Session 3
Approaches to Current Guidelines—United States and Europe



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Session 3 Approaches to Current Guidelines—United States and Europe

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop This page intentionally left blank.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Housing Standards: Development of Guidelines and the Process for Change William J. White The 1996 Guide for the Care and Use of Laboratory Animals (Guide) is the most recent version of seven editions of the document beginning with the 1963 edition. The 1963 Guide was developed by a committee of seven members and consisted of 33 pages divided into three sections, whereas the 1996 Guide was developed by a committee of 16 members and spanned 125 pages divided into five sections. The charge to the 1996 Guide committee was to develop a guidance document for laboratory animal care and use—not to develop regulations. COMMITTEE FOR REVISION OF THE GUIDE The writing of the 1996 Guide spanned five committee meetings and involved seven major drafts with numerous minor drafts developed over a 2-year period. The major sections of the Guide were selected based on the principal components of an animal care and use program. Sub-committees of the parent committee prepared drafts of sections for full committee review and discussion. Literature searches were provided by the National Agricultural Library. The final document underwent two rounds of external review before being published. The charge to the committee and the committee’s approach set the tone for the document. It was thought that previous guidelines were accepted and generally were serving well; hence the committee was charged with updating and improving, as well as addressing any short-

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop comings. It was believed that radical departure would probably be difficult to justify, and the committee wanted to be certain that the guidance was compatible with existing regulations in the United States. It was clear to the committee that a broad vision was necessary because the document would have to be applied to diverse units, settings, and situations. The recommendations made in the Guide had to be balanced between science, animal well-being, ethics, and resource requirements. The committee believed it was essential to reaffirm the institutional animal care and use committee (IACUC) as the principal local oversight mechanism and empower it to administer a performance-based approach. COMMUNICATING THE PERFORMANCE-BASED APPROACH The performance-based approach specifies the desired outcome and provides criteria for assessing the outcome, but it does not specify how to achieve the outcome. In constructing the Guide, it was appropriate in some instances to provide examples, but to emphasize clearly that multiple methods could be acceptable and the choice of method had to be adjusted, based on circumstances. Given the lack of data on which to base detailed guidance in many aspects of animal care and use, the performance-based approach used in the Guide encouraged the development of data that could be used to improve animal care and use. The committee began the process by a careful review of the existing guidance and regulations. It considered whether there were problems with existing guidance and whether new science or technology was available that needed to be addressed. It examined the literature, especially that generated since the last Guide was published, to determine whether new peer-reviewed literature provided significant information that required inclusion. The committee thought it was important to use all sources of information in constructing the Guide. In particular, opinion and data from the public, as well as the affected community, were actively sought through public meetings and written comments. Every committee member attended the public meetings and read all written materials submitted. The quality of information available to the committee varied, from statements of opinion, to unpublished reports, to comprehensive peerreviewed scientific studies. The committee analyzed the peer-reviewed literature, which varied considerably in adequacy and approach. In some cases, only a single study under a defined set of conditions using limited measures was available. In other cases, a series of studies with multiple measures exploring a range of conditions or practices could be found, whereas in other cases, published reports could be found that surveyed large numbers of animals with limited measures and limited control.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Guidance developed by the committee had to be qualified, based on the quality of the information available. Of particular concern was the general applicability of findings across multiple strains, age, sex, and species. In addition, the magnitude of the changes found and their potential impact on study variation and animal well-being had to be weighed carefully. Some studies used insensitive measures that could be confounded by other variables. Data from such studies were interpreted to have some value, but recommendations had to be tempered. Often there were only a limited number of studies that directly addressed a particular topic, and these studies often were unlinked or in some cases were conflicting. In a number of cases, studies could be classified as proof of principle, but with no exploration of mechanism or their general applicability, and they seldom could be verified independently. In a number of instances, professional judgment had to fill in gaps where studies were lacking. Overall, however, if there was little evidence available, the committee avoided the temptation to make assumptions and to extend conclusions beyond available data. Of concern to the committee was that any guidance had to fit practically and logically into existing animal care programs and had to be of sufficient impact/importance to suggest action. The committee spent time analyzing how new guidance would apply to different animal care and use situations. It was important to assure that the guidance made sense and, if there were exceptions, to indicate how common they were and why they occurred. The committee also tried to determine whether the proposed changes in guidance would generate unintended consequences. Thus, if a guidance recommendation improved one aspect of animal well-being at the expense of another, such as causing a potential increase in animal usage by the application of some forms of environmental enrichment, it was necessary for the committee to determine whether the trade-off was appropriate. IMPACT OF RECOMMENDATIONS The committee was also concerned about the impact of recommendations on the conduct of research or testing including a potentially increased risk of microbiological contamination. Implementation of recommendations that might contribute to microbiological contamination could invalidate many types of research and thus result in greater animal usage. The guidance provided in the Guide had to be achievable, such that the intended benefit would be proportional to the resources required. The committee felt that any changes proposed in the Guide had to be defensible at least in proportion to their specificity. For example, if cage space allocated per rat of a given weight was currently 23 in2 and it was suggested to change it to 30 in2, why was 28 or 35 in2 not chosen? It was clear

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop that more than good intent was required to make changes—in fact, good data were needed to be specific in making such changes. The committee believed that the guidance had to be very clear. Any recommendations had to use terms that were clearly defined either within the document or within appropriate references. In many cases, the committee provided examples to clarify intent and to expand the meaning of terms. The committee also thought it appropriate to ensure that the characteristics of intended outcomes of the recommendations were clearly described. Overall, the tone of the document was an explanatory one in which the rationale behind the recommendations was given in some detail. The committee believed that wording was critical in developing the document. It avoided poorly defined or emotional terms. It used words to indicate importance as well as limits of application or knowledge. It reserved the word must for programmatic issues for which there was no other interpretation or method. Must was also used where there was overwhelming scientific information or ethical considerations. There are very few musts in the 1996 Guide. The word should was used as a strong recommendation for achieving a goal, but it was clearly recognized that some individual circumstances justified an alternative strategy. Words such as can, might, could, recommend, and encourage were considered alternative verbs to indicate that the recommendations may have to be modified, multiple methods of achieving the outcome were possible, only limited information was available, or that the guidance may only apply to certain circumstances. PRACTICAL ISSUES IN THE DEVELOPMENT OF GUIDANCE FOR HOUSING STANDARDS One of the most difficult sections to construct in the Guide was the animal environment section, which included housing needs of laboratory animals. Although it was intuitive that the housing environment of laboratory animals somehow affects their performance and well-being, there was not a great deal of information available to provide very specific recommendations. In most cases, only unrelated proof of principle studies that demonstrated housing/environmental effects on animals or research results were available. In a number of studies, there were clear design flaws, which included the use of small numbers of animals, the use of a single species, stock, or strain, and the failure to dissect out confounding variables such as the effects of group size and animal density with respect to cage space effects.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Temperature and Humidity A review of housing guidelines and published data pertaining to temperature and humidity reveals the gaps in our knowledge that make it difficult to specify precise environmental conditions. Most common laboratory animals are adaptive homeotherms and as such make anatomic, metabolic, and physiologic adjustments in response to their environment to maintain well-being. Environmental adaptation in both wild and laboratory animals suggests that consistency in environment may not be “normal” or perhaps even desirable. To demonstrate effects caused by temperature or relative humidity, it may be necessary to have a complex/ unique set of conditions present unless extreme and clearly unacceptable conditions are utilized. For example, testicular degeneration/infertility in mice has been shown to occur when temperatures exceed 83°F within the secondary enclosure. It would appear that the rationale for specifying any temperature or relative humidity conditions within the laboratory, other than avoiding extreme conditions that clearly could cause harm to the animals, would be to control research variation caused by unpredictable adaptation to housing conditions. The adaptive processes may, in fact, serve the animals quite well, but those are the processes that may interfere with research results. The question then remains as to how much variation due to adaptive processes is acceptable and, hence, what limitations must be placed on temperature and relative humidity. It also begs the question of why such changes would not be sorted out by the use of appropriate controls. Clearly, a number of variables would affect these adaptive processes, including the type of housing (e.g., pen, run, open cage, microisolation cage, isolator), the type of ventilation system used within the primary and secondary enclosures, the specifics of cage/room coupling of ventilation, as well as stratification of temperature and relative humidity within the room itself. Interaction of other environmental factors with the thermal regulatory behavior of rodents is also an important consideration. Substantial existing data demonstrate that singly housed mice prefer ambient temperatures between 28°C and 30°C whereas group-housed animals prefer temperatures between 24°C and 27°C. The ability of group-housed animals to share metabolically generated heat by huddling together explains the differences in selected ambient temperatures between group- and singly housed animals. The resultant effective ambient temperatures in both group- and singly housed mice are compatible with the estimates of thermal neutral zones for mice of 28°C to 30°C. This range is at variance with the human comfort zone of 22°C (± 2°C), which appears to correspond more closely to temperatures recommended within guidance documents.