flow from the Federal Food, Drug, and Cosmetic Act, as amended. Further policy guidance is provided through FDA Information Sheets.
Members of the workgroups generally concluded that aspects of the regulations and policies governing human subjects protection constitute a burden. This burden is caused to some extent by the fact that institutions are regulated by two Federal organizations – FDA and OPRR - whose regulations and policies sometimes conflict. In addition, the two federal organizations operate with distinctly different approaches – OPRR requires an assurance from the institution conducting research that it will comply with the requirements of the laws and regulations governing humans subjects protections and relies heavily on the institution's adherence to that assurance; FDA operates as a regulatory agency and relies primarily on an inspection system. While substantial effort has been undertaken to harmonize the regulations and policies, differences between OPRR and FDA continue to exist.
A variety of specific issues emerged in addition to the operational, regulatory, and policy issues resulting from the programs being administered by two Federal organizations, albeit within the same Department.
- Each study site in a multi-site research study is receiving individual reports of adverse events occurring to research subjects at other sites because of a regulatory requirement that sponsors of multi-site clinical trials notify IRBs of these events. The receipt of data by the IRB that are neither aggregated nor interpreted is not providing useful information to allow it to make an informed judgment on the appropriate action to be taken, if any.
- The policies require that research protocols be initially reviewed by the IRB before funding decisions are made by the Federal funding agencies. Given the steadily increasing workload, and the fact that only a portion of grant applications submitted for NIH funding are actually funded, IRBs may not be making the most efficient use of their scarce resources.
- The regulations require that research protocols be re-reviewed each year. They are, however, quite prescriptive in defining when and how IRBs must conduct those reviews. While agreeing with the necessity for periodic review, members contend that the rigidity of the regulations preclude them from adapting their review to the level of risk existing in individual studies, to the level of workload, or to unforeseen situations. Policy changes, recently published in the Federal Register
with regard to expedited review, do provide additional flexibility in this regard, however.
- The assurance document is considered to be too complex and not serving its intended purpose as an educational tool for the institution. In addition, there are a variety of assurances for different situations, which adds to the complexity. It should be noted that there is consensus between the research community and the OPRR on the need to reengineer this process.
- There was general recognition, again on the part of the research community representatives and the OPRR, that education programs for all participating in programs of human subjects protection are undervalued and underfunded.
- Finally, there is a need to ensure adequate resources for Institutional Review Boards.
Each of these issues is described in detail in section V, pp. 33-37.
Solutions are provided to resolve these issues and increase the efficiency of the human subjects protection program without decreasing the intended levels of protections. These suggestions include clarifying existing regulations and replacing the receipt of individual off-site adverse event reports with aggregated and interpreted analyses from data safety monitoring boards (DSMBs); increasing the coordination between NIH and FDA and reconciling regulatory and policy differences that exist; granting the IRBs more flexibility to determine the timing of their initial reviews, and the timing and format of their continuing reviews; reengineering the OPRR assurance process with a corresponding enhancement of the education program; encouraging additional resources for IRBs; and exploring alternatives to the current process-based form of regulation, such as a third-party accreditation program or results-based techniques, if it reduces regulatory burden. Each of these solutions is described in detail section V, pp. 37-41.
Animal Care and Use
The Federal Government, through the PHS and OPRR, within the DHHS, and the Animal and Plant Health Inspection Service (APHIS) within the USDA, has promulgated regulations and policies which govern the care and use of animals that are involved in the conduct of research, research training, or biological testing activities. The USDA regulations flow from the Animal Welfare Act. Further policy guidance is provided in a USDA document entitled Animal Care Policies
The PHS policies are contained in the Public Health Service Policy on Humane Care and Use of Laboratory Animals and have a statutory basis in the Health Research Extension Act of 1985. The PHS Policy incorporates, by reference, the Guide for the Care and Use of Laboratory Animals (1996)
, prepared by the National Academy of Sciences' Institute for Laboratory Animal Research. Further policy guidance is provided through "Dear Colleague" letters from the OPRR.
A non-profit organization, the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC)
, accredits active animal care and use programs. In addition to oversight by OPRR and USDA, most major research institutions voluntarily seek accreditation by AAALAC. AAALAC does not create its own standards, but relies instead on established sources, primarily, the Guide. NIH, as a matter of policy, encourages institutions to be accredited by AAALAC.
The workgroup generally concluded that aspects of these regulations and policies constitute a significant burden. This burden is caused in large part because institutions are regulated by two Federal organizations with distinctly different approaches and significantly differing requirements. OPRR requires an assurance and relies heavily upon the institution's assurance that it will operate within existing laws, regulations and policies; USDA acts as a regulatory agency and relies primarily on an inspection system.
Beyond differences in approach, the two organizations frequently issue different requirements governing the same issue. Some, but not all, of the differences emanate from differing authorizing statutes. Depending on the specific item, one organization's requirements may or may not be more restrictive than the other. The practical consequence for the institution, however, is that it must operate on the basis of the more restrictive provision, regardless of the issue, so as to be in compliance with the more restrictive organization. Specifically mentioned as burdensome were redundant, legally-mandated program reviews and facility inspections, and AAALAC site visits, cumulatively occurring a minimum of 3-4 times per year, and the consequent paperwork burden; yearly reports to OPRR, UDSA, and AAALAC that request different information; and inconsistent requirements by OPRR and USDA on how often the Institutional Animal Care and Use Committees (IACUC), the Committee charged by the research institution to oversee its animal care and use program, should conduct protocol reviews.
