Current concepts of Harm–Benefit Analysis of Animal Experiments – Report from the AALAS–FELASA Working Group on Harm–Benefit Analysis – Part 1

[Virtual Presenter] Animal experiments involve the use of animals in scientific research, education, and testing. Careful consideration is required regarding the potential benefits and potential harms caused to the animals. A systematic approach called Harm-Benefit Analysis (HBA) is employed to evaluate these potential benefits and harms..

[Audio] In the development of scientific knowledge, it is crucial to consider the potential harm caused to animals in research. The concept of harm-benefit analysis aims to evaluate the necessity and justification of using animals in scientific research. This analysis involves identifying the potential harm caused to animals and weighing it against the expected benefits of the research. The goal is to ensure that the use of animals is justified and that the benefits outweigh the potential harm..

[Audio] In today's lecture, we will discuss one of the most important aspects of animal experimentation: Harm-Benefit Analysis. The concept of Harm-Benefit Analysis was first introduced by Russell and Burch in their book "The Principles of Humane Experimental Technique" in 1959. It is based on the 3Rs: Replacement, Reduction, and Refinement. The purpose of Harm-Benefit Analysis is not only to ensure the welfare of animals but also to evaluate the potential benefits of the research against potential animal welfare concerns. Responsible individuals in the field must understand and address Harm-Benefit Analysis in protocols and project applications. To do so, it is recommended to review existing literature, define and understand current concepts and elements of this analysis, and recommend ways to implement it. Practical cases will be discussed to illustrate common situations in the research environment and how Harm-Benefit Analysis can be applied. The global importance of Harm-Benefit Analysis is emphasized by organizations such as AAALAC International and the World Organization for Animal Health. As responsible individuals, it is our duty to understand and address Harm-Benefit Analysis in our research, ensuring the welfare of animals and weighing the potential benefits of our studies against potential animal welfare concerns..

[Audio] The literature search included publications on harm-benefit or cost-benefit evaluations of the use of animals in research, education and testing. We also included some material on cost/harm/risk-benefit analysis from human medical trials as well as studies on risk-benefit perceptions in general. Guidelines and policy statements on the use of animals in research and education from various organizations such as CIOMS, ICLAS, OIE, US Government, European Commission, FELASA, and AALAS were reviewed. Different domains or factors that may impair animals and are relevant to the consideration of harm were identified. These factors can be categorized into subgroups such as 'animal welfare harms', 'animal rights/intrinsic nature harms', and 'quality harms'. It is worth noting that 'animal welfare harms' is the largest subgroup..

[Audio] The concept of Harm-Benefit Analysis was initially developed in relation to experimentation on human subjects. The Nuremberg Code emphasizes the importance of considering the harms and benefits in relation to experimentation. It states that experiments should yield fruitful results for the good of society and should not be random or unnecessary in nature. The Code also stresses on the need for experiments to avoid unnecessary physical and mental suffering and to ensure that the degree of risk never exceeds the humanitarian importance of the problem being solved. The Nuremberg Code recognized animal studies as a crucial first step in protecting humans from primary exposure to risks. This established a results-based scientific foundation, believing that similar outcomes in animals would justify the performance of the experiment in humans. Following the Nuremberg Code, the Belmont Report in the United States and the World Medical Association Declaration of Helsinki elaborated ethical principles for human studies. These reports emphasized the importance of evaluating the harms and risks to human subjects in relation to the benefits gained from the study..

[Audio] The expertise required for conducting a harm-benefit analysis involves knowledge in various areas, including the scientific use of animals, experimental design, statistics, veterinary practice, and animal husbandry and care. This expertise is necessary to assess whether the harm caused to animals is justified by the expected outcome, considering ethical considerations and potential benefits to humans, animals, or the environment..

[Audio] The harm factors identified in the literature review include animal welfare harms, animal rights harm, and quality harms. These factors include the species and choice of animals used, their level of sentience and consciousness, and the overall quality of the animals. Other factors include the duration of the experiment, the number of animals used, their origin, acquisition, and transport, as well as the care and housing of the animals, including their handling, health care, and the possibility for them to express normal behavior. Additionally, staff competence and quality are important factors in ensuring the well-being of the animals. Other harms mentioned include hunger and thirst, discomfort, pain, injury, or disease, as well as fear, anxiety, and distress experienced by the animals during the experiment. The frequency and severity of procedures also play a role in the overall risk of harm to the animals. Furthermore, there are ethical considerations to take into account, such as the intrinsic value and rights of the animals, as well as the potential genetic manipulation and impact on the natural world..

[Audio] The concept of Harm-Benefit Analysis in animal experimentation is constantly evolving. The consideration of using animals in experiments, regardless of the level of harm they may experience, is one important aspect. Poor-quality studies can also cause harm if they produce misleading results. The level of harm depends on the animal's sentience and awareness of its situation. Some species are considered more sentient than others, making the choice of animal used a significant factor in the evaluation of harm. The 3R principles recognize the potential for "replacement" of higher, sentient animals with insentient ones. The Bateson cube model emphasizes the importance of the quality of the experimental design, presenting it as a separate domain, independent of harm and benefit. The definition of "conscious living higher animals" is a continuously evolving and controversial topic, drawing parallels to Singer's discussion of speciesism. Different approaches have been developed to compare harm levels across different domains, including categorizing harm into severity classes. The baseline for the lowest level of harm, zero (0), is generally described as any procedure comparable to a needle injection in Europe. Understanding the biology and behavior of non-human primates, who are often considered "conscious living higher animals," is crucial. In conclusion, Harm-Benefit Analysis is a complex and continuously evolving concept requiring a thorough consideration of the use of animals, the level of harm they may experience, and the overall experimental design..