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Bedding Recent studies have shown that bedding types that allow burrowing or nesting allow operating ambient temperatures to be increased from an ambient of 22°C to an effective ambient of 29°C. By contrast, bedding that allowed only resting on its surface, but not burrowing, increased temperatures by 2 to 4°C depending on the bedding type. These findings beg the question of whether rodents are using bedding for thermal regulation rather than for psychological enrichment, as suggested in some guidance documents. It is possible that we are recommending the correct thing in terms of the use of bedding or nesting materials for the wrong reasons. Cage Space Cage space is another environmental parameter for which there are very few specific data. Providing an adequate amount of cage space is generally thought to be important for animal well-being. Unfortunately, guidelines have been established based on consensus, surveys, some data, and appearance to observers. Although it is intuitive that relationships must exist between cage space and parameters thought to indicate overcrowding, these relationships have never been studied well and are prone to be influenced by a wide range of variables. Most studies have not separated out the effects of group size (number of animals in an enclosure) from density (space provided to each animal regardless of the number in the group). These effects are independent of each other and may be affected by sex and the age of the animals in the enclosure. In general, single housing appears to be the most likely to elicit negative effects on the animals. Recommendations for cage space were developed in the early 1960s and published in the first ILAR Guide as suggestions, not standards. In 1969, a density-based set of recommendations using six weight categories was developed in all likelihood from a survey of common practices coupled with limited unpublished data. Although this guidance was modified slightly in ensuing years, principally by adjusting weight ranges and providing for very large animals, the body weight/space relationship remains almost linear, which is suspicious. European regulations currently in effect express this same relationship simply, and often use a continuous rather than a discontinuous format. Newly proposed European regulations deviate significantly from this space allocation, but the changes do not appear to be based on peer-reviewed literature specific to species and weight. Significant data exist to establish that rodents are thigmotaxic, i.e., they prefer to be along the edges of cages rather than in the exposed center of the cage. Moreover, they appear to utilize hiding places/shelters.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Specifying cage space requirements by virtue of density guidelines appears to be contrary to these natural behaviors because it disproportionately increases the unused center portion of the cage versus the used perimeters of the cage. It is quite probable that cage space, like temperature, cannot be specified very tightly and that a range of available floor space or usable surface is acceptable depending on the type and quality of the space. There is clearly a need to explore requirements of rodents and other animals with respect to group housing because it appears that there are complex relationships that differ with group size. Sufficient evidence exists to suggest that enclosure design or complexity can alter space requirements. NEED FOR ADDITIONAL SCIENTIFIC DATA Clearly, much more information needs to be generated before any changes are made in guidance. Complex interactions need to be more clearly understood and considered across a wide range of applications of these guidance documents. It is unlikely that a very defined amount of critical space can be shown to be an absolute requirement, and it is unlikely that relationships are going to be linear. Key information is not available on topics as simple as occupied floor area versus body weight. It is difficult to conceive how guidance documents can be updated without a great deal more peer-reviewed information. At the very least, in generating such information, more than proof of principle studies alone need to be done, and it is imperative that multiple parameters be measured and that both positive and negative controls be provided. It is also essential that there be consideration of confounding variables and confirmation of findings under field conditions. There should be some ranking of physiologic/metabolic and behavioral significance because simply describing that a condition exists and is statistically significant may not be adequate justification for providing for all eventualities in animal housing.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Revision of Appendix A to the European Convention ETS 123: The Participants, the Process, and the Outcome Derek Forbes Papers presented by earlier speakers have emphasized that the “Guidelines for accommodation and care of animals” presented in Appendix A of the Convention have proven to be very useful and have been widely applied. However, since 1976 when the Convention was first applied, scientific knowledge and experience have advanced considerably. Moreover, there has been an increased public interest in and awareness of animal usage in experimentation and a regard for their welfare. The author as a representative of a nongovernmental organization (NGO; see below) recognizes and acknowledges the importance of the participation and input from the wide spectrum of interested parties who have contributed to the process in satisfying, to the extent possible, the needs of animals used in research, those who work with them, and the public on whose behalf the work is done. The participants who are involved in the Working Party preparing for Multilateral Consultation of Parties to the Convention include the following: Parties: Belgium, Netherlands, Cyprus, Norway, Czech Republic, Spain, Denmark, Sweden, Finland, Switzerland, France, United Kingdom, Germany, European Community, and Greece. Signatory States: Bulgaria, Ireland, Portugal, Slovenia, and Turkey. Observers—Member States: Austria, Croatia, Hungary, Italy, and Malta.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Observers—Nonmember States: Australia, Canada, Holy See, Japan, New Zealand, and the United States of America. Participants Who Are Experts from International Organizations: Canadian Council on Animal Care, European Biomedical Research Association, European Federation of Animal Technologists, European Federation for Primatology, European Federation of Pharmaceutical Industries and Associations, European Science Foundation, Eurogroup, Federation of European Laboratory Animal Breeders Associations, Federation of European Laboratory Animal Science Associations, Federation of Veterinarians of Europe, Institute for Laboratory Animal Research, International Council for Laboratory Animal Science, International Society for Applied Ethology, and World Society for Protection of Animals. An examination of the list reveals first that all the organizations represented were nongovernmental, pan-European, or internationally recognized. Second, the organizations included those whose primary concerns were research based, or who had expert knowledge of the science and care of animals used in research, as well as those who concentrated on the protection of animals used in the laboratory and the ethological restrictions that such use imposed on the animals. Although the interests may appear diverse, experience gained from working alongside persons from such groups has shown that everyone involved was very aware of the paramount need to satisfy the animal’s welfare and ensure its well-being. During the course of the revision, the process has developed and evolved in content from that which was included in the original Appendix A. The strategy was determined within the working party by the member states. Initially, the general part of the appendix was updated. Thereafter the sections dealing with species of animals most commonly used in research and that had been included in the original convention were revised. However, it was realized that other animals were used in research for which there were no agreed-upon standards within Europe. This realization led to the decision to include all of the following groups within the remit of the revision. The full list of species now includes rodents and rabbits; dogs, cats, and ferrets; nonhuman primates; birds; farm animals (sheep, goats, cattle, horses, (mini)pigs); fishes; and amphibians and reptiles. A group of experts drawn from the NGOs considered each of the groups listed. The constitution of each group included individuals representing the diverse interests of the experts as described above. The format inevitably was conducive to change because it was necessary to reach some consensus within each of the working groups. The overriding prerogative was to try to achieve an enriched environment that satisfied the ethological needs of the animal, with special attention being given to the

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Breakout Session: Approaches for Implementing Current US and European Guidelines for Housing Standards for Dogs and Cats Leader: Robert Hubrecht Rapporteur: Thomas Wolfle The session began with a review of dog cage or pen size guidelines, policies, and regulations in the United Kingdom and the Council of Europe (CoE 2001), in Canada (according to pertinent documents of the Canadian Council on Animal Care [CCAC; www://ccac.ca]), and in the United States (according to the Guide for the Care and Use of Laboratory Animals [NRC 1996]). Video examples were shown of stereotypies in dogs (e.g., cage chewing) and remediation with cage enrichment. A time-budget chart was presented showing that dogs spend large amounts of time on elevated resting platforms. Early socialization, habituation, and training were reviewed, and a behavioral technician playing with dogs in an enriched play environment was presented to set the stage for discussing space requirements. Participants expressed the concern that too little space restricts group size and associated social interaction. They felt that the size of cages or pens should be judged adequate only when the following needs are accommodated: (1) species-specific activity and interaction; (2) enrichment, such that the animals are able to manipulate and control particular aspects of the environment; and (3) essential space for resting, temperature control, sanitation, and noise control. To discuss these concerns, the leader posed the following questions:

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop What factors led to the CoE’s large cage size? Participants noted that smaller cages are required in the United States compared with those described in the CoE documents, yet few abnormalities are noted in the US cages when adequate socialization is provided. Participants seemed to agree that science-driven cage size recommendations are needed, and that ever-larger cage size mandates without supportable science are not justified. Focusing on cage size, rather than on behavior, forces the use of engineering, rather than on performance, standards. How should environments be designed? Participants indicated that performance-oriented approaches to cage size and environments are the most appropriate. The definition of these performance goals revolves around behavioral assessment and includes the considerations described below. Some participants felt that spatial requirements for dogs in research should take into account the whole experimental program as well as species needs (although dogs are not different from other species in this respect). In addition, they felt that acceptable environments should allow the following: positive interaction with humans, harmonious conspecific social housing and exercise, and opportunities for reasonable species-specific behavior such as play and gnawing. Moreover, it was felt that the occurrence of stereotypies and other abnormal behavior should be minimized. The life-to-death experience was considered by some participants to be critical in ensuring high standards of welfare and high-quality science. One participant felt that standards at supply sources (i.e., breeders) are important, and there should be good communication between suppliers and users. Consideration should be given to the animals’ use in acute versus long-term studies, or survival studies in which the animal might be adoptable. Some participants felt that housing standards should take into account the adaptability of the species (although it is not clear that this factor is any greater than for some other species commonly used) and the variability of different breeds. Should the length of time that a dog spends in a facility be a factor in the standards provided? The focus of the question above was whether additional attention should be paid to addressing the needs of dogs used in longer-term studies. Some participants argued that dog housing should meet the needs of the species regardless of the length of time the animals might need to be housed in it. In addition, some opined that a multiplicity of standards for studies of different length might lead to unnecessary bureaucracy and confusion. The participants did not reach any consensus on this question.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Should standards be based on engineering, performance, or a mixture of the two? Participants expressed the belief that a mixture of the two standards is best. There is a need to concentrate on performance standards because they often indicate the true success or nonsuccess of the dog enclosure. However, engineering standards are also useful to ensure the fulfillment of minimum standards. How should changes be implemented? When developing standards, participants indicated that it is necessary to begin with the requirements of the dog, and then move on to regulatory issues. More guidance is needed to evaluate the adequacy of environments in order to assess performance standards. It is important that any new standards be phased in, and that anticipated costs of implementing new standards be included in applications for funding. Many felt that more training of personnel is needed to recognize normal and abnormal animal behavior. Participants emphasized the need for consideration of the research mission in making changes. Involvement of the Principal Investigator in planning prospective changes in housing and enrichment is essential to ensure the high quality of ongoing data. What arguments should be used in the process? Many participants felt that changes should be made with due caution and based upon scientific evidence, professional judgment, and widely accepted “Best Practice.” To avoid reinventing the wheel, and to help harmonize international standards, it is advisable to refer to existing standards (e.g., NRC 1996, CoE 2001, and other nations’ codes of practice). What does the public expect? The view was expressed that science is carried out on the public’s behalf and indirectly with their consent in general terms. Therefore, the public has a particular concern for the welfare of species commonly used as companion animals, and standards used in the laboratory should reflect that fact. How should economic arguments be weighed against biological arguments? This question, stated another way, asks how the cost-benefit of animal research should be established. Some expressed the view that political decisions mandating engineering standards are likely to be unduly expensive without concomitant benefit to the animals. Good science and good welfare go together, and ongoing assessments provide valuable answers to the cost-benefit question. Central to the

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop assessment is an understanding and application of science-driven performance standards. While many felt that global harmonization of animal care and use practices offers many potential benefits both to humans and to animals, some expressed the notion that harmonization would be unlikely if the engineering standards are politically motivated. Is further science needed? How should it be directed? Participants readily endorsed the need for additional research (such as is listed below) for better planning of research. However, some felt that greater use of sound experimental design and statistics is necessary to accommodate any new science-derived changes in the use of animals in research. Participants also recommended expanded use of biologic telemetry. What are the needs for housing- and welfare-related research? Areas described above. Further investigation/research is needed regarding economical and practical ways of enriching the pen environment and of taking into account the needs and sensory modalities of dogs. Relation between pen size, contents/structures/other enrichment, number of individuals, and behavior, preferably under carefully controlled experimental conditions. Ways to ameliorate the negative effects of single housing. Do exercise plans for single-housed dogs actually make a difference? Ways to prevent and manage aggression. Determination of the effects of sound on dogs Cost versus benefit of different toys and chews (no such studies have been attempted in canids). Comparison of different methods of presentation of toys and chews, and determination of the effectiveness of various types of enrichment in single housing and in larger groups. Influence of breeding for the selection of desirable characteristics. Psychological and physiological effects of transport. Design of metabolism cages to reduce their impact on dog welfare. REFERENCES CoE [Council of Europe]. 2001. European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS 123). Future Principles for Housing and Care of Laboratory Rodents and Rabbits. Strasbourg: Council of Europe. NRC [National Research Council]. 1996. Guide for the Care and Use of Laboratory Animals. 7th ed. Washington, DC: National Academy Press.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Breakout Session: Nonhuman Primates Leader: David Whittaker Rapporteur: Randall J. Nelson Participants discussed the questions that appear below, in general consideration of the guideline revision process—Who, How, and Outcomes: How should the next revision of the Guide for the Care and Use of Laboratory Animals (the Guide) (NRC 1996) be conducted? Participants believed that expert groups chosen to address specific issues should conduct the revision of the Guide. Is the lack of scientific knowledge in an area sufficient reason not to move forward with revision? Session Leader David Whittaker believed not. The Council of Europe (CoE) formed expert groups to deal with formulated guidelines, but eventually legislative recommendations for acceptance or nonacceptance of guidelines developed. The CoE participants believed that competent authorities (i.e., ministries) who implemented laws protected against conflict of interest. Is a smaller group of experts more efficient in developing guidelines? Participants affirmed small-group efficiency in contrast to the inertia of larger groups. They also opined that competent authorities should agree in advance to abide by the recommendations of the expert groups unless they vary radically from socially accepted norms. Moreover, they felt that: (1) expert groups should provide technical information early in

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop the process because subsequent change is difficult to implement; (2) large groups are more costly and difficult to manage; and (3) industry should be involved from the beginning, as should all of the stakeholders. To what extent has social housing of nonhuman primates (NHPs) been accomplished in Europe? Individuals in the group indicated that only about 1% of NHPs in the United Kingdom are singly housed and in those cases only for scientific reasons. Many felt that positive reinforcement training is beneficial in facilitating the handling of socially housed NHPs. Some also felt that regulations should influence, rather than require, compliance with factors such as social housing and that influence should be exerted to achieve “best/good practices.” How does one determine best/good practices? There was no consensus among the participants on this question. It was pointed out that the United Kingdom maintains a central clearing-house for best/good practices However, the UK does not promote the blanket utilization of justification of exceptions because doing so discourages the consideration of alternatives and refinements. Nevertheless, participants felt that there should be ready access to information about best/ good practices so that refinements can be made with a minimum of regulatory burden. Further discussion elicited the following opinions from the participants: Consistency in the guidelines and the authority to impose them is lacking in instances in which few scientific studies are available to sub-stantiate expert opinion and professional judgment. The scientific and animal care communities need to convince competent authorities to be supportive of the need to gain more scientific data on factors such as cage sizes. They also need to convince society that such studies are worth the initial investment, because it may be perceived that funds are being redirected from health-related research. The fundamental issues are economics and politics. In studies that will have an impact on welfare issues, expert groups should agree on the range of experimental variables before the studies are performed, to avoid instances in which the scientific validity of the results is called into question. How do we legitimize the science needed to fill gaps in the literature related to welfare issues? Participants provided perspectives and outlined the following potential strategies for change:

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Scientists and veterinarians need to be proactive with legislators from the very beginning to effect the change in societal attitudes needed to make funding of these studies more likely. The Medical Research Council gives monies for appropriate changes in approaches to be made, but if they give monies, the resultant changes are required. Thus, they have the “force of law” behind their support. Data mining may be beneficial in obtaining needed scientific data with little or no cost. The data may already be available in some instances. Veterinary outreach to investigators and to the community is an important way to educate others about best/good practices. Qualified experts should attempt to identify the “bad science” in extant guideline documents, thus increasing the validity and applicability of the documents before refining them or rewriting them. Participants recommend that a list of perceived gaps in the scientific basis for welfare decisions should be maintained. Although not all gaps may be filled at the time of any revision of guidelines, maintenance of these lists will facilitate their consideration at a later date. These lists act as bellwethers for areas where additional guidance may be needed. Additional indicators may come from indirect observations. For example, in instances in which guidance is less than adequate, interinstitutional variation in the implementations of guidelines due to professional judgment may indicate areas where additional guidelines are necessary to promote consistency in welfare and care. Minimum acceptable standards may need to be established to facilitate consistency in enforcement. Without minimum standards, enforcement may be perceived as arbitrary. Difficulties may arise when members of expert groups are included for political reasons. All stakeholders should be included, but representation should be balanced to ensure efficiency. Some participants asked whether the questions being asked are the right ones. It was suggested by some that the goal should be the maximum improvement in welfare relative to the amount of effort generated to reach that goal. What concerns exist relative to the way the Guide deals with NHPs? Participants identified four concerns: Occupational Health—Occupational health is fraught with variability across institutions as a result of vagaries in guidelines. Personal protective equipment in laboratories and proximity issues were discussed. Exposure as a function of proximity to NHPs and duration of exposure should be dealt with more specifically because investigators are looking for guidance.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Positive Reinforcement Training—Positive reinforcement training is not dealt with in detail but could facilitate welfare in instances of social housing. Social Housing—Species-specific considerations are not extensive in the Guide. Social contact without social housing (by touch windows) may allow animals to withdraw when necessary, which achieves welfare goals. However, it may also reduce the vulnerability of individuals to injury, which is of concern to those who question the utility of social housing as a default condition. Animal Welfare—There is a need to think about welfare from the “standpoint of the animal.” CONCLUSION The participants stressed that “one size does not fit all,” especially with respect to NHPs. Individuals of the same species often behave quite differently under the same environmental and behavioral situations. Participants felt that the “Redbook” (NRC 2003) successfully maintains this philosophy throughout discussions of individual experimental situations and other documents should be continued in this stance. It was felt that guidelines should include the consideration of an individual’s needs, experimental contingencies, and ethical responsibilities. REFERENCES NRC [National Research Council]. 1996. Guide for the Care and Use of Laboratory Animals. 7th Ed. Washington, DC. National Academy Press. NRC. 2003. Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research. Washington, DC. The National Academies Press.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Breakout Session: Rabbit Housing Leader: Vera Baumans Rapporteur: Jennifer Obernier Guidelines for this breakout session encouraged its leader and participants to debate current research on rabbit housing standards and guidelines in light of current scientific information. In particular, the participants discussed the pros and cons of group housing, the standards and guidelines that govern minimum caging size, and the climate of the housing environment. GROUP HOUSING Both the Council of Europe (CoE 1986) and the Guide for the Care and Use of Laboratory Animals (the Guide) (NRC 1996) recognize that rabbits are social creatures and should be housed, when possible, in social groups to maximize species-specific behaviors and minimize stress-induced behaviors. The participants readily agreed that in some cases, for scientific or veterinary reasons, rabbits should not be group housed. However in most cases, social housing is an excellent idea, provided there is complexity in the caging. Complexity may include providing visual barriers and hiding places to minimize aggressive encounters and to allow animals to avoid contact by withdrawal. Social housing does have drawbacks, such as fighting, which can cause injury, and the need for improved animal husbandry and housing, to ensure the adequacy of food and water and the hygiene of the cage.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop CAGE SIZE Participants discussed the Council of Europe proposal to revise Appendix A of the European Convention ETS 123. This revision establishes a new minimum cage size standard based on weight, such that one or two compatabile rabbits of less than 4 kg should be housed in a cage with a floor area of 42 cm2 and a height of 45 cm, including a raised area of approximately 55 × 30 cm. Without a raised floor space, the floor area for one rabbit should be 5600 cm2 and 6700 cm2 for two rabbits. Existing standards and guidelines for rabbit caging size also base minimum cage size on weight, including (1) the European Convention ETS 123, which sets a standard of 2500 cm2 floor area and 35 cm of vertical space for a rabbit of less than 4 kg, and (2) the Guide, which recommends allocating a rabbit less than 4 kg approximately 2800 cm2 of floor space and approximately 35.5 cm of vertical space. During the discussion, participants agreed that basing cage size on weight is not optimal because it does not take into consideration that young rabbits are active and need more space in relation to their body weight than adults. CLIMATE The Council of Europe has proposed specific standards for the climate of rabbit housing, including temperature and humidity standards. However, participants pointed out that these standards were arbitrarily set and not based on science. Furthermore, it is unclear whether fluctuations above and below these standards during cleaning and scientific manipulation have any impact on animal well-being. Some participants felt that additional research is needed to understand seasonal fluctuations and the effects of extending the boundaries of the temperature and humidity standards proposed by the Council of Europe. REFERENCES CoE [Council of Europe]. 1986. European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS 123). Strasbourg: Council of Europe. NRC [National Research Council]. 1996. Guide for the Care and Use of Laboratory Animals. 7th Ed. Washington, DC: National Academy Press.

OCR for page 91
The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop This page intentionally left blank.