Online Issues

Journal Vol 49 (4)

Introduction

Mitigating Risk, Facilitating Research

Kathryn A. Bayne and Nelson L. Garnett

Kathryn A. Bayne, MS, PhD, DVM, DACLAM, is Global Director for the Association for Assessment and Accreditation of Laboratory Animal Care International in Frederick, Maryland. Nelson Garnett, DVM, DACLAM, is a former director of the NIH Office of Laboratory Animal Welfare and is currently a consultant for laboratory animal care and use programs, based in Dickerson, Maryland.

Address correspondence and reprint requests to Dr. Kathryn A. Bayne, Director, AAALAC, 5283 Corporate Drive #203, Frederick, MD 21703 or email kbayne@aaalac.org.

The fundamental raison d'être of the laboratory animal veterinarian, institutional animal care and use committee (IACUC¹), IACUC administrator, institutional compliance office/officer, training coordinator, and other related positions and groups at institutions that use animals for research, testing, and teaching is to ensure the humane, responsible, and productive use of animals in those activities. All of these people and groups support both science and animal welfare.

The US system of animal welfare oversight has been covered in several review articles in recent years (Garnett 2005; NRC 2003), and all of the authors in this issue of the ILAR Journal allude to or cite key components of the policy and regulatory framework of oversight. Therefore, rather than an exhaustive review, we provide here a brief summary of the relevant documents and oversight bodies.

The Animal Welfare Act (AWA) regulations (9 CFR), enforced by the US Department of Agriculture's (USDA) Animal and Plant Health Inspection Service (APHIS) Animal Care unit, apply to registered research facilities that use species covered under the act. The Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, authorized by the Health Research Extension Act (HREA), is implemented by the National Institutes of Health's (NIH) Office of Laboratory Animal Welfare (OLAW¹) and is applicable to all PHS-supported activities involving live vertebrate animals. The PHS Policy includes, by reference, the NRC Guide for the Care and Use of Laboratory Animals (the Guide; NRC 1996). Eligibility for NIH (and other PHS) grant and contract support requires compliance with the PHS Policy and conformance with the recommendations of the Guide. In addition to the USDA and NIH, the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC¹), a private, nonprofit, voluntary accrediting organization, provides oversight through a peer review process, the Guide, and other applicable standards to evaluate institutional animal care and use programs. Other federal and nonfederal sponsors and stakeholders have requirements that apply to their specific programs, but most other oversight mechanisms in the United States derive from, or are similar to, those outlined above.

The NIH Grants Policy Statement (NIH 2003) describes key terms and conditions (in addition to those mentioned above) that investigators must meet and maintain in order to receive NIH grant support. If a researcher fails to maintain these terms and conditions (e.g., allows an ongoing NIH-funded protocol to expire), the NIH may disallow charges and seek recovery of grant funds. The connection between ongoing grants and sustained compliance is sometimes underappreciated by research administrators and investigators and provides a powerful incentive for postapproval monitoring.

Biomedical research is a complex environment in which to work, but necessarily so, for working with animals is a privilege that comes with significant obligations. The balance among the factors that affect scientists' ability to do research—the high cost of doing research, the complex legal and regulatory environment that applies to the research enterprise, societal issues, and the scientist's passion for discovery—is a delicate one. The stakeholders in biomedical research are numerous and have diverse, and sometimes divergent, opinions about the costs and benefits of animal-based research. As observed in one report,

[a] quality program is critical for quality science. There are ethical, legal, and public relations reasons for ensuring that such programs meet contemporary standards and guidelines for animal use. . . . No program can be successful unless personnel using or caring for laboratory animals are well qualified by training or experience. Lines of authority, policies, and procedures for animal care and use programs are to be set forth in writing, well understood, and implemented by all persons involved. . . . Costs for animal care and use programs have escalated considerably over the last several decades. Nevertheless, adequate funds for operation of sound animal care and use programs must be budgeted by research institutions.

Although the criteria described above for a successful animal research program and the escalating costs for conducting this type of research may sound like current concerns for the research community, they were articulated 20 years ago (see NIH 1988 for these two excerpts):

The public is concerned with issues involving the use of animals in research, testing, and education. In particular, there is growing apprehension by the public as a whole, and legislative representatives at all levels, about the use of animals in what some perceive to be inhumane or unnecessary activities. Any institution which uses laboratory animals must not only operate a sound program, but be prepared to be publicly accountable for the program in which animals are involved.

Thus the issues are not new, nor have they been resolved. In response to these enduring concerns, institutions over the last 2 decades have striven to implement internal systems to enhance the quality of their animal research programs. Specialized courses (e.g., IACUC 101, IACUC 201, IACUC Advanced, the annual Public Responsibility in Medicine and Research (PRIM&R) conference, modules offered by the American Association for Laboratory Animal Science (AALAS) and by AAALAC) are now available for training new IACUC members as well as committee members with more seniority. Laboratory animal veterinarians have had the opportunity to become board certified for more than 50 years, and in recent years several programs have been launched to provide credentialing of individuals in research support (e.g., technicians, animal facility managers, IACUC administrators). These credentials have enhanced the professional development and knowledge of staff members, resulting in a higher quality of service provided to both the investigator and the institution.

Many institutions have also determined that it is in their best interest to have a compliance office or officer whose full-time responsibility is to supplement the oversight provided by the IACUC. This individual or office frequently is also responsible for in-house training to ensure compliance with institutional and government requirements.

With the help of a network of professional and paraprofessional staff who provide support services, scientists must navigate an array of federal (and sometimes state and local) laws, regulations, and policies to reach their objective of advancing knowledge. In fact, the management, implementation, and oversight of an animal research program can be likened to the nested Russian matryoshka dolls, with the animal experiment as the inner doll and the multiple layers of support and oversight in increasing layers around it. The potential burden on the researcher of the numerous governmental checks and balances was the subject of a 1999 report by the NIH Project to Reduce Regulatory Burden (Mahoney 1999). The objective was to study and identify duplicative and unnecessary federal regulations governing research. The following recommendations resulted from the study:

Establish a group of advisors composed of institutional representatives who would collaborate with the NIH Office for Protection from Research Risks (OPRR; now OLAW), the USDA, and AAALAC in the formulation and interpretation of policies and guidelines.
Reduce the number of redundant reviews and inspections while maintaining sufficient oversight.
Recommit to efforts to develop a common reporting format for the separate yearly reports required by OLAW, the USDA, and AAALAC.
Establish a common protocol review frequency based on the level of risk.
Consider revising several USDA policies not considered effective.
Reassess the adequacy of training for OLAW site visitors, USDA inspectors, and AAALAC consultants; provide additional training, as necessary, to increase the consistency of interpretation of existing law, regulations, and policies; and provide USDA field inspectors with training in basic scientific principles and experimental design, laboratory animal science, and the philosophy underlying the use of animals in research.
Facilitate transportation of research materials by the US Fish and Wildlife Service.

For a time after the release of this report, regulatory burden reduction was a priority for the relevant agencies, but there were limited gains in addressing the specific recommendations and enthusiasm waned as other issues took priority.

Another interesting realization emerged during the NIH regulatory burden reduction initiative (Garnett, personal observation): much of the burden attributed to federal regulation and policy may actually be self-inflicted. That is, many of the federal rules and policies are written in performance-based language that allows institutions to customize their own implementing policies as long as they meet certain criteria. Thus institutions are free to apply their own interpretations to the development of institutional policies that may intentionally or unintentionally amplify the burden of compliance. The reasons for such amplification range from misinterpretation to risk aversion to a genuine desire for a consistent level of excellence for all institutional programs.

It is also true that federal regulations and policies are often blamed for imposing the "burden" associated with practices that would actually be considered minimally acceptable by any reasonable scientific, professional, or ethical measure. How many "burdensome" programs and practices—disease surveillance, environmental controls, aseptic surgery, pain management, biosafety, quality assurance—would likely continue in the absence of any federal requirements? For institutions interested in quality animal-based research programs, the answer is "most."

Klein and Bayne (2007) recently proposed that institutions could avoid additional burdensome regulations by implementing a comprehensive program of animal care and use based on scientific data pertaining to ways to improve animal welfare and research quality. Such a program would rely on the application of performance standards as well as an institutional team of administration, research staff, animal care personnel, the IACUC, occupational health and safety staff, physical plant personnel, and the public. The institutional team has a responsibility to take a "preventive medicine" approach to research oversight by identifying areas of the program that would benefit from additional attention or resources. This approach resonates with the opinion expressed by Newcomer (1997) that a successful animal care and use program does not rely on a single individual (the "lone magician," in his words) in the institution (e.g., the veterinarian, or the IACUC chair) to ensure program compliance and progress.

In addition, each institution must create a culture of care, conscience, and responsibility embraced by each individual involved in the animal care and use program (Klein and Bayne 2007). Institutional commitment is the key to creating this culture. Also important are the availability of adequate resources (funding, personnel, and time), an empowered institutional official, harmonization of practices and procedures between the central animal facility and satellite facilities, clear lines of authority, and adequate systems of oversight. The institutional official should be well informed about the program and its needs, and his/her support for the program should be visible at all levels of the organization. The establishment and nurturing of a communication "matrix" among staff in the various program components—the scientific staff, IACUC, veterinarian, occupational health and safety, physical plant personnel, and the institutional official—can ensure that all relevant parties clearly understand the goals for the program.

Several strategies for achieving an institutional culture of compliance are described in this issue of the ILAR Journal. We deliberately invited a range of opinions on the subject of techniques to achieve adequate institutional oversight. Collectively, the authors offer a sample of common approaches to institutional oversight, representing the various institutional personnel and groups that have a key role in program success: researchers, IACUC chairs, veterinarians, upper administration, IACUC consultants, and compliance officers. Their views range from the perspective that a properly engaged IACUC is all that an institution of any size needs to provide adequate oversight, to the perspective that IACUC members (at least at large institutions) need assistance to effectively discharge all of their regulatory and institutionally imposed responsibilities. We believe that this diversity of opinion reflects that of the broader biomedical research community that there is no single best solution.

Each author is clear, however, about the need for the institution to mitigate risk. And what is at risk is quite evident. Real or alleged noncompliance can jeopardize research funding, the individual researcher's reputation, and the credibility of the institution. Laboratories and data can be destroyed and personal safety threatened by animal rights activists. Animal welfare can be compromised and research progress delayed. It is therefore incumbent upon each research program to self-identify potential areas of vulnerability.

But the risks of noncompliance in a single program or institution have much broader implications, because all animal research institutions are interconnected. As Klein and Bayne (2007, 6) note, "Allowing . . . institutional flaws to persist or inadequately addressing noncompliance can result in a loss of public trust not only in the institution but also in the research enterprise. . . ." Thus the stakes are high and each institution must ensure that mechanisms are in place for either preventing problems or minimizing the potential harm caused by noncompliance.

The authors in this issue of the ILAR Journal variously address the need to mitigate risk associated with animal-based research and describe different ways to achieve the delicate balance between regulatory burden and research conducted in a humane and responsible manner. But they are all strongly committed individuals at the core of the research enterprise and they are unanimous in their desire to both facilitate research and ensure the humane care and use of research animals.

Abbreviations used in this Introduction: AAALAC, Association for Assessment and Accreditation of Laboratory Animal Care International; IACUC, institutional animal care and use committee; OLAW, Office of Laboratory Animal Welfare

References

AWA [Animal Welfare Act], PL 99-198 (7 USC, 2131 et seq.). Available online (http://www.aphis.usda.gov/animal_welfare/awa.shtml), accessed May 7, 2008.

CFR [Code of Federal Regulations], Title 9, Chapter 1, Subchapter A, 2002 (revised). Available online (http://www.aphis.usda.gov/animal_welfare/awr.shtml), accessed May 7, 2008.

Garnett N. 2005. Laws, regulations, and guidelines. In: Akins CK, Panicker S, Cunningham CL, eds. Laboratory Animals in Research and Teaching: Ethics, Care and Methods. Washington: American Psychological Association. p 163-170.

Health Research Extension Act, PL 99-158 (42 USC, 289d). Available online (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), accessed May 7, 2008.

Klein H, Bayne K. 2007. Establishing a culture of care, conscience, and responsibility: Addressing the improvement of scientific discovery and animal welfare through science-based performance standards. ILAR J 48:3-11.

Mahoney J. 1999. NIH initiative to reduce regulatory burden: Identification of issues and potential solutions. Available online (http://grants.nih.gov/grants/policy/regulatoryburden/index.htm), accessed April 23, 2008.

Newcomer C. 1997. Behold! The animal care and use magician! Where is the "institution" in your animal care and use program? Connection Newsletter, p 10-11, AAALAC International. Available online (http://www.aaalac.org/publications/newsletter.cfm), accessed April 23, 2008.

NIH [National Institutes of Health]. 1988. Institutional Administrator's Manual for Laboratory Animal Care and Use. NIH Publication No. 88-2959. Bethesda: NIH.

NIH [National Institutes of Health]. 2002. Office of Laboratory Animal Welfare, Public Health Service Policy on Humane Care and Use of Laboratory Animals. Available online (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), accessed May 7, 2008.

NIH [National Institutes of Health]. 2003. National Institutes of Health Grants Policy Statement. Available online (http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_2003.pdf), accessed May 7, 2008.

NRC [National Research Council]. 1996. Guide for the Care and Use of Laboratory Animals. Washington: National Academy Press.

NRC [National Research Council]. 2003. Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research. Washington: National Academies Press.