[Audio] Now that we have discussed the potential risks and harms involved in animal research, let's turn our attention to the other side of the equation - the benefits. This is a crucial aspect of Harm-Benefit Analysis and one that must be carefully considered in any animal experiment. The benefits refer to the scientific quality of the research, including the potential outcome and the actual outcome of the experiment, which can have a significant impact on the validity and reliability of the results. Additionally, we must also take into account the potential benefits to society, such as advancements in human health, veterinary medicine, safety testing, and the advancement of scientific knowledge. The use of animals in research has been widely accepted by both science and society, and is seen as a necessary and beneficial tool in these areas. However, the use of animals is not without controversy, and ethical and moral considerations must also be taken into account. Regulations help to ensure that the use of animals in research is justified and the potential benefits outweigh the potential harms. In Europe, for example, there are requirements for project summaries to be made available to the public, outlining the potential benefits of the research. Similarly, in the United States, the process for obtaining such information is similar. Ultimately, the goal of Harm-Benefit Analysis is to carefully weigh the potential benefits against the potential harms and make a well-informed decision on whether or not to proceed with the experiment..

[Audio] The benefit factors identified in the literature review by Brønstad et al. can be categorized into three dimensions: quality dimension, promise dimension, and actual benefit dimension. The quality dimension encompasses "good science" and dissemination of results, including originality, realistic potential, and benefits for humans, animals, and the environment. The promise dimension involves economic interests, health interests, and surrogate outcomes versus health outcomes, which apply to the broader group of Cephalopods rather than individual research animals. The actual benefit dimension includes safety interests, knowledge interests, educational interests, and primary versus secondary benefits. According to Mellor, economic benefits alone should not be used to justify animal experiments, but in some cases, they can coexist with benefits for the environment, animal health and wellbeing, and knowledge gained..

[Audio] Animals may receive indirect benefits from participating in research projects, such as serving as proxies for other species, without directly benefiting from the research itself. Additionally, animals may participate in research similar to humans, without their informed consent, to determine the potential benefits of a new therapy. Furthermore, animals are used for other societal objectives, including improving the quality and potential of experiments, publishing and disseminating results, and contributing to organizational reputation and success. These secondary benefits can have a positive impact on the wider community, through economic, educational, and social contributions made by the organizations, scientists, and support staff..

[Audio] The different models of harm-benefit analysis have their own strengths and weaknesses. Categories are useful for simplifying a complex picture, but they depend on defined categories..

[Audio] Models like the Bateson model have been widely recognized for their pedagogic value to illustrate the concept of HBA. While these models are normative, illustrating that high harm and low benefit projects should be rejected, they are not necessarily operational so they cannot always be applied productively in challenging situations commonly encountered by oversight bodies. To be able to do this, there must be a clear definition of the different categories and scales, so that input information is represented properly in the graphic model..

[Audio] As we continue our exploration of Harm-Benefit Analysis in animal experiments, we have reached slide number 14 in our presentation. This slide focuses on the various considerations involved in the estimation of harm levels in animal experiments. The concept of harm is a complex issue, especially when it comes to animal welfare. Different severity categories have been established, but there are still challenges in accurately determining the level of harm caused by a particular experiment. A study from Denmark showed that only 15% of genetically-modified animal strains experienced severe discomfort, while the majority showed no discomfort at all. This raises the question of whether harm is only relevant for animals with the ability to suffer, meaning those with consciousness. This brings us to the ethical dilemma created by advancements in gene technology. The incorporation of new xenogeneic traits can result in potentially harmful and unforeseen phenotypes. In these cases, it is important to consider the level of consciousness of the genetically-manipulated species and the impact of the induced phenotype on their well-being. However, it is worth noting that there may be a conflict between the researcher's perception of what is ethically relevant and the public's perception. It is important for responsible entities conducting Harm-Benefit Analysis to be aware of and address these potential discrepancies. Furthermore, as we conduct HBAs, we must be prepared to face dilemmas on a regular basis. We may need to rely on previous studies or information from colleagues in our estimation of harm levels, which may not always accurately predict outcomes. It is essential for us to remain vigilant in evaluating each individual case rather than relying on a general or universal categorization system. As we near the end of our presentation, it is crucial to remember that Harm-Benefit Analysis is a dynamic and ongoing process. Responsible entities must continuously review their practices and remain attentive to potential changes in protocols and guidelines. This concludes our discussion on the complexities of estimating harm in animal experiments..

[Audio] The results reveal that most respondents consider the harm to animals as a fundamental issue in ethical evaluation, whereas the benefit for humans is deemed important but less critical. Additionally, respondents indicate that the harm-versus-benefit is a fundamental issue in ethical evaluation. These findings imply that there is a strong emphasis on reducing harm, and the consideration of benefits is not as prominent. This underscores the necessity for a more balanced approach in ethical evaluations, where both harm and benefit are taken into account..

[Audio] The text discusses the potential drawbacks of simplification and routinization in the Harm-Benefit Analysis (HBA) process in animal experiments. According to research, using certain models to aid in HBA may reduce the quality of information, appreciation of unique proposals, moral sensitivity, and attention of responsible entities. Additionally, simplification may lead to a decrease in ethical language and a disconnect from the consