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The role of the animal ethics committee in achieving humane animal experimentation Schuppli, Catherine Anne 2004

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THE ROLE OF THE ANIMAL ETHICS COMMITTEE IN ACHIEVING HUMANE ANIMAL EXPERIMENTATION by Catherine Anne Schuppli B.Sc, The University of Guelph, 1987 M.Sc, The University of Alberta, 1992 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE STUDIES (Animal Science) We accept this thesis as conforming to the required standard  The University of British Columbia April 2004 © Catherine Anne Schuppli, 2004  Statement of Co-Authorship  Name: Catherine A. Schuppli Degree: Doctor of Philosophy Thesis Title: The Role of the Animal Ethics Committee in Achieving Humane Animal Experimentation Title of Chapter 2: Expanding the Three Rs to Meet New Challenges in Humane Experimentation A version of Chapter 2 has been accepted for publication. Schuppli CA, Fraser D and McDonald M (2004) Expanding the Three Rs to Meet New Challenges in Humane Animal Experimentation. Alternatives to Laboratory Animals. It was co-authored by D Fraser and M McDonald, both supervisory committee members. These co-authors acted in the role of typical supervisory members. The main ideas for the manuscript were developed and researched by Catherine A. Schuppli. Co-authors supervised, helped interpret material, and edited drafts.  Catherine Schupplij  David Fraser  Date  ABSTRACT Institutional Animal Ethics Committees (AECs) are the principal means of ensuring the ethical use of animals in research in many countries, yet we understand very little about how they function and how effective they are in implementing policy and achieving their stated aims. To answer these questions, an ethnographic study involving participant observation and in-depth interviews with 28 members of four university AECs in western Canada was carried out. The major focus of protocol review by committee members was reducing harm to animals, with limited focus on the ethical justification of research despite this being stressed in policy as a goal of AECs. In part, this may be due to confusion over the relation between AEC review and scientific peer review by granting agencies, with some members believing that ethical justification is decided by scientific peer review. Members were also unclear on the distinction between the different elements that go into decisions about ethical justification. Use of costbenefit assessment, although prescribed by policy, did not cover the various other decisionmaking approaches that members described using (e.g. moral intuition). Comments by members identified several factors that could hinder application of the Three Rs (Replacement, Reduction, Refinement); these include an incomplete understanding of the concepts, different interpretations of harm, and different beliefs about the moral significance of pain and suffering. Moreover, some ethical issues do not lend themselves to the utilitarian thinking underlying the Three Rs. Independence of the AEC from the institution (as required by policy) may not be realized because of the predominance of institutional scientists on AECs, recruitment of affiliated community members, and the potentially intimidating atmosphere for community members. Also, policy is unclear about the role of the community member. AEC effectiveness could be improved by clarifying the role of the community member, the relation between AEC and scientific peer review, and the elements of cost-benefit assessments, by expanding policy to acknowledge the various issues and approaches used in decision-making, identifying standards for assessing AEC performance, and expanding the Three Rs to respond to the range of views and values that enter into decisions by AEC members.  TABLE OF CONTENTS ABSTRACT  "  TABLE OF CONTENTS  >"  LIST OF TABLES  vi  PREFACE  vii  ACKNOWLEDGEMENTS  viii  CHAPTER 1 - Thesis Introduction  1  Animal Experimentation and Ethical Concerns Animal Ethics Committees Thesis Research References  1 4  7 9  CHAPTER 2 - Expanding the Three Rs to Meet New Challenges in Humane Animal Experimentation  Introduction Background of the Three Rs Challenges to the Three Rs Special Consideration for Certain Species Quality of Life of Animals in Science Genetically Modified Animals Animal Models of Disease Solutions Conclusions References  •  •  CHAPTER 3 - The Interpretation and Application of the Three Rs by Animal Ethics Committee Members  12  12 13 15 15 15 16 19 19 22 23 27  Introduction 27 Methods 28 Description of Research Process and Data Analysis 33 Results 35 Replacement 36 1. Replacement not seen as Scientifically Suitable 37 2. Confidence in Researchers to Implement Replacement 38 Reduction 39 1. Lack of Expertise of Members 41 2. Confidence in Researchers or Granting Agencies to Apply Reduction 42 3. Concern for Harm Versus Numbers 43 4. Leniency for Productive Researchers 45 Refinement 46 1. Mitigation of Pain 48 2. Humane Endpoints 51 3. Skill and Training 51 iii  4. Environmental Enrichment 5. Improved Handling of Animals 6. Using Species of Lower Sentience Discussion Variation in Application of the Three Rs Lack of Expertise Peer Review versus AEC Review Lack of Consensus on Minimizing Overall Harm Different Views of Pain and Suffering and their Moral Significance Interpretations of the Three Rs Replacement Reduction Refinement Training and Policy  52 55 55 56 56 56 57 58 . . . 60 61 61 61 62 64  Conclusions and Implications for AECs References CHAPTER 4 - Decisions about the Use of Animals in Research: Ethical Reflection by Animal Ethics Committee Members Introduction Methods Results Procedural Steps in Protocol Review Cost-Benefit Assessment Limitations of Cost-Benefit Assessment . Teaching Protocols Role of Peer Review in Decisions . . . Other Approaches to Decision-Making Focus on the Animal Role of Emotion and Moral Intuition Role of Different Philosophical Beliefs Decisions by Precedent Three Rs Cues Leading to Greater Scrutiny Species of Animal Trust in Investigator Quality of Completed Application Form Reaching a Decision Discussion Decisions about Ethical Justification of Research Peer Review Decisions about Modifications Decision-Making Frameworks Conclusions References  64 65 70 70 71 72 72 73 74 76 76 81 81 82 84 84 85 85 86 88 89 90 92 92 93 96 98 99 99  CHAPTER 5 - Animal Ethics Committee Composition and Process: A Framework for Assessing Committee Effectiveness 102 Introduction 102 Methods 103  103 Committee Composition 103 Expertise and Balance 103 Recruitment and Motivation for Joining 105 Length of Term in Office 109 Training 110 Committee Process 111 Committee Discussion at Meetings 111 Meeting Format, Preparation, and Length 113 Committee Dynamics 116 Experience of Community Members 118 Role of Chairperson 121 Discussion 123 Committee Composition 123 Solutions 126 Recruitment of Members 130 Solutions 132 Turnover 132 Solutions 133 Workload 133 Solutions 134 Commitment to AEC Process by Members 134 Solutions 135 Training 135 Solutions 136 Conclusions 136 References 136 Appendix 5.1 A checklist for assessing the performance of Animal Ethics Committees, including a list of potential problems related to composition and process, questions to help diagnose problems, with possible solutions 140 Results  CHAPTER 6 - General Discussion and Recommendations Three Rs Protocol Review Process Community Member Decision-Making Approaches Ethical Justification of Research Policy Implementation and Training of Members Institutional and AEC Culture Responding on National and Local Levels References APPENDIX I - Interview Schedule  144 144 145 146 148 149 153 153 155 157 160  v  LIST O F T A B L E S Table 3.1  The size of Animal Care Committees from four universities in western Canada, and the number and types of protocols reviewed per meeting and per year during years 1999-2001 30  Table 3.2  Pseudonym, gender and role of 28 study participants serving on Animal Care Committees from four universities in western Canada 32  Table 4.1  Number (and Percent) of research protocols assigned to different decision categories by three Animal Care Committees in western Canada from 1999-2001 91  Table 5.1  Composition of Animal Care Committees at four universities in western Canada 104  Table 5.2  Type of member, gender, years served, and how appointed of 28 Animal Care Committee members from four universities in western Canada 107  Table 5.3  Time spent in preparation for monthly Animal Care Committee meetings for those committee members who read all protocols in detail and those who read several protocols in detail and scanned the remainder 115  vi  PREFACE Description of Authors' Role A version of Chapter 2 has been accepted for publication. Schuppli CA, Fraser D and McDonald M (2004) Expanding the Three Rs to Meet New Challenges in Humane Animal Experimentation. Alternatives to Laboratory Animals. It was co-authored by D Fraser and M McDonald, both supervisory committee members. These co-authors acted in the role of typical supervisory members. The main ideas for the manuscript were developed and researched by Catherine A. Schuppli. Co-authors supervised, helped interpret material, and edited drafts.  vii  ACKNOWLEDGEMENTS I gratefully acknowledge the support of the International Foundation for Ethical Research (IFER), a University of British Columbia Graduate Fellowship, and the Animal Welfare Program in sponsoring this research. I am grateful for the creation of the Animal Welfare Program at the University of British Columbia for it opened my eyes to the possibility of pursuing a career in an area that was of great personal interest. I could not have succeeded if it were not for the help and support of my supervisor David Fraser and my supervisory committee members Dan Weary, Michael McDonald, Sue Cox, Jim Love, and Fern Brunger, as well as all the graduate students in the Animal Welfare Program. I could not have had a better environment in which to learn, flourish and have fun. David is an outstanding supervisor. He was always supportive and enthusiastic about my research topic, and all his efforts to help me were done with extreme commitment, and thoroughness. His insights on my research were always a tremendous help, especially when I was struggling to work through complex interpretations of my data. I particularly benefited from David's excellent writing skills. He has a miraculous ability to rearrange words in a sentence so it sounds better and ends up half the length. I learned things about grammar that I had never been taught before: how not to use a dangling participle, how to use the semi-colon and the dash (which I had never used before), hyphenating compound modifiers and so on and so on! Unfortunately I am not sure I was the best grammar student because the lessons seemed to continue - and repeat themselves - right until the end. Dan played a key role in maintaining my enthusiasm for my work and the PhD process in general because I could feed off his "supernatural" energy. One of the great things about my thesis topic was that it enabled me to work with researchers from other disciplines and thus I really benefited from having several members from the Centre for Applied Ethics on my committee. I remember having conversations with Michael where he would see through all my muffled thoughts and be able to come up with key insights that really helped me to expand my learning. Fern started out on my committee but left UBC to go to another job midway through. It is to her that I owe gratitude for starting me on the path of doing qualitative research, and using methods from cultural anthropology. Fortunately, I was lucky enough to find an equally good replacement for Fern when she left. Sue was always very kind and supportive, and she kept me on track of being a good qualitative viii  researcher. She also kept me on my toes! The greatest thing about being a member of the Animal Welfare Program was that I learned so much about animal welfare, my own thesis being one small part of my entire learning experience. I also learned so many other "important" things: ritual practises of some rare Asian culture, the pros and cons of monster trucks...! I have so many fond memories of all the graduate students in Rooms 180 and 190; there were great lunch time conversations with Cassandra, Jen, Anna, Art, Anton, Heiko, Paulo, Dave, Shack, and Dan. Those were the days when we fit around the coffee table! I also have to thank my fellow qualitative researchers, Nicole, Carol, and Anton for all the great conversations we had about what the "heck we were doing." My time at UBC has been rewarding (although perhaps a bit long), but I am glad I transferred into the Animal Welfare Program. I managed to meet my goal of finishing my PhD by... well nevermind.  CHAPTER 1 - Thesis Introduction Animal Experimentation and Ethical Concerns  The use of animals in experiments has had a long, distinguished but checkered history. As early as the 2 century a Roman physician, Galen of Pergamon (ca. 130-210 C.E.), experimented nd  on pigs, dogs, and other animals to study anatomy (Rudacille 2000; Guerrini 2003). The use of animals and human cadavers for anatomical demonstrations was routine in universities across Europe beginning in the 14 and 15 centuries (Guerrini 2003). Later, the English physician th  th  William Harvey (1578-1657) was one of the first to use an experimental approach using living and dead animals to study blood circulation. With his research methods forming a model for future research, the use of animals to study physiological mechanisms flourished in the 17  th  century and beyond (Guerrini 2003). Animal experimentation continued to increase, especially in the latter decades of the 19  th  century, but not without opposition. Although most animal experimentation occurred in Germany and France, the animal protection movement was concentrated in Britain (Guerrini 2003). Popular attitudes towards animals began to change in the 17 century (Harwood 2002) amidst th  debate amongst philosophers about the moral status of animals. Rene Descartes (1596-1650) proposed a view of animals as machines, lacking consciousness and incapable of feeling pain. Therefore, vivisectionists could be secure in the belief that they were inflicting no pain while performing experiments. But even as Descartes made these claims, others objected vehemently that he was underestimating the experiential lives of animals (Harwood 2002; Preece 2002). French philosopher Voltaire (1694-1778) disagreed with the mechanistic view of Descartes and argued that animals were sentient and he considered it barbaric to use animals for vivisection (Preece 2002). The German philosopher Emmanuel Kant (1724-1804) viewed animals as things (without rationality) and stated that the duties we have concerning animals are indirect ones, specifically (in the words of Guerrini, 2003, p 64) that "cruelty to animals would damage human moral sensitivity and therefore was to be avoided. But humans had no moral obligations toward animals." In contrast, English philosopher Jeremy Bentham (1748-1832), founder of modern utilitarianism, argued for direct duties towards animals. Bentham significantly changed the nature of debate by arguing that because animals are capable of happiness and have a basic interest in 1  not suffering, they warrant ethical consideration in his utilitarian scheme. Bentham judged actions according their consequences, thus any act causing more pain to animals than pleasure to humans is immoral (Taylor 2003). English philosopher the third Earl of Shaftesbury (1671-1713) argued that virtuous behaviour promotes the good of humankind, and that therefore we should treat animals with kindness and affection (Preece 2002). Concern about animal experimentation and anticruelty sentiment intensified in the 19  th  century within a general milieu of humanitarian reform, and scientific experiments on living animals were the targets of some of the greatest protests involving both the public and scientists (Turner 1980). Many scientists outside Britain were targeted. Francois Magendie (1783-1855), a prolific French vivisectionist, was one particular target. Magendie was a pioneer of experimental physiology, who revolutionized methods of scientific study using systematic analyses (Orlans 1993; Guerrini 2003). He had a reputation of being cruel and unfeeling towards his research subjects, and his public demonstrations of his work were not well received in Britain (Orlans 1993; Rudacille 2000; Guerrini 2003). A well known British experimental physiologist and supporter of vivisection, Marshall Hall (1790-1857), in response to concerns of the public, suggested a form of self-regulation by a "society for physiological research." In 1831 he proposed five guidelines (Guerrini 2003, p 78) which were remarkably similar to the "Three R" principles created much later by two scientists, Russell and Burch in 1959. Hall's principles were: 1.  Experiments should be absolutely necessary, and all alternatives should be explored.  2.  Experiments should have clear and attainable objectives.  3.  Experiments should avoid unwarranted repetition, which includes being aware of the work of past experiments.  4.  The least possible pain should be inflicted.  5.  Experiments should have witnesses to certify results and lessen the need for repetition.  However, Hall's proposed society was not created until 40 years later. In the late 1800s, animal experimentation continued to increase in many medical schools in England, France, and Germany. In the US, which was slightly behind Europe, physician  2  William Henry Welch (1850-1934), having trained in Germany, became a pivotal figure in the development of scientific medicine and a strong advocate for the use of experimental animals. He played a key role in opposing critics of animal experimentation and led the fight against federal legislation to restrict animal experimentation from 1896 to 1901 (Rudacille 2000). In Britain the antivivisection movement included some very influential and respected members of the cultural establishment such as writers Robert Browning, Lewis Carroll, and Alfred Tennyson, social reformer the seventh Earl of Shaftesbury, and Queen Victoria herself in the 1800s, and G.B.Shaw in the 1900s (Preece 2002). Francis Power Cobbe (1822-1904), an upper-class Englishwoman, was one of the most influential members of this movement, founding two different antivivisection societies (Preece 2002). Antivivisectionists were not just concerned about the death of animals, but they were also concerned about suffering, and in particular the pain, that animals experienced (Turner 1980). There was revulsion for what appeared to be deliberate and calculated "torture" of animals by rational scientists (Turner 1980; Orlans 1993). An important development in the mid-1800s was the introduction of anaesthesia. Although it could have addressed concerns about pain experienced during vivisection, its use was inconsistent (Turner 1980; Guerrini 2003). By the late 1800s scientists supporting vivisection recognized the need for public support and responded to growing antivivisectionist pressure by creating organizations such as the British Association for the Advancement of Medicine by Research in 1871. This organization sought to establish a code of conduct for using animals (Orlans 1993). The combined public and scientific support for regulation of animal experimentation set the stage for new legislation. In 1876, the Cruelty to Animals Act was passed by the British government, becoming the first law regulating animal experimentation. It required licensing of researchers, inspections of facilities by authorities, and restrictions on the performance of experiments without anaesthesia. This law remained unchanged for 110 years (Home Office 1986). Despite the successes of the antivivisection movement, scientists were also experiencing their own successes. During the 1870s two scientists - German physician Robert Koch (18431910) and French chemist Louis Pasteur (1822-1895) - played a key role in the development of the germ theory of disease (Turner 1980; Guerrini 2003). Their work lead to huge strides in microbiology that resulted in significant improvements in human health, with animals playing key roles in these advances. Thus, support for the use of animals in experiments grew as a result 3  of the growing successes of experimental medicine and the gradually accumulating weight of evidence of the utility of animal models. Finally, the weight of medical progress in the first half of the 20 century began to marginalize the antivivisection movement. th  Animal Ethics Committees The 1960's saw a resurgence of widespread public attention and concern over the use of experimental animals amid an atmosphere of increased public consciousness of human and animal rights in Europe and North America (Guerrini 2003). In response, over the next 30 years many developed countries introduced or revised practices for the governance of experimental animal use. A similar trend occurred for the regulation of humans in research, beginning with the Nuremberg Code in 1946. In Canada, the Canadian Council on Animal Care (CCAC), a national peer review organization, was established in 1968. Canada was one of the first countries to introduce the local institutional Animal Ethics Committee (AEC) , known in Canada as the 1  Animal Care Committee (ACC). Gradually, other countries introduced this model of governance during the next 2 decades beginning with Switzerland (1978), and followed by the United States (1979), New Zealand (1987), Sweden (1988), and the Netherlands (1997). Although the United Kingdom already had strong government regulation in place, it added AECs in 1998. Canada differs from other countries in that there is no national legislation to enforce compliance by animal users. However, government research granting agencies require that institutions that use animals must receive ACC approval in order to receive funding from those agencies, and several provinces now make compliance with CCAC standards a requirement under provincial law. Animal Ethics Committees are responsible for ensuring the ethical conduct of research using animals, much as committees for human research - Institutional Review Boards (IRBs) in the US, Local Research Ethics Committees in the UK - were created to protect the rights and welfare of human subjects used in research. Animal Ethics Committees are generally located at each institution that uses animals for research, teaching or testing, but they can also be regional,  For simplicity, the term "Animal Ethics Committee" is used to describe committees known by various names: Animal Care Committee in Canada, Institutional Animal Care and Use Committee in the USA, Animal Experimentation Ethics Committee in Australia, Animal Experimentation Committees in the Netherlands, and Ethical Review Process in the UK. 1  4  as in Sweden. A major function of the AEC is to review all proposed research involving animals at the institution, judge it on the basis of its ethical acceptability, and minimize harms to animals in various ways. Approved research is usually determined by balancing the potential benefits of the research against the harms to animals. In general, the higher the level of anticipated harm, the stronger must be the value of the research. Opinions differ over what constitutes a benefit resultingfromanimal experimentation. Canadian policy includes benefits that contribute "to fundamental biological principles, or to the development of knowledge that can reasonably be expected to benefit humans or animals" (CCAC 1993). In the US, Public Health Service policy includes as benefits "the improvement of the health and well-being of humans as well as other animals," the "advancement of knowledge," and "the good of society" (Public Health Service 1985). UK policy is the most explicit of these three countries (Home Office 1986): a project license shall not be granted for any programme that is not undertaken for the following reasons: the prevention or the diagnosis or treatment of disease, illhealth or abnormality, or their effects, in man, animals or plants; the assessment, detection, regulation or modification of physiological conditions in man, animals or plants; the protection of the natural environment in the interests of health or welfare of man and animals; the advancement of knowledge in biological or behavioural sciences; education or training; forensic enquiries; and the breeding of animals for experimental or other uses. Committees try to minimize harms including pain from experimental procedures together with reduced comfort or well-being resultingfrominappropriate housing, care, and handling. Several systems for categorizing the degree of pain or suffering experienced by animals have been created. These tend to focus on the duration and frequency of a procedure and the degree to which pain-relief drugs can mediate pain and distress. The CCAC has adopted a scale of "Categories of Invasiveness in Animal Experiments" rangingfromexperiments that cause little or no discomfort or stress (B), to experiments that cause minor stress or pain of short duration (C), to procedures which cause severe pain (E) (CCAC 1993). The Guidance on the Operation of the Animals (Scientific Procedures) Act 1986 of the UK categorizes degree of pain according to "Severity Bands" including mild, moderate, and substantial, with examples of procedures in each 5  category. Their final category, called Unclassified, is for decerebrate animals or animals undergoing terminal anaesthesia (Home Office 1986). The US Animal and Plant Health Inspection Service does not classify pain and distress directly, but rather according to the need or use of pain-relieving drugs (AWA 1985). Animal Ethics Committee decisions are also guided by the "Three Rs" (Russell and Burch 1959) - Replacement, Reduction and Refinement - which are widely recognized fundamental principles for minimizing harms to animals. The Three Rs serve as complementary rules of thumb to reduce overall suffering of experimental animals in three distinct ways. Replacement consists of "methods which permit a given purpose to be achieved without conducting experiments or other scientific procedures on animals." Reduction involves "methods for obtaining comparable levels of information from the use of fewer animals in scientific procedures, or for obtaining more information from the same number of animals." Refinement involves "methods which alleviate or minimize potential pain, suffering, and distress and which enhance animal well-being" (Balls et al. 2000). The ACC in Canada is similar in composition to comparable committees in other countries and usually includes a selection of members drawn from within the institution: scientists and/or teachers experienced in animal care and use, veterinarians, non-animal-users, and animal technical staff, together with people independent of the institution and representing community interests. Relative proportion of each type of member varies between countries. For example, committees in Canada must have at least one scientist, one veterinarian and one community member (CCAC 2000). Committees in Sweden have an equal number of community members and scientists or members who work with laboratory animals (The Swedish National Board for Laboratory Animals 1979). The Netherlands requires equal numbers of experts in animal experimentation, animal welfare, alternatives, and ethics, although only two of them must not conduct experiments on animals (The Dutch Experiments on Animals Act 1997). Ideally the composition of the committee will provide the expertise needed to properly review proposals including technical expertise for assessing procedures and management, expertise on the Three Rs, as well as expertise to broaden discussion by including community standards.  6  Thesis Research Although AECs play a key role in ensuring the humane treatment of research animals, they have received remarkably little attention from the research community. In contrast, a reasonable amount of research and discussion has been conducted on the functioning and effectiveness of IRBs in human research. For example, several journals, such as "IRB: Ethics and Human Research," published by the Hastings Center, have been created to present issues specifically related to IRBs. Using the Canadian model, this study attempts to improve our understanding of AECs by focussing on several key aspects of the functioning and structure of committees: (1) the adequacy of the Three Rs and their underlying philosophical principles, (2) application of the Three Rs by committee members, (3) decision-making processes of members, and (4) committee composition and process. This research provides much needed insight into how ACCs function, where there are gaps between policy and practice, where clarification of policy is needed, how the system can be improved, and where further research is needed. The thesis is organized into four independent research papers followed by a final discussion. The thesis begins with a theoretical analysis of the continued appropriateness of the Three Rs. The Three Rs were introduced as guiding principles for humane use of experimental animals in 1959, but new developments in biological research and in ethical concern over animals raise questions about their continued adequacy as a basis for ethical review. Chapter 2 examines the underlying utilitarian philosophy of the Three Rs as a basis for determining whether they are still appropriate and sufficient today, with particular reference to four research issues. This research identifies where the Three Rs may need broadening and where other principles may need to be considered. Chapter 2 also sets the stage for empirical work using qualitative methodology in the remaining chapters. Use of qualitative methodology has become widely accepted among social scientists. Much literature has been written in the last 30 years about the methodological principles and philosophical underpinnings of different approaches of qualitative research as well as the practises used (for example, Glaser and Strauss 1967; Miles and Huberman 1994; Hammersley and Atkinson 1995; Corbin and Strauss 1990; Denzin and Lincoln 2000). Use of  7  qualitative methodology has proven very useful in understanding how humans think about the treatment of animals. For example, several authors have used these methods to advance our understanding of the attitudes and values of members participating in biomedical research (Arluke 1990; Arluke and Sanders 1996) and in the animal rights movement (Jasper and Nelkin 1992; Herzog 1993). This research helps to inform and improve communication in the often polarized debate about the use of animals in research. In this research, an ethnographic approach was chosen in order to gain a deeper understanding of ACC functioning from the perspectives of individual committee members. Data collection included both participant observation and by open-ended semi-structured interviews with ACC members from four universities in western Canada. In Chapter 3, transcripts were analyzed to understand how members interpret and apply the Three Rs in making decisions about proposed research. Very few studies have focused on the Three Rs in practice. As two of the few examples, Hagelin et al. (2003) examined modifications requested by AEC's in Sweden and found that the majority of requests were related to Refinement; and Purchase and Nedeva (2001) examined the impact that the UK's Ethical Review Process has had on attitudes of animal users to the Three Rs. The present research identifies potential inconsistencies in the application of the Three Rs with possible solutions. Chapter 4 examines the decision-making processes used by committee members in practice to make decisions about whether proposed research is justified and what modifications to recommend to investigators. A rational cost-benefit assessment is assumed, recommended, or required for making decisions in most policy and by most commentators. Thus, systematic decision-making frameworks have been created to formalize cost-benefit assessments (Smith and Boyd 1991; Mellor and Reid 1994; de Cock Buning and Theune 1994; Stafleu et al. 1999). However, decision makers in other natural settings rarely use rational approaches (Klein 1998). This research examines how members actually make their decisions. This work suggests that it may be necessary to recognize that different approaches contribute to the review of proposals, and that policy needs to allow for this diversity. Chapter 5 examines additional factors that potentially affect AEC functioning and ultimately AEC decisions: committee composition, methods of recruiting members, motivation for joining, workload, committee dynamics, and member training. Drawing on comparisons with ethics committees for human research, common problems are identified and used to create a 8  hypothetical framework for assessing the performance of a committee with diagnostic tools for correcting shortcomings. This approach should enable AECs to find and correct problems and to educate members so as to prevent potential problems.  References Arluke A 1990 Uneasiness among laboratory technicians. Lab Animal 19: 20-39 Arluke A and Sanders C R 1996 Systems of meaning in primate labs. In: Arluke A and Sanders C R (eds) Regarding Animals pp 107-131. 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Oxford University Press: New York, USA Preece R 2002 Awe for the Tiger, Love for the Lamb. A Chronicle of Sensibility to Animals. UBC Press: Vancouver, Canada Public Health Service 1985 United States government principles for the utilization and care of vertebrate animals used in testing, research, and training IV 50 FR 20864. National Institutes of Health: Bethesda, USA Purchase F H and Nedeva M 2001 The impact of the introduction of the ethical review process for research using animals in the UK: attitudes to alternatives among those working with experimental animals. Alternatives to Laboratory Animals 29: 727-744 Rowan A 1984 Of Mice, Models, and Men: A Critical Evaluation of Animal Research. State University of New York Press: Albany, USA Rudacille D 2000 The Scalpel and the Butterfly. The Conflict Between Animal Research and Animal Protection. University of California Press: Berkeley, USA Russell W M S and Burch R L 1959 The Principles of Humane Experimental Technique. Methuen: London, UK Smith J A and Boyd K M 1991 Lives in Balance. The Ethics of Using Animals in Biomedical Research. Oxford University Press: Oxford, UK Stafleu F R, Tramper R, Vorstenbosch J and Joles J A 1999 The ethical acceptability of animal experiments: a proposal for a system to support decision-making. Laboratory Animals 33: 295-303 Strauss A and Corbin J 1998 Basics of Qualitative Research. Techniques and Procedures for 10  Developing Grounded Theory. Sage Publications Inc.: Thousand Oaks, USA Taylor A 2003 Animals and Ethics. An Overview of the Philosophical Debate. Broadview Press: Peterborough, Canada The Dutch Experiments on Animals Act 1997. Section 18. http://www.nca-nl.org/ylcce55eJ on: November 7, 2003 The Swedish National Board for Laboratory Animals 1979 Provisions On Animal Experiments, http://www.cfh.se/ Accessed on: December 8, 2003  Turner J 1980 Animals, Pain, and Humanity in the Victorian Mind. Reckoning with the Beast The Johns Hopkins University Press: Baltimore, USA  11  CHAPTER 2 -  Expanding the Three Rs to Meet New Challenges in Humane Animal Experimentation  2  Introduction  The Three Rs (Replacement, Reduction, Refinement), proposed over 40 years ago by Russell and Burch (Russell and Burch 1959), have become widely accepted principles for the governance of humane animal experimentation. They are recognized by policy makers, scientists, and humane organizations, and they form the basis of ethical review of animal use by Animal Ethics Committees (AECs) and comparable bodies. The Three Rs have remained valuable partly because they are easily understood and easily remembered principles which capture key ethical issues that have traditionally arisen in animal-based science. However, new developments in biological research and in ethical concern over animals raise questions about the adequacy of the Three Rs as a basis for ethical review. First, research involving genetically modified (GM) animals and animals bred as disease models present new challenges which, at least superficially, seem not to be adequately addressed by applying the Three Rs. Moreover, the Three Rs rest on the principle of minimizing harms to animals, but it is not clear that this fully captures contemporary ethical concerns about animal use. Recently, for example, there has been an increased emphasis on enhancing the quality of life of experimental animals through environmental enrichment (Rollin 1988; Morton 1995) and appropriate humananimal bonds (Davis and Balfour 1992; Hemsworth and Coleman 1998; Burgdorf and Panksepp 2001). Special consideration - even total exemption from harmful research - has been proposed for certain species, without regard to cost-benefit analysis. All this suggests that it is time to reevaluate the adequacy of the Three Rs and their underlying principles. This chapter addresses, from the perspective of an Animal Ethics Committee, whether the Three Rs are still appropriate: what are they missing, should we expand them or discard them, and are there other appropriate ethical principles? The utilitarian basis for the Three Rs is  A version of this chapter has been accepted for publication. Schuppli CA, Fraser D and McDonald M (2004) Expanding the Three Rs to Meet New Challenges in Humane Animal Experimentation. Alternatives to Laboratory Animals  2  12  examined in order to provide a better understanding of their possible limits.  Background of the Three Rs In order to understand the Three Rs and their philosophical underpinnings it is useful to revisit the original text of Russell and Burch. When the Three Rs were developed, they served as a useful means to bring order to the subject of humane animal experimentation. One of Russell and Burch's main arguments for the humane treatment of animals, still echoed today, is that humane treatment is a prerequisite for successful science. They wrote that "the greatest scientific experiments have always been the most humane and the most aesthetically attractive, conveying that sense of beauty and elegance which is the essence of science at its most successful" (Russell and Burch 1959, p 157). Nearly 40 years later, at a major workshop on alternatives, the participants endorsed the implementation of the Three Rs as being in the interests of both scientific excellence and the highest standards of animal welfare (Balls et al. 1995). Guided by the terms of reference of the Universities Federation for Animal Welfare (UFAW), Russell and Burch followed a utilitarian approach to animal ethics. A utilitarian approach seeks to reduce the amount of suffering, and increase the amount of pleasure, for all affected parties including, in the case of laboratory animal use, both sentient animals and humans. For a utilitarian, an action is judgedrightwhen the balance of good versus bad consequences outweighs that of any alternative action. This is also the basis for the ethical analysis of costs and benefits normally used by Animal Ethics Committees to assess justification of research. Russell and Burch aimed to reduce suffering of laboratory animals by reducing the sum total of distress, which included pain and fear, using the Three Rs as convenient rules of thumb to achieve this. Russell and Burch used "distress" for what philosophers call negative hedonic forms of utility, where the sum total consists of the amount of negative hedonic states (distress) multiplied by the number of animals exposed. For utilitarians, a general aim should be to reduce the level of distress, or the number of animals subjected to distress, or some combination of the two. Russell and Burch also specified that their focus was on the "techniques of experimentation itself (p 5) and only incidentally were they concerned with laboratory animal husbandry, although they repeatedly noted the connection between unsuccessful experimentation and distress in animals whether caused directly by experimental procedures or indirectly through  13  inappropriate husbandry. Replacement was defined by Russell and Burch as "any scientific method employing nonsentient material which may... replace methods which use conscious living vertebrates" (p 69). Non-sentient material includes "higher plants, micro-organisms and the more degenerate endoparasites, in which nervous systems and sensory systems are almost atrophied" (p 69). They divided Replacement into two main categories: relative replacement (animals are used but distress is thought to be eliminated, as in non-recovery experiments on anaesthetized animals or in in vitro experiments), and absolute replacement where no animals are used at all. Reduction was defined as a means of lowering "the number of animals used to obtain information of given amount and precision" (p 64). In discussing Reduction, Russell and Burch emphasized the importance of having an intellectually sound basis for the development of hypotheses as opposed to trial-and-error experimentation, and they also focussed on the problem of variance control. They argued that control of variation through good experimental design, and reduction of variation between individuals through breeding or control of environmental conditions, generally resulted in smaller sample sizes. They cited studiesfromthe 1950s that were just beginning to realize that inbreeding and hybrids could increase uniformity in some traits. Michie (1955) realized that environmental conditions can also affect uniformity, suggesting that"... whatever conditions, both genetic and environmental, are best for the health of the individual animals are also best for promoting the biological uniformity of the colony." Refinement was defined as any development leading to a "decrease in the incidence or severity of inhumane procedures applied to those animals which still have to be used" (p 64). The goal of Refinement is to reduce to an absolute minimum the amount of distress imposed on animals. Russell and Burch also identified that in some cases when extremely large numbers of animals are used, even if a procedure is well refined, the experiment may not be justified unless Reduction can be applied (p 66). They gave the example of large numbers of animals used by laboratories with limited staff who are unable, due to time constraints, to monitor the welfare of each individual animal.  14  Challenges to the Three Rs Special Consideration for Certain Species When considering a research protocol involving non-human primates or companion animals, Animal Ethics Committees might find that no matter how much the investigator can reduce and refine, questions still remain about whether the species in question should be used at all. Indeed, some believe that certain species should be exempted on principle from any harmful research. For example, several countries have taken various steps to ban or limit the use of Great Apes for harmful research (Home Office 1986c; Ministry of Agriculture and Forestry 1999; Netherlands Centre for Alternatives to Animal Use 2001; The Swedish National Board for Agriculture 2003). The utilitarian approach used by Russell and Burch could be used to promote an almost total ban on the use of the Great Apes on the grounds that they are capable of suffering more than simpler animals, and hence that the projected benefits of most research projects would not likely warrant the costs. However, the ban on the use of certain species, irrespective of costs and benefits, clearly steps outside a utilitarian approach. Similar issues arise over companion animals where societal context can privilege some species over others because of their relationship with humans (Swabe 1996). In a Western context, dogs, cats, and horses are considered companion animals, and their use in research is in conflict with this societal norm. For example, Orlans (1993) describes the strong lobby that developed during the 1980s in the US against the use in research of dogs relinquished to shelters. Currently in the UK, special protection is given to dogs, cats, and horses under the Animals (Scientific Procedures) Act 1986 (Home Office 1986b). If Animal Ethics Committees are to be responsive to social norms about the value ascribed to different species, then the assurance that research has been conducted in accordance with the Three Rs could still be insufficient. Here again, the reasoning seems to step outside the utilitarian thinking that underlies the Three Rs.  Quality of Life ofAnimals in Science Russell and Burch put particular emphasis on reducing pain and distress arising from experimental procedures. However, since the 1950s, arguments have been proposed for enhancing the quality of life of experimental animals beyond simply preventing negative hedonic  15  states. For example, Rollin (1988, p 235) says that a research animal should have a right to "... being housed and fed in accordance with its nature, to exercise, to company if it is a social being etc.; in short, to being treated as an end in itself." Two developments in animal welfare science have contributed to the current emphasis on quality of life for animals. The first, environmental enrichment, involves some modification of an animal's environment that improves its welfare. Many laboratories "enrich" environmental conditions for laboratory animals by increasing space allowances, social contact, and environmental complexity (Fraser et al. 2000). Environmental enrichment may attempt to promote natural behaviour such as play and exploration, or reduce abnormal behaviours such as stereotypies. Recent scientific methods, such as preference testing, provide tools that allow us to better assess what types of captive conditions animals prefer, assuming that they choose environments in which they experience more positive hedonic states and/or less negative states (Dawkins 1990). Second, an increasing body of evidence suggests that the nature of the relationship between humans and animals strongly influences animal welfare (Davis and Balfour 1992). Many species can discriminate between individual human beings and it has been shown that rats prefer contact with individuals with whom they have safely interacted in the past (Davis 2002). This ability to discriminate enables animals to react to people as conditioned stimuli, associating laboratory procedures with them and thus perhaps creating conditioned fear responses which may also interfere with variables being tested. In agricultural species fear responses elicited by a handler are thought to be major factors in animal welfare (Hemsworth and Coleman 1998; Rushen et al. 1999). On the positive side, Burgdorf and Panksepp (2001) found that adolescent rats will work to gain access to simulated play with human handlers; this is true especially for singly housed rats that could not engage in normal social interactions with other rats. When considering Refinement, Animal Ethics Committees do not commonly acknowledge handling as a potential stressor, or positive handling as a potential contribution to well-being, and investigators are not usually asked to provide this information for research protocol review.  Genetically Modified Animals Recent increases in the use of GM animals pose serious challenges to both Reduction and  16  Refinement. Over the last 10 years, many GM animals, mostly mice, have been produced worldwide for use in basic and applied research, in the production of pharmaceuticals and nutrient products, and in safety testing. This use of GM animals is beginning to reverse a 30 year trend toward steady reduction in use of experimental animals in the Western countries. For example, from 1999 to 2000 the UK reported an increase (of 2.9%) in overall numbers for the first time since 1976, mostly because more GM animals were used (Home Office 2001). This increased use is likely due to the greater variety of available applications using GM animals, to the very large numbers of animals needed for the production and maintenance of colonies, and to the inefficient methods used to develop new transgenic lines or mutations. Transgenic modifications are currently achieved rather inefficiently by the use of many animals to produce a small proportion of functional transgenics. Many of these animals are surplus. For example, the successful development of transgenic animals with a desired genetic modification is achieved through the testing of many DNA constructs on a largely trial-and-error basis (Moore and Mepham 1995). The techniques of pronuclear microinjection and embryonic stem cell manipulation also require large numbers of animals. In mice, for example, the proportion of resulting offspring which carry an additional gene after microinjection is usually very small (Moore and Mepham 1995; Gordon 1996). Technology is also inefficient in "phenotype driven" N-ethyl-N-nitrosourea (ENU) projects which attempt to link known genes to function in mice by producing random mutations in known genes. In these projects, each mutagenesis screen requires tens of thousands of mice and about 1-10 % of mice screened produce useful phenotypes (Nolan et al. 2000; Hrabe de Angelis et al. 2000). Finally, once a line is established it may be necessary to continue breeding animals, many of which will not be studied (Dennis 2002). Because of the nature of genetic modification research, successful Reduction is limited and Animal Ethics Committees often have to make decisions about very large numbers of animals. One relevant question is whether the surplus animals are harmed. In fact, many surplus animals are exposed to harmful procedures. For example, during the development of a transgenic animal, donor females may be induced to superovulate with hormones, male mice are vasectomized to induce pseudopregnancy in female embryo recipients, embryos are surgically transferred to recipients (Dennis 2002; Brown and Corbin 2002; Wells 2002), and lethal or  17  deleterious mutations may occur in the offspring, often in homozygotes born in later generations (Moore and Mepham 1995). Once a transgenic line is established, most surplus animals will come from breeding colonies. While many of these animals may have normal phenotypes, some may have health problems related to the gene alteration (Dennis 2002). Given that there is some level of harm for many of the animals, an analysis of costs and benefits might suggest that such high numbers inflate the level of harm to such a degree that the benefits would have to be very high to justify the research. Russell and Burch (1959, p 66) themselves questioned the acceptability of even well refined experiments requiring large numbers of animals. Increased use of GM animals may also pose a challenge to Refinement, mostly related to consequences of altering genes. For example, unpredictable adverse effects can result from the random integration of the transgene into the host genome, which can cause insertional mutations and disrupt natural gene expression (5-15% of cases, Constantini et al. 1989). Further, in addition to the desired expression of the transgene, there may also be unpredictable side effects of gene expression which can seriously compromise welfare. In particular, the physiology of a transgenic animal may be altered by pleiotropic effects. For example, the "giant mouse", which has been genetically engineered with a human gene that stimulates the production of growth hormone (hGH), suffers from chronic kidney and liver dysfunction, develops tumours, has structural changes in the heart, liver, kidney and spleen, has high infant and juvenile mortality, and has a shortened life span and reduced fertility (Brem and Wanke 1988; Berlanga et al. 1993). Reducing pain and distress in these animals with multiple pathologies would be quite problematic. In addition, because such side effects are often unknown and unpredictable in the creation of new transgenic lines, Refinement is particularly challenging as researchers do not know what to expect and plan for. In such cases, Animal Ethics Committees cannot make well informed judgements about the level of harm relative to the expected benefits in order to decide whether proposed research is justifiable. GM animals also pose a threat to Replacement. Moore and Mepham (1995) suggested that "because of the increasing potential of transgenic animals for experimental and commercial purposes, the trend for replacing animals in experimentation with non-animal alternatives may be reversed."  18  Animal Models of Disease Disease models, whetherfromspontaneous mutations, directed genetic modifications, or induced by procedures, present particular challenges to Refinement. Firstly, for many models reduction of welfare is intrinsic to the objective because the purpose is to mimic the pathology, pathogenesis, and/or symptoms of a human disease (Svendsen and Hau 1994). Secondly, in the case of genetically based disease models, the need for breeding colonies with the disease may increase the number of animals that will potentially suffer. Also for these models, because welfare is compromised by genetic make-up, the usual Refinement options to mitigate harms due to experimental procedures may not be applicable. Thirdly, in many cases the disease model is studied with the goal of creating therapies for that particular disease. In such cases, there may be no known means of treating the disease symptoms, or disease symptoms may need to be present in order to study efficacy of the treatment therapy. The use of transgenic disease models may also create a trade-off between the Three Rs. On the one hand, it is claimed that these models are more effective because they allow researchers to introduce known human genes which may better mimic the pathologies of the human disease, ultimately reducing numbers of animals. On the other hand, the level of harm may be increased for the diseased animals. Using a utilitarian cost-benefit analysis, these experiments may be justifiable because the overall amount of harm is reduced (relative to benefits) by these more accurate models. However, such trade-offs may not be supported by public opinion, for example if the level of suffering for the affected animals is very high. Here again, societal values may go beyond the utilitarian philosophy underlying the Three Rs.  Solutions  Some of the above challenges can be addressed by an expanded or modified interpretation of the Three Rs, while others seem to require going beyond the Three Rs and their utilitarian basis. For the challenge created by the large numbers of animals used for genetic modification, a partial solution may lie in Reduction through developing more efficient ways to produce GM animals and the use of cryopreservation of transgenic embryos (Rail et al. 2000) or spermatozoa  19  (Marschall and Hrabe de Angelis 2003) to avoid the need to maintain founder colonies. Animal Ethics Committees could encourage the use of such new technologies as they become available. In addition, following the UK approach (Home Office 1986a), concerns about large numbers of animals, particularly in the development of new GM lines with potentially multiple and unpredictable impacts on welfare, could be addressed by ensuring that all animals, including surplus animals, are counted in the analysis of costs and benefits. Hence, decisions about proposed research could become better informed because they more accurately reflect real costs to the animals. Also, a continuing and comprehensive research effort is needed to track whether cost-benefit predictions are accurate, in particular whether the large numbers of compromised animals really do, over time, result in sufficient scientific benefits to warrant the trade-off. Even with a more accurate calculus, a utilitarian framework may not address all concerns about Reduction. It may be that even for well refined research projects, there is a limit to acceptable numbers of animals used in a study, regardless of the benefits. Moreover, despite the popularity of GM approaches, Animal Ethics Committees and researchers might help keep numbers in check by questioning the necessity of using GM animals when other plausible approaches are available. To respond to concerns about quality of life for research animals, the traditional interpretation of Refinement - as minimizing distress during procedures - could be expanded to include enhancing welfare during breeding and rearing. Indeed, some organisations have taken this approach (ICCVAM 1997; UFAW 1998; Balls et al. 2000; FRAME 2002). For example the Fund for the Replacement of Animals in Medical Experiments defines Refinement as, "... the modification of any procedures that operate from the time a laboratory animal is born until its death, so as to minimise the pain and distress experienced by the animal, and to enhance its wellbeing. Giving due consideration to issues of animal welfare is not only importantfromthe viewpoint of ethics, it is also a matter of good science" (FRAME 2002). One challenge to enhancing welfare of research animals is created by a potential trade-off between improving the quality of life of animals and the interests of science. Changes in husbandry practices intended to improve animal welfare might influence the variables being measured in a study. Hence, scientists might argue against such changes because new data would not be comparable with old data, and new baselines might need to be generated. In this case,  20  recognition of husbandry and handling as variables in experimental design could allow researchers to include such effects in their research and move toward improved animal welfare. On the other hand, housing animals in standard (relatively deprived) laboratory environments may not provide conditions for normal functioning of the animal, and thus such animals might be poor research models yielding questionable external validity and replicability. For example, Garner and Mason (2002) found that bar-mouthing in caged voles, an example of stereotypical behaviours that are widespread in laboratory animals, shows fundamental similarities with human behaviours arising from basal ganglia dysfunction. Hence, reducing stereotypies through appropriate husbandry techniques could enhance validity and replicability, as well as welfare. This approach may require some fundamental rethinking of the way in which we care for animals in science; striving to control variation through uniform barren cage environments may, in fact, produce flawed models. Some of the concerns that arise from the use of GM animals could also be addressed by particular interpretations of Refinement. Refinement can be made difficult by the unpredictable nature of side effects in GM animals and the difficulty of refining potentially untreatable disease symptoms in disease models. For these animals, there is a risk of significant suffering, and monitoring and assessing welfare are especially important (Mepham et al. 1998; Animal Procedures Committee 2001). For disease models, proceedings from a European Centre for the Validation of Alternative Methods Workshop (Mepham et al. 1998) suggest that researchers should "model the earliest stage of the disease which is required to produce effective therapies, without necessarily producing a model which exhibits all symptoms of the disease." A different solution would be to share data about the welfare impacts of different gene modifications (Mepham et al. 1998), including failed attempts at modification, so that this work is not duplicated. The challenges to the Three Rs, discussed above, highlight the limitations of the utilitarian foundation on which the Three Rs are based. Although the utilitarian ethics of the Three Rs cover many of the moral concerns that arise, in some cases we may need to supplement utilitarian approaches with other ethical principles, to reflect the scope of society's moral concern about animals. In the case of Great Apes, bans or limits on their use appear to reflect a rightsbased, deontological argument that these species should be awarded special rights because of  21  their cognitive and behavioural complexity. In the case of companion animals, bans or limits reflect a relational ethic that accords special consideration to certain species based on the relation we typically have to those animals. Such principles do exist in legislation and policy, for example in restrictions on the use of cats, dogs, and horses in the UK (Home Office 1986a). Identifying when we have moved beyond a utilitarian framework will help the further development of suitable policy. In addition, as GM and other new types of research develop, Animal Ethics Committees need to discuss concerns about acceptable levels of harm and animal numbers, regardless of benefit. Some of the concerns that fall outside the Three R's framework might be captured by adding a fourth "R" for Responsibility. Responsibility, as proposed by the International Foundation for Ethical Research (IFER 2002), could be elaborated to include responsibility to not violate community standards, responsibility to enhance the quality of life of animals in humane care, and responsibility to reflect real costs in analyses of costs and benefits.  Conclusions The Three Rs have had tremendous impact on how Animal Ethics Committees regulate, make decisions about, and promote the care of animals used in science. Understanding the philosophical underpinnings and historical context of these ethical principles enables us to identify where there has been shifting ground so that we understand their scope and limitations. This paper illustrates some key challenges to the Three Rs and possible solutions. The Three Rs, if broadly conceived, can accommodate some of the new concerns. However, not all ethical issues in animal research lend themselves to the utilitarian thinking that underlies the Three Rs. Even if we added a fourth "R" (Responsibility), as a reminder of other ethical principles that may not be captured by the Three Rs, these principles should continue to be challenged and debated as societal values change. Debate about the Three Rs is important because it allows us to get at more substantive issues of importance to the humane treatment of animals in science and helps point us in new directions. We can expand the Three Rs and our thinking to respond to other views and values, to include a broader ethical evaluation, so that Animal Ethics Committees, while using the Three Rs, also think outside the traditional formulas.  22  References  Animal Procedures Committee 2001 Animal Procedures Committee on Biotechnology, http/www.homeoffice.gov.uk/ Accessed on: June 2, 2003 Balls M, van Zeller A-M and Haider M E 2000 The Three Rs declaration of Bologna. 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Humana Press Inc.: Totowa, USA  26  CHAPTER 3 -  The Interpretation and Application of the Three Rs by Animal Ethics Committee Members  Introduction  The Three Rs - Replacement, Reduction, and Refinement - are widely recognized as fundamental principles for the humane treatment of animals used in research, teaching, and testing. Since their creation in 1959 (Russell and Burch 1959), much discussion has revolved around their meaning and application, and how they can be expanded to respond to new developments in animal research and animal ethics (Smith and Boyd 1991; Flecknell 1994; Balls et al. 1995; UFAW 1998; Festing et al. 1998; Mepham et al. 1998; Smaje et al. 1998). The Three Rs serve as complementary rules of thumb to reduce overall suffering of experimental animals in three distinct ways. Replacement consists of "methods which permit a given purpose to be achieved without conducting experiments or other scientific procedures on animals." Reduction involves "methods for obtaining comparable levels of information from the use of fewer animals in scientific procedures, or for obtaining more information from the same number of animals." Refinement involves "methods which alleviate or minimize potential pain, suffering, and distress and which enhance animal well-being" (Balls et al. 2000). Many countries, such as Canada, Australia, New Zealand, The Netherlands, the United States, and the United Kingdom, have opted for a system whereby each institution that uses animals for research, teaching or testing, establishes a local Animal Ethics Committee (AEC). Although systems differ in terms of their legislative basis, structure and function, one of the most important roles of these committees is to review proposals to use animals for research, testing or teaching before work begins and approve/modify /reject each one on the basis of ethical concerns. One of the primary mandates of these committees is to ensure that the Three Rs are implemented, through either modifications to research proposals, training for researchers and animal care staff, or improvements to animal facilities. Despite the importance of the Three Rs, there has been little analysis into how AEC members understand and apply these concepts in their decisions. As three of the few examples, Hagelin et al. (2003) examined modifications requested by A E C s in Sweden and found that the majority of requests were related to Refinement; Purchase and Nedeva (2001) examined the impact that the Ethical Review Process in the UK has had on attitudes of animal users to the 27  Three Rs; and through a survey and interviews in the US, Graham (2002) found that members from three committees within one institution felt that the Three Rs should be more diligently applied for proposals that incurred more than slight pain. Other empirical studies have examined decision-making by AECs (Dresser 1989; Pious and Herzog 2001), or university students acting as hypothetical members (Galvin and Herzog 1992), or animal users (Stafleu et al. 1989; Stafleu et al. 1993), without particular emphasis on the Three Rs. Several theoretical frameworks have been proposed for evaluating the acceptability of animal experiments (Smith and Boyd 1991; Porter 1992; Theune and de Cock Buning 1993; Stafleu et al. 1999; Delpire et al. 1999). Overall, there has been little empirical study to examine the role that Three Rs play in actual AEC decisions. In the present study, in-depth, open-ended interviews with AEC members from four universities were analyzed to understand how members interpret and apply the Three Rs in making decisions about proposed research. The study addressed the following questions: were AEC members interpreting the Three Rs appropriately and consistently, were members focusing on a particular "R" more than others, are the Three Rs functioning as an effective mnemonic tool in the review of proposals, and what implications does this have for the humane treatment of research animals? The study also identified conflicts, beliefs, and impediments that stood in the way of fuller implementation of the Three Rs.  Methods This study was part of a larger investigation into the functioning and effectiveness of AECs (known as Animal Care Committees (ACCs) in Canada). A two-year ethnographic study was conducted from September 2000 until August 2002 at University A where I served as an ACC member. In the style of cultural anthropology data collection included both participant observation and semi-structured interviews (Bernard 1995). This study received ethical approval from the Behavioural Research Ethics Board at University A in February 2000. Pseudonyms for participants were used infieldnotes and interviews to ensure confidentiality, and informed consent was obtained from all participants. Purposive sampling of committees and interview participants was used. So that my sample did not reflect only one university ACC culture, I interviewed members from four 28  university committees in western Canada. A goal was to learn about a range of experiences; therefore, committees were chosen to represent variation in the type of research reviewed (Table 3.1), and variation in workload. Statistics about the number of protocols each committee 3  reviewed per year and per meeting were obtained from each ACC manager. All committees reviewed protocols for biomedical research and for teaching; some also included wildlife, agricultural and veterinary research (Table 3.1). Committees were also chosen based on geographical proximity. Committees varied in size (9-17 members), and in the number and types of protocols reviewed per year (averaging 13-311; Table 3.1). All committees reviewed protocols from Categories of Invasiveness A to D (scale of animal pain and suffering ranging from the lowest category A to the highest category E; Canadian Council on Animal Care (CCAC), 1993). Three universities had reviewed more than one protocol from Category of Invasiveness E during the study. The majority of protocols had been peer reviewed by granting agencies before submission to the ACC. There was no external peer review of proposed teaching protocols using animals. In two institutions, the veterinarian reviewed the protocols before submission and members were encouraged to contact researchers prior to the ACC meeting if they had any questions about their submitted protocol.  Committees reviewed proposals for research, teaching, and testing. The term, "protocol" is used to include all types. 3  29  Table 3.1  The size of Animal Care Committees from four universities in western Canada, and the number and types of protocols reviewed per meeting and per year during years 1999-2001.  University Feature  A  B  C  D  Number of members in 2002  16  9  17  13  Number of meetings / year  12  12  10  11  Protocols reviewed / year (range)  239-267  7-19  173-203  309-313  Protocols reviewed / meeting (range)  6-34  0-4  10-32  15-49  Biomedical  yes  yes  yes  yes  Wildlife  yes  yes  no  yes  Agriculture and Veterinary  yes  yes  no  yes  Subject areas covered:  I interviewed 28 ACC members: six community representatives, 13 university scientists experienced in animal research, four university animal care technicians, three university veterinarians, and two university non-animal-users (Table 3.2). Recruitment of participants was done through initial contact with the Director of Animal Care from each university. The Director then approached potential participants at an ACC meeting with a letter of invitation from me, and volunteers contacted me directly via email or telephone. At university D, the Director forwarded email addresses of interested participants to me and I contacted them directly. The knowledge by the Director at University D of who might participate may have placed pressure on the participants to either volunteer or not volunteer depending on whether the Director supported the research or not. It may have also placed pressure on participants to report views that were not critical of the Director or the institution. The sample included most committee members (13) from university A and at least one of each type of member at the remaining universities, although only two committees included non-  30  animal-users and only three included an animal technician as voting members. I interviewed most members from University A where I was a participant observer so that I could take advantage of the relationships and trust I had developed with them. A strength of this research design is that these members acted as "key informants" to help shape the direction of the research. In addition, my experience as a participant observer helped to create a more open atmosphere during interviews because interview participants felt that I could be trusted to present their views accurately. Community members, veterinarians, non-animal-users and animal technicians were under-represented in the sample of participants. This is because these members are usually minority members of ACCs. In order to increase my sample I would have had to conduct interviews with members from other universities further away which was not feasible. The limitations of my small sample size meant that I may not have been able to capture the patterned similarities and differences in the expressed views of different types of members. However, I used comparisons with studies in the literature to look for similarities and differences to help build on the results of this research and increase external validity (Morse and Field 1995). As a participant observer, I served as student representative on the ACC at University A. From September 2000 until April 2003 I attended 26 meetings, reviewed and evaluated 587 protocols, and attended 26 animal facility inspections. Observations of meetings and informal discussions with committee members were recorded in field notes. After 13 ACC meetings an interview schedule was designed guided by my experiences as a member and by my understanding of the issues, concerns, values, experiences as expressed by ACC members.  31  Table 3.2  Code Name  Gender Role  Ben  Male  Animal Technician  Betty  Female  Animal Technician  Sam  Male  Animal Technician  Sophia  Female  Animal Technician  Carmen  Female  Community Representative  Cassandra  Female  Community Representative  Craig  Male  Community Representative  Mary  Female  Community Representative  Rachel  Female  Community Representative  Scott  Male  Community Representative  Angela  Female  Non-Animal-User  Peter  Male  Non-Animal-User  Al  Male  Scientist  Alex  Male  Scientist  Andy  Male  Scientist  Bob  Male  Scientist  George  Male  Scientist  Ken  Male  Scientist  Male  Scientist  Male  Scientist  Male  Scientist  Philip  Male  Scientist  Sue  Female  Scientist  Teresa  Female  Scientist  William  Male  Scientist  Alfred  Male  Veterinarian  Ingrid  Female  Veterinarian  Rose  Female  Veterinarian  4  Mark Nik  4  Oliver  1  2  3  4  5  Pseudonym, gender and role of 28 study participants serving on Animal Care Committees from four universities in western Canada  4  1  2  3  5  Institutional member experienced in animal research Non-institutional or non-affiliated member Member from within the institution who does not work with animals Members were also current or past chairperson of the Animal Care Committee Institutional researcher experienced in animal care and use 32  Interviews were semi-structured and lasted on average 1.3 hours (range 1-2.25). Interviews were conducted in locations chosen by participants. Thus interviews took place in an office or meeting room at the workplace of participants. Two took place in meetings rooms that I had arranged on the participant's behalf. Interviews were tape recorded and transcribed verbatim. I transcribed 15 interviews and three people transcribed the remaining ones. Of the interviews I did not transcribe, I read through transcripts and listened to the tapes. In order to document institutional variations in the process of ACC decision making, at each university I was an observer at one committee meeting while on location for one-on-one interviews. Questions were formulated (and modified during the study) based on my experience as a participant observer and on preliminary analysis of transcripts (see Interview Schedule Appendix I). They were open-ended and posed in a way which allowed members time to reflect and elaborate on points they considered important. Interviews began with background questions about how long the participant had been an ACC member, how they became a member, and questions about meeting structure and preparation time. The members were then invited to talk more specifically about their approach to reviewing and evaluating protocols, what modifications they would request, what protocols they found challenging, and so on. At some point, those who had not touched on the Three Rs spontaneously were invited to talk about their understanding and use of the Three Rs. Other questions (not reported in this chapter) included personal attitudes and ethics regarding animal research, inter-personal dynamics at meetings, and ideas for improving the governance system. Given that the interviews were semi-structured and participant-driven, not all participants were asked exactly the same questions.  Description of Research Process and Data Analysis The goal of analysis of data was to identify themes on the basis of their salience for understanding the values, behaviours, issues, and responsibilities experienced and expressed by ACC members. In data analysis, I paid attention to commonality as well as outliers among comments to ensure a broad understanding of the issues. Although analysis focused on individual participants, attention was also paid to the influence that institutional culture might have had on committees, to the influence that the collective views of members had on ACC culture, and to the patterned similarities and differences in the expressed views of individual types of committee  33  members. Initial themes arose from participant observation which became incorporated into questions in the interview schedule. For example, it became apparent that the role of the ACC in evaluating scientific merit was a contentious issue among committee members and needed further investigation. While conducting interviews, I observed themes which frequently reoccurred and thus over time interview questions changed to reflect this. For example, members talked about the role of the chairperson to ACC functioning, and thus this became a theme for future questioning. Transcript data was broken down analytically and interpreted in an orderly fashion using a system of coding (Morse and Field 1995; Strauss and Corbin 1998; Charmaz 2002). The analysis and development of themes was based on building from the data up to identify concepts that fit the data. Initial codes were often descriptive with little interpretation (e.g. definition of "Replacement"). Over time, as my comprehension of the data grew, I was able to understand and explain the variation in the data and see relationships between codes. Thus, codes became more complex, were grouped with other codes and so on. During all stages of coding, memos were written about possible interpretations of data, relationships between codes, and emerging themes. These memos were constantly revisited and revised as I developed better understanding. For example, repeated occurrences of participant phrases like "red flags" lead me to develop a the theme labeled "cues". I described this theme as cues which triggered the attention and scrutiny of members and increased the likelihood of a negative recommendation for a protocol. Properties of this theme included species of animal, trust in the investigator, quality of completed application form, and discrepancy with policy. Some of these properties were labeled as initial codes and were linked together under the theme "cues" at a later stage of analysis. This analysis lead me to understand an important aspect of decision-making processes of ACC members. At the final stages of analysis, I compared my findings to published works in order to place my results "in the context of established knowledge and clearly identify those results that support the literature or that claim new contributions" (Morse and Field 1995, pl30). For this chapter, analysis focused on the interpretations and application of the Three Rs by individual participants. Analysis included searching for the terms and also for evidence that the concepts of the Three Rs were used, even if members were not using the terms.  34  Results The Three Rs were mentioned by only two members, Rose and Scott, in describing how they review protocols. Although the terms were not mentioned by other members, aspects of the Three Rs were mentioned. A l l members were familiar with the terms when prompted, with one exception (an institutional non-animal-user). Reduction and Replacement were most commonly mentioned when members spoke about the Three Rs. In particular, the majority of members mentioned the need for protocols to justify the number of animals to be used. When I asked members (27) whether the Three Rs were useful or meaningful to them, responses varied widely. Some members considered that the Three Rs were not meaningful, but the majority related that the Three Rs were an important component of the review process. For example, a veterinarian (Rose) cited the Three Rs as "my gospel." Rose also taught a course on the Three Rs for animal-users. For an animal technician (Sam) the Three Rs "are a really big thing." One non-animal-user (Peter) captured the perspective held by most of the other members on his committee saying the Three Rs are "quite central in fact." A scientist (Ken) felt that in the "last few years, yes we have been using these Three R's quite a bit." Another scientist (William) believed in the importance of the Three Rs but felt that his committee was not necessarily applying them: So those principles are in my mind all the time when I'm reviewing. How rigorously they're applied, that's kind of another question. I think we perhaps tend to let them slide a little bit sometimes. We do not really pressure researchers to refine their techniques. Or we don't overly pressure them to reduce the number of animals they use. We're fairly lenient in approving the numbers that are asked for, provided they're not outrageous. Two community members similarly felt that they or their committee should apply the Three Rs more often". Mary felt that she did not focus on them enough but her committee did: "They are there; I probably don't pay as much attention to them as I should." Similarly, Carmen did not use them in her own review of protocols and felt her committee used them, "every so often ... but, it is not being used as much as it could, I think." Comments from members of one committee indicated that one community member  35  (Scott) played a major role in making the Three Rs a key focus of protocol review, by constantly bringing them up in meetings and by acting as a cue in the memory of members, even when he was not present at meetings. For several members, the Three Rs were not consciously in their minds while reviewing protocols, although they were using the concepts. A community member (Cassandra) found the Three Rs intuitive: I don't, when I get a protocol, go "Okay, here are the Three Rs," and I keep this in mind when I go along. Again, I think it's a little bit intuitive,... But no, I don't strictly follow it. It's just kind of a background to the overall picture. Two animal technicians felt that the Three Rs were second nature because they were applying them in their work every day. Sophia said that Reduction and Refinement were always in her mind: "When I look at the protocols I don't really think about that because those are the things I am trying to do all the time anyway." Similarly Ben said that, "You're always looking at that [Three Rs]. Even though I'm probably not even thinking of it, I'm doing it everyday without even thinking of it. It just comes second nature." . At the other end of the spectrum, three scientist members responded that they did not find the Three Rs meaningful. One (Alex) assumed it was not his role to apply the Three Rs because the researchers had already applied Reduction and Replacement. Another (Sue) found them "insulting" because she felt that scientists would not use animals if they did not have to. Finally, Philip felt that for most wildlife research the animals could not be replaced, therefore the Three Rs "aren't really that meaningful." In the following three sections, I examine the Three Rs separately, including how members interpreted them, how important they considered them to be to their decision-making, and whether and how they applied the concept.  Replacement  Committee members clearly understood Replacement, including (in the terminology of Russell and Burch, 1959), both Relative Replacement (animals are used but distress is thought to be eliminated, as in non-recovery experiments on anaesthetized animals or in the use of in vitro methods to replace procedures such as monoclonal antibody production) and Absolute 36  Replaeement (no use of animal material). One scientist (Mark) echoing Russell and Burch, argued that the use of in vitro models is a good preliminary step: I think we're doing a lot of tissue culture now because it allows us to discover and to find pathways so that we can then test in vivo, where if we start with animal experiments right off the bat, you're essentially going in blind. So I think, in using non-animal models for understanding pathways and stuff, I think you're in a position to design more directed animal experiments. And to me that's just good science; it's not just good economics. Six members expressed strong views about finding Replacements (such as computer models) for teaching, as opposed to research. A scientist (Sue) felt that Replacement was applicable to teaching to avoid "consuming our way through hundreds of rats unnecessarily to demonstrate the presence of a blood vessel somewhere." One community member (Rachel) said that in addition to watching out for Replacements for monoclonal antibody production, "The other time I look at the Replacement part is the teaching protocols because I do think videos would be just as good, if not better." Another community member (Craig) also questioned the use of animals for some teaching exercises: I wonder about computer simulations for ... teaching. When it's a teaching thing for getting these kids to handle animals then you think, okay, you've got to do that. But when they just want to explore different parts of the anatomy and stuff, there ought to be some sort of a video interactive kind-of-thing where you've got a whole bunch of different choices and you can blow it or you can do the right thing. There ought to be some sort of Replacement video. Although Replacement was well understood by members, comments indicated that its wider use may be impeded because members saw Replacement as not suitable for most research, and because they had confidence in researchers to implement Replacement themselves. 1. Replacement not seen as Scientifically Suitable The majority of members shared the view that Replacement is not a suitable option for  37  most research. As one scientist (Teresa) reported: "I very strongly believe that what you see in the petri dish may not be what's happening in the whole organism in vivo." Another scientist (Philip) felt that, "Certainly in terms of Replacing, it doesn't work 9 times out of 10." A third (William) recounted: Generally we cannot tell how this procedure will work without testing it on the incredibly complex living system. And it's hard to argue against that. Something as simple as a drug's effect on a tumour: you can do as many in vitro experiments as you want but until you inject that drug into an animal and you know its progress through the liver, circulation, excretion, you can't tell what it's going to do in a living system. 2. Confidence in Researchers to Implement Replacement The majority of members felt confident that researchers would be knowledgeable about suitable Replacements, more so than A C C members. When asked whether the use of replacements is driven by researchers, one scientist (William) answered, Yes, investigator-driven is probably where most of the Replacements come from, as opposed to our making recommendations. Plus, as a committee, we probably wouldn't be aware of Replacement options in a lot of cases. The researcher would likely be more familiar with that than we would. As William noted, it may be difficult for A C C members to know the current literature on Replacements. One scientist (Nik) felt that the veterinarian member was most familiar with Replacement options and the question on the protocol application form was acting as a reminder to researchers to consider Replacement. The role of the A C C as a reminder to researchers was also raised by a veterinarian (Rose): So, realistically we know there are limitations to most of the Replacements, so it is up to us to recognize what they are and to just make sure that we make the investigator aware that they should be paying attention to them. One scientist (Sue) felt that Replacement might be "redundant." She felt very strongly about the expertise and will of researchers to find Replacements and believed that people's  38  perceptions of researchers was mistaken: "There seems to be an assumption there that people are off using animals willy nilly when they could be using cell culture. How often have we seen that happen? I have never seen that happen." She noted that with animals, There are all sorts of burdens in maintaining animals that you don't necessarily have if you can buy up a cell culture and run it for a while and shut down when you are done and bring in some more later, and so on and so on. So if you could do something in cell culture, I think that most people would do it in cell culture. Although one community member (Rachel) had confidence in researchers to apply Replacement, she also pointed out that when policy is clear on identifying Replacement options, such as the use of in vitro monoclonal antibody production, she was better able to target protocols that could use this Replacement option.  Reduction Reduction was considered an important part of reviewing protocols by the majority of members, and most members used a fairly accurate and uniform interpretation of the term. They expected researchers to propose the minimum number of animals needed to achieve the goal of the study, along with justification of those numbers. Many members also emphasized that they were equally concerned about animals being "wasted" if researchers did not use enough animals to achieve their scientific goals. A few members had quite a sophisticated understanding of Reduction. For example a veterinarian (Rose) discussed the importance of understanding the goals of the study, the research approach, experimental design, sharing data, and the use of pilot studies: We don't just question them [numbers of animals] because they are high; we may understand why they are high. There may be large numbers but they may be well justified and explained and statistically relevant, but we also equally question the numbers that are really small. If we don't think you are going to get the answer to your question with this tiny number, then that is not necessarily a wise use of animals... Reduction is also in the experimental design: if you can use the same animal as the control,... if there are ways to use data that is already out there so  39  that you can use less, if there are ways to do a pilot study and maybe that is all you would use rather just jumping in gung-ho and asking for 200 animals. So we have a lot of strategies for reduction as well, but it is all based on statistics and an understanding of where the model is going to go. In addition, she and a few others discussed the importance of the ACC or some other establishment coordinating needs of researchers to reduce animal numbers by sharing research materials such as tissues, organs, blood or surplus breeding animals. It was also apparent that more centralized institutions, where animal facilities were together and under institutional supervision by veterinarians and animal technicians had been able to coordinate sharing efforts better than individual animal facilities located in different buildings supervised by animal technicians employed by individual researchers. In general, comments about justification of numbers tended to focus on sample sizes rather than experimental design and statistical analysis. Members seemed satisfied with either a statistical justification, such as poweranalysis, or testimony by the researcher of their familiarity with the level of variation and required sample sizes. Two members pointed out that the number of animals is "tricky" to evaluate because it requires a good understanding of experimental design, and only one member indicated that they evaluated design for the purpose of reducing numbers. At two universities, the protocol application forms had specific questions related to experimental design and statistical analysis, whereas the others had a general question asking for justification of numbers. Members recognized some forms of inappropriate justification of numbers. For example, in describing sections of the protocol application form that were often filled out poorly, a community member (Cassandra) recounted that numbers were not justified appropriately: I don't like the answers that say ... "Well, I need 10 animals for statistical significance and I can only get four experiments done in one month and there are 12 months per year, so therefore I need 10 x 4 x 12." I hate those kind. This shouldn't be driven by how many experiments you can do in one year. I want to see ... "How many do you need to get the evidence that you need to support your theory?'"  40  An animal technician (Betty) expressed a similar concern: "What I see a lot of the time is justification based on how many animals we can do per week. And that to me is not really a justification of animals." Although Reduction was generally considered important in the protocol review process, comments suggest that the implementation of Reduction by ACCs may vary as a result of the following four factors.  1. Lack of Expertise of Members Some members, especially community members and animal technicians, felt that they lacked the expertise to critically evaluate numbers of animals and therefore relied on the scientific animal-user members. One community member (Rachel) noted that among other things on the protocol form, she did not understand, Justification about numbers -1 don't think I will ever have a complete understanding of that -1 mean anybody can multiply it out and figure out if they can add correctly, but are those numbers statistically justified? I mean I don't know because I'm not an animal researcher. An animal technician (Sophia) agreed. "I don't really know enough about statistical analysis to pass any judgement. I have to rely on the other people in the group to do that." However, Reduction may end up being overlooked by scientists who may also feel unqualified to judge numbers because the study may not be in their field. Sue felt that too many details about numbers were unnecessary because she was not qualified to judge the scientific design of the experiment: I understand what they [researchers] are trying to do is justify their numbers, but you get drawn into the core of their research science hypothesis-testing which is completely outside of most of ourfields,and so youfindyourself wading through and you end up counting up numbers to see if those add up ... . That level of detail is not helpful. As Sue noted, some members spend a lot of time adding numbers, making sure the proposed sample sizes add up to the total number of animals needed, without necessarily achieving 41  Reduction. As a result, some scientist members preferred flexibility in the system, such as providing the A C C with "ball-park" numbers and requesting more animals later if necessary.  2. Confidence in Researchers or Granting Agencies to Apply Reduction In general, scientist members were less concerned than other members about applying Reduction. As with Replacement, half of the scientist members felt that Reduction is not the role of the A C C because they believed that researchers themselves are the most qualified to select animal numbers or that granting agencies had already reviewed numbers. Three scientists felt that it was rare that the committee requested a reduction in numbers because researchers generally requested justified amounts. Bob said, "Occasionally we run across a protocol where the numbers are too small, and you have to go back and say, 'Look, you're wasting animals. Get the numbers to a ... level that is necessary,' but that is very rare. Most people ask for what is needed." Alex felt that researchers could be trusted to apply both Reduction and Replacement largely because animal research is expensive: I am assuming that the person who is doing the work has already determined that they need to use animals for that work. They are not trying to use an excessive number of animals. They are probably trying to use a reasonable number or minimum necessary to get the results because animal work, apart from the ethics, animal work is expensive and nobody wants to spend money. Research money is hard to come by. I think people do tend to use the minimum numbers of animals that they need to for their research ... . So I think the investigator is already applying the principles of Reduction and Replacement as much as they can. Other members agreed that economics has a positive influence on Reduction. One scientist (Mark) suggested that economics plays a role in implementing all the Three Rs: On the one hand it's [Three Rs] an animal welfare issue, and on the other hand it's an economic issue. It's just plain expensive to do animal research... . When designing experiments on a limited budget you're forced to incorporate the Three Rs into your research just to limit your animal costs. Some members disagreed, claiming that economics alone and trusting researchers would not  42  limit numbers effectively, and that numbers would increase if the ACC was not reviewing animal use. One animal technician (Sam) said that attitudes towards Reduction have changed: I think that people [investigators] have become a lot more sensitive, [but] not everyone. I think if we removed the committee, there will be investigators who will be back to 150 to 400 [per protocol]. Differing opinions were raised about the role of peer review by granting agencies in implementing Reduction. Members generally accepted approval by peer review as an assurance of scientific merit. Three scientists claimed that if a protocol was funded by an external peerreview granting agency, then experts had already reviewed it for scientific merit and Reduction. For Ken that meant that the ACC had no authority to require modifications to the protocol. In contrast, another scientist (Andy) who also sits on grant peer-review panels said that, "The peerreview committee is probably counting on local groups, the Animal Care Committee, to look at the numbers." Another scientist (Sue) also pointed out the influence that grant allocations can have on Reduction: Has the Animal Care Committee talked to the CIHR [Canadian Institute for Health Research] lately about all of the bizillions of people they are funding to make transgenic mice? At least at one level there is no sign of reducing the use of rodents. The people being rewarded handsomely in this country are the people who are making transgenic animals.... So I just sort of see the Reduction thing as kind of unrealistic, I guess.  3. Concern for Harm Versus Numbers Members disagreed about the relative importance of Reduction versus Refinement. About half of the members appeared to be more concerned about "what is actually going to happen to the animal" (Oliver) than the numbers per se. While describing the difficulties in evaluating numbers, a scientist (Andy) remarked: For me the numbers are almost beside the point. We do spend a lot of time on it. You want to make sure that it's not a ridiculous number, but I think more  43  emphasis should be placed on the protocol. So if I'm doing the protocol properly, it doesn't matter whether I use 10 animals or 500 animals. For some members, reducing numbers was of interest only if it contributed to reducing harm. For example an animal technician (Sam) commented, I'm not terribly interested in statistics. If there was a lot of surgery going on, if it was going to be incredibly painful with long-term recovery, I would like really small numbers. Similarly, a scientist (Sue) linked the need for Reduction to the Category of Invasiveness: Large numbers of animals used in procedures that are really stressful for animals, yeah, then I do look at the numbers and say, "Well couldn't you do this with three instead of 30?" But when we get down to the B level protocols, then no I don't think about numbers. Then it's, "What numbers do you need to properly do the work?" Sue also expressed a common view that if harmful procedures are not used - for example, if an animal is used only for breeding - then numbers are not a concern: I don't have a problem with numbers per se ... . You can get into very large numbers of animals to get a segregant that you need. On the other hand, the animals themselves have nice lives. The ones that you don't need are not suffering in any way; they are usually normal. As a different viewpoint, several members suggested that some harmful procedures are not justifiable, regardless of numbers of animals used. For a community member (Rachel) any exposure to harm was unacceptable: It doesn't matter if they're doing it to 1 or 50, if it's going to be causing a problem for the mice, they shouldn't be doing it to any. If they can justify that they [mice] actually cope quite well with that, and it's going to give them some information as part of the outcome of the experiment, then it doesn't matter to me, the numbers.  44  A repercussion o f weighing harm more heavily than numbers was illustrated by a veterinarian (Rose), who suggested that for some invasive studies, reducing harm means euthanising unwell animals before the completion o f the study; this is desirable, but may end up increasing numbers to achieve the scientific goals o f the study. In contrast, for three members, reducing numbers is relevant regardless o f harm, a view that was motivated by a belief in the sanctity o f life. A community member (Scott) who played a strong role i n upholding the Three R s on his committee, described a conversation he had with a fish biologist: People ask me how I measure success o f what I do here and I say, not very often, not very well. But I do quote one teaching protocol, where he [researcher] was using 12 fish for a particular area o f education. A n d after we talked to h i m , he reduced it to 1. A n d this particular person said to me, " Y o u mean that saving the lives o f 11 fish is important to you?" A n d I said, " O f course it is."... Y o u have to start somewhere and you have to keep moving. A n d 11 fish was highly significant to me. In protocols with large numbers, such as for drug development or transgenic production, there was a concern that individual animals become less valued. One animal technician (Sam) described his concern about attitudes o f researchers: Sometimes when you've got large numbers, the odd six mice don't really matter. A n d the whole point o f this is, that when you do have a protocol, they all matter .... They become a bit like fodder when you're dealing with big, big numbers. In addition, four members felt that for large numbers there is often more ambiguity about what is going to happen to each animal and therefore a committee w i l l recommend a smaller number to begin with.  4. Leniency for Productive Researchers One scientist (William) recounted that familiarity with a researcher and their scientific productivity may influence the type o f modifications an A C C may request. Although he felt that  45  members of his ACC, "always try and look very critically at the number of animals requested," he noted that he would be more lenient in requesting changes in numbers for a known researcher who was productive and whose research was beneficial. They could very likely determine which drugs are going to be most effective with a smaller number of animals, and then, if that proves to be useful, they could then expand that into the full investigation. I did not make that recommendation to the researcher .... As a committee, we could pressure that researcher to change his techniques. But you know, he's very productive, the work is very significant, it's a standard protocol.... Is it worth pressuring him to change a very significant part of his research protocol? Maybe yes, maybe no. In summary, although the concept of Reduction was reasonably well understood, there was evidence of variation in how effectively it is applied because of (1) an apparent lack of evaluation of experimental design, (2) differing views on whether researchers, granting agencies or the ACC should evaluate numbers of animals, (3) concern for harm versus Reduction, (4) lack of agreement on whether Reduction should be applied to less invasive studies, and (5) lack of agreement on how strict the ACC should be in enforcing Reduction.  Refinement Refinement appeared to be the least well understood of the Three Rs. Of the 23 members who were asked about the meaning of Refinement, 7 responded that they did not know and a similar number used a somewhat unconventional interpretation or had some misunderstanding of the term. Nonetheless, all members, including those who did not understand the term, used elements of Refinement in their review of protocols. As a animal technician member who had a reasonable understanding of Refinement, Sam talked about its importance when reviewing protocols: "I mean I bring that [Refinement] to bear on ... the choice of animal, the procedure, how long it is going to go on, and the endpoints." Sam also believed that providing environmental enrichment is a component of Refinement. For a veterinarian (Rose), The animal should start out comfortable and stay as comfortable as it can  46  throughout the whole procedure, no matter what you are doing to it. So if there is a better way to handle it, if there is a better way to anaesthetize it, a better way to inject it, there is a better way to get your sample, then you have a responsibility to do that out of respect for that animal. For Rose, Refinement is important "because that is where the well-being comes in. That is where the welfare issues come in. That is where you can make a difference." However, the meaning of Refinement was often misconstrued. When a scientist (Nik) described his understanding of Refinement, he confused it with Replacement: "Well, that gets us back into whether we use animals or don't use animals, I suppose to some degree." A n animal technician (Ben) seemed to suggest that Refinement is related to improving techniques to make the job easier for researchers: "Refinement is, if I can in a sense refine some of the techniques that you're using, if I can change it a bit to make it a bit more comfortable to the researchers I'll suggest that to the researchers." Five members described Refinement with a less common interpretation, as a way to "refine" technique in order to reduce numbers of animals needed. A scientist (Al) suggested as examples: "There may be new tools developed to better evaluate certain animals so you don't need as many animals. The evaluation technique is more refined, so you would minimize the variation in the data set, you would need a smaller number of animals." Using different terminology, all members recounted that minimizing harm caused to 4  animals was an important function of the committee. For example, a scientist (Oliver) described Refinement as "minimizing suffering". A non-animal-user (Peter) felt that researchers were "active co-conspirators [with the ACC] in this effort to try to decrease the overall suffering of animals." A scientist (Sue) said, "I don't mind animals being killed; I don't have a problem with that, but I do mind them suffering unnecessarily." A community member (Mary) pointed out that animals should be "treated with the least amount of distress." A veterinarian (Alfred) was concerned about alleviating "pain and discomfort." A scientist (William) tried to assure himself that the research is "being done without undue discomfort to the animals." Several members expressed their concerns in terms of proper treatment of animals. A scientist (Ken) felt that the A C C should ensure that "the animals are treated carefully, humanely and whatever is possible  For simplicity, the term "harm" will be used to include stress, distress, discomfort, suffering, and pain.  3  47  with the scientific merit in mind." One scientist (Al) along with two other members indicated that they were not willing to approve protocols with any suffering: "If the animals are suffering, even one or two animals is too much, too many." Similarly, one community member (Carmen) felt the role of the committee was, "to ensure that research that goes on at the university ... is meritorious and that no animals are suffering because of it." Several community members and animal technicians related their concerns in less typical terms. To address her concerns about harm, one community member (Cassandra) asks committee members, "Well, doesn't that hurt?" Another (Craig) used cruelty as a criterion: I find out how they're going to euthanise, what kind of surgery procedures, and how they're going to anaesthetize the animal, and whether that sounds cruel. Three members talked about enhancing the quality of life of research animals, including positive states such as pleasure. An animal technician (Ben) recounted that in his job he wanted to make life pleasant for animals. I probably go overboard more on the research animals here, to make sure if there's any discomfort or anything like that, there are ways to alleviate it; that's kind of my whole ethics of the animals. I don't like to see them suffer and I want to make sure that the time that they have here is as pleasant as possible. A community member (Mary) added that animals should have "the best quality of life." A scientist (Sue) expressed similar concerns over debilitating side-effects in transgenic and inbred strains of mice: "What point do you decide that is causing their quality of life to diminish?" Many examples of Refinement were mentioned which could be grouped under the following six headings.  1. Mitigation of Pain Most members emphasized reducing pain resulting from procedures. For a scientist (Alex), "I think maybe pain for the animals is probably the one thing that I look for most, to see if there is any pain involved, any unnecessary pain." A veterinarian (Ingrid) focussed more on pain relief and the importance of monitoring: 48  I think if you see any procedure where it results in an animal's demonstrating symptoms of pain for that species, it is unacceptable .... There should medications given appropriately, for long enough ... and because a lot of studies are novel... monitoring, frequent monitoring is really important - by people who really know what they're looking for ... you have to do whatever you can to basically keep them pain-free at all times. Many members recounted deferring protocols based on concerns over inadequate pain mitigation. One non-animal-user (Angela) recalled deferring protocols if the researcher did not demonstrate that they were "serious enough on drug administration or pain control." A veterinarian (Alfred) suggested, "One thing we would send them back for is if they said, 'Okay, we're going to compress the carotid arteries,' and they don't have any description of surgery and anaesthetic and post-operative pain care." In conversations about protocols that members found challenging to review, a community member (Cassandra) spoke of procedures where there was untreated pain: "It must hurt so much. I guess just any procedure where I perceive there is pain to the animal and it is not taken care of by an analgesic, those always bother me." Another community member (Rachel) expressed similar concerns about, "anything that causes pain. So there's been some spinal cord studies, chronic pain studies. Those ones have been a bit difficult." A scientist (Oliver) believed that his entire committee felt the same as he did, "So I think the main things that concern me - and are probably the same ones that concern the committee - the things that really cause pain in animals that can't be avoided." In describing their understanding of pain, members reflected two perspectives: an anthropomorphic or human analogy perspective, and a physiological perspective that did not necessarily involve suffering. These perspectives resulted in differing judgements about the necessity or degree of pain mitigation. Those who were more anthropomorphic usually gave the animals the benefit of the doubt, assuming that if a human would feel pain, then so would the animal and therefore the pain should be mitigated. When an animal technician (Sophia) reviews protocols she tries "putting yourself in the position of the animal." A veterinarian (Ingrid) imagined how people would feel: "You're sort of making a translation from how people are. You see what people go through, and even with the best drugs that exist you still might not be able to maintain the pain-free status." A community member (Mary) struggled with how to describe her  49  perspective. "I mean sometimes it can bother me when I'm looking at mice ... I wouldn't particularly like to see a human being suffering or injured." In contrast, two scientists were more guarded in attributing states of suffering to animals. George spoke at length about whether animals experience pain and suffering, and the importance of not making anthropomorphic assumptions. It's terribly arrogant of me to know what the rat's feeling because I don't know ... just how much pain and suffering (what we think is pain and suffering) is the animal really going through, and is it necessary? ... Well they certainly feel pain, but pain is a very loaded word. So I mean I've done analgesic tests to see the effects of drugs that prevent what we think to be pain. They are pretty good, they're pretty predictive. [But] it leads us into the danger of assuming what the animal feels... George linked this skepticism to an ethical question about the moral significance of pain in the laboratory: And I've seen rats and small animals in the wild and some of them get into terrible states and then they get chopped by some carnivore very quickly terminated .... And if it [the research] really is necessary because there's no other way to answer the problem, then I tend to go with it, because real life out there for animals is very nasty. Philip expressed a similar view: I don't know what it [suffering] means and if someone tries to convince me that my animals are suffering and if they are equating that with the suffering we see in Africa in a famine situation, I just, I have difficulty with that whole concept... I kind of think that there is so much suffering - human suffering - in the world, that to try and even equate some of the animal's suffering, at least what I inflict on animals, is just such nonsense that it's absurd. For Philip (a wildlife researcher), breeding success is a better indicator of whether a procedure causes suffering. 50  But I know from experience that you can take more blood than we are currently allowed to take, and from a breeding bird, and it doesn't have any effect on breeding success or egg composition or anything, and it certainly doesn't kill the animal. And so I kind of fall into this school where if I've done that validation, and I go out and take 20% from an animal, then there is nothing really wrong with me doing that because the most valuable endpoint is: does it survive? Breeding is a good example. The first thing animals do when they start to suffer is they stop breeding.  2. Humane Endpoints Humane endpoints were commonly cited as an example of Refinement. Close to half the members brought up the term itself. A scientist (Nik) used lack of a well-defined endpoint as a reason for deferring a protocol. Concerns may be if... the endpoints are not clearly identified, or if we are concerned what the endpoints may be ... An endpoint can't be an L D  50  [to  determine the dose of toxin which kills 50% of exposed animals], that sort of thing. If there is any indication that they [researchers] are using those kinds of things or if... animal welfare is a major concern with regard to the endpoint of the experiment, those kind of things would result in a deferral. Another scientist (Oliver) noted that, "We [the committee] do spend a lot of time on endpoints in mice and send protocols back a lot with copies of humane endpoints from the CCAC Guide." A third scientist (George) was concerned about setting humane endpoints in disease models and toxicity testing: "Some disease models and ... some of the toxicity things .... Some loads kill animals very quickly, and I think we can reduce that.... You could limit the endpoint." One committee apparently had a lot of debate about whether they should approve L D  50  experiments.  In the end they developed a policy that allows such research only as "a pilot study ... to establish parameters." After that they require setting an endpoint before "death and suffering."  3. Skill and Training  51  Most members mentioned the need for appropriate training or skill of researchers and animal technicians, and many supported a plan (current in Canada at the time) to require training for animal users. A community member (Craig) felt that assurances about expertise would increase his trust that procedures were done well. One question I always have is: "Does this person know how to do what he sets out to do?"... I know that's an issue right now - that they [CCAC] want to train and certify people for it. I think that'll help. That would increase my trust level for these things. A scientist (Ken) begins his review of protocols by assessing the training of the researcher. Well, first, the first thing is who is the PI [primary investigator], and who's going to work with that person - whether these people all have animal training or not. And we want to make sure that everyone who handles the animals ... have taken the animal care course. So once we are satisfied with that - personnel - then we look at the animals. One community member (Carmen) noted that if the skill of a researcher is in question, then in centralized facilities, the committee can require that trained staff carry out the procedures and monitoring. Alternatively,, pilot studies, were commonly recommended if there was concern about the expertise of the researcher. For example, a veterinarian (Ingrid) suggested: "And sometimes you know if it's a novel technique or approach, suggest a pilot project first and only approve a pilot number of animals before actually approving the body of the study."  4. Environmental Enrichment Environmental enrichment was mentioned by about one quarter of the members although questions about environmental enrichment were present in only one university's protocol application form. In general, non-scientist members tended to more strongly support efforts for improving the living conditions of animals. Several members viewed environmental enrichment as a means to promote natural behaviour or natural living conditions. A scientist (Teresa) suggested that, "if we are really serious about Refinement we should put the animal in a situation which is more natural to them. And I don't think that we can actually do that a lot." For Teresa a 52  natural situation included providing enrichment as well as handling rats during their nocturnal active hours so as not to stress them with noise and light during their inactive period. She commented that the ACC was more focussed on pain mitigation and not really addressing the issue of environmental enrichment. She felt that this was partially related to the difficulties of assessing stress in different species, "But I'm not sure if we have a very good handle on what is distress for an alligator or a monkey or a turtle or a rat." When on a site visit of a facility, a community member (Cassandra) asked about the natural habitat of a bird species and when informed that the birds used grass said, "Why can't we put a wall with fake grass out there so they can simulate that... if they normally have that to hide ... when certain things come up that scare them or stress them or whatever." Another community member (Carmen) included ways to occupy time as a form of environmental enrichment: If you're going to put [a mouse] in a cage where he can't move around - let's just say, he can't move around at all - with a restricted diet and there is absolutely nothing for him to do, I have a problem with that right away.... If they keep the animal as much as possible in his own habitat... then I am okay. A third community member (Mary), in discussing the importance of "enhancing the well-being of animals", said, "If you're looking at that from the animal's perspective, and the natural behaviour is digging and they can dig, well then why not?" A scientist (Philip) suggested perches for birds and social housing for social species. A veterinarian (Ingrid) suggested supplying "igloos" for mice, toys for rabbits and cats, and scratching posts for cats, "to make it as nice for them as possible." Contrasting opinions were presented about the potential confounding effects of stress and/or environmental enrichment on the validity of the data. Some suggested that environmental enrichment has a negative effect on results. For example a scientist (Nik) recounted that, You get... those who say it interferes with the results of the experiments. Enrichment can interfere with the stress levels and hormone levels, like everything else that can influence your results. Nik seemed to imply that if environmental enrichment reduces stress, then this could be bad for results. Veterinarian Ingrid expressed similar concerns:  53  You don't want to be entering a factor into an experiment that could be a confounding factor, and then negate the whole experiment. So for each group of animals that we introduced enrichment with, I... had it in writing from the researcher: this is what we'd like to do for them; is that okay with you? Will it interfere with your work? In contrast, a community member (Scott) was concerned that stress would be bad for data: If you have taken an animal out of its normal context, you've put a lot of stress on that animal. There has been work which I've read, for example, about the multitude of reactions that the rat will go through after the first 30 seconds after being handled. That always brings to my mind the question of how valid is the result of the research when we don't know how that stress is affecting that research. In relation to stress, two members espoused Russell and Burch's view that humane treatment of animals is a prerequisite for good science. One scientist (Mark) expressed this strongly: I think that everyone can actually work efficiently together to ensure that people are doing good science and that they're making humane use of the animals. Because if they're not, what's the point? It's stupid. It's just - if your animals aren't properly treated then your data's basically contaminated. It's corrupt. No point doing the experiment. A veterinarian (Rose) made the argument for refining repeated blood collection techniques using a telemetry device "because it is better science; it is better for the animal." On the other end of the spectrum, a scientist (Teresa) was not convinced that environmental enrichment was achievable or desirable. How to remove stress from an animal? I don't think we can even assess it because distress for you and me may not be stress for another person, and I don't think we should completely remove stress altogether. It's like removing that altogether, we may need some amount of stress, to stimulate you and bring some of these hormones up but we don't know how much. I don't think we are really looking at 54  that on the committee. Overall there seemed to be wide discrepancy about the role of environmental enrichment in reducing stress and its effect on scientific data.  5. Improved Handling of Animals Four members raised concerns about the manner of handling animals. A community member (Carmen) felt that it was important to "respect the animal and you treat and handle him correctly," and a veterinarian (Alfred) always asked for clarification from researchers about whether animals were "handled in a humane manner..." Another veterinarian (Ingrid) described the success of a student "work-study" position that was aimed at making animals more accustomed to handling: So we would have a work-study student just come in and all they would do is sit with the rabbits or play with the cats, play with the rats, play with the mice, and that was it.... I think that definitely helped. You know, the animals were friendlier, seemed happier, were easier to handle which means less stress on them. A scientist (George) believed that appropriate handling reduced stress in animals but that it hard to train animal users. You can make animals feel much more comfortable and that's what we should try to do. I find it very hard to train students, though I show them myself. I'm very allergic to animals, but I pick up rats and I put them on my chest and I blow on their nose, and I can sneak in and give the injections and they don't even know they've had it... . But... that's very hard to do. The reality is, you know, lots of people are scared.  6. Using Species of Lower Sentience Two members mentioned that using a species of lower sentience was important. An animal technician (Betty) suggested that, The more intelligent they are, I think all sorts of things become a lot more difficult  to manage and make sure that they have an environment that's proper for the animals and everything else. So again, the lower ... sentience species that you can use, I think the better. A community member (Scott) described Refinement as, "Don't use an elephant if you can use a mouse."  Discussion Considering the integral and universal role of the Three Rs in policy statements, it is perhaps surprising that the majority of ACC members did not mention the Three Rs when describing their approach to reviewing protocols. This suggests that the Three Rs are not serving as an effective mnemonic tool to remind members to consider Replacement, Reduction and Refinement when reviewing protocols. As some members suggested, however, the Three Rs may be so entrenched in the minds of members, or so intuitive, that members are applying aspects of the Three Rs without consciously using the terms. On the other hand, one member had not even heard of the Three Rs. Also, given that the Three Rs are fairly straightforward principles for protocol review, one would expect more consistency in applying them.  Variation in Application of the Three Rs The application of the Three Rs appeared to be influenced by differences among individuals in expertise, lack of consensus about the responsibilities of ACCs to implement the Three Rs, lack of consensus on minimizing overall harm to all animals versus avoiding excessive harm to specific individuals, different views of animal pain and suffering and their moral significance, and different interpretations of the Three Rs.  Lack of Expertise Some members felt they lacked the expertise or familiarity with a particular field of study to evaluate a protocol, particularly for Replacement and Reduction. Community and animal technician members tended to rely on scientist members. This seems like a reasonable relationship in that non-scientist members are unlikely to have as much expertise as scientist  56  members. Perhaps the role of the non-scientist members is less to implement the Three Rs and more to question and remind the committee to do so. However, some scientists also felt they lacked the necessary expertise, and many members indicated that the researchers themselves were the most qualified, and could be trusted, to apply Replacement and Reduction. Indeed, in many cases researchers may have applied Reduction; for example, advances in the control of genetic variation through the use of inbred strains, specific pathogen-free rodents, and controlled environments has enabled researchers to reduce sample sizes in experiments (Festing 1995). However, the AEC is in a unique position to gather and disseminate information about new developments in the Three Rs, which researchers may be unaware of. As Purchase and Nedeva (2001) suggested, perhaps at least one AEC member, such as the institutional veterinarian, should be responsible for being up-to-date on new developments and providing this information to the AEC and researchers. This will require that the institution supports this effort by ensuring that these individuals have the time to carry out this responsibility. The governing body, such as the CCAC, could also serve an educational role in this case. Despite the arguments by some committee members that the high costs of animal research would provide sufficient incentive to researchers to Replace or Reduce, other members cautioned that the AEC should not rely on economics. My experiences from attending AEC meetings indicate that researchers may not know about, or may not be equipped to use, some Replacements such as in vitro monoclonal antibody production. Moreover, economic incentives clearly do not apply to some Refinements, such as environmental enrichment and increased cage space, which tend to increase costs (Hubrecht 2000).  Peer Review versus AEC Review In general, policy requires that AECs ensure that all approved protocols have been peerreviewed for scientific merit. In Canada, judgments made by peer-review processes associated with competitive funding are usually accepted for the purposes of the AEC (CCAC 1997). However, confusion over the role of peer review versus AEC review may reduce the application of Reduction and Replacement by the AEC. Although some members believed that peer review by a granting agency covered Reduction and Replacement, granting agencies generally review protocols for scientific merit, but not necessarily for harm to animals. Also, funds are generally allocated on the basis of scientific validity of protocols rather than the efficiency with which they 57  are to be carried out (Festing 1995). It was also recognized in this study that animal numbers may be overlooked by granting agencies, because they expect the AEC to do it or because they are evaluating research programs and not necessarily individual experiments. One committee addressed this problem by having a question on the protocol application form that asked whether that particular animal experiment had been peer reviewed. Therefore, numbers of animals and possibilities for Replacement may not have been evaluated during peer review. The degree to which AECs should be involved in judging scientific merit has often been contentious (Orlans 1987; Rowan 1990; Prentice et al. 1992). In a survey of IACUCs in the US, Graham (2002) found different opinions about the responsibility forjudging scientific merit. In a questionnaire sent to 480 IACUC chairs, 35% responded that assessing scientific merit was not an IACUC responsibility (Borkowski et al. 1997). In contrast, Gruber and Kolar (1997) recounted that discussion at Animal Test Advisory Committee meetings in Germany often revolved around scientific merit. According to Prentice et al. (1992) most scientists should be qualified to evaluate some aspects of scientific merit: experimental design, sample size, statistical analysis, and training and experience of researchers. However, the judgement of the scientific importance of the research may require specific expertise in a discipline (Prentice et al. 1992). Given that peer review can fail to address Reduction and Replacement, and that some AEC members are qualified to judge basic aspects of scientific merit, it appears that some review for scientific merit by the AEC would help to ensure that concerns about the Three Rs are addressed. Further analysis of the relation between scientific merit review and animal use review would be valuable (see Chapter 4).  Lack of Consensus on Minimizing Overall Harm A major and largely unrecognized area of disagreement among members concerned their views on what is harmful to animals and morally acceptable. On the surface, at least, most members demonstrated a utilitarian approach to their decision-making, seeking to balance the benefits of the research against the costs to animals and aiming reduce the total amount of suffering for all affected sentient parties. Hence, if members believed that there was no harm to the animals, then they were not concerned about the number of animals used, but if they believed that harm would be caused, then they were concerned about reducing the harm or reducing the number of animals. 58  However, some members stepped outside a typical Utilitarian approach by viewing a certain level of harm as "unacceptable," regardless of any consideration of benefits, the number of animals involved, or overall suffering. At one extreme, some said that they would not approve research where any animal was caused to suffer. Since invasive protocols were being approved at all universities, these members may be using a restricted meaning of suffering. What level of harm is considered "unacceptable" will be a matter of personal conviction (Orlans 1997). Some members appeared to recognize harm associated with experimental procedures but not that associated with housing and husbandry. Some, for example, believed that the typical living conditions of research animals provided adequate welfare. However, there is increasing evidence that the standard laboratory environments of many research animals do not support a high level of animal welfare. For example, stereotypies (repetitive behaviours), which are considered indicative of suboptimal housing (Mason 1991), are widespread among caged rodents, including mice (Stauffacher 1992; Wiirbel et al. 1996; Nevison et al. 1999). Therefore, animals that are not undergoing procedures may still be harmed to some degree. To minimize such harm, Reduction and Refinement are still relevant, even where experimental procedures are innocuous, at least until we are certain that we are raising and caring for animals in a manner that truly satisfies their needs. Considerations of unacceptable harm should also be influenced by policies. In Canadian policy, some procedures, such as the use of muscle relaxants without the use of anaesthetics during surgical procedures, are considered unacceptable (CCAC 1993). In such cases it seems that the key concern is to eliminate a harmful procedure (a form of Refinement), not merely to minimize numbers (Reduction). Similarly Fentener van Vlissingen et al. (1997) recounted that guidelines and legislation generally do not support reusing animals for more than one procedure in order to reduce numbers, even if the overall amount of discomfort to animals is thereby decreased. In discussing possible trade-offs between the Three Rs, Hau and Carver (1994) suggested that the welfare of individual animals should not be compromised in order to implement Reduction. In summary, given the different views between members and policies on what is considered harmful to animals and morally acceptable, perhaps here is area that would benefit from further discussion, especially with regard to our increasing knowledge about different causes of harm. Naturally, we cannot expect hard-and-fast rules about concepts that are complex and highly contentious such as conceptions of harm. 59  Different Views of Pain and Suffering and their Moral Significance Application of Refinement may also be complicated by differing interpretations of pain, suffering, stress, and distress. For example, members varied in their interpretation of pain, as well as beliefs about the moral significance of pain, with different interpretations resulting in different views about the need for and degree of pain mitigation. Members who assessed pain in animals using a human analogy followed a precautionary principle in recommending pain mitigation. Others support this view; for example Morton and Griffiths (1985) suggested that, "painful conditions in humans should be assumed to be painful in animals until evidence can be produced to the contrary." The Public Health Service (1985) in the US requires that, "unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals." In contrast, other members held a less common view that an animal may not "feel" pain or suffer, even though there are physiological indicators of a pain (Bermond 1997). Complicating matters, legislation and policies regarding which scientific procedures lead to animal pain and distress also differ between countries (Balls et al. 1995; Purves 2000). As many have noted, a key to solving this problem is developing good criteria for the assessment of pain for different research species (Morton 1990; Flecknell 1994) and to treat individual animals accordingly. However, scientists disagree on definitions, as well as measurements or assessments of pain and distress (Purves 2000). Here is another important opportunity for AECs to play a key role in helping researchers access current information about pain assessment and mitigation. Members also varied in their interpretation of suffering. For example, a wildlife biologist did not consider that an animal was suffering unless the future breeding success of that individual would be impaired, whereas other members clearly took a different view. Varied interpretation by members may reflect the larger scientific and philosophical debate about these concepts (Donnelley 1989). Indeed, scientists studying animal welfare often draw different conclusions because they use different criteria, some relying on biological functioning (breeding success and health), some on presence of natural behaviours, and some on evidence of subjective states such as pain, fear and comfort (Duncan and Fraser 1997). One of the strengths of the AEC governance system is that it includes a variety of views through its diverse committee membership. Hopefully, this will enable AECs to capture a more complete view of pain and suffering. So that committees can have meaningful discussion and be able to identify fundamental considerations 60  that determine their decisions, it would also be helpful for committees to discuss explicitly these issues, so that important differences in ethical perspective will be articulated rather than left implicit.  Interpretations of the Three Rs Replacement Views on Replacement found in this study are similar to those found in the scientific community. Many researchers, like many AEC members reported here, feel that it is impossible to replace the in vivo model entirely, and that in vitro tests are complementary rather than alternative (for example, see Garattini 1997). In a UK survey, licensees (scientists) felt most strongly that Replacements were not of equivalent value to animal experiments (Purchase and Nedeva 2001). Therefore, Replacements may not be fully implemented by AECs because of doubts about their adequacy. Although limited Replacement alternatives may exist for many studies, there is a role for AECs, with the help of governing bodies such as the CCAC, to be upto-date on new developments and vigilant to opportunities for applying Replacement.  Reduction Rather than simply seeking Reduction, many members wanted researchers to present numbers that were appropriate for achieving the scientific goals of the study, neither too few nor too many. Similarly in Sweden, Hagelin et al. (2003) found that AEC members equally requested both increases and decreases in numbers. The fact that members expressed a willingness to increase numbers in some cases suggests that members were cautious of not wasting animals through inadequate sample sizes (which might lead to repeating a study, thus ultimately increasing numbers) or that members had researcher's interests in mind and were not trying to impede research. Although Reduction was considered an important part of the review process, evidence suggested that the committees had little impact on reducing numbers. It was remarked that a lot of time was spent trying to count numbers presented in a protocol but only rarely were changes in numbers requested. Similarly, in Sweden only 1% of requests for changes in submitted applications were related to Reduction (Hagelin et al. 2003), and since the inception of the ethical review process in the UK most "Named Animal Care and Welfare Officers" (animal technicians) 61  reported seeing little change in numbers (Purchase and Nedeva 2001). Another possible impediment to Reduction was that experimental design and statistical analysis were rarely considered. Rather, the majority of members seemed content to have a ballpark number of animals, with some evidence of justification which focussed mostly on treatment sample sizes. In order for an AEC to have greater impacts on Reduction, they may now require a sophisticated understanding of experimental design and statistical analysis. There are many good strategies for Reduction (for example, Festing et al. 1998), but this study suggests that AECs may not be knowledgeable or qualified to make suggestions. Committees might benefit from the membership of a statistician (Engeman and Shumake 1993) or as the European Centre for the Validation of Alternative Methods suggested, the institution may need a "named statistician" (Balls et al. 1995) to act as a consultant for researchers. Alternatively, here is another opportunity for the CCAC (or comparable governing body) to play a more active educational role and to provide guidance on these issues. Since only two universities in this study asked specific questions about experimental design and statistical analysis in their protocol application form, more emphasis could be placed on these topics in the protocol application form, to act as a reminder to individual AEC members and researchers.  Refinement  Since many members were more concerned about harm than numbers, the greatest impacts of the Three Rs is likely to come from Refinement. Similarly, in Sweden, the vast majority of requests made to researchers were related to Refinement (Hagelin et al. 2003). In this study Refinement was the least understood of the Three Rs. This may not be surprising because as a label, the term Refinement is the least intuitive of the Three Rs and as a principle it includes a vast number of applications. By not understanding the term, A E C s run the risk of overlooking important improvements in the welfare of research animals. In line with Russell and Burch (1959), many members focussed on procedures and pain when considering Refinement. Less attention was paid to quality-of-life concerns related to environmental enrichment, husbandry, and handling. In general, community members and animal technicians were more concerned about these issues. These concerns may be addressed during inspections of animal facilities by AECs, rather than during the protocol review. However, in two reviews of housing conditions for research animals in the UK, Hubrecht (1995) and Jennings et 62  al. (1998) found that Refinement, particularly, housing and husbandry, were neglected for rodents and rabbits. Stauffacher (2000) found that despite great efforts to Refine experimental procedures, most regulations on housing and husbandry had remained the same for rabbits in Europe. In Sweden, only about 12% of requests for modifications from committees were related to housing and husbandry versus 43% for euthanasia, endpoints, anaesthesia, and analgesia (Hagelin et al. 2003). As a safeguard for animals, and to capitalise on its educational role, the AEC could emphasize these other concerns in the application form. A workshop on advancing Refinement (Smaje et al. 1998) pointed out that although protocol application forms normally addressed Refinement related to procedures, Refinement of husbandry was not addressed. Similarly, Bradshaw (2002) suggested that the term welfare should be included in the title of AECs in Australia, in order to further emphasize welfare issues surrounding housing and husbandry of animals, beyond ethical questions of whether the animals should be used. Perhaps improving members' understanding of Refinement will require the creation of another "R" (in keeping with the Three R mnemonic) or another principle, separating welfare concerns caused by procedures and those caused by housing and husbandry. In order to improve the implementation of Refinement, AECs may need access to educational material or training to help clarify their understanding of the concept as well as to broaden their focus. One hindrance to implementing quality-of-life concerns of Refinement is persuading scientists that it will not negatively affect experimental results (Hubrecht 2000). ACC members in this study demonstrated concern about the effects of enrichment and stress on scientific results. Although more research is needed, there is increasing evidence that improving the welfare of animals is important to scientific validity for many studies (Wiirbel 2001). For example, social, physical and handling factors can affect immunology, endocrinology, brain development, and behavioural responses (Poole 1997). It has also been shown that stereotypical behaviour in caged voles living in standard laboratory conditions reflects an underlying neural dysfunction (Garner and Mason 2002). However, environmental enrichment increased bar-related stereotypies in male mice from six strains (Nevison et al. 1999). Including questions about environmental enrichment, husbandry and handling in protocol application forms could provide an avenue for increasing awareness and consideration of these factors for experimental results and the welfare of animals. In addition, since these factors have not been traditionally considered by scientists, we might expect a temporary increase in animal use while scientists compare previous baseline results with 63  results of new studies that address concerns of quality of life of animals.  Training and Policy This study has highlighted the need for more training of AEC members and improved policy. Not only were members inconsistent in their interpretation and application of the Three Rs, the Three Rs were not serving as an effective mnemonic tool. Instructional material for AEC members might benefit from more explicit emphasis on the Three Rs and members might also benefit from discussion about the interpretation of the Three Rs. In Canada, for example, the Three Rs are defined once in CCAC policy as "those using animals should employ the most humane methods on the smallest number of appropriate animals required to obtain valid information" (CCAC 1993), although more explicit reference to Refinement is made in reference material on endpoints (Roswell 1990). The situation is similar in the US where the Animal Welfare Act does not use the Three R terminology (Orlans 1996). In contrast, in relation to ethical review process in the UK, the guidance on the operation of the Animals (Scientific Procedures) Act 1986 (Home Office 2000) emphasizes the Three Rs much more, including case studies of how the Inspectorate's assessment and inspection processes can ensure application of the Three Rs (Home Office 2003). The Australian and New Zealand Council for the Care of Animals in Research and Teaching (ANZCCART) provides documentation for Animal Ethics Committees with detailed explanations and reference material for the Three Rs (ANZCCART 2003) . Perhaps Canada could follow the lead of these countries. Following the model for human Research Ethics Board members in Canada (National Council on Ethics in Human Research 2004) , another way for AEC members to improve their understanding of issues is to set up a national LISTSERV where members can discuss relevant issues online. By combining this approach with policy and improved training for AEC members with more emphasis on the Three Rs, more consistent and more thorough application of the Three Rs might be achieved.  Conclusions and Implications for AECs The composition of the AEC might help reduce the inconsistency in applying the Three Rs seen in this study. An AEC brings different people with different expertise and values to the table. No one individual is expected to understand all aspects of a protocol. Indeed, community 64  representatives may need to rely on other members experienced in animal research, to address some aspects of the Three Rs such as appropriate analgesia and experimental design. However, this study suggests that factors other than expertise can also affect the consistent application of the Three Rs. More consistent application of the Three Rs might be achieved if AECs (1) were trained to apply the Three Rs more systematically, (2) were provided with up-to-date information on the Three Rs, (3) better assessed Reduction, and (4) broadened the focus of Refinement. Governing bodies and policy makers could also play an important role in helping AECs to address these issues. There is also opportunity for discussion and consensus-building on key issues such as the relation between peer review for scientific merit and AEC review, and the role of and limits of economics as drivers of the Three Rs.  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Ethology 102: 371-385  69  CHAPTER 4 -  Decisions about the Use of Animals in Research: Ethical Reflection by Animal Ethics Committee Members  Introduction  Institutional Animal Ethics Committees (AECs) are the principal means of ensuring the ethical use of animals in research, teaching, and testing in many countries. They have the responsibility of ensuring humane care and use of animals by reviewing proposals to use animals and by educating animal users in their institutions. The task of the AEC is a challenging one, requiring an understanding of complex and contentious concepts such as pain and distress, and a technical understanding of scientific procedures and animal care practices. Understanding how these committees make decisions about the care and use of animals is a key step in ensuring that this system functions effectively. In general, AECs make decisions at two levels: Firstly they must ensure that the proposed research is justified, and secondly they must decide what modifications are required to minimize harm to animals. Typically, decisions about whether an experiment should proceed have their roots in Utilitarianism, involving a search for the action that will result in the most favourable ratio of benefits to harms. Thus the committee might typically weigh the potential benefits to humans or animals against the harms to the animals used in research. In general, the higher the level of anticipated harm, the stronger must be the value of the research. Harms include pain from experimental procedures, and reduced comfort or well-being resulting from inappropriate housing, care, and handling. Various frameworks based on cost-benefit assessments have been developed to aid members to make orderly and systematic decisions about the ethical acceptability of experiments (Smith and Boyd 1991; Mellor and Reid 1994; de Cock Buning and Theune 1994; Stafleu et al. 1999). Another framework is based on a 'Schweitzerian' reverence for life ideal (Porter 1992). Ideally these frameworks should help to increase consistency in decision-making, although their effectiveness has not yet been tested. However, decision makers in natural settings rarely use rational approaches (Klein 1998). In fact, intuition and mental simulation are prominent approaches. Galvin and Herzog (1992) found that students acting as AEC members sometimes used different paths of reasoning to arrive at the same decision, and sometimes used similar  70  reasoning to arrive at different decisions. In order to improve the functioning of AECs we need to understand how AEC members make decisions in their natural setting. Only a few studies have made headway in this area. Two studies surveyed actual committee members. They examined consistency of decision-making across institutions (Dresser 1989; Pious and Herzog 2001) and within committees (Pious and Herzog 2001). Stafleu et al. (1989; 1993) examined to what extent cost-benefit assessments are used by scientists, veterinarians, animal technicians, but not specifically AEC members. Galvin and Herzog (1992) surveyed undergraduate psychology students acting as hypothetical committee members. In most cases the importance of several factors (preselected by the researcher) to decision making was rated. Only one study specifically attempted to characterize individual decision-making processes by analysing written responses to an open-ended question (Galvin and Herzog 1992). The present study used an ethnographic approach to explore how AEC members make decisions about proposed research in practice. Through in-depth interviews with individual AEC members, I examined to what extent cost-benefit assessments are used to make decisions about the justification of research, and about necessary modifications, what other decision-making approaches are used, and what factors influence decisions.  Methods See Chapter 3 for description of general methods. Interviews began with background questions about how long the participant had been an ACC member, how each became a member, and questions about meeting structure and preparation time. For this study, members were then invited to talk more specifically about their approach to reviewing and evaluating protocols: how protocols were reviewed, how decisions were made, whether they used any guiding principles for decisions, what modifications they would request, what protocols they found challenging, trust in animal researchers, and personal attitudes and ethics regarding animal use in research.  71  Results Procedural Steps in Protocol Review When asked how they reviewed protocols and decided whether to approve protocols, most members did not have a well articulated description of their decision-making process. Rather, they typically gave a procedural description that revolved around the content of the protocol application form. Several members reported reading through the protocol application form once for a general overview and then a second time to examine it in more detail. Typically, members began by examining whether all clerical information had been filled in: names of investigators, contact information and so on. Members generally checked whether the protocol was identified as peer-reviewed, usually by a funding agency. This was then followed by reading the lay summary which gave an idea of the objectives and overall value of the research. From that point members began looking, to various degrees, at details of the design of the experiment, numbers of animals, procedures, monitoring of animals, endpoints, drug administration and so on. A scientist (Andy) described a typical review process: Well, I very quickly go through the mechanics. Have theyfilledin all the spaces? Are all the signatures there, all the phone numbers there? You just have a set list. The manager provides this guide sheet which ... makes it easy to review a protocol. So it allows you to do quick checks on certain aspects. And then you look for the lay description - which I think is pretty important because it's something that other people [the public] are going to be able to access. You make sure that the procedures are complete. I know some people complain about the fact that the procedures are too long. Forget it - if you need ten pages to explain the procedures, that's great. But again it needs to be emphasized that those ten pages are not a grant request - define what it is that you're doing for your animals. I spend probably most of my time trying to figure out the numbers. I think a lot of people try doing that. It was forever that we had problems with [investigators] not understanding what moribund and mortality meant.... So we [ACC members] had to really dissect the difference between an acute study and a chronic study. End points ... was another one that caused fights. Everyone [investigators] had a  72  different notion of what the end points of the study might be or moribund end points. That's been repaired. The nice thing about this group (and I hope it's happening everywhere else), is that it's constantly updating [the review procedure]. So as they go through the review process they can identify the weaknesses, where people are continually making the same mistakes. I do follow the guide that the committee manager gives us. Lots of it is fairly straightforward. I try to flag things as being minor concerns and then I have a set of serious concerns. And then it's sort of a balance between the serious concerns and the minor concerns that make my decision.  Cost-Benefit Assessment With one exception, members began with the premise that a study required justification in order to proceed, but their criteria for justification varied. Some accepted evidence of some potential benefit to humankind, animals, the environment, or the advancement of science, regardless of harm caused to animals; others required evidence that such benefits outweighed harm caused to animals; others accepted evidence of approval by expert peer-review. In some cases, justification was considered to be important only in those extreme cases where costs were perceived to be extremely high or benefits were perceived to be very low. Half of the members specified that they used a form of cost-benefit assessment to evaluate justification of proposed research, by assessing costs against expected benefits. Simply put, a veterinarian (Ingrid) suggested that her committee would defer a protocol where it, "didn't seem that the benefits of doing this work outweighed the costs to the animals it was going to entail." Costs were often described in terms of the Category of Invasiveness (CCAC 1993). For example, after describing her approach to decision-making, a scientist (Sue) agreed that she used a cost-benefit analysis, although she had not labelled it in those terms: A cost-benefit analysis for protocols - that is a good way of looking at it. So E level protocols have to have a tremendously strong potential or a strong benefit in order to be done. The D level protocol doesn't have to be so strong and so forth. A veterinarian (Alfred) justified vaccine research in terms of the greater number of animals that  73  would benefit as a consequence: I say we're causing disease that is out there in nature all the time, and we're trying to find ways of preventing it. And so that's how I'll justify challenging ten pigs, because I might save discomfort in ten thousand pigs.  Limitations of Cost-Benefit Assessment  Members identified several shortcomings to the use of a cost-benefit assessment. Firstly, some members felt that there were certain limits to acceptable levels of suffering to animals, regardless of benefits of the research. An animal technician (Ben) recounted that, The invasiveness had to be within an acceptable range .... You may have a miracle drug but if the invasiveness is off the scale, then it's still not justified for the animal. A veterinarian (Rose) believed that no research in the Category of Invasiveness E should be permitted. A community member (Scott) felt the same about L D  50  experiments (to determine the  dose of toxin which kills 50% of exposed animals). A veterinarian (Ingrid) would not approve a burn study. A scientist (George) considered that procedures that produced "very debilitated, sickly, moribund animals" should be limited. Although some members felt specific procedures were unacceptable, an animal technician (Betty) struggled with weighing costs against benefits because she found it difficult to decide what was an acceptable amount of suffering (where to "draw the line"), especially for important health research: I think sometimes it's very difficult because you can see the value but ultimately the animal's still suffering.... I think it's something that's not really black and white - it's very grey, and it's very difficult to make that decision ... if it's lifethreatening in humans and you want to, you know, make a change. How far do you go? Betty also described how rational assessments of potential benefits and costs might not be  74  a suitable approach for lay members (representing public concerns) because they may consider some procedures unacceptable based on moral intuition and not a rational calculus: To a lay person those [cost-benefit assessments] are ... not concrete things and I would think there are some things that... they just think, "Why would you ever do that?" There's no way that there is any kind of cost-benefit, because that particular thing just looks so horrific to them. They just don't see the benefit in this. And I think they should be allowed to express that because really that's what the public would express. Secondly, some members felt that cost-benefit analysis may be impossible to use because benefits may be too difficult to assess. A scientist (Bob) pointed out that his committee mostly focussed on costs because of the difficulties of predicting potential benefits: Benefits of science are totally unpredictable. It is often 50 years later when we can actually benefit. So ... making decisions about benefits is difficult. I think it is mostly cost that we look at. I mean there are some areas where ... I think they're making huge strides in terms of cancer. I think there you have to downplay some of the costs a bit just because these people are having huge successes, especially with some kinds of cancer. So I think in some areas it is clear what the benefits are but overall I think that is really hard. Thirdly, several members implied that they rarely involved cost-benefit analysis because they felt that any benefit justified an experiment regardless of costs to animals. As a community member (Rachel) put it: Obviously I completely believe in animal research or I wouldn't be on the committee. So if anybody is going to come up with some good, no matter how minuscule it is, out of any one of those proposals, then I think it's justified. Similarly, although a scientist (Ken) described using a cost-benefit assessment, he indicated that any benefits of health research were sufficient to justify an experiment: Most of the medical discoveries come about after using animals. So you have to  75  weigh out the benefits versus the killing of animals and as long as it is helping (providing a benefit to the human condition) then, we should keep using them. Finally, members differed in what they considered benefits. For example, members often described benefits from health research as worthwhile. In contrast, 4 members felt that benefits from using animals for cosmetic development or testing was not sufficient to justify the use of animals. Teaching Protocols Although members were not specifically asked about teaching protocols, these were often brought up in interviews and they raised particular contention among members. Six members were concerned that for at least some teaching protocols, the learning experience for students did not appear to be valuable. For example, a community member (Rachel) said, "I don't think they are getting anything from it." A technician (Sam) viewed teaching protocols as a "contentious issue" because he had worked with students who appeared to have learnt nothing from classes using animals. Similarly a scientist (Bob) felt that using animals in teaching was justified only for some courses: I just don't see the point in having first year biology students cutting up rats. This "hands on" argument is probably okay for pre-med types, third or fourth year, definitely pre-med types, but just for general teaching I just don't buy that. You can watch videos or computer animations or something like that. It is just as good. In contrast, another scientist (Alex) felt that, "If the department or faculty feels that an animal experiment is necessary for teaching, it should be their decision." Members recounted that committee discussions about the justification of teaching protocols continued to take place, without any resolution.  Role of Peer Review in Decisions In general, comments seemed to confuse peer review, scientific merit, social value, and the justification of research, indicating that members were not drawing clear distinctions between these concepts. For clarity in reporting the views, let us define these terms as follows. Scientific  76  merit (terminology used by members) is the value of the work as a contribution to science and includes scientific relevance, quality of the experimental design, appropriateness of animal model and procedures, and skill of the researcher. Social value is the ability of the work to make a positive contribution to society. Justification of the research refers to a rationale for the work to proceed; this might involve weighing the scientific merit and social value against costs including monetary costs and harm to animals. Three patterns emerged about how peer review by granting agencies or experts affected decisions. First, many members (12) took peer review as an assurance of scientific merit but they varied in their definition of scientific merit. Most members were hesitant to critique peer review because they believed that it was not the responsibility of the ACC or because they were not qualified to assess scientific merit. A scientist (George) described this common view in the following way, I don't get stuck up in the science because that's supposed to be done by somebody else, and there's not enough information.... So the science is not really a problem area because you have to assume that other people have reviewed the project. Another scientist (Sue) said: I don't think that we [ACC] should be trying to take on the role of being scientific reviewers because the expertise is not there on the committee and never will be, can't be. You really need the experts in the field to evaluate the scientific value of something. A scientist (Teresa) also believed it was not the role of the ACC to judge scientific merit but she was uncertain whether this was consistent with the mandate of the committee. In contrast, a scientist (Mark) expressed the less common view that the scientific merit should be evaluated; in fact, it was his major focus in reviewing protocols: To me the major issue is quality of science. So whenever I review a protocol, that is the one thing I am constantly trying to evaluate: is this good science? My thoughts would be that we do get protocols where I would question the peer  77  review process that has been used in awarding the funds to a particular investigator. One thing about the World Wide Web now, is we have access to an investigator's scientific research record, or their publications, [and] the citations those publications received. And there are times when people do meet peer review criteria based on, "I have received a grant from a peer review agency," in which case you are not formally supposed to question whether this is scientifically meritorious, but I would still question it. And I have done that on committees where I feel the publication record is not good and the publications that they are getting are in poor quality journals that are never cited. However, Mark also added that his committee may not have the power to give a negative recommendation for an application if it had been approved for funding. Second, the majority of members (22) seemed to take a stronger position that approval by peer review was an assurance not only of scientific merit but also of social value and that the research was justified to proceed without further review. Thus, the role of the committee was mainly to focus on minimizing harm to animals. Over half of the members (9) that reported using a cost-benefit assessment remarked that they accepted approval of a protocol by a peer review committee as justification for the study to proceed, without further weighing of costs and benefits. For example, a scientist (Alex) view was that, if the research is supported by peer-reviewed grants, I don't concern myself too much with the purpose of the study. I am more concerned with, is the study going to involve any pain for the animal? A scientist (Al) felt it was not the mandate of the committee to "directly evaluate the merit of an experiment. It is mostly to evaluate whether the animals are being used properly, and are not suffering, and are not stressed." In this conversation with Al, the term merit seemed to imply more than just scientific merit. Others who did not follow a cost-benefit approach also felt the same way. For example, although a scientist (Alfred) wanted some evidence of "a logical reason why they're doing this trial," in response to whether he would challenge the peer review process he answered, I probably won't question the research so much as I'll question, you know, why do 78  they need this number of animals, why does this animal appear to be the model that they've chosen. Thirdly, some members seemed to feel that establishing scientific merit (through peer review) is by itself sufficient to justify the work proceeding without considering the social value or costs of the work. The terms "scientific merit" and "justification" of the research were often used as equivalent in such comments. As a community member (Rachel) recounted: When I was talking to a person at the conference, they were saying, "Don't you have to think about whether the research is justified?" And I don't usually think about it that way. I kind of think that the science is the part that I am hoping that if they had to get to funding and peer review, then somebody is justifying the science and I don't have to worry about that, and I'm just worrying about the animals. ...You can only assume that's why peer review is out there; somebody is giving [investigators] the okay to do it and I don't think I can judge that. Although members generally demonstrated a high level of trust in peer review, eleven members believed that ACCs should reserve the right to question the quality of any peer review if they were concerned, in part because they lacked confidence in the peer review process. A community member (Scott) pointed out the danger of relying entirely on peer review. He suggested that because peer review only assesses one part of the cost-benefit assessment, (namely, the scientific merit) ACCs need additional elements to decide whether research is justified: I wonder how concerned they [granting agencies] are with anything other than the strict scientific merit. I wouldn't think so. The question of value for pain, if I may use that expression, is not considered at that level. And if the ACC is not going to use that judgement, then nobody is going to. So I think that is a proper thing for an ACC to do. A scientist (Bob) pointed out the problem with granting agencies that provide funding for programs as opposed to individual experiments. In these cases, peer review may not evaluate each experiment in an application:  79  Some granting agencies like NSERC [Natural Science and Engineering Research Council] don't evaluate the project; it is evaluating the career of the researcher. So just because NSERC is giving somebody money doesn't mean that the project being proposed in the protocol is reviewed by NSERC. So I don't think we can rely exclusively on the peer review thing. As a result of concerns about inadequate peer review, a few members indicated that they would be more likely to scrutinise the justification of studies with higher levels of invasiveness. For example, a scientist (Sue) said, We may be looking at an E level protocol, and we're being told that it is funded and it has been peer reviewed, and if it truly is - if a committee of experts has looked at this work and said, "This is so important, it really has to be done. It's going to prevent all sorts of suffering down the road if it works out. It's well worth doing." - if they have done that, well then maybe it should go forward. But on the other hand, I am never really certain that that process has really taken place. And I get really conflicted about that, because I often think, "No, this person has been funded in this general area, but not exactly for this exact experiment." And Sue added that, "The more invasive and so on, the more I feel compelled to really look hard at it and wonder if it ought to be done at all." Typically, there were differences in opinion within a committee about the role of peer review of scientific merit as illustrated by an animal technician (Betty) in her description of a typical ACC meeting: I've seen sometimes in the past where ... you got one committee member talking about the fact that this doesn't make sense .... As an example, maybe somehow in the design it doesn't look right, and they're saying, "Well, I'm not sure that this should go forward the way it is." And then you'll have another committee member say, "But he or she is funded by so and so." And somehow that makes it God. And I disagree with that because I think that, you know, on principle, the granting agency is a great way go, but... even though the idea's good but there is some fundamental flaw in his design - which maybe the granting agency never 80  ever saw - then I think you should have the right to say, "Yeah, maybe the idea was good but not the way you're proceeding."  Other Approaches to Decision-Making Despite the prominence of cost-benefit assessments and the importance placed on peer review, some members used other approaches in their decision-making, although these had some overlap with cost-benefit approaches.  Focus on the Animal  Some members focus their protocol review on trying to understand what is happening to the individual animal throughout handling and experimental procedures. One scientist (Sue) considered this so important that she saw other issues as distractions and tried "to stay focussed on the animal."An animal technician (Betty) put her approach in these terms: I tend to be looking at the protocol more from the animal aspect and I'm trying to understand what's happening to the individual animal - not really thinking of the scientific design and those sorts of things. A focus on the animal occasionally involved a process of projection. Two members reviewed protocols by imagining themselves as the animal subjects. For example, a guiding principle of one animal technician (Sophia) was, "putting yourself in the position of the animal." A veterinarian (Rose) used projection to assess the level of harm to animals, which she then balanced against benefits: So if you try to visualize yourself as the animal on this protocol, you have to know what is going to happen to you. You have to try to anticipate what kind of pain and distress that might involve, and then look at whether or not the merit is going to justify that. Similarly, members would also make decisions by projecting onto animals what humans would experience. For example, a veterinarian (Ingrid) described the difficulties of pain management: You're sort of making a translation from how people are. You see what people go 81  through, and even with the best drugs that exist you still might not be able to maintain the pain-free status. Mary linked her concern about some procedures to her concerns about human suffering, "I wouldn't particularly like to see a human being suffering or injured." A scientist (George) took the opposite approach, suggesting that it was "arrogant" of humans to believe they could understand an animal's viewpoint and that there is a danger of ACC members, "assuming what the animal feels." In a slightly different manner, an animal technician (Sophia) used projection to imagine herself as the technician or researcher who would be carrying out the proposed procedures and asked herself, "Can I do this myself? Would I feel comfortable doing this myself? ... Could I psychologically do this to an animal and not feel bad about what I was doing?"  Role of Emotion and Moral Intuition Emotive language was used mostly by community members, to describe both their approach to decision-making and their reactions to certain procedures. Two community members described their approach to protocol review as "gut feel" rather than a well-thought-out logical judgement. Cassandra described her approach as a "smell test": I want to be able to walk in there and say, "This doesn't sound right to me. This sounds like too much animal use, or those animals are suffering, or this doesn't sound like an experiment that really has some global value to it, so why should we be subjecting animals to this?" Cassandra also described her approach in terms of community standards combined with a costbenefit assessment: My area of expertise is: "How does the average member of the public feel about what's going on here, and does it fit within what our society views as acceptable?" - balancing the interests of the animals against the need for us to advance knowledge and understanding. Similarly Carmen described her approach as, "I focus on the animals, mainly - which type of animal and what is being done with them and how do I feel - my gut reaction to it." In addition,  82  Carmen also used the "body language" of other committee members during meetings as indicators of whether she should be concerned about an aspect of the protocol. Although as a community member Craig did not understand all the technical aspects of a protocol, when he reviews procedures he asks himself, "whether that sounds cruel." Several members described a personal struggle between emotional and logical responses to protocols. An animal technician (Ben) described his attempt to keep emotions out of his decision making: I try to keep my own emotions out of it, so try to keep it clear, because I certainly can get emotional when you see some of these procedures, and think, "Oh that just looks so terrible." But I try to keep that aside and just look at it strictly on the technical point of it. So - and sometimes I will admit - it's hard to keep your emotions in check. A community member (Mary) described a similar experience of struggling to separate emotions from logic when reviewing protocols for companion animal species: You deal with it on the intellectual level and the emotional level. ... I can look at this intellectually, and I understand it all, but when I review that, does it bother me? Yes it does. Several members described the use of animals in research as a "necessary evil," whereby they did not like using animals for research, but saw animal research as necessary for progress. For example, a scientist (William) expressed a love for cats and a personal struggle with carrying out research on animals in general: "I did quite a bit of animal work as a graduate student, working with rodents. And the more I worked with them, the more I hated it." Several members recounted feeling disturbed about the treatment of research animals. The reaction of an animal technician (Sophia) to one meeting was, "I came out of that meeting feeling very depressed, thinking, 'Why am I in this work? This is awful. This is just awful what they are doing.'" A community member (Cassandra) also described her feeling when she returned to ACC work, after having been on leave, "So I think when I came back, having had a step away from all the scientific side, the first thing that hits you again is, 'These poor animals.'"  83  Role of Different Philosophical Beliefs  Throughout the interviews members often described their personal ethical philosophy regarding the use of animals in research. These views included ideas about rights, stewardship, sanctity of life, and the advancement of science. A community member (Scott) expressed a view aligned with some animal rights thinking, claiming that, "It is morally indefensible to use animals to promote the better health or the appearance of mere human beings." In a different vein, another community member (Cassandra) spoke of use of animals as "a privilege, not a right." Cassandra also expressed a sanctity of life view: "I can't kill a spider; I put them out the window. You know, any kind of cruelty to animals really bothers me." A community member and theologian (Craig), saw his role as being a steward of animals: "They're my animals to give to these investigators, and I ask myself, 'Can I give my animals to them? Will it help the world?'" Similarly Carmen believed that we, "have to respect the animal and treat and handle them correctly" in order to use them for research. Most members emphasized advancement of science and seeing animals as tools to achieve this, while respecting society's (or their) concern about animal suffering. For example, a scientist (Alfred) said, "If you want to make meaningful research or progressive research I think that an animal model is one of those things that will work.... But let's look at things to alleviate that pain and discomfort."  Decisions by Precedent  Several scientist members mentioned that their decisions were aided by comparing current protocol applications to past protocols. Their knowledge of "good" protocols versus "poor" protocols gave them a reference point from which to compare current protocol application forms, much as in case law. Naturally this required the experience of being on the ACC for some time. Oliver felt his decision-making process was based more on personal experience than reading guidelines: I guess being on the committee for that long and seeing what is done to the animals in different protocols - and kind of getting a view about what is acceptable and what isn't in terms of what has to be in an experimental protocol is how I would judge a given protocol. Because, you know, any protocol we get, in virtually all cases, we will have seen similar protocols from other investigators 84  and kind of remember ones that were really good - that had great endpoints, that clearly described the procedure, that are clearly using the minimum numbers of animals that are needed, that had a good justification for why they were using that species - and you could use that as a kind of bench mark. William described developing a similar approach: In the first meeting I went to, I agonized over it, because I don't know should this one be rejected or accepted and what's the criteria for accepting or rejecting? How bad is this one? ... I'm much more comfortable now after having done it for two years. So I think you gain experience by looking at good applications and looking at bad applications. There is a little bit of a learning curve.  Three Rs Two members indicated that the Three Rs were an integral part of their decision-making process and made sure they had been implemented where possible. A veterinarian (Rose) recounted that she was "implementing the Three Rs all the way through" the review process before applying a cost-benefit assessment. Most other members demonstrated that aspects of the Three Rs, although not specifically mentioned, were also influencing their decisions (See Chapter  3).  Cues Leading to Greater Scrutiny Members used certain cues in protocols as "red flags" to trigger additional attention and scrutiny, thus increasing the likelihood of a negative recommendation. One such cue was a discrepancy with policy or guidelines, either national or from the institution itself. For example, members cued on the use of inappropriate procedures such as in vivo monoclonal antibody production when in vitro methods were available. Other cues were a high potential for animal suffering, either because protocols were classified as a Category of Invasiveness D or E, or because the investigator was unfamiliar or unskilled with a procedure. Technical experts, such as the animal technicians and veterinarians, also noticed procedures that they perceived to be incorrect such as an inappropriate choice of anaesthetic.  85  Three other factors - species of animal, trust in investigator, and quality of the completed application form - also served as cues leading to greater scrutiny.  Species of Animal About half the members mentioned that choice of animal influenced their decisions, either because of the species' level of sentience and capacity to suffer, or because of the value placed on different species by themselves or society. Six members mentioned that they would pay more attention to protocols using cats and dogs, either because of their own relationship with these species as companion animals, or because of perceived concern by the public about their use. For example, a veterinarian (Rose) felt that ACCs needed to be sensitive to the fact that some people value companion animals and non-human primates more than rodents: I would say the ones that are most contentious and therefore more difficult to approve are definitely the ones that use the companion animals, there is no question. As soon as you want to use ... a cat or a dog, then you right away have to put it into a different category in your mind. Non-human primates - fortunately we don't have to deal with them at this time at this university - but if we were to get non-human primates, then again it is a whole other ethical issue immediately, without even knowing what is going to happen to them. It is the very choice of the model at that point. I don't think that should be ignored. Thus, Rose felt that one needed to question the appropriateness of using these animal models, while at the same time acknowledging that a high level of sentience in rodents also requires concern: There is a lot respect for rats and mice and how intelligent they are, especially if you work with them all day long. And there is a lot of caring that goes on, and there is a lot of looking at this little animal as a little animal, and we encourage that. But there is no question that there is a lot more of us that grew up with dogs and cats and still have them as pets than do rodents. And the rodent to us is still the little grey mouse living in our cupboard, so we put them in a different category.  86  Similarly, several members mentioned that the use of non-human primates was also a concern because of their similarity to humans in their behaviour and consciousness. Although a scientist (George) approved protocols using non-human primates when he agreed that it was the appropriate model, he was uncomfortable with their use: The more you watch them, the more you can say they are not far away from us and the more fidgety one gets about it - morally fidgety. So I have problems with primate stuff. Members also recounted that they, their committee, or society valued rodents (particularly mice) and fish less than other species such as companion animals, pigs, and sheep. A scientist (Oliver) wondered if his committee was less concerned about the welfare of mice as a result of a cultural attitude towards pest species: What happens to a mouse maybe concerns [people] less than what happens to a cat or a sheep or a pig. ... We spend a lot of time on the committee worrying about humane endpoints for mice, but you get mice in your house and you put down traps, you put down poison - neither of which would be acceptable means of euthanasia for experimental animal mice. I think as a consequence maybe we don't... . I don't mean to say that the committee doesn't spend as much time worrying about mice welfare issues because we do spend a lot of time on endpoints in mice. Some members suggested that committees should be sensitive to the emotional experiences of animal technicians working with companion animals, partially because research on companion animals and other larger species tends to focus on individuals, thus allowing technicians or animal users to become more emotionally attached. A veterinarian (Rose) suggested that investigators using dogs should involve themselves in all aspects of their research in order to ascertain whether the emotional experience would be bearable for them and to empathize with their animal technicians: If you are a principal investigator and you want to use a dog, then you should be there from beginning to end, and then at the end, still tell me if you want to use a  87  dog. Because you don't have to carry all that emotional baggage; if you don't want to, you can pawn it off on your grad student, or you can pawn it off on the facility, or you can hire somebody specifically to do that, or you can have a technician. But ultimately you are the guy that said, "I gotta use a dog." Finally, although species influenced decisions for many members, seven members suggested that as long as the choice of animal model was appropriate, then they were equally concerned for the welfare of all species.  Trust in Investigator  For many members, familiarity with the skills of investigators and their past interactions with the ACC played a role in how protocols were judged. Although members generally felt that most investigators could be trusted to carry out procedures as they had outlined in their protocol application, some investigators were not trusted because the ACC had encountered problems before. Problems were usually related to lack of concern for the welfare of the animals or previous violations of standard operating procedures. Members reviewed these "problem" protocols with more scrutiny. A scientist (Andy) felt that familiarity with the track record of an investigator was "absolutely critical" for protocol review. He felt the ACC processed his own protocols faster than others because of his strong record: I think our protocols probably go through faster than another person doing the exact same work ... because, one, they know me, and two, they know the group down here. And they know this group will call them in a moment's notice. So they don't have to worry about me. A community member (Rachel) described her reaction to protocols from a problem investigator, "Geez, it is the  Centre" and you just know that even though they have written  it on paper as to how wonderful they're going to carry on their experiments, just somehow in the back of your mind you think they're not going to do that - that they are hiding in that little building and they are doing whatever they please. As a solution, when Ken's committee encountered protocols from "problem" investigators they  88  required these investigators to sign agreements that they would carry out modifications required by the committee. In situations where there was a concern about a particular investigator, members reported that they would sometimes request that the veterinarian or technicians monitor the situation. Several members saw animal technicians as particularly important (either as ACC members or within laboratories) because they are more likely to know the practices of individual investigators and can notify the ACC or the university veterinarian when they are concerned. A community member (Cassandra) commented that animal technician members were valuable because, "they know what's going on ... the difference between the written submission of an investigator and the actual practice of the investigator, and I think that kind of input is very important." Animal technicians in this study were generally less trusting of researchers than other committee members and this was because of past experiences with researchers.  Quality of Completed Application Form Eight members commented that judgements were affected by the diligence with which the investigator filled out the protocol form. Poorly filled out forms, with information missing or sloppy writing, were considered to reflect a lack of respect for the ACC oversight system. For example, a scientist (Teresa) said that, I will defer a protocol when basically I think it has been written without respect for the people who are going to read it and where ... the way it is written is very casual, without a lot of thinking. Similarly, an animal technician (Sam) reported that: I think it's incredibly rude if people fill them out poorly because I feel it's saying, "So what? It will be passed. It's okay." I feel that's wrong.... They should be sent back, and be filled out correctly. In addition, some suggested that poorlyfilledout forms may also reflect poor diligence in caring for animals. For example, a community member (Craig) said that, "I go through it with a fine tooth comb and say, does this person look like she will be very diligent in looking after an animal?" Likewise, another community member (Rachel) put it this way, 89  I think that some of them are pretty sloppy, and I think if you can be that sloppy with writing down some words on a piece of paper,... are you that sloppy in the work that you do? Similarly some members viewed inconsistencies in the way that the application form was filled out as reason for a negative recommendation because investigators were not portraying information accurately. Inconsistencies included whether the listed drugs matched the drugs described in procedures or whether the Category of Invasiveness matched what was expected from procedures. For example, a community member (Rachel) described how she searched through protocols: I look at mortality and morbidity [percentages asked for on the form] and mostly to see if they filled it out incorrectly. Like, a lot of them write 0 for morbidity, where there's no way that is 0.... I try to look at the medication section as to whether everything written there fits in somewhere within the procedures. An animal technician (Betty) reviewed them in a similar way: I start to look for similarities. In other words, if here they are talking about mice, but all of a sudden they are asking for a rat, then I want to know why the discrepancies? ... In here it describes they'll be using the anaesthetic pentobarbital, and over in this list they'll have a list of all the things they are going to inject into the animal. I want to make sure both lists kind of match because sometimes they've listed it here but they forgot to put it in here.  Reaching a Decision On all four committees, members had to decide whether to: (1) unconditionally approve the protocol, (2) approve with conditions or comments, thus requiring the investigator to submit a revised protocol to the Chair and the university veterinarian, (3) defer the protocol, thus requiring a revised protocol to be resubmitted to the entire committee, or (4) reject the protocol. Most members made their final decision about a protocol after discussion and consensus at a meeting of the committee. Some concerns could be addressed by other committee members at the  90  meeting whereas others had to be addressed by the investigators themselves. Members often used some proportional weighting system, where the greater the number of problems or the greater the seriousness of the concerns, the greater the likelihood of withholding approval. Protocols were rarely rejected at two universities (data was not available for all universities). At University A the majority of protocols were approved with conditions rather than outright, and at University B and C about half were approved outright (Table 4.1). University B seemed to encourage more discussion of protocols with investigators before meetings. Members approved protocols with conditions when their concerns were minor and did not affect the welfare of the animals. These tended to be protocols in the low Categories of Invasiveness. Generally, approval with conditions resulted from missing information (e.g. missing justification of numbers or drug doses) in cases where the committee felt confident that the investigator could provide that information or add straightforward amendments.  Table 4.1  1  Number (and Percent) of research protocols assigned to different decision categories by three Animal Care Committees in western Canada from 1999-2001  Decision  University A  University B  University C  Approve  98(13.1)  191 (53.5)  162 (51)  Approve with conditions  602 (80.3)  86 (24.1)  87 (28)  Defer  50 (6.7)  78 (21.8)  56(18)  Reject  0  2 (0.6)  10(3)  1  Numbers from years 1998 and 1999. Protocols that were deferred tended to be described as ones where there was too much  missing information in order to make an evaluation. A scientist (Oliver) felt these decisions were subjective but he felt that, If there are enough things missing from the protocol - where I don't have a clear idea of what is going to happen to an individual animal, how long an individual animal is going to be studied... - those are the criteria I would use for deferral. And it would continue to be deferred until the information was supplied to the satisfaction of the committee.  91  Deferred protocols also included ones where there were serious concerns about animal welfare or suffering and these included pain studies, lack of pain management after surgery, a Category of Invasiveness level E protocol without a pilot study, chronic studies, use of transgenic animals with little knowledge of side effects of transgenesis, lack of expertise by researchers, or a lack of trust in the investigator. Other deferrals resulted from lack of peer review or serious concerns about the scientific merit or benefits of the research or a poorly written lay summary, usually containing too much technical jargon. Members differed in whether they favoured deferring protocols with poorly written lay summaries.  Discussion Decisions about Ethical Justification of Research Cost-benefit assessment is the standard, rational approach for assessing the ethical justification of experiments as prescribed by policy in Canada and as required by law in a number of countries including the UK, the Netherlands, Germany, and Sweden. Many members in this study reported using a cost-benefit assessment, but there was huge variation in how it was applied. Some members saw certain costs as unacceptable, thus trumping benefits. Others saw any benefits as justifying the experiment, thus trumping costs. Members also differed in their views on which benefits helped to justify research. There was also recognition that cost-benefit assessments are inherently problematic. Although such assessments give the impression of being objective, costs and benefits are neither quantifiable nor in commensurate units, and benefits are difficult to predict. Moreover, as this study shows, cost-benefit assessments may not be an appropriate decision-making model in all cases because certain people use other approaches, or because other considerations, not classified as benefits or costs, are also regarded as important to decision-making. Cost-benefit assessments rest on a utilitarian theory of ethics whereas this study demonstrated that other ethical theories, including ones based on rights and stewardship, came into play. Other studies of naturalistic decision-making have shown that people rarely use objective approaches of weighing options (Klein 1998), although Klein primarily studied decision-making in the context of time pressure and fairly high stakes, such asfirefighting. Other approaches that entered into decision-making included empathy with animals, 92  comparison with perceived community standards, attempts to be consistent with previous decisions, and moral intuition. Emotion and moral intuition appeared to play an important role, especially for community members. In interviews and surveys of committee members Galvin and Herzog (1992) found that decisions were influenced by how upsetting the experiment was to the reviewer; both rational and emotional factors were thought to interact to produce afinaldecision. Use of moral intuition is not unexpected given the large role of value judgements in committee decisions. For example how one decides what level of animal suffering should be accepted, regardless of benefits of the research, is likely to invoke moral intuition. These views may be difficult to articulate within a rational or objective framework. For expert decisionmakers the use of "gut feel" can be a valuable tool in making decisions about complex issues. This ability is usually the result of much experience, although on the surface appears arbitrary (Klein 1998). Although use of moral intuition may run counter to the ideals of rationality and objectivity - strongly valued within scientific culture - it may be an important element of committee decisions and a valuable trigger for further scrutiny of a protocol. The approach used to make decisions may ultimately affect the type of concerns that a committee member will be attentive to. For example, the approach of reviewing a protocol from the perspective of the animal, even projecting oneself into the experiences of the animal, may result in particular attention to pain control, housing conditions, and handling. Galvin and Herzog (1992) found that projection was used to both reject and approve protocols, depending on how the reviewer imagined the situation. Attempts to be consistent with previous decisions may help to standardize decisions, but in order to advance the governance process, AECs should be alert to cases where new developments have occurred and previous decisions may no longer be appropriate.  Peer Review Peer review played a large and rather poorly articulated role in the decision-making process. Here, we need to distinguish three elements that may relate to peer review: scientific merit, social value, and ethical justification. Understanding the meaning of these concepts is sometimes complicated by different terminologies and definitions that exist in the literature. The j scientific merit of a project can include both scientific value (the ability of the work to make a positive contribution to advancing scientific knowledge, particularly in basic research) and the 93  technical merit of the proposed project including the use of testable hypotheses, good experimental design, appropriateness of the animal model and experiment for achieving the desired result, aptness of the experiment to answer the question, and skill of the investigator (Prentice et al. 1992). Thus, an experiment may have high technical merit but still have low value because it contributes little of importance to our scientific knowledge base. Other authors, using different terms, have chosen to distinguish scientific value from technical merit, notably Delpire et al. (1999), Stafleu et al. (1999), and de Cock Buning and Theune (1994). This might be a useful distinction because experiments with scientific value can be seen as one a subset of experiments that are considered valuable to society. Social value has been described as the "significance of animal experimentation" (de Cock Buning and Theune 1994) and "the interest of the experiment for human beings" (Stafleu et al. 1999) while for Delpire et al. (1999), social value only applies to contributions to health. For this discussion, I will adhere to the definition outlined in the results section, which includes all these meanings. Many types of science are considered to have social value and hence justify animal use; these include human or animal health, basic science (scientific value), environmental protection, economic, and education (e.g. Stafleu et al. 1999). Technical merit can be seen as a necessary but not sufficient condition for establishing social value in that a flawed experiment is unlikely to achieve its social purpose, although historically, what we would call flawed experiments have sometimes played an important role in scientific advances. Following assessments of the technical merit and social value of an experiment, AEC members must decide whether the research is ethically justified to proceed; are both the technical merit and social value of the research high enough to promise benefits that outweigh the imposed costs to the animals? Members in this study generally took peer review as an assurance of technical merit. This fits with the purpose of peer review, although there are possible weaknesses. For example, as noted by some participants, peer review is often done at the level of the overall project, not the individual experiment, so it is possible that a weak experiment could be proposed within an overall project that has passed peer review. Other studies have found that IACUC members differ in their views on the role of assessing scientific "merit" (Rowan 1990; Borkowski et al. 1997; Graham 2002), but the precise meaning of scientific merit is unclear in these cases. At a minimum, peer review should at least establish the scientist's competence to do work in the area, 94  so it provides at least some assurance of technical merit. Many members took peer review as an assurance of technical merit, social value and overall justification of the proposed research. They assumed that there was no need to weigh costs to animals against benefits of the research if peer review had been done, leaving the AEC merely to assess and reduce costs. As a result, considerably less attention was paid to benefits than to costs. Acceptance of peer review as an assurance of ethical justification may represent misplaced trust because peer review usually does not specifically ask reviewers to consider costs to animals or to balance these against social benefits. Given this interpretation of peer review by some members, we need either (1) to clarify the role of peer review for AECs, or (2) to expand the role of peer review so that it meets the expectation (by AEC members) that it involves an assessment of social value and overall justification, including an evaluation of costs to animals. However, even if peer reviewers were asked to assess whether the benefits of the experiment warrant the costs to animals, peer review (being done by scientific specialists) would still give us only the scientific specialists' view. If we want a broader view - including community standards - then the AEC still has to make this assessment. Thus, the view of some members that peer review is sufficient to establish that an experiment is justified (and that the AEC should merely deal with reducing harms), is not consistent with the stated purpose of the AEC. Nevertheless, peer reviewers and researchers could be asked to provide specific information about potential benefits that would enable committees to make better ethical decisions. For example, peer reviewers could assess experimental design in the context of the Three Rs and assure AECs that the minimum number of animals was selected by the investigator. Peer reviewers of funding agencies also generally make judgments about the relative significance to society of the research (importance of the problem being addressed), and this information might help AECs with their assessments of the potential benefits of the research. Concern about the benefits of teaching protocols might also be addressed by requiring external peer review of these protocols. It may also be necessary to carry out further research on the pedagogical benefits of using animals in teaching in order to gain a better understanding about when and for what purposes animals are useful for teaching. In cases where animal harm is high or benefits are low, AEC members in this study appeared to place more emphasis on assessing justification, and seemed more likely to employ cost-benefit assessments. Similarly, in the study of Stafleu et al. (1993), researchers did not 95  consider experiments acceptable if animal discomfort was high and social value was low. Experiments where social value was low were considered acceptable only when animal discomfort was also low. However, protocol rejection rates were low in this study as in several others done in the USA (Pious and Herzog 2001), Germany (Gruber and Kolar 1997), Canada (Bowd 1997), France (Verschuere et al. 2000) and Sweden (Hagelin et al. 2003). Low rejection rates may reflect, in part, a tendency of AECs to see their role as overseeing care, and reducing harms, but not as rejecting experiments, especially for protocols they take as peer-reviewed. However, low rejection rates may also suggest that the system is working well enough that investigators rarely bring poorly conceived protocols to the AEC. Overall, in this study, criteria for the ethical justification of research varied and assessments of justification did not appear to be a major activity of AEC members. Orlans (1997) also found that IACUC members did not pursue ethical review "very deeply", and other studies of IACUCs have found little consensus in their approach to assessing justification of research (Dresser 1989; Pious and Herzog 2001). In contrast Galvin and Herzog (1992) found that hypothetical IACUC members (undergraduate psychology students) applied cost-benefit assessments to all decisions of whether to approve or reject. However, these students may not reflect real-life decisions of actual IACUC members. Lack of consistency by members in this study and others may be a result of policy that does not clearly distinguish between the different components that go into decisions about the justification of research, as outlined in the discussion on peer review.  Decisions about Modifications Although members in this study may not always have assessed potential benefits, they were nevertheless examining costs, and in this study and others (Dresser 1989; Stafleu et al. 1999; Hagelin et al. 2003), members put a lot of effort into reducing laboratory animal pain and distress. In fact, most of the committee deliberations appeared to revolve around possible modifications to reduce pain and distress. Members used various cues to focus their attention on specific protocols. Similarly, expert decision makers are often quite skilled at noticing cues and anomalies in patterns (Klein 1998). The species in question clearly was an important factor in decision-making. This may sometimes fit with a cost-benefit approach, as the greater mental complexity of non-human 96  primates may well open them to ways of suffering that do not apply to, say, fish. However, preferential treatment of dogs and cats, may be a case where personal and community standards are being applied in a way that does not reflect a simple weighing of costs and benefits. Similarly, Galvin and Herzog (1992) found that a variety of factors related to the species of animal entered into decisions of members; these included phylogenetic considerations, capacity to suffer, labels (pet versus pest), and abundance in the wild. Although most IACUC members emphasized the importance of well-justified experiments for all vertebrate species, Graham (2002) found that the use of non-human primates influenced the number of animals approved in the protocol and the diligence of assessing scientific merit. Some of the easiest decisions of AECs occurred over the use of in vivo monoclonal antibodies or the failure to follow established Standard Operating Procedures. These were cases where there was a clear policy. In these cases the AEC can act in fairly straightforward and decisive manner, in contrast to often difficult decisions on other issues. Having more cases of clear policy (produced by a governing body like the CCAC, or by the AEC itself) may be an effective way to help AECs act decisively. Trust in individual investigators played a key role in decision-making. Members seemed to accept that some investigators can be trusted and others cannot. Attention to potential "problem" protocols may be a helpful safety mechanism for protecting animals. If this is so, then this is an important argument in favour of using local (rather than more centralized) institutional committees to review research protocols. One unusual cue in this study was how well the application form was completed by investigators. This is understandable given that the committee has mainly the form to work with. It could potentially represent unwarranted trust in indirect evidence (care in completing the form taken as evidence of care in carrying out the procedures). However, scientists who attach enough importance to the AEC review process to take care in completing the form may also attach importance to following AEC requirements, so the use of indirect evidence (the form) may be warranted to a degree, although there was no evidence that this is true. Experienced committee members may have recognized this connection. This warranted use of the form as indirect evidence of animal care may offer a different explanation for studies that have found that Research Ethics Boards for human research sometimes turned ethical review into merely a bureaucratic process of ensuring the forms were completed fully (McDonald 2001). 97  Attention to such indirect evidence may also stem from members grasping for ways to evaluate what is written on paper. One of the obstacles faced by AECs is that they have very little feedback on the ultimate effect of their decisions. Once a decision is made, for all protocols except deferrals, the majority of members do not see responses from investigators. Members will visit facilities on occasion but rarely see specific procedures, and the CCAC will usually visit only once in 3 years. As a result, there is very little association between making a decision and learning about its outcome. Feedback is important for increasing expertise in decision-making. A more evidence-based system would not only enable AEC members to improve their ability to make good decisions, but it would also make the process more transparent and enable the public to evaluate the effectiveness of AEC decisions.  Decision-Making Frameworks Systematic frameworks that have been developed to improve the decision-making process of AECs (Smith and Boyd 1991; Porter 1992; Mellor and Reid 1994; de Cock Buning and Theune 1994; Stafleu et al. 1999) are likely to increase objectivity, transparency, and consistency in decisions, all of which are valued goals of the review process. In a similar fashion, Pious and Herzog (2001) suggested that consistency could be improved by adopting approaches recommended for editorial peer review: developing specific evaluative criteria, decomposing global ratings into smaller categories, and averaging across multiple judgements. Systematizing decisions will likely help to ensure that all morally relevant concerns are raised. For example, several frameworks could be used to assess benefits and scientific quality more systematically than was done by the committees studied here (Smith and Boyd 1991; de Cock Buning and Theune 1994; Stafleu et al. 1999). Other factors, such as trust in investigator, not traditionally considered a part of protocol review, may also need to be recognized as valuable information. These frameworks can also provide a mechanism for discussion without necessarily turning the process into a exercise of calculation (de Cock Buning and Theune 1994; Stafleu et al. 1999). The disadvantage of these frameworks is that they tend to emphasize a single mode of decision-making (often cost-benefit assessment) and thus do not leave much scope for other approaches such as moral intuition. Hence, they may invalidate how some (especially nonscientist) members naturally make decisions. Indeed, results of this study support the observation by Galvin and Herzog (1992) that people use different patterns of moral reasoning. One of the 98  strengths of the AEC governance system is that it allows a range of approaches to decisionmaking from members representing scientific, humane, institutional, and community interests. The lack of clear policy over how decisions should be made, seen in the US, may actually be an advantage for permitting a variety of decision-making approaches. In order to make decisions more systematic (and thereby hopefully more consistent) it may be preferable to set out the information required rather than the logic to be applied to the information. Decisions will still involve individual judgement, but the information that goes into the decisions may be more consistent.  Conclusions Although most policy and commentators assume, recommend or require a rational costbenefit assessment for making decisions about animal use, many AEC members use other approaches. These include empathy with animals, comparison with perceived community standards, attempts to be consistent with previous decisions, and moral intuition. Thus, imposing rational systems based on cost-benefit assessments may not be suitable, especially for nonscientist members. If we want a broader view - including community input - the door is open, not only for other standards, but also for other styles of making decisions. Decisions will require that all relevant information is provided but how the decision is made could vary. Expertise in decision-making could also be improved if members received more evidence on the outcomes of their decisions. The poorly understood relationship between AEC review and peer review needs to be addressed, ideally through discussion between peer reviewers and AECs. First, we need to clarify what are the elements of scientific merit and social value, and be clear on who is covering what. Finally, the AEC should not be bound by peer review because it does not offer the same assurances (notably community input) that the AEC brings.  References  Borkowski G, Hunter A, Field K and Sischo W M 1997 Institutional Animal Care and Use Committees: a survey covering 10 years of experience. Contemporary Topics in 99  Laboratory Animal Science 36: 42-45 Bowd A D 1997 The educative role of an animal care committee in Canada: a case study. Animal Welfare 6: 309-315 C C A C 1993 Guide to the Care and Use of Experimental Animals. Canadian Council on Animal Care: Ottawa, Canada de Cock Buning Tj and Theune E 1994 A comparison of three models for ethical evaluation of proposed animal experiments. Animal Welfare 3: 107-128 Delpire V C, Mepham T B and Balls M 1999 A proposal for a new ethical scheme addressing the use of laboratory animals for biomedical purposes. Alternatives to Laboratory Animals 27: 869-881 Dresser R 1989 Developing standards in animal research review. Journal of the American Veterinary Medical Association 194: 1184-1191 Galvin S L and Herzog H A 1992 The ethical judgement of animal research. Ethics and Behavior 2: 263-286 Graham K 2002 A study of three IACUCs and their views of scientific merit and alternatives. Journal of Applied Animal Welfare Science 5: 75-81 Gruber F P and Kolar R 1997 Animal test advisory commissions: ethics committees in Germany. In: van Zutphen L F M and Balls M (eds) Animal Alternatives, Welfare and Ethics. Proceedings of the 2nd World Congress on Alternatives and Animal Use in the Life Sciences, UtrechfThe Netherlands pp 373-376. Elsevier Science B.V.: Amsterdam, The Netherlands Hagelin J, Hau J and Carlsson H E 2003 The refining influence of ethics committees on animal experimentation in Sweden. Laboratory Animals 37: 10-18 Klein G 1998 Sources of power: How people make decisions. MIT Press: Cambridge, UK McDonald M 2001 Canadian governance of health research involving human subjects: Is anyone minding the store? Health Law Journal 9:1-21 Mellor D J and Reid C S 1994 Concepts of animal well-being and predicting the impact of procedures on experimental animals. In: Baker R M, Jenkin G and Mellor D J (eds) Improving the well-being of animals in the research environment, Sydney, Australia pp 3-18. ANZCCART: Glen Osmond, Australia Orlans B F 1997 Ethical decision making about animal experiments. Ethics and Behavior 7: 163-171 Pious S and Herzog H 2001 Reliability of protocol reviews for animal research. Science 293: 608-609 Porter D G 1992 Ethical scores for animal experiments. Nature 356: 101-102 Prentice E D, Crouse D A and Mann M D 1992 Scientific merit review: the role of the IACUC. 1LAR News 34: 15-19  100  Rowan A N 1990 Ethical review and the animal care and use committee. In: Donnelley S and Nolan K (eds) Animals, Science, and Ethics. The Hastings Center Report pp 19-24. Smith J A and Boyd K M 1991 Lives in Balance. The Ethics of Using Animals in Biomedical Research. Oxford University Press: Oxford, UK Stafleu F R, Baarda B D, Heeger F R and Beynen A C 1993 The influence of animal discomfort, human interest and scientific quality on the ethical acceptability of a projected animal experiment as assessed with questionnaires. Alternatives to Laboratory Animals 2T. 129-137 Stafleu F R, Heeger F R and Beynen A C 1989 A case study on the impact of clinicallyobserved abnormalities in mice with gallstones on the ethical admissibility of a projected experiment with gallstone-bearing mice. Alternatives to Laboratory Animals 17: 101-108 Stafleu F R, Tramper R, Vorstenbosch J and Joles J A 1999 The ethical acceptability of animal experiments: a proposal for a system to support decision-making. Laboratory Animals 33: 295-303 Verschuere B, Autissier C, Degryse A D, Gallix P, Gotti B, Laurent J, Leinot M and Peyclit I 2000 Ethics committee recommendations for laboratory animals in private research in France. Laboratory Animals 34: 236-243  101  CHAPTER 5 -  Animal Ethics Committee Composition and Process: A Framework for Assessing Committee Effectiveness  Introduction Since the 1960's research ethics committees have become a widely used model for decision-making. Animal Ethics Committees (AECs) are responsible for ensuring the ethical conduct of research using animals in institutions. Similarly, Institutional Review Boards (IRBs) were created to protect the rights and welfare of human subjects used in research. Many similarities exist between these two models in their function, composition, and processes, and insights can be gained from both sets of experiences. Responsibilities of AECs include the review of proposed research protocols, inspection and monitoring of animal facilities and practices, establishing animal care and use policy, and providing training and education for animal users. Decisions about animal use by AECs are influenced by policy and guidelines, institutional culture, views and values, and decision-making processes of individual members. In addition, factors related to how well the committee functions can also affect decisions: committee composition, committee process, committee group dynamics, and training. Animal Ethics Committee membership varies depending upon the needs of each institution but usually includes a selection of members drawn from scientists and/or teachers experienced in animal care and use, veterinarians, institutional non-animal-users, people representing community interests, and animal technical staff. Typically for both IRBs and AECs, the committee includes at least one community or non-affiliated lay member. They are usually a minority on a committee that is composed mostly of scientists or others experienced with research. There have been reports that lay members often feel intimidated, and/or disrespected by the scientist members (Orlans 1993; Brown 1994; Theran 1997; Smith and Jennings 2003; Sengupta and Lo 2003). These observations raise questions about the effectiveness of these committees; however, very little research has focussed on how effective AECs have been. Increasing our understanding of how AECs function is essential to assessing how well this system of governance succeeds in ensuring the ethical conduct of research. This study examines factors that potentially affect AEC functioning and ultimately AEC 102  decisions, beyond the decision-making processes of individuals. Using the Canadian "Animal Care Committee" (ACC) as a model, the research focuses on committee composition, membership recruitment, motivation for joining, workload, committee dynamics and member training. The research identifies problems, suggests possible remedies, and proposes diagnostic tools to assess committee functioning.  Methods Chapter 3 describes the general methods used. For this study, interviews with members began with questions about how long they had been a member, how they became a member, how they were trained, meeting format, preparation time for meetings, length of meetings, and their thoughts on the workload. Members were invited to talk about their personal experiences as a member, inter-personal dynamics at meetings, and the role of the chairperson. The experiences of community members were emphasized in results and discussion because they play a key role as the only non-institutional member. Six community members and 13 scientists were interviewed (Table 3.2). Thus, analysis may not reveal all patterned similarities and differences in expressed views of community members. However, data from the literature was also used to build theories and understanding about these members. For each member, the average amount of preparation time per protocol was estimated as the typical amount of preparation time per meeting reported by the members (t), divided by the typical number of protocols the member reviewed (n). For members who reviewed all protocols, n was simply the average number of protocols reviewed per meeting by that committee in 19992001. For members who only reviewed some protocols in detail (and scanned the rest), n was estimated by apportioning the number of protocols among the average number of eligible members. This will slightly overestimate time because time spent scanning the remainder of protocols (which was unknown) was included in t.  Results  Committee Composition Expertise and Balance 103  The number of voting members on each committee varied from 7-17 (Table 5.1). All four committees were similar in composition, with most (> 70%) members being employed by the university. Of those, scientists made up the majority of the voting membership (5-10), followed by animal technicians (1-4), student members (1-2), veterinarians (1-2), and non-animal-users (12). Each committee had one or two community representatives. Veterinarians were voting members on two committees. Disciplines that scientists represented were: human and veterinary medicine, genetics, pharmacology, pharmaceutical sciences, dentistry, gynaecology and obstetrics, kinesiology, psychology, nursing, nutrition, biology, and agriculture. Community members were a lawyer and a nurse at one university, a clergy member and a member of the animal rights movement at another, two members of the Society for the Prevention of Cruelty to Animals (SPCA) at another, and an insurance industry professional at another.  Table 5.1  Composition of Animal Care Committees at four universities in western Canada  University Type of Member  A  Scientist  C  10  3  10  5  Animal Technician  2  I  4  1  Non-Animal-User  0  l  1  0  1  Veterinarian  l  1  1  2  1  l  1  2  Community  2  2  1  2  Total Number of. Voting Members  15  7  17  11  Student  1  2  D  B 1  ,  2  1  2  2  1  2  Chairperson of committee is from this group Ex-officio and non-voting members  Members generally reported that the expertise on their committee was balanced, as long as all members were present at meetings. Several members were concerned that the relative number of different members could affect committee function. All committees were consensus based, although one member described a previous system of decisions by majority vote. There was  104  concern that views of community members would carry little weight in discussions because they were outnumbered by affiliated and mostly scientist members. A n animal technician (Betty) stated, I think what our committees actually lack is a layman's voice. I think having one or two lay people - like when you look at a committee that's our size, 20 people when you only have two people who kind of fit that role and you've got eighteen others that represent science in a sense - I'm not saying that the committee is on purpose being biased, but to me it still is sort of biased. On the other hand, a scientist (Philip) described a protocol that was rejected because the single community member dissented. Another scientist (George) felt that a larger number of lay people should be on his committee for the purpose of increasing public awareness about animal research: I suppose a quarter to a third should be lay, or lawyers or priests or whatever. I think it's important that they see what we're doing because we're not allowed to work behind closed curtains. A n animal technician (Sophia) felt that there should be more than one veterinarian member to ameliorate the potential conflict that veterinarians face because they represent both investigators and the A C C : The veterinarian  who may really agree with you, has another role to play which  makes me think he can't really say what he really thinks. He has to do things in the correct political way and that is his position - to look at things from both points of view. And he is very good at giving people the benefit of the doubt, and it really surprises me how he can keep feeling that way because I probably couldn't. It is difficult. I think that is why having two vets is good because he could play that role and the other one could be the "bad" vet.  Recruitment and Motivation for Joining Methods of recruitment and motivation for joining varied considerably. In all four universities, there was a tradition of recruiting a representative from each university department  105  that uses animals for research. Therefore, the majority of scientist members were nominated by their own department or by the ACC (Table 5.2). Two veterinarians and one animal technician were members because their job required it. In contrast, one scientist was nominated by the university veterinarian because he was perceived, in his own words, to be a "complainer" and it was felt that "the best way to get complainers to engage is to get them on the committee." In general, the committees appeared to have little control over (or interest in) who was recruited from the animal use departments and often left it up to the departments to nominate a member.  106  Table 5.2  Type of member, gender, years served, and how appointed of 28 Animal Care Committee members from four universities in western Canada  Type of Member  Gender  Years ServedHow Appointed  Animal Technician  Male  0.5  Nominated  Animal Technician  Female  18  Nominated  Animal Technician  Male  1  Volunteered  Animal Technician  Female  3  Volunteered  Non-Animal-User  Female  3  Nominated  Non-Animal-User  Male  20-25  Nominated  Scientist  Male  15  Nominated  Scientist  Male  3  Nominated  Scientist  Male  8  Nominated  Scientist  Male  6  Nominated  Scientist  Male  Nominated  Scientist  Male  >10 10  Scientist  Male  2  Nominated  Scientist  Male  12  Nominated  Scientist  Male  8  Nominated  Scientist  Male  0.5  Volunteered  Scientist  Female  3  Volunteered  Scientist  Female  4  Volunteered  Scientist  Male  2  Nominated  Veterinarian  Male  3  Nominated  Veterinarian  Female  2  Required  Veterinarian  Female  12  Required  Community  Female  2.5  Nominated  Community  Female  6  Nominated  Community  Male  3  Nominated  Community  Female  6  Nominated  Community  Female  1.5  Nominated  1  3  4  1 2 3 4  2  Nominated  Male 14 Volunteered Community Institutional member experienced in animal research Member from within the institution who does not work with animals Institutional researcher experienced in animal care and use Non-institutional or non-affiliated member 107  In contrast, community members were actively sought by, and tended to be acquainted with other committee members. On one committee, the two community members were relatives of the committee manager; on another, the community member was a neighbour of a veterinarian member; on the third committee, the community member was a member of the same church as a past animal facility manager. On the fourth committee, the community members were recruited through the local SPCA. Two community members commented that recruitment of community members was challenging and needed to be addressed. Cassandra noted the conflict that arises in recruiting members. On the one hand, "you don't want to go out in the community and say, 'Hey, guess what? We do all this stuff to animals ....' That's a little problematic." But without this communication, as she noted, How do you go out and recruit? I don't know how the other [ACCs] do it and I think it should be a goal. The same way as you want quality people from other areas on your committee, you want to have a quality community member who is going to be able to give some good input. One committee had an animal rightist community member who opposed the use of all animals in research; however, other members of his committee reported that he appeared to be an active and well respected contributor to meetings. As a scientist (Philip) described it, That [animal rights] is his personal view, but he doesn't let that get in the way of how he works on the committee. He's always there to make sure everything is done properly. He's usually the one who will ask a question [about a protocol] that looks to everyone else to be benign, just because he sees that as his job - to raise the profile and ask the questions. But we can work with him. He's great to work with. In fact, this community member reported that he volunteered because he felt that he could make a contribution to implementing the Three Rs. Six members volunteered to join the committee for a variety of reasons. One scientist (Teresa) volunteered because she felt she had relevant experience. Five members volunteered because they were unhappy about some aspect of the ACC protocol review process and were 108  hoping to change it. These included two animal technicians (Sam and Sophia) who felt that the ACC was not looking at protocols with sufficient scrutiny. As Sam described reacting to some ACC decisions by wondering, "How the hell was that protocol passed?" As an animal user submitting protocols, Sue was not impressed by previous interactions with the committee and wanted to find out how the process worked: The reason I volunteered to be on it was because I was not impressed at the receiving end, and I thought that something was not right... and I thought, "Man, ... What is going on over there?" And once I got there I turned around quite quickly. I thought the committee was doing a good job. For another scientist (Al), the motivation to join was also based on previous frustrations with the ACC: When Ifirstgot on the committee my attitude was totally different from what it is now. When Ifirstgot on I looked upon the committee as a really negative thing and I was thinking, "I had better get on the committee to make sure that they don't overdo things, so if anything happens I would be there to maybe put in a few words." Al also knew of other members who joined the committee with similar concerns. Several comments by scientists suggested that they viewed their role as representing their departments, to ensure the process was fair to them. For example, Philip commented that, We've [animal users] got a really good rapport with the ACC. Now part of that... is the fact that we've got representatives from our own departments on there, so that's good. You feel that someone is in there fighting for your corner, or at least representing your corner.  Length of Term in Office Length of membership ranged from 0.5 to 25 years with an average of 6.5 years (Table 5.2). Committees differed in the permissible term of office according to their individual terms of reference. Universities A and B appointed for 2-year renewable terms, and University C appointed 109  for 3-year renewable terms. University B was the only university that nominally placed a limit on the number of renewable terms to a maximum of 4 years, although two of its members were significantly over the limit during this study. All universities had at least two members who had been members longer than two terms. At University A, eight of 13 members interviewed had served for more than four years. At University C, the term length of veterinarian and one technician was long because membership was a requirement of the job. Three members made comments about the importance of turnover in members. As Sophia put it, there is a risk of members becoming less effective if they serve on the committee for too long: There is dead weight on there. There's people who never come to the meetings, so why are they on it? ... There are people who just sit around and don't say anything and I think they are there for a reason, but you can't really force people [to contribute]. Mary's committee rotated some members in order to keep the committee "fresh". For example, a member would serve 6 months consecutively followed by a 6-month break. The rotating members continued in this pattern until they had served their full terms. As a lay member, Cassandra felt that in order for her to maintain a community perspective, she needed to quit after 6 years of service.  Training With one exception, all members "trained on the job", with very little or no formal guidance about their role and that of the committee. Typically, a new member received a copy of the CCAC Guidelines, along with some other documentation, such as the terms of reference of their committee, and then they attended and observed several meetings before taking on the responsibility of reviewing protocols. The majority of members felt that this was the best way to prepare them for their role for several reasons. Some animal technicians and scientists felt that they were already knowledgeable about the oversight system because of their experience as animal users. Two community members did not want formal training so that they maintained a fresh outlook or a "gut-feeling" approach to reviewing. For example, Cassandra said, If I am going to be a true lay member, a lay community member, I can't know too 110  much. ... You use what I call the 'smell test.' I want to be able to walk in there and say, "This doesn't sound right to me. This sounds like too much animal use, or those animals are suffering, or this doesn't sound like an experiment that really has some global value to it, so why should we be subjecting animals to this?" A scientist (Bob) felt that learning as you go is good: "You come as a blank slate, not preprogrammed.... You quickly learn. I don't think training is useful." Only a veterinarian (Rose) would have liked more training for members to provide a basic understanding of animal welfare: One of my big interests is in training the Animal Care Committee member. ... I have a really vested interest in having a committee that is well trained to evaluate these protocols from an animal welfare perspective. What I think they [members] have to bring to the table is a background in understanding all of the specifics that have to do with how an animal is to be treated. Several members felt that some training about the techniques of genetic modification would have been useful. As a mechanism for training, several members found that reading too much documentation was cumbersome. Many recounted that they read the C C A C Guidelines initially, although not necessarily in detail, but they did not refer to them again. A scientist (Mark) relied on the veterinarian to be familiar with the guidelines. Another scientist (Philip) felt that additional reading material was not useful: If you had also tried to document those [examples of past decisions] and given them to me in advance, I would have been looking at reading 20 pages of stuff which I would probably not have read anyways. So I don't think that in terms of my function on the committee, I don't think I really missed anything or would have improved had I been given anything.  Committee Process Committee Discussion at Meetings Members voiced concerns that committee discussion was influenced by the size of the  111  committee and attendance at meetings. An animal technician (Sophia) and a scientist (Oliver) felt that larger numbers of members created more discussion which was necessary for an effective review process. As a result, Sophia was not happy about the option of splitting her committee into two groups: "We sit and talk - there is a lot of discussion on a lot of [protocols] - and I think you need all those people there to really discuss it properly." In addition a veterinarian (Rose) felt that face-to-face discussion was essential: We do allow people, if they can't make it to the meeting, to submit a written review. If everybody did that we wouldn't have a committee. There has to be faceto-face. A lot of things come out during that face-to-face meeting that you are not going to get through e-mail, you are not going to get through passing the protocols around. It is a different process. I really believe that committees have to do that. As much as you don't want to, and as much you don't think you have enough to discuss, and everybody is too busy and "yadda yadda yadda." The committee ... has to be sitting down. A scientist (Ken) also felt discussion was essential, In discussion you can get everything clear. ... Everybody's concerns are monitored carefully and handled carefully and if everybody's happy after the end of that particular protocol, then it is approved. On the other hand, Alex thought that his committee worked more slowly because his committee (15) had grown: I think the same things were brought out when we did them quickly as when we did them slowly. It's just that now I think we spend more time on the troublesome applications. It's not a bad thing. More discussion is probably a good thing, but I think also the bigger the group is, the longer it takes. When there's a small group there, then usually things go through faster. However, a scientist (Sue) felt that her ACC could be bigger to compensate for absenteeism among scientists:  112  On any given day a couple, at least, are missing, so the committee is not particularly balanced each time, depending on who is missing. We have quite a large component of people who don't have animal care expertise on the committee. So we have potentially two lay people. So when you boil it down to who is functioning on the committee - sort of excluding the chairperson, excluding the manager, excluding the lay people, excluding the [student member] in a sense who is left? It's not that big a group for the number of protocols we do. I think it could be bigger. Interestingly, Sue did not consider the chairperson, community, and student members as "functioning" members.  Meeting Format, Preparation, and Length All committees normally had one meeting per month and reviewed an average of 18 protocols per meeting (range 0-49) and an average of 191 protocols per year (range 7-313) from 1999 to 2001 (Table 3.1). All committees reviewed proposals for biomedical research and teaching; some also reviewed proposals from wildlife, agricultural, and veterinary research (Table 3.1). All committees reviewed proposals from Categories of Invasiveness A - D (scale of animal pain and suffering ranging from the lowest category A to the highest category E (CCAC 1993)); three universities had reviewed more than one at level E from 1999-2001. Apart from University B (where all members read protocols), all committees had a system whereby protocols were assigned to two members for detailed review. This involved obtaining any necessary information and presenting a summary to the committee. Besides these primary reviewers, the chairperson, the veterinarian and the community member were also responsible for reading all protocols in detail. Most members briefly scanned through the protocols that were not assigned to them. Members described their brief review as reading titles and lay summaries, scanning for anything that "stood out," reading protocols that were more invasive, reading ones that were written by "problem" investigators, or reading ones for which they felt they had appropriate expertise. Scanning, for some members, was quite brief. Several members read protocols of lower Categories of Invasiveness (B) only during meetings. One community member (Cassandra) did not read the procedures section because she felt she did not sufficiently 113  understand the technical aspects. One scientist (Oliver) was concerned about the impact that absenteeism of members has on this type of review process: Well, we get too many protocols where neither of the [two] reviewers of the protocol are there and that is a problem. We get the written submission but sometimes we don't even have a written submission from them. So you start to worry about the effectiveness of the review process. The majority of members prepared for meetings during the previous weekend. Several members, in particular community members, said that other personal and work obligations affected how much time they were able to spend in preparation. For the members who read several protocols in detail, and scanned the remainder, median preparation time for meetings was 2.75 hours per meeting (range 0.75-7) and median time per protocol was 51 minutes (range 21150) (Table 5.3). For those who read all protocols in more detail, median preparation time was 6.4 hours per meeting (range 0.75-12) and median time per protocol was 23 minutes (range 4-60). Overall, chairpersons, animal technicians, and veterinarians spent more time preparing for a meeting than other members. Chairpersons spent 6-10 hours in preparation. Two community members (Craig and Scott) spent a low amount of total time but this reflected the small workload of their committee (average one protocol per meeting). Although actual amounts of time spent is not known for all members of this committee, they recounted that because workload was small they read every protocol in detail. A community member (Scott) suggested that his review time was reduced because many protocols involved fish which were easier than reviewing mammal protocols. On all committees except University B, all the scientists reviewed their assigned protocols in detail and scanned the remainder. Although community members were supposed to read all protocols, two did not. In general, those who read all protocols in detail spent more total time preparing for the meetings but less time per protocol, and vice versa for those who only read their assigned protocols in detail. Even though there was variation in the amounts of time spent preparing, when members were asked about whether they had a reasonable amount of time to prepare for a meeting in order to do the job well, all except one scientist (George) answered in the affirmative. George, who spent from 2-3 hours, felt that he was rushing to get through them.  114  Table 5.3  Time spent in preparation for monthly Animal Care Committee meetings for those committee members who read all protocols in detail and those who read several protocols in detail and scanned the remainder.  Type of Member  Code Name  Preparation Time per Meeting (hours) 1  Estimated Preparation Time Spent Per Protocol (minutes) 2  All Protocols Reviewed in Detail Animal  Ben  8  17  Animal  Sam  8  23  Animal  Sophia  9  60*  Veterinarian  Alfred  5.5  11  Veterinarian  Rose  Community  Carmen  1.5  4  Community  Rachel  8  23  Community  Craig  1  60  Community  Scott  0.75  50  3  30*  Several Protocols Reviewed in Detail and the Remainder Animal  Betty  4  86  Non-Animal-User  Angela  2  21  Scientist  Al  4  69  Scientist  Alex  1.75  30*  Scientist  Andy  0.75  45*  Scientist  Bob  4  69  Scientist  George  2.5  43  Scientist  Ken  2  30*  Scientist  Mark  5  75*  Scientist  Nik  1.5  26  Scientist  Oliver  1  30*  Scientist  Sue  3.5  60  Scientist  Teresa  3  51  Scientist  William  7  150  Community Cassandra 3 If participants gave ranges, then medians are shown.  51  115  For each member, the average amount of preparation time per protocol was estimated as the typical amount of preparation time per meeting reported by the members (t), divided by the typical number of protocols the member reviewed (n). For members who reviewed all protocols, n was simply the average number of protocols reviewed per meeting by that committee in 19992001. For members who only reviewed some protocols in detail (and scanned the remainder), n was estimated by apportioning the number of protocols among the average number of eligible members. This will slightly overestimate time because time spent scanning the remainder of protocols (which was unknown) was included in t. * Indicates actual time spent per protocol in minutes as reported by the member. 2  3  Meeting length ranged from 2-3 hours for all universities. University B, with the fewest protocols, spent about one quarter of meeting time reviewing protocols and the remainder for discussion of policy issues and animal health reports. All members recounted that meetings usually carried on as long as necessary. If they went too late, then items were tabled until the next meeting. For one committee the single community member had to leave at a specific time, although on occasion the meeting apparently continued beyond that time. All members felt that meeting length was generally sufficient to do the job well. However, Oliver was concerned that there might be insufficient time when his committee reviewed more than 40 new protocols. Several other members were concerned that although total meeting length was fine, some protocols were rushed through at the end of a meeting because time spent on each protocol was not distributed well. They felt that the last protocols, which were usually the less invasive ones, did not always receive sufficient focus. Sue said, I think how we distribute it is sometimes out of balance in terms of some applications getting an awful lot of our time, and that leaves us maybe short of time to look at others.... I am uncomfortable with running out of time because that means that some applications are not looked at in the detail that I would like them to be looked at. ... It might just lead to two or three more comments that might just give a more balanced or thorough look at the protocol.  Committee Dynamics Interpersonal Dynamics The majority of members related that they were happy with their committee atmosphere, that their views were valued, and that group dynamics were comfortable and respectful. A 116  community member (Cassandra) felt that committee functioning and the contentment of members was essential to an effective ACC oversight process, but she felt the CCAC did not pay enough attention to this issue during their site assessments. Five members reported that they had negative experiences with other committee members. For example, an animal technician (Sophia) felt she could voice her opinions, but she perceived that her committee was not always receptive: "Sometimes in those meetings people go, 'Oh there she goes again. I wish she would just shut up!'" In response to a question about whether her comments were addressed adequately by the ACC, Sophia said, Not all the time. Yeah, I say what I think and some people completely disagree with me and I accept that because they may know a lot more about the area than I know.... I know that they write down what I say, but I also know that they go through and revise what has been said. I am not 100% confident that what I said has actually gone through [to the investigator]. Several members commented that individual members can influence committee functioning. A scientist (Oliver) spoke about the influence that one committee member had on his committee, partially because his views differed significantly from the rest of the committee: But in the past I noticed the way the committee worked really depended on whether he was there or not. I don't think that is as much the case now and I don't notice that it makes much difference who is there or isn't there. A community member (Cassandra) pointed out that the positive receptiveness of one member on her committee largely influenced the way that the entire committee behaved, highlighting the importance of good role models or leadership. A veterinarian (Rose) added that, If you are at a committee meeting and the scientist is obviously making people feel uncomfortable, then somebody has to be brave enough - whether it be the Chair or whoever - to take a stand and point out that problem. Not only can members influence the committee dynamics, all members on one committee mentioned that one of their community members had a strong influence on the types of questions that were raised in discussion, even when he is not present at meetings. As a non-animal user said: 117  "When [community member  ] is not here in fact, somebody's bound to say, 'What would he  say?'" On the other hand, although dynamics change, two members felt that outcomes did not. For example one scientist (William) said, Committee dynamics always change depending on the bodies that are there, but I don't think outcomes change. I think the level of discussion, the intensity of discussion might change, but I don't get the impression that the variations in the committee structure change any outcomes.  Experience of Community Members Several members commented that the committee atmosphere was intimidating for community members. A community member (Carmen) raised several problems encountered by community members: feeling intimidated by scientists (even though they did not directly make her feel that way), being perceived as having insufficient expertise, and the difficulties of being an "outsider". She suggested that these challenges require a unique personality. Carmen felt fortunate that she was able to turn to another committee member for discussion before a meeting, rather than during a meeting: Because I have the relationship with  , I go to her for clarification. Now, if I  didn't have that relationship, I don't know how I would feel, having to ask other people at the meeting ... being put on the spot or raising something that I am unsure of. But you know, you don't want to sound as if you don't know. That could be an issue for community reps; the level of comfort of speaking up or asking ... because they [other ACC members] are intimidating. But they have never given me any reason to feel intimidated, I just am. They don't talk down to me, and they don't give me that feeling, but you can't help but do. The other thing too is that they all know each other, and they have relationships, and you don't. So you're always the outsider, and it's hard to come to a meeting as an absolute outsider, who only half knows what you are talking about. It's takes a unique personality to be able to.  118  Two other community members reported that they initially found the committee atmosphere intimidating but not after realizing that they were as competent as other members and, in Craig's case, appreciated by the committee. When asked if he found the committee intimidating, Craig commented, I did initially. And then I realized, "Look, these are just normal people. They're academics but, you know, I'm not a really stupid person." I understand that they appreciate what I think; they've expressed a lot of appreciation for me. So that has really helped me. Mary gained confidence to raise questions when she realized that scientists members, like her, did not always understand technical information and she felt that over time, familiarity with other committee members created a less intimidating atmosphere. Six institutional members commented that community members were very important members of the committee. A nonanimal-user (Angela) supported the view that community members can play a valuable role of posing the "obvious" and "unsophisticated" questions: The lay people (I think) actually make the meeting even more interesting from my perspective because they'll often ask the questions that nobody else around the table wants to admit they don't know the answer to, and they'll ask some really obvious question, you know, "I really just don't understand this" and somebody explains it to them and the rest of us go, "I'm glad somebody asked this." A scientist (Bob) sympathized with the challenges faced by community members: "Sometimes I think the lay people are fairly silent but I can understand, especially the technical stuff - it must be really hard to jump in." A community member (Rachel), felt her committee listened to her, although she still remained quiet: I think sometimes I feel that I should probably say more but then I think, well - not that people aren't listening to me and they don't think that my opinion isn't valid but a lot of times I sit back and wait for somebody else to bring it up because somebody usually will. Several community members had experienced negative interactions with other committee 119  and C C A C members. Mary recounted a scientist member saying to her, "It is important to have a community member, but they are a pain in the ass." Cassandra felt that negative attitudes also existed within the C C A C . She recounted how a member of the C C A C assessment team had asked questions and made impolite comments about her in her presence during a C C A C university site assessment. As a result, she felt that C C A C site assessments should include talking to individual committee members about their personal experiences as an A C C member. In addition, although two community members felt that their comments were well received, they complained about a lack of appreciation by other committee members for the work that they were contributing. Carmen voiced her thoughts strongly: I have a full-time job and job commitments and family commitments, and commitments to my own boss who is allowing me to take time off. And I run to the meetings for 2:00, and then to find that two or three just don't show, and we don't know why they don't show, and one of the main reviewers sends a piece of paper with his or her comments on, and so that doesn't give me a good feeling. One committee provided an honorarium for their community members but Carmen did not feel that, in her case, an honorarium would have helped her feel appreciated. Three members felt that a less intimidating atmosphere for community members could be achieved by increasing the number of them. They also noted the importance of choosing community members with appropriate personalities. Carmen felt that in addition to sharing the responsibility of attending meetings, having more than one community member would also provide moral support: There should never be only one. When I first started there was two, and we used to sit together and it was good. Because then we felt some camaraderie.... If there is two community reps there, then if there is some emergency or disaster I can say, "I can't come." Mary also felt that she would benefit from being able to discuss issues with other community members: "Our Animal Care Committee has usually two community representatives; we talk to each other about concerns. This helps." She also discussed the idea of having a mentor system or a "chat group" for community members that could apply to a larger scale, so that members from  120  different institutions could "offer support" to each other and discuss "issues of concern". Bettyagreed, but in addition to increasing numbers, she felt that the choice of community member was also important, especially when there is only one, And so to me, if you only have one lay person you have to be very careful of who you pick so that they have that ability to do that [voice their opinion] - because if they don't, then again, it's almost like having no lay person. You know, they just sit back in a corner and don't say anything, because they're too scared or whatever. Both Cassandra and Carmen felt that their own confident and outgoing personalities, as well as a receptive committee, enabled them to contribute. As Cassandra put it, I think the ability for the lay member to have any input is dependent on the personality of the member and committee at large. So whether or not they want to listen to me depends upon them and whether or not I feel comfortable enough, or I am the kind of person who will put myself forward. On that basis, I have no problems in those meetings. I feel quite comfortable to say what I think, and I think people listen or are polite enough to listen, but you have the floor. ... I don't know to what extent they actually accept what I say and act upon it. Certain members certainly give the appearance of doing that. In summary, the committee was sometimes found to be intimidating for community members because they may feel they lack expertise, they are outnumbered by institutional and scientist members, they are outsiders on a largely institutional committee, and also because other members may not value the community member's presence. Some negative interactions had occurred with various members and individual members could influence the committee atmosphere.  Role of Chairperson I asked most members what they thought the role of the chairperson was or what their experience had been with their chairpersons, particularly during meetings. Generally, members felt that the chairperson is particularly important in keeping the meetings efficient, maintaining an open and respectful atmosphere where all views or approaches are accepted, playing a neutral role  121  by participating i n discussion without influencing decisions, ensuring that issues are not missed, keeping the investigator's interests i n mind, and helping a committee reach consensus. Some members also described the chairperson as a moderator or an administrator. A s an animal technician (Betty) put it: Their role is to make sure everybody has a voice. To me, they really even shouldn't be there to cast the vote one way or the other, in a sense. They're more to, you know, get the facts on the table, and find out what facts are missing and also to make sure that everyone who sits around that table has an equal voice. A scientist (William) described his chairperson i n the following way: They observe the proceedings and moderate the proceedings. They do not have a strong input.... They need to be neutral. They have a hard job to do too, 'cause they're the front line when people [investigators] get annoyed at decisions that have been made. This last quote also brings up the dual role the chairperson plays working with the committee and also with investigators, some of whom are committee members. A scientist (Mark) mentioned that the chairperson needed to keep the process efficient and on track, and to have the strength to deal with conflicts with investigators or other committee members. He described the role of the chairperson as: M a k i n g sure it's an efficient process. M a k i n g sure that people don't lose sight of what we're actually reviewing. Some people w i l l show up at a committee meeting with a particular agenda. So there's something they may take offense to on a protocol that's not specifically related to that protocol but maybe to general policy. Or maybe i f they themselves have had a protocol reviewed and had somebody question it, they basically end up with a 'beef. I think it's up to the Chair to make sure that that kind o f discussion isn't part o f the review process ... and to not pussyfoot around difficult situations. Y o u do deal with some difficult protocols and the Chair's got to have the intestinal fortitude to address those issues and reject and terminate people's protocols i f they have to, and not try and give people one  122  last chance, which has been an issue. Two scientists (Bob and Nik) commented that the length of meeting was greatly influenced by the ability of the chairperson to "keep the meeting going", to not "tolerate a lot of idle chatter" nor to "dither." In contrast to the other universities, University B (with a small committee) appeared to have a chairperson that was an equal participant in discussion and decision-making and members felt it worked well. Craig described him as, "not the 'neutral facilitator of a process' kind of guy. He's getting his digs into certain things,... I've always appreciated his perspective, actually. I really do." Of the four current chairpersons, three were animal users and one was a non-animal-user. One non-animal-user felt that the chairperson should have an arms-length relationship with the committee: "The Chair should in fact be somebody who can't be twisted by the department Chair, or by somebody with big grant-driven leverage."  Discussion Committee Composition The committees in this study were similar in size to comparable committees in the US, notably Institutional Animal Care and Use Committees (IACUCs) as reported by Borkowski et al. (1997; mostly < 14 voting members, median 7), and IRBs as reported by De Vries & Forsberg (2002; average of 13 members) and Jones et al. (1996; 14 members). In composition, the committees were also similar to IACUCs (Rowan 1990; Orlans 1997) and most human IRBs (Jones et al. 1996; De Vries and Forsberg 2002; Sengupta and Lo 2003) in that scientists and institutional members dominate the membership, with one or two community representatives. This is in accordance with the terms of reference of the committees in this study and also with Canadian policy which requires at least one community member (CCAC 2000). Similarly, the US Animal Welfare Act (AWA 1985) and the Public Health Service Policy (Public Health Service 1986) require that IACUCs have one member who is not affiliated with the institution. These policies do not require specific proportional membership. Internationally, there are large discrepancies in committee composition with a higher  123  proportion of community members in some countries. In the UK, the Home Office guidelines for committee composition for the Ethical Review Process suggest that it is "desirable" to have "one or more lay people independent of the establishment" (Home Office 1998). Animal Ethics Committees in Sweden have an equal number of lay members and scientists or members who work with laboratory animals (The Swedish National Board for Laboratory Animals 1979). The Netherlands requires equal numbers of experts in animal experimentation, animal welfare, alternatives, and ethics, although only two of them must not conduct experiments on animals (The Dutch Experiments on Animals Act 1997). Australia requires no less than one third of the membership to be lay people and from animal welfare agencies (Australian National Code 1997). If the composition is not appropriate, there may not be enough attention to the interests of the animals and to the justification of research to satisfy community values; thus, a key purpose of the committee may be thwarted. This study highlighted three ways that this can happen: (1) when the committee does not have enough independence from the institution, (2) when community or other minority members have inadequate voice and/or feel intimidated, and (3) when the chairperson does not direct the committee appropriately. First, AECs and IRBs have been criticized for an imbalance in membership in favour of scientists and institutional members (Orlans 1997; Office of the Inspector General 2000; Bauer 2001; National Bioethics Advisory Commission 2001; De Vries and Forsberg 2002). It is claimed that a large imbalance in membership can render the process biased towards the interests of scientists and the institution in promoting the continuation of research (Rowan 1990; Orlans 1997; Bowd 1997; Bauer 2001). Gruber and Kolar (1997) described results of a German Animal Protection Organization inquiry which found that the majority of members representing animal protection felt AECs were unduly allied with the institution, even though animal protection members made up one third of the committee membership. As a result, in discussion about revision of the German Animal Welfare Law they demanded an increase in membership up to 50%. As in this study, community members from various ethics committees have reported feeling that they had limited power because they are outnumbered, especially in majority vote systems (Orlans 1993; Brown 1994; Bauer 2001). Adding to the potential bias is that chairpersons are often scientists in both AECs (Bowd 1997; Orlans 1997; this study), and in IRBs (De Vries and Forsberg 2002). Canadian policy recommends that to avoid conflict of interest, the chairperson should not be the veterinarian or an institutional manager of an animal facility (CCAC 2000). They suggest that scientists are strong 124  candidates for chairperson, as long as they are not involved in a significant portion of animal use at the institution. The US has no specifications about who the chairperson should be other than to have significant stature (AWA 1985). A scientist chairperson may have sufficient expertise to understand protocols and thus be able to converse with and gain respect from investigators. It is probably easier to recruit an animal user as chairperson because they have vested interest in the review process. However, as one institutional non-scientist chairperson pointed out in this study, a non-scientist chairperson is desirable because they provide more independence from research interests. For this reason Australia recommend that the chairperson be a "non-scientific senior member of the institution" because they are familiar with the institution, are impartial, and provide credibility when explaining the institute's decisions concerning animal research (Australian National Code 1997). Second, an unbalanced membership can also create an intimidating atmosphere for nonscientists and in particular for community members. Half the community members in this study felt intimidated by serving on a committee mostly of scientists, felt sensitive to being perceived as lacking knowledge about the technical aspects of protocols, or felt like an outsider in the interpersonal environment of the committee. A survey of IACUC community members showed that 13% felt intimidated by other members, although the majority felt free to express their views (Theran 1997). Several examples were raised in this study about the positive and negative influence that individual members can have on the respectful atmosphere of the committee and in one case, on the substance of discussion. In addition, the attitude of the scientific members of the ACC toward non-scientist members might influence the degree of intimidation that minority members feel. Most members in this study recounted that their views were respected by their committees, but some negative interactions between members had occurred. Five other studies found that community members had experienced hostility from other committee members and lack of respect for their concerns (Orlans 1993; Robb 1993; Brown 1994; Theran 1997; Gruber and Kolar 1997). Similarly, in interviews with IRB members, Sengupta and Lo (2003) found that while most members had positive interactions with scientist members, many also had experienced feeling that their opinions were discounted, not understood, and not taken seriously. One community member in this study felt her presence was unwelcome but tolerated, similar to IRB members who felt that scientists tolerated community members because legislation mandated their presence (Sengupta 125  and Lo 2003). Two community members also felt that their time commitments were unappreciated by the committee. However, in a survey, Theran (1997) found that 88% of community IACUC members felt the committee valued their opinion. Feelings of intimidation or isolation may be felt by other members on the AEC. Animal technicians are often minorities and in some cases may also be employed by investigators, some of whom may be on the committee. This may introduce a power dynamic that may hinder openness about their concerns during meetings (Heidbrink 1987). This study also found that one technician had experienced feeling that their opinion was discounted by the rest of the committee. Although there was no evidence in this study (only 2 were interviewed), institutional non-animaluser members, who are usually a minority, might also face similar challenges. Student members may face similar challenges. In addition, scientists, although not minorities, may feel fearful of raising objections against their colleagues' protocols. Third, poor leadership by the chairperson can permit a deleterious committee atmosphere to go unchecked; with members feeling intimidated or not respected, or with some opinions dominating discussion. The role of the chairperson was seen by most members as a neutral facilitator to create an open and respectful atmosphere where all views are considered. The style of leadership is important because a forceful chairperson can control discussion and discourage frank debate (Lo 1987). As Lo also discussed, committees are at risk of "groupthink" whereby they inadvertently pressure members to reach consensus, avoid controversial issues, underestimate risks and objections, fail to consider alternatives, or fail to search for additional information (Janis and Mann 1977).  Solutions Both in this study and others there is evidence that steps are needed to avoid an intimidating atmosphere for some committee members. Increasing the number of minority members, along with good leadership by the chairperson and a respectful and open committee, can provide strength and support, thus reducing the intimidation felt by these members. Specific training of members about their roles and the role of the committee might help to compensate for disparities between members so that new members feel less intimidated and so members understand the value of contributionsfromall members, especially the community members. In some cases, better understanding of the official mandate of the committee may also 126  provide weight behind arguments that are in opposition to the majority, e.g., by empowering dissidents to frame their arguments in terms of the Three R's. Some members felt that a confident and outgoing personality of the community member helps to overcome these problems and facilitate effective community membership. Other research has suggested that the personality traits a community member should possess include: confidence, strength of character, no fear of asking questions, ability to withstand group pressure, enthusiasm, pleasant personality, diplomacy, good communication skills, ability to present well reasoned arguments, and ability to be satisfied with minor impact (Orlans 1993; Brown 1994; Dresser 1999; Jennings and Miller 2000). However, it seems unsatisfactory if an extraordinary personality is sometimes required for a community member to be effective. Skilful intervention by the chairperson and other members improve the committee atmosphere; as Mench and Stricklin (1991) noted, members who are "encouraged to voice their concerns and whose opinions are respected are less likely to feel isolated or overwhelmed, even if they find themselves consistently in a minority." In addition, Verweij et al. (2000) pointed out the importance of maintaining an environment that is comfortable and "safe" for all members because ethical deliberation sometimes involves articulation and critical assessment of fundamental views which can cause feelings of apprehension. Therefore, to create a comfortable and respectful committee atmosphere, it might be helpful to provide leadership training for the chairperson. Solving concerns over the lack of independence will require a closer examination of the role of the committee and especially the community member. The proper structure of a committee must follow from a clear understanding of its function. First, what does independence mean? For IRBs, Brody (1998) suggests that policy is vague about whom the committee is meant to be independent of. Policy is similar for AECs. Should it be independent from particular researchers at the institution so that protocol review can still be carried out within the institution, or independent from the institution and from the research perspective? The latter is a problem if the committee is made up of largely institutional and scientist members. One solution is to move to greater independence from the institution, such as the use of regional committees, as in Sweden (The Swedish National Board for Laboratory Animals 1979). Another solution emphasizes achieving independence through the strong participation of noninstitutional members. What proportional membership would ensure full participation by community members? This is an empirical question which has not yet been answered. This study provides some 127  evidence that more than one community member is desirable. One of the benefits of having many institutional members experienced in animal care and use is that they may be familiar with investigators and animal facilities and thus provide relevant information to AEC deliberations: expected benefits of research, quality of care of animals, and level of expertise of animal users. However, adding non-institutional members can reduce the imbalance without reducing the number of institutional members. Although membership by other institutional minority members, such animal technicians and non-animal-users, will not impact independence from the institution, they will provide views different from the views of scientists. Therefore, the appropriate proportion for these members should also be considered. A clear understanding of the role of the committee and the community member would help to answer questions about committee structure. Unfortunately, policy statements about these roles are often quite vague. Canadian policy describes the community member as "representing community interests and concerns, and who has no affiliation with the institution" (CCAC 1993). An orientation package indicates (not clearly) that the community member should: 1) build trust between the local community and the research institution, 2) provide public accountability, 3) support animal interests, and 4) contribute community interests and concerns to the discussion (CCAC 1999). Policy in the US offers little guidance to individuals asked to serve as community members (Dresser 1999). The US Animal Welfare Act describes them as representing "general community interests in the proper care and treatment of animals" and as being "not affiliated in any way with the institution and not a member of the immediate family of a person who is affiliated with the institution" (AWA 1985). The rationale presented by the US Congress in 1985 for the inclusion of a community member on IACUCs is that, "where federal funding is concerned, decisions concerning social values should be made in a forum that includes societal involvement" (Orlans 1993). UK policy only says that the lay members should be independent of the establishment (Home Office 1998). Which interests should be represented by the community member? Some countries distinguish between community members who are members of the animal protection movement and those who are not. Animal protection groups sometimes assume that the community member should represent the interests of the animals (Brown 1994; Smith and Jennings 2003), although policy is often vague on this point. In fact, both types of community members can serve quite different roles. Policy for IRBs specifies that community members and non-scientist members are 128  supposed to make the IRB more sensitive to the concerns of research subjects and to the populations from which they are drawn (Sengupta and Lo 2003). The equivalent for AECs would be to specify membership from the animal welfare community to ensure that an animal advocate is involved in decision-making. However, representing the interests of the community goes beyond animal advocacy, and community members could help to broaden the discussion in other ways. Other views about the role of the community member have been proposed (Rowan 1990; Mench and Stricklin 1991; Robb 1993; Orlans 1993; Brown 1994; Orlans 1997; Dresser 1999; Smith and Jennings 2003). These fall into six categories: 1) providing a perspective that is independent of institutional and research agendas, 2) providing a broad perspective to committee discussion and decision-making, which includes public input, 3) serving as a reminder of the outside world, 4) helping to ensure the integrity of the process, making research institutions more open and accountable to the public, 5) providing an interface between the institution and the general public, 6) protecting animal interests, and 7) raising ethical issues (which are less likely to be raised by scientists (Orlans 1993)) and thus making scientists more reflective about their work. Unlike categories one to four, categories five to seven might require choosing people with particular skills or connections. Providing an interface between the institution and the general public (5) typically means that the community member "be able to act as a sounding board for public attitudes, as well as relay information about the institutional animal care program to the community" (Mench and Stricklin 1991). Therefore, choice of community member is likely to be important. For example creating communication with the humane movement might require choosing members via their network. However, engaging with the community at large would be difficult even with a larger number of community members on the committee, and is complicated by the requirement for confidentiality. Protecting animal interests (6) requires choosing people who are skilled and motivated to do so, such as members from the humane movement. Similarly, increasing ethical debate (7) may require persons skilled in ethics, although regular community members might achieve this (Orlans 1993). Ordinary lay language descriptions also can enhance ethical evaluation of proposals (Dresser 1999). Nevertheless, a larger number of community members may be required to ensure that interests of the animals are not overridden by the interests of the institution and research. Independence (1) also requires consideration about the social value of research. Although 129  the peer review process of granting bodies will judge the merits of a proposal, their decisions do not generally assess the ethical use of animals; therefore, community members might play an important role in keeping these considerations in discussion. If community members are intendedto ensure the integrity of the process (4), then a reasonable number of community members may be needed. However, the community might be concerned that the integrity of the process is diminished so long as institutional members outnumber non-institutional members. Ensuring a broad perspective in the committee (2) will definitely require a reasonable number of community members. IRB guidelines in the US go even further to require a diversity of membership including consideration of race, gender, and cultural backgrounds (Department of Health and Human Services 1991). Perhaps AECs should follow their lead? Naturally, the personalities of community members and dynamics of the committee will affect how well these goals are achieved, making it difficult to make hard and fast rules about proportional representation. Overall, given the vagueness in policy and the variety of interpretations found in the literature, it appears that we need further clarification of AEC function, and the role of the community member, in order to design an appropriate committee. The community member clearly plays an essential role in helping the AEC achieve its mandate and they face unique challenges being a minority on many committees and the only noninstitutional members. A good functioning committee will profit from a membership of all types of members with different expertise and views. Although members in this study were content with the level of expertise on their committees, only two committees had a non-animal-user, one of which was a chairperson. The committees might benefit from choosing other institutional members with specific expertise such as, an ethicist or a statistician (Engeman and Shumake 1993; Balls etal. 1995).  Recruitment of Members As this study demonstrated, methods of recruiting members are quite variable and can potentially impact the effectiveness of a committee. Choice of recruitment strategy will depend on what role you want the new member to play. At a research institution, a committee can recruit from departments that are traditional animal users, often leaving it up to the departments, as was the case in this study. This encourages some ownership by interested "stakeholders" so as not to 130  alienate them and to provide a mechanism for feedback to and from the animal users. Recruiting new members through word of mouth is a common strategy (Rowan 1990; Orlans 1993) and was used by committees in this study. Recruiting in this manner runs the risk of recruiting members who are perceived and motivated to "fit in" with the committee and their views, perhaps preventing other views. Recruiting close friends or relatives as community members reduces the arm's length relationship between institutional and community members, and raises the issue of whether community members are acting independently. In this situation, community members may not feel at ease to criticize their "friend's" institution. However, as one member pointed out, familiarity with another member may also provide an opportunity for members to discuss concerns outside meetings, especially for members who may intimidated to bring up certain concerns in a meeting. Familiarity with a prospective member can also provide more information about whether they will be suitable for the job. Alternatively, there is also a risk that community members accept their friend's views, without truly bringing a community view. Committees must be cautious when they recruit through word of mouth because they increase their chances of encountering these problems. Members' motivation for joining may influence the effectiveness of the committee. Whenever a committee is formed for a purpose, there is a risk that people will join for reasons other than to promote the committee mandate. Some scientists and animal technicians in this study apparently joined to defend departmental interests or to pursue personal interests because they had a grievance with the committee process. Some members may join to defend an interest group, even to the point of thwarting the committee's mandate. For example, it has been suggested that an animal rightist member may oppose all research, or may not participate in discussion, or may use confidential information in a subversive manner (Finsen 1988; Rowan 1990; Orlans 1993). In reality, in this study and another (Rowan 1990), an antivivisectionist member on a committee was not a problem. In contrast, some scientists in this study admitted to joining to try to limit the committee's actions. As Finsen (1988) suggested, "Excluding the abolitionist perspective from representation on IACUCs, the committees insulate themselves from philosophically confronting an important perspective." Including members from the animal protection movement, including abolitionists, might also act as a tool to increase meaningful dialogue and trust between the research community and the animal protection movement (Rowan 1990). 131  Solutions Fear of animal protectionist members may stem from a misunderstanding of animal protectionists by scientists and vice versa (Herzog 1994). Better education of both parties may need to be included in training of members. Another simple way to help remedy anxiety over animal protection members would be to achieve better balance on the committee so that any one group does not dominate. By limiting the number of community members, it places an unnecessary burden on the one or two members to be "perfect" members, to meet all the demands of their role. If committees want to achieve broad representation, and independence from the institution and research agendas, then committees should not be afraid to broaden their search for new members. Generally, the community has no say in who represents them. This makes it difficult to claim that the "community" members really represent community interests. One way to engage the community in choosing a representative is recruiting by advertisements, through organizations or through local newspapers and bulletin boards. For example, one committee in this study approached the local SPCA for members. Similarly, Australia and New Zealand solicit "umbrella" organizations such as the Australian and New Zealand Federation of Animal Societies for volunteers. For non-animal-welfare community members they advertise in local newspapers, request three references and follow up with an interview (Bradshaw 2002). In Canada, the Canadian Federation of Humane Societies will provide names of members who have expressed an interest in volunteering on an ACC (Brown 1994). The mandate of the committee could be published inviting those who accept and want to pursue the mandate. For all AEC members, regardless of motivation for joining the AEC, of recruitment strategy, or of personal views, there is a need for all members to want to support a clearly articulated mandate of the committee. This should be the primary criterion for membership if the committee is to fulfil its mandate. Therefore, care must be taken when recruiting all members. For all prospective committee members, interviews could be used to discuss their motivations and to further establish their support for the mandate.  Turnover Turnover was low in this study. There is little information about turnover in AECs but 132  Orlans (1993) found similar sluggish turnover in 7 committees in the US. In this study, some members considered low turnover to increase the risk of members becoming complacent or bored and of community members becoming co-opted. Low turnover may also stifle the introduction of new ideas through new membership, limit the possibility of new volunteer membership, and increase the risk of indoctrination.  Solutions To avoid these problems, committees could limit the terms of office for its members, or at least reassess the contributions of members before renewing a term. Bradshaw (2002) suggested limiting terms of office of community members to 3-4 year terms.  Workload Three of the committees in this study reviewed about 3 times more protocols per meeting and year than many IACUCs in the US (<100 per year for 70% of IACUCs, Borkowski et al. 1997) and than animal test advisory committees in Germany (72 per year, Gruber and Kolar 1997), and similar numbers to a UK Local Research Ethics Committee (10-40 per meeting, Blunt et al. 1998) although some universities review many more (>500 per year Borkowski et al. 1997; Steneck 1997). For one Local Research Ethics Committee in the UK, members spent 7-8 hours per month on committee work, presumably including meeting time (Blunt et al.1998), similar to several members in this study. Are these committees able to function well given their workload and time constraints? Committee members in this study felt the time they spent in preparation for and during meetings was sufficient, but they differed widely in the time they considered sufficient, with chairpersons, veterinarians, and animal technicians generally investing the most time, perhaps because they were all highly committed to the AEC review process and well versed in technical aspects of the procedures. Scientists generally reviewed their assigned protocols and scanned the rest. This may be because these members are confident in the quality of the review by the primary reviewers, or because their time is constrained, or because they are not fully committed to the process. Certainly community members who had full-time jobs complained of the difficulty of reading all protocols and were not always able*to achieve that goal. Hence, some member's views on their time commitments would presumably change if they read all protocols in detail. 133  Concern about the considerable workload of committee members is common in the literature (Strachan 1994; Steneck 1997; Office of the Inspector General 2000) but there is very little information about actual workloads. In the present study, although the estimates of preparation time per protocol were very approximate, they indicated a degree of trade-off between time spent per protocol and the number of protocols reviewed. Members who were assigned several protocols per meeting spent a median of 51 minutes per protocol whereas those who reviewed every protocol spent a median of 23 minutes, and some members on committees with many protocols spent much less. Thus, it appears that two strategies were used to cope with heavy workload: assigning protocols to only selected members for detailed review, and reducing preparation time per protocol. The effect of these strategies on the review process requires attention. Although the approach of two primary reviewers helps minimize time commitments for members, it was never intended that members would not read all protocols to the point of making an informed judgement. Comments in this study raise the question of whether protocols are receiving ample review by people with different views and expertise to make such judgements and to discuss their concerns as a group. It appeared that many members are not reading all protocols, scanning them very briefly in some cases, or scanning them during meetings.  Solutions There is likely some upper limit to what members are willing or able to invest and level of attention to protocol review varies depending on workload or approach to review. Ideally, everyone would read every protocol in sufficient detail. To solve this problem a committee can divide up the protocols between members, which was done in this study (risking no or little review by the remaining members) or the institution can increase the number of committees to compensate for increased workload (with challenges for recruiting enough volunteers). This study opens the door for more empirical and quantitative investigation to identify the upper limit on how much time members will typically spend on AEC work, and how do committees best deal with excessive demands.  Commitment to AEC Process by Members There was evidence that some AEC members in this study were not fully committed to the 134  AEC process: members were regularly absent from meetings (this offended one community member), some reviewers did not review their assigned protocols, and some members were satisfied with spending relatively low amounts of preparation time. Possibly, people who join the committee for reasons other than to promote the committee mandate are less committed. Lack of commitment by members may lead to less thorough review of protocols because there will be reduced face-to-face discussion and fewer members will be commenting during committee meeting discussion.  Solutions Similar to solutions for recruitment, when members are nominated to join the committee, all members need to want to support a clearly articulated mandate of the committee. Additional solutions are: monitoring and limiting absenteeism, increasing numbers of members to make up for those that cannot attend on occasion, increase the recognition given to AEC members by their institution so that they can afford to take more time if needed, offering an honorarium to compensate for lost time, and discussing time commitments with prospective members to ensure that they are willing and able to commit.  Training The method of training members in this study was to provide CCAC Guidelines and other relevant documentation, with no formal instruction about their significance and how they should be used, followed by learning "on the job". Members generally expressed satisfaction with this approach. One member felt that members generally needed more "animal welfare" training and a few members would have like training about genetic modification. Given that some members complained about having to read too much documentation, it is possible that some members did not receive a thorough understanding of the process and their role, and that some form of interactive training would be better. Sengupta and Lo (2003) found that many IRB members, having had similar training, felt they would have benefited from more intensive training, although they also felt that attending meetings and listening to others was most helpful in understanding the scientific and ethical issues. Survey results indicated that community members would have liked more information on animal welfare, the role of the community member, choosing animal models, case studies from other IACUCs, and would have liked access to on-line discussion (Theran 135  1997).  Solutions  Although members were satisfied with their training, this study has highlighted some obvious areas where members appear to lack training; the mandate of the committee and the mandate of the community members. However, the role of the community member is unclear in policy materials, and includes some possible conflicts. Policy may have to be clarified so that members can get a clearer picture of what is expected of them. The way in which members are trained may be important. Members were satisfied with their training but they had not been exposed to other methods. It appears that some non-text-based training would be beneficial to augment the current system. A variety of ethics training courses have already been designed for animal users (Smith and Jennings 1998).  Conclusions Committees and oversight bodies, such as the CCAC assessment panel, need to assess the performance of AECs regularly in order to correct any shortcomings. Understanding the potential problems an AEC might face and possible solutions provide the tools for assessing and improving performance of committees. Appendix 5.1 lists a series of questions that AEC members or governing bodies could ask to identify potential shortcomings in the AEC function, followed by a list of questions that could help to identify possible reasons for these shortcomings and which will direct committees towards solutions. Success will require members to honestly evaluate their effectiveness both as individuals and of the committee as a whole. This approach may enable AECs to find and correct problems and to educate members about potential problems.  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Canadian Council on Animal Care: Ottawa: Canada Home Office 1998 Guidance on the Operation of the Animals (Scientific Procedures) Act 1986. HC 321. Appendix J: The Ethical Review Process. http://www.archive.officialdocuments.co.uk/document/hoc/321/321-xj.htm^cce55ec? on: April 8, 2004 Janis I L and Mann L 1977 Decision-making: a psychological analysis of conflict, choice, and commitment. Free Press: New York, USA  Jennings M and Miller J 2000 Harmonising IACUC practices. In: Balls M, van Zeller A-M and Haider M E (eds) Progress in the Reduction, Refinement and Replacement ofAnimal Experimentation. Proceedings of the 3rd World Congress on Alternatives and Anima Use in the Life Sciences, Bologna, Italy pp 1705-1711. Elsevier Science B.V.: Amsterdam, The Netherlands Jones J S, White L J, Pool L C and Dougherty J M 1996 Structure and Practice of Institutional Review Boards in the United States. Academic Emergency Medicine 3: 804-809 Lo B 1987 Behind closed doors, promises and pitfalls of ethics committees. The New England Journal of Medicine 317: 46-50 Mench J A and Stricklin R W 1991 Institutional animal care and use committees: who should serve? Institute for Laboratory Animal Research News 33: 31 -37 National Bioethics Advisory Commission 2001 Ethical and policy issues in research involving human participants [final report and recommendations]. http://bioethics.georgetown.edu/nbac/human/overvoll.pdfy4cce55ec? on: July 28, 2003 Office of the Inspector General 2000 Protecting Human Research Subjects: Status and Recommendations, http://oig.hhs.gov/oei/reports/oei-01-97-00197.pdf Accessed on: July 31,2003 Orlans B F 1993 Community members on animal review committees. In: Orlans B F (ed) In the Name of Science. Issues in Responsible Animal Experimentation pp 99-117. Oxford University Press: New York, USA Orlans B F 1997 Ethical decision making about animal experiments. 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RSPCA: Horsham, U K Steneck N H 1997 Role of the Institutional Animal Care and Use Committee in monitoring research. Ethics and Behavior 7: 173-184 Strachan J 1994 As non-scientist, what can I ask for? In: Effective animal experimentation ethics committees: Proceedings of a Conference, University of Adelaide pp 133-134. ANZCCART: Glen Osmond, Australia The Dutch Experiments on Animals Act 1997. Section 18. http://www.nca-nl.org/ Accessed on: November 7, 2003 The Swedish National Board for Laboratory Animals 1979 Provisions On Animal Experiments, http://www.cfh.se/y4cce55erf on: December 8, 2003 Theran P 1997 The SCAW IACUC survey: Part II: The unaffiliated member. Lab Animal 26:3132 Verweij M, Brom F W A and Huibers A 2000 Do's and don'ts for ethics committees: practical lessons learned in the Netherlands. 