Other issues increasing regulatory burden that were identified include:
- There are a variety of requirements imposed by the USDA that the members of the research community considered to be in need of reexamination. These are the prescriptive documentation of literature searches undertaken to assure that alternative, less painful, research procedures do not exist; limitations on experimental surgery and the current definition for major surgery promulgated by USDA and the Guide; a concern that the number of categories contained in the current classification for identifying pain experienced by research animals might be expanded, as well as certain paperwork requirements mandated by the current categorization; and USDA's use of non-scientifically-based engineering standards to define animal housing requirements.
- Members experienced receiving inconsistent interpretation of requirements across the three organizations. Concern was also expressed that because of USDA's broader mandate (meat inspections, animal park inspections, etc.), their animal inspectors were sometimes unfamiliar with research and the research environment.
- Finally, the complexity of regulations, administered by the Department of Interior's Fish and Wildlife Service, regarding the transportation of animals and biological materials from non-human primates, has the unintended consequence of delaying the conduct of research.
Each of these issues is described in detail in section VI, pp. 47-51.
Suggestions are provided to reduce the regulatory burden for each of these issues. The members suggested a mechanism to collaborate more formally with the oversight organizations. They proposed the establishment of a group of advisors comprised of institutional representatives who would collaborate with the OPRR, USDA, and AAALAC in the formulation and interpretation of policies and guidelines. Additional suggestions included reducing the number of required, redundant program reviews and facility inspections, and the associated documentation, from a minimum of 3-4 per year to 1-2 per year; providing consistency in requirements that are currently in conflict; allowing the IACUC to exercise final oversight authority on requirements currently imposed by USDA that are of particular concern to the research community; maintaining USDA's current pain classification schedule but reducing some documentation requirements; utilizing scientifically-based caging guidelines rather than USDA's engineering standards; increasing staff training, particularly for USDA inspectors; and reducing the paperwork and associated delay that occurs with the Fish and Wildlife Service's restrictions on the transportation of research materials. Each of these suggestions is described in detail in section VI, pp. 51-55.
Hazardous Waste Disposal
The Federal Government, through the Environmental Protection Agency (EPA), has promulgated regulations and policies that govern the disposal of hazardous wastes. The EPA regulations flow from the Resource Conservation and Recovery Act (RCRA). Further policy guidance is provided in management memoranda.
While the RCRA regulations are the main focus of this study, there is a variety of other Federal legislation that affects research institutions in this general area. Most notable is legislation related to worker protection, nuclear materials, and clean air. The Occupational Safety and Health Administration (OSHA) regulates worker protection from chemicals and hazards. The Nuclear Regulatory Commission (NRC) regulates radioactive waste; however, if the substance is a mixed waste, i.e., if radioactive waste is mixed with hazardous waste, the respective components of the mixture are regulated by NRC and EPA. EPA also regulates the Clean Air Act. In addition to the Federal laws, a variety of State laws also may regulate various aspects of research. These State laws also may be more restrictive than the Federal laws.
The workgroup generally concluded that aspects of the RCRA regulations and policies constitute a significant burden. This burden is caused in large part because the regulations are inflexible, emphasize process rather than outcome, and are written primarily for large scale manufacturing processes, not for the types of activities that occur in the laboratories of research institutions. Items that were specifically mentioned are as follows:
- There are a variety of definitions imbedded in the regulations that might be appropriate for large scale manufacturing plants but do not fit the research environment, are frustrating to the research community, and ultimately lead to inefficiencies.
- There are multiple and conflicting regulatory requirements among various Federal and State agencies and there is no "referee" to resolve these differences. Members report that interpretations of these regulations differ both among the EPA Regional Offices, and between the States and the EPA, and that the research institutions are seemingly without a recourse to resolve these differences. In addition, the research institutions often find themselves burdened by the overlapping jurisdictions of EPA, NRC, and OSHA and because there is no immediately accessible point within the Executive Branch available to the research community to resolve the inevitable conflicts that arise.
- The regulations are very prescriptive on the length of time that wastes can be stored on a university campus, and on what constitutes a university campus. Because universities, unlike chemical industries, generate small amounts of a large number of wastes and because campuses, or components of a campus, are sometimes proximate but not contiguous, the net effect of this inflexibility is to preclude the research institution from accumulating sufficient amounts of wastes to make cost-effective disposal determinations.
- The research community has not achieved the same collaborative relationship with EPA that it has achieved with the science agencies. Such a relationship could facilitate the resolution of the issues that have arisen.
- Certain paperwork requirements may not be satisfying their intended purpose and their current format might be reexamined.
Each of these issues is described in detail in section VII, pp. 59-61.
The issues that were raised by the members are not new and have been raised repeatedly by, among others, the National Research Council
, the Government-University-Industry Research Roundtable
, and the American Chemical Society
. Several solutions are provided to reduce the regulatory burden. These include developing a new paradigm using a performance-based approach. A model currently under discussion is a demonstration program, proposed by several northeastern universities under EPA's Project XL program. By setting performance standards through a "Laboratory Environmental Management Standard" and seeking exemptions from regulatory language that creates many of the inefficiencies noted earlier, the universities intend to demonstrate superior waste management.
Other suggestions include amending or clarifying EPA's regulations with regard to selected definitions and issues that are particularly problematic for research institutions; recommending that the Office of Science and Technology Policy (OSTP) undertake an initiative to rationalize the current regulatory environment for research institutions; establishing a collaborative relationship between the EPA and the research community; ensuring consistent interpretation of regulations by asking that EPA undertake a comprehensive training program for its staff and establishing an appeals process to resolve interpretive differences; and amending EPA's regulations to allow institutions to accommodate to monthly fluctuations in the amount of wastes generated, and to allow more flexibility in determining how long hazardous wastes and mixed wastes can be stored at an institution. Each of these suggestions is described in detail in section VII, pp. 61-65.