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Three Rs Chapter 3 demonstrated that members were inconsistent in their interpretation and application of the Three Rs, that the Three Rs were not fully effective as a mnemonic tool, and that current CCAC policy provides few details on the Threes Rs. In addition, sometimes members relied on peer review and on investigators who submitted protocols to implement Replacement and Reduction. Thus, both policy and training for members could benefit from more emphasis on the Three Rs, including how to interpret and apply them. Appropriate implementation of the Three Rs may also require expanding the concepts themselves to capture new developments in animal welfare science, biological research, and in ethical concern over animals. Of the Three Rs, Refinement was the least understood by AEC members in this study. In keeping with the traditional definition of Refinement (Russell and Burch 1959), members tended to focus on minimizing pain caused by procedures. Committee members might broaden their focus if the concept of Refinement was expanded to include current concerns over the quality of life of animals, with more explicit acknowledgment of different types of harms, including those caused by housing and handling. I would also recommend that AECs take a more evidence-based approach through incorporating research from animal welfare and ethics into their decision making. It may also be helpful for policy to articulate more explicitly ethical considerations other than minimizing harms. For example, some members in this study were concerned about the use of non-human primates and companion animals as experimental subjects, either because of the species' level of sentience and capacity to suffer, or because of the value placed on these species by themselves or society. This may be a case where personal and 144  community standards are being applied independent of a simple weighing of costs and benefits. Recognition of differences in our ethical concern for different species might help committee members to better articulate their concern. The UK has increased protection for dogs, cats, and horses (Home Office 1986b), and several countries have taken various steps to ban or limit the use of Great Apes for harmful research (Home Office 1986c; Ministry of Agriculture and Forestry 1999; Netherlands Centre for Alternatives to Animal Use 2001; The Swedish National Board for Agriculture 2003). How to include ethical considerations beyond cost-benefit assessments may require further discussion and debate at a national level in Canada.  Protocol Review Process Chapter 5 raised the question of whether protocols are receiving ample review by people with a sufficiently broad range of views and expertise and who are able to discuss their concerns as a group. It appeared that many members are not reading all protocols, often because of the way the committee has agreed to divide the workload. In such cases members may scan them very briefly, or scan them during meetings. Also, several members were concerned about the effectiveness of the review process when members were absentfrommeetings. In this scenario, discussion may be limited when only a few members are familiar with a protocol and when there is reduced face-to-face discussion. One reason for these problems might be that members have an excessive workload. Individual committees should evaluate whether there is evidence of any of these problems with the review process. Solutions will depend on the reasons for inadequate review. If committee members find the workload too high, then committees will need to discuss these issues internally and come to an agreement about what time commitments members can handle. Institutions may also have to consider increasing the number of committees or the number of committee members to reduce workloads. In part, clarification of the goals of the review process in policy statements would help guide committees to assess their review practises. For example, if one goal is to achieve a broad perspective, then the use of two reviewers to conduct in-depth reading of protocols may not be meeting the goals of the review process.  145  Community Member Chapter 5 showed there is substantial confusion over the role of the committee as a whole and of the community member in particular, presumably arising in part from a lack of clear policy. The community member can play an important role in helping institutions ensure that their activities are defensible to the broader public, but this will require clear policy on the role of these community members. Canadian and US policies describe the community member as representing "community interests" and having "no affiliation with the institution" (AWA 1985; CCAC 1993). A CCAC orientation document for community members also suggests other roles for the community member including that they should represent animal interests (see below for others) (CCAC 1999). UK policy states that the lay members should be independent of the establishment (Home Office 1998). These descriptions leave room for interpretation. For example, representing the interests of animals and representing the interests of the community (which may put human interests ahead of animal interests) may be two incompatible goals. Similarly, whom should the community member and the committee be independent of? Should they be independent from the specific institution, or from the entire research perspective (Brody 1998)? If community members are intended to be independent from the institution and research interests, then many community members in this study would not meet this criterion. Most community members were affiliated (through friendship or kinship) with institutional members of the AEC, and only two members were associated with the animal protection movement. Hence, there is room to question how independent these members were from the institutions and research interests. In addition, some feeling of intimidation among community members, and occasional negative interactions with other institutional members, as found in this study and others (Robb 1993; Orlans 1993; Brown 1994; Gruber and Kolar 1997; Theran 1997) might limit their contributions to discussions. Another factor that could affect independence of the AEC is the reporting structure of the institution. Members are often appointed by and AECs report to senior administrators, which raises another question about independence of the AEC from institutional interests. The combination of these factors may result in insufficient attention paid to the interests of the animals and the community to satisfy community values; thus, a key purpose of the committee may be thwarted. To meet the requirement of independence, committees may need to change their practises 146  of recruiting community members. For example, as opposed to recruiting through word of mouth, committees could broaden their search for new members by advertising through organizations or through local newspapers and bulletin boards (Bradshaw 2002). Committees can also engage the animal protection movement in nominating one of their own members to serve on an AEC. In all cases, members need to support the mandate (which needs to be clearly articulated) of the committee. To ascertain whether new members are committed to the process, policy could outline the types of questions that could be asked when interviewing new members. Another solution would involve increasing the participation of community members. This may require increasing the number of minority members, along with good leadership by the chairperson to help create a respectful and open committee atmosphere, so that community members do not feel intimidated. Improved recruiting strategies and respectful committee atmosphere should help committees achieve independence from institutional and research interests, but even with these changes, whether the AEC can really achieve independence when committee composition is made up largely of institutional and scientist members needs further consideration. If the community member is expected to represent both community interests and animal interests, perhaps an additional solution would be to include two types of community members: one drawn from the animal protection movement and charged with considering the interests of the animals, and another one drawn from the community at large to represent community interests beyond simple animal advocacy. Current policy may make unrealistic demands on the community member. A CCAC orientation package (CCAC 1999) and reports in the literature (Rowan 1990; Mench and Stricklin 1991; Robb 1993; Orlans 1993; Brown 1994; Orlans 1997; Dresser 1999; Smith and Jennings 2003) cite a variety of functions that the community member is intended to serve. Some are reasonable expectations; those include adding a broad perspective to committee discussion and decision-making, serving as a reminder of the outside world, helping to ensure the integrity of the process, and making research institutions more open and accountable to the public. Other functions are unlikely to be served unless people with specific connections or particular skills are recruited. These functions include providing an interface between the institution and the general public, and raising ethical issues (although regular community members might achieve this (Orlans 1993)). Engaging with the community at large would be difficult even with a larger 147  number of community members on the committee, and is complicated by the requirement for confidentiality. Given some of these difficulties, perhaps it would be more realistic to limit the expected function of the community member to being a "public witness to the activities of the research facility" (Dresser 1999). In any case, a clearer understanding of the role of the community member should help answer questions about how committees should be composed, how community members should be recruited, and who should be recruited. In addition, if the entire committee has a clearer understanding of the role and significance of the community member, it may help to create a less intimidating atmosphere for these members. Overall, clearer guidance in policy will enable committees to assess their own performance in order to solve problems they encounter as well as provide a clear basis for CCAC assessment panels to review the functioning of AECs.  Decision-Making Approaches Many governing bodies prescribe or endorse cost-benefit assessments for decision-making by AEC members; these include the UK (Home Office 1998), Australia (Australian National Code 1997), Canada (CCAC 1993), and Sweden (Swedish Animal Welfare Act 1988). In contrast, the US endorses no specific balancing principle (AWA 1985; Public Health Service 1986). This study found that although some members do engage in a mental weighing of costs and benefits, other approaches are also actually used. These include empathy with animals, comparison with perceived community standards, attempts to be consistent with previous decisions, and moral intuition. Chapter 4 demonstrated that emotion and moral intuition appeared to play an important role, especially for community members. There is a risk that current policy, in emphasizing cost-benefit assessment, will be seen as invalidating other approaches, particularly those used by community members. Given that community members may already feel marginalized by being a minority on the AEC, this could further reduce their contributions to the committee process. There is also a risk that by insisting on cost-benefit assessment where benefits are often impossible to estimate, policy pins the approval process on highly subjective notions of the value of research (see later discussion) - an area where community members may feel unable to comment with authority. A solution would be to expand policy to acknowledge other elements that go into assessing research: for example, 148  conformity to community standards for avoiding suffering. Policy could also outline the elements that should be considered by AECs when making decisions rather than the logic to be applied to the information. Another important consideration for improving AEC effectiveness is that there may be very little association between making a decision and learning about its outcome. This study found that some members used how well an application was filled out by investigators as indirect evidence of care in carrying out the procedures, perhaps because they mostly work with forms. Feedback is important for increasing expertise in decision-making. Members may need to visit facilities more often and observe specific procedures or the veterinarian may need to report back about specific procedures to the committee. A more evidence-based system would not only enable AEC members to improve their ability to make good decisions, but it would also make the process more transparent and enable the public to evaluate the effectiveness of AEC decisions.  Ethical Justification of Research Chapter 4 indicated that committees may not be putting sufficient emphasis on assessing the justification of research to meet the official expectations of AECs. CCAC guidelines state that the AEC must ensure that the proposed research is justified: "be convinced ... of the need for animal use, and that the expected benefit will outweigh the cost" (CCAC 1997). Evaluating the ethical justification of experiments includes assessing technical merit (the use of testable hypotheses, good experimental design, appropriateness of the animal model and experiment for achieving the desired result, aptness of the experiment to answer the question, and skill of the investigator), social value (the ability of the work to make a positive contribution to society), and harm to animals. However, as this study showed, members often take expert peer review by granting agencies as an assurance of both technical merit and social value, and thus see no need for further weighing of benefits against harms. In such cases AECs tended to focus on minimizing harm and gave little attention to ethical justification. One possible solution would be to provide AECs with more guidance on their role in meeting the expectations of policy. In part, this may require clarifying policy so that it provides a fuller description of what elements should be considered in decisions about the ethical justification of research, and policy may need to emphasize the requirement for making that 149  assessment. By explicitly breaking decisions about justification down into its components, committee members will be better equipped to assess whether the research is ethically justified and perhaps be able to identify which of these components has actually been covered by peer review by granting agencies. Policy may also need to clarify the role that expert peer review plays in these decisions. Peer reviewers can be expected to assess the technical merit of proposals. They may also assess the expected benefits, but generally they do not appear to evaluate harm to animals nor consider the Three Rs. In addition, given that some granting agencies fund broad research programs rather that specific experiments, it is unlikely that experts on peer review panels are reviewing the details of scientific quality of individual protocols. Thus, it seems that peer review may sometimes miss key components expected of an AEC evaluation. However, AEC members may rely on expert peer review because they feel ill-equipped to make a full assessment of costs and benefits. Thus, we need to ask what AECs can reasonably be expected to evaluate? 1. Technical Merit. First, it seems reasonable to expect scientist members on an AEC to assess technical merit of proposals at least at the level of appropriate experimental design, statistics, and appropriateness of the animal model. 2. Harms and the Three Rs. With appropriate training committee members should be able to apply the Three Rs. Similarly, with appropriate training members should be able to evaluate harms to animals, although some members (the veterinarian, animal technicians, and possibly community members from the humane movement) will be more skilled at this. However, as Chapter 3 pointed out, there are difficulties with assessing harms; members varied in their interpretation of pain and what they considered harmful, as well as beliefs about the moral significance of pain and suffering, with different interpretations resulting in different views about the need for and degree of pain mitigation. In particular, notions such as pain, suffering and distress are greatly debated by scientists and philosophers, and there may be conceptual confusion at the national or policy level making the challenge that AEC members face very great. Lack of clarity in the meaning of these concepts makes it hard to apply cost-benefit assessments in a standard manner. 3. Social Value. Social value may be the most difficult for AEC members to assess. Some scientists may be able to assess social value for proposals that are in their own field of expertise but community members would certainly have difficulty doing so. 150  Predicting potential benefits of research is notoriously difficult, yet it is the cornerstone of arguments for the justification of the use of animals in research. In some cases, the benefits of experiments seem quite clear. For example, safety testing of products provides clear benefit to the public by helping to eliminate unsafe products from the marketplace. On the other hand, predicting health applications of fundamental research and the probability of achieving those desired benefits is inevitably more speculative (Jennings and Silcock 1995; Dresser 2001). Therefore, such research is not easily accommodated within a cost-benefit assessment. In one attempt to evaluate how often predicted benefits are realized, Lindl et al. (2001) found that 40% of proposals reviewed by a German animal ethics committee did not realise their expected benefits. Since benefits are a key element of assessing justification, how can we make this process more effective? If AECs are not themselves able to predict benefits, then one solution would be to provide information from other sources wherever possible. Perhaps investigators could be asked to describe the benefits expected to flow from the work. CCAC policy (1993) could be expanded to outline in more detail the different types benefits as is done in the Animals (Scientific Procedures Act) 1986 (Home Office 1986a) in the UK. These include contributions to improving human and animal health, the protection of the natural environment in the interests of health or welfare of man and animals, the advancement of knowledge in the basic sciences, education or training, and the breeding of animals for experimental or other uses. Investigators could then be asked to rate the importance of the contribution. If the research contributes to fundamental knowledge, then how important is the contribution to thatfield?If the research contributes to some clinical application, then how significant is the health problem? What is the likelihood that this research will contribute to this clinical application and how long might it take to realize the benefit? By breaking the assessments of benefits down into constituent components it will make explicit the kinds of issues AECs should consider and highlight points of uncertainty or disagreement in discussions. However, benefits may be over-estimated by investigators. In a research culture which is highly competitive for funding it is likely that investigators will emphasize and amplify the value and expected benefits of their work. This makes it particularly critical for independent assessments of the benefits of the proposed research. Scientific peer reviewers may be better equipped than AECs to provide an objective evaluation of potential benefits. Therefore, an alternative solution would be to have scientific peer 151  reviewers provide the necessary information (as outlined above) to AECs as a basis for costbenefit assessment. Whether or not scientific peer reviewers or AECs are actually good at evaluating expected benefits of individual projects is an empirical issue that has not really been addressed. This is an important question because not only do we expect these review committees to achieve this key aspect of their mandate, but by examining how often predictions about benefits are realized provides opportunities for improving AEC and scientific review performance in the long term. If scientific peer review committees are able to assess expected benefits, then another approach would be to rely on peer review to also assess the ethical justification of the work. In this case, peer review committees would have to change their practise to include a cost-benefit evaluation. This might require changing the composition of peer review committees to include members with expertise in evaluating animal harm. In this case, AECs could accept that a positive peer review establishes that benefits outweigh harms leaving AECs with the reduced mandate of reducing harm and rejecting protocols where they consider the level of harm to be too high for community standards regardless of cost/benefit ratios. However, an advantage of having AECs review proposals is that they provide a broad perspective because their membership includes scientists, community members, animal technicians, non-animal-users, and veterinarians. Therefore, expert peer review may not provide fully adequate assessment of the ethical justification of the research because they are largely scientist-based. However, carrying out cost-benefit analysis for protocols raises inherent and perhaps unsurmountable problems. Costs and benefits are concepts that are difficult to operationalize; they are neither readily quantifiable nor in commensurate units. Moreover, as this study shows, costbenefit assessment may not be an appropriate decision-making model in all cases because certain people use other approaches, or because other considerations, not classified as benefits or costs, are also regarded as important to decision-making. Cost-benefit assessments rest on a utilitarian theory of ethics whereas this study demonstrated that other ethical theories, including ones based on rights and stewardship, came into play. Other studies of naturalistic decision-making have shown that people rarely use objective approaches of weighing options (Klein 1998). Given the problems with cost-benefit assessment at the level of individual protocols, perhaps the case for justification of animal research should be made at an aggregate level. That is, we could ask whether the overall benefits accruing from animal research in general appear 152  sufficient to justify the current level of use of animals. In this scenario the existing decisionmaking system dealing with research priorities, budgets and policies would serve to identify worthy areas of research in a process involving public officials, scientists, patient advocates and others (Dresser 2001). The AEC is then exempted from having to consider the (often imponderable) likely future benefits of a given experiment, and instead their role would be to minimize harms to animals particularly by applying the Three Rs. In summary, there is a need to sort out some basic issues in the ethical justification of research. Can AECs make assessments? Could changes in policy help them do it better? What are the relative roles of expert peer review and AECs in covering the different elements of costbenefit assessment? Could expert peer review committees change their practises to meet the needs of AECs, leaving AECs to focus only on harm assessment? Could research using animals be justified at the aggregate level? Which of these options will likely meet public expectations of providing adequate protection for animals used in research? Answers to these questions will likely require discussion and consensus-building at the national level and discussion with granting agencies.  Policy Implementation and Training of Members Implementation of policy can be influenced by training of members. As Chapter 5 highlighted, providing members with lengthy, written policy and guideline documents may not be sufficient training. Alternative methods of training should be considered. Institutions may need to reward (financially or otherwise) AEC members so that they are willing to spend time training or upgrading for AEC work. If committee members do not have the time to commit to training, then institutions may have to hire staff, such as an animal welfare officer, who would be responsible for addressing concerns about the Three Rs and other welfare issues. The new 2003 CCAC requirement for animal-user training should help committees in their efforts to implement the Three Rs.  Institutional and AEC Culture  Although committees differed in the types of research they reviewed and their workload, 153  there was very little evidence that views of members reflected a particular culture that varied between universities. Given that this research focussed on the views of individual members, of which only a sample were interviewed from each institution, patterns in institutional culture may have been difficult to find. However, a distinctive feature of one committee was its level of comfort with having an animal rightist community member. Other members of that committee made it clear that they highly valued the contributions of this particular community member and made sure that his views were considered even when he was not present at meetings. This community member played a key role in reminding the committee to apply the Three Rs. Perhaps because he had been an effective member for 14 years he had clearly helped to shape the culture of that committee. There was not much consistency between members of the same group (i.e. scientists, animal technicians, veterinarians, non-animal-users, and community members). Rather, each group in general represented a wide range of views. However, groups demonstrated similarities in views in three respects. First, community members tended to use emotion and moral intuition in their approach to decision-making, more than other members. Second, scientists tended to be more willing than other members to trust the expert peer review process to assess technical merit and social benefits, and also to trust investigators to implement Reduction and Replacement. This is in keeping with common attitudes of scientists who believe in scientific autonomy and prefer oversight from within professional scientific circles (Krimsky 1984). Third, animal technicians tended to show the lowest level of trust that investigators would carry out procedures as they had written them in their application form. This is an important observation since animal technicians are working on the "front lines" of animal research and witness common practises of animal care, handling, and procedures. Their experiences provide valuable evidence of how well animal users are performing. If technicians are cynical, this could be a red flag that all is not well. Further research on the prevalence of this mistrust, and reasons for it, would be helpful. Generally a range of views was represented in each committee and each category of member. On the one hand, the variety of views suggests that indoctrination had not occurred despite the generally low turnover in membership, and that the committees continued to capture a broad range of views perhaps representative of the various communities. Diversity in views will be desirable for some issues: diverse expertise to meet all the needs of the committee, diversity in values to balance the interests of animals with the interests of science, and diversity of approaches 154  to decision-making, especially when it reflects personal values. However, in this study, the variation in views may also have resulted from lack of uniform understanding of certain concepts, such as the Three Rs, and different perceptions of the mandate of the AEC and the role of peer review. Such reasons for diverse views are less encouraging, as the goal is presumably diversity, not simple misunderstanding or discussion at cross purposes. Clearly, on these issues consistency in views is preferable so that all members are working towards achieving the mandate of the committee.  C  S  Different motivations for joining the AEC may account for some diversity in views, with some members joining to support the mandate of the committee while others joined to pursue other agendas. Interestingly, fear is sometimes expressed about animal protectionists joining AECs to work against the committee mandate (Finsen 1988; Rowan 1990; Orlans 1993). This may be misplaced concern because according to policy, community members are supposed to represent animal interests. This study suggested that it is more likely to be scientists who have joined out of motivation to limit the committee's role, although the limited evidence collected suggested that they quickly changed their views and became positive participants of the AEC process. However, if members remain uncommitted to the AEC process - they are routinely absent from meetings, or they only review a few protocols per meeting - then the advantages of having a broad perspective will be lost. The physical set up and management of animal facilities, although not specifically a reflection of culture, appeared to play a role in the implementation of the Three Rs by AECs. Comments in Chapter 3 suggested that centralized animal facilities seemed to provide some assurance to AEC members that Refinement would be applied because the committee, through university staff, had better control over animal care. In addition, centralization seemed to improve Reduction efforts by making it easier to coordinate the sharing of tissues, organs etc. among investigators.  Responding on National and Local Levels  Some of the improvements identified above can be made at the local level. These include increasing training for members on the Three Rs, agreeing on how to handle division on work, and developing a shared view of the role of the AEC. It might also be helpful for AECs to 155  explicitly discuss certain contentious issues such as different conceptions of pain and suffering and their moral significance, so that differences in ethical perspectives are clearly articulated. Other improvements will require national guidance and consensus. National policy should clarify key concepts such as the Three Rs, different types of harm, and ethical justification; clarification is also needed on the role of AEC members and the committee as a whole. Discussion will be required to address the relationship between scientific peer review and AEC review, predicting benefits, and the role of cost-benefit assessments for justifying research. As Chapter 4 illustrated, having more cases where there is clear policy, such as in the case of in vitro monoclonal antibody production for Replacement, enables AEC s to act more decisively. This should result in greater consistency in decision-making, increase the effectiveness of the AEC, and provide clear guidance for committees and the CCAC to assess and improve AEC performance. In the US, Orlans (1993) recognized the need for national discussion about certain ethical concerns and suggested establishing a national commission on animal experimentation to "thrash out some of the ethical concerns that are voiced by some members of the public, including the limits of primate research, use of purpose-bred animals, and the encouragement of alternatives. It could make policy recommendations on the specific functions of Institutional Animal Care and Use Committees and elucidate the role of community members - issues that are still poorly defined." Canada is fortunate to have the CCAC, which represents a variety of stakeholders and thus could be the basis for discussing these issues. Discussion will not only address current challenges and shed light on whether our current governance system is meeting public expectations, but it will also provide an opportunity to think about our vision of future governance and to map out how we might achieve change. In addition, observations from this study about the role of expert peer review have illustrated how the AEC functions within, and is influenced by, a larger culture of research and society. It is important to recognize and understand the variety of factors that can influence our ability to achieve adequate protection for animal research subjects. First, decisions by AECs will likely be influenced by commercial pressure. In biomedical research, tremendous financial investment goes into developing products and therapies, and this pressure for commercialization undoubtedly influences animal research. Second, the types of projects that AECs review will be influenced by decisions in social policy about what research to fund, by new scientific 156  developments, and by changes in societal views on the ethics of animal use. Decisions about health policy and health research funding will have direct impacts on animal use, in particular in the type of research and the scale of animal use. For example, current emphasis on genomics related to disease prevention has resulted in huge increases in the creation and use of genetically modified animals around the world. Partially through the efforts of AECs in implementing the principle of Reduction, numbers of animals had been decreasing since the 1970s. However, increases are occurring again, primarily due to the use of genetically modified animals which present serious, and as yet unanswered, ethical and animal welfare problems. Thus, successes of AECs in reducing animal numbers and minimizing suffering can sometimes be thwarted by developments outside their control. Recognition of these relationships is important because it helps us to understand the limitations of the AEC in upholding high ethical standards of research.  References Australian National Code 1997 Code (2.2.2. - 2.2.7) Australian National Code of Practice for the Care and Use of Animals for Scientific Purposes. Australian Government Publishing Office: Canberra, Australia AWA 1985 Animal Welfare Act (7 U.S.C. 2131) 9 CFR, 2.31 (a) (b). http://www.nal.usda.gov/awic/legislat/awabrief.htmv4cce55erf on: December 8, 2003 Bradshaw R H 2002 The ethical review process in the UK and Australia: the Australian experience of improved dialogue and communication. Animal Welfare 11: 141-156 Brody B A 1998 The Ethics of Biomedical Research. An International Perspective. Oxford University Press: Oxford, UK Brown S 1994 Choosing a community representative(s) for Animal Care Committees (ACC). In: CCAC 1994 Ontario Regional Workshop. Animal Care Committees: Role and Responsibilities, North York: Canada pp 31-35. Canadian Council on Animal Care: Ottawa: Canada CCAC 1993 Guide to the Care and Use of Experimental Animals. Canadian Council on Animal Care: Ottawa, Canada CCAC 1997 CCAC Guide to Protocol Review. Canadian Council on Animal Care: Ottawa, Canada CCAC 1999 Community Representation: The Public Conscience. http://www.ccac.ca/english/accs/accframeintro.htmy4cce55erf on: July 30, 2003 Dresser R 1999 Community representatives and nonscientists on the IACUC: what difference should it make? Institute for Laboratory Animal Research Journal 40: 29-33 157  Dresser R 2001 When Science Offers Salvation. Patient Advocacy and Research Ethics. Oxfo University Press: New York, USA Finsen L 1988 Institutional animal care and use committees: a new set of clothes for the emperor? The Journal ofMedicine and Philosophy 13: 145-158  Gruber F P and Kolar R 1997 Animal test advisory commissions: ethics committees in Germany. In: van Zutphen L F M and Balls M (eds) Animal Alternatives, Welfare and Ethics. Proceedings of the 2nd World Congress on Alternatives and Animal Use in the Life Sciences, Utrecht,The Netherlands pp 373-376. Elsevier Science B.V.: Amsterdam, The Netherlands  Home Office 1986a Animals (Scientific Procedures) Act 1986 Chapter 14 5. (3) Project Licenc The Stationery Office: London, UK Home Office 1986b Guidance on the Operation of the Animals (Scientific Procedures) Act 1986. Chapter 5.22 Cats, Dogs, Equidae and Non-Human Primates. The Stationery Office: London, UK Home Office 1986c Guidance on the Operation of the Animals (Scientific Procedures) Act 1986. Chapter 5.23 Other Restrictions: The Stationery Office: London,'UK Home Office 1998 Guidance on the Operation of the Animals (Scientific Procedures) Act 1986. HC 321. Appendix J: The Ethical Review Process. http://www.archive.officialdocuments.co.uk/document/hoc/321/321-xj.htmy4cce55erf on: April 8, 2004 Jennings M and Silcock S 1995 Benefits, necessity and justification in animal research. Alternatives to Laboratory Animals 23: 828-836 Klein G 1998 Sources of Power: How People make Decisions. MIT Press: Cambridge, UK Krimsky S 1984 Regulating recombinant DNA Research. In: Nelkin D (editor) Controversy. Politics of Technical Decisions pp 251-280. Sage Publications, Inc.: Beverly Hills, USA  Lindl T, Weichenmeier I, Labahn D, Gruber F P and Volkel M 2001 Evaluation of authorised experiments on laboratory animals with regard to the following frame of reference: the aim of the research to be carried out, its scientific usefulness and its medical relevance. Alternativen zu Tierexperimenten 18: 171-178 Mench J A and Stricklin R W 1991 Institutional animal care and use committees: who should serve? Institute for Laboratory Animal Research News 33: 31-37 Ministry of Agriculture and Forestry 1999 New Zealand. Animal Welfare Act 1999. The Use of Non-Human Hominids (Section 80 (l)(c)) Accessed on: June 17, 2003 Netherlands Centre for Alternatives to Animal Use 2001 End to research with chimpanzees in the Netherlands, http://www.nca-nl.org/ Accessed on: June 3, 2003 Orlans B F 1993 Community members on animal review committees. In: Orlans B F (editor) In the Name of Science. Issues in Responsible Animal Experimentation pp 99-117. Oxford University Press: New York, USA 158  Orlans B F 1997 Ethical decision making about animal experiments. Ethics and Behavior 7: 163171 Public Health Service 1986 Public Health Service Policy on Humane Care and Use of Laboratory Animals IV.A. 3.a., b. http://grants.nih.gov/grants/olaw/references/phspol.htm Accessed on: November 6, 2003 Robb J W 1993 The role and value of the unaffiliated member and the nonscientist member of the Institutional Animal Care and Use Committee. Institute for Laboratory Animal Research News 35: 50-53  Rowan A N 1990 Ethical review and the animal care and use committee. In: Donnelley S and Nolan K (eds) Animals, Science, and Ethics. The Hastings Center Report pp 19-24.  Russell W M S and Burch R L 1959 The Principles of Humane Experimental Technique. Methuen: London, UK Smith J A and Jennings M 2003 A Resource Book for Lay Members of Local Ethical Review Processes. RSPCA: Horsham, UK Swedish Animal Welfare Act 1988 The Animal Welfare Ordinance (SFS 1988:539 Section 49). http://www.algonet.se/~stifud/act-ordinance.html Accessed on: February 3, 2004 The Swedish National Board for Agriculture 2003 Provisions On Animal Experiments (SJVFS 2003:17), Chapter 3, Section 9.  Theran P 1997 The SCAW IACUC survey: Part II: The unaffiliated member. Lab Animal 26: 3132  159  APPENDIX I - Interview Schedule Questions to get at themes 1. How long have you been a Animal Care Committee member? 2. How did you become a member? 3. What is your own research field? 4. What training or experience has been useful to you in order to prepare for the role as an Animal Committee member? 5. What sort of training would you have liked to have had that would have been helpful? 6. In preparation for a meeting, about how much time do you take e.g. Hours per month? A) Is it a reasonable commitment for your personal time and B) Do you find that this is adequate time to do the job well? 7. Do you think there is adequate time to review protocols during a committee meeting? 8. How often do you get out to visit different facilities at your institution? How important do you feel those experiences are to your job? 9. How confident are you that investigators carry out procedures according to what they said they will do in their protocol? 10. How important is it for you and the committee to be familiar with the investigator, their track record, facilities etc? 11. What aspects of the forms are commonly not filled out well by investigators and why? 12. Could you walk me through the process of how you would go about reviewing a protocol? 13. What guiding principles do you use when reviewing and making decisions about protocols? 14. How do the Three Rs influence your decisions? 15. What makes the difference between protocols that are approved with provisos versus deferred versus rejected? 16. Have you ever rejected protocols? If so, what types and on what basis were they rejected? (Optional depending on their discussion of rejection of protocols) 17. If they do not explicitly bring up cost/benefit analysis ask: Do you try to balance the costs to the animals against benefits? 18. If you think about protocols that are more difficult to review, what factors would make a 160  protocol difficult to review? 19. How do you decide what to do in these cases? 20. How do CCAC guidelines influence your review of protocols? 21. How does the species of animal affect your decisions? 22. What role do you think the committee should play with regards to judging scientific merit of a protocol? 23. What does unnecessary pain and distress mean to you? (Optional)  Questions about Committee 1. How do you view your role on the committee? 2. How do you view the role of the committee? 3. How do you think society views ACCs? 4. How well balanced is the committee in terms of expertise? Are there any roles that are currently unfilled? 4. What role does the Chair play? 5. Do you feel that your concerns are adequately acknowledged or addressed? 6. How do the interpersonal dynamics change at different meetings? 7. What sort of experiences do you share with friends or family or other people outside the committee? (Optional)  General Questions 1. What do you think are the key factors that affect the humane treatment of experimental animals in your institution or in other institutions that you are familiar with? (Optional) 2. What are the biggest impediments to improving the system? 3. What are the areas that need the most improvement? 4. Are there questions I should ask you but didn't? 5. Could you describe what your own personal ethics are with regards to the use of animals in research. If they have trouble then offer them the following four choices: Here are 4 general categories of different ethical views, do you feel you fit into any of these? 161  a) Utilitarian: Sees animal use as justified if benefits exceed costs including pain and suffering to animals. b) Rights: Respect and protect the rights of animals to life and self-determination regardless of the consequences. c) Stewardship Approach: Entitled to use animals but need to exercise proper care and respect for them. d) Advancement of Science: Emphasizing advancement of science and seeing animals as tools to achieve this, while respecting society's concern to animal suffering.  Questions for Chair 1. How long have you been a Chair? 2. How did you become a Chair? 3. What kind of training did you receive to prepare you for the role as Chair? What would help? 4. What are some of the challenges you face as a Chair? 5. What is the process for reviewing provisos when they come back from an investigator?  162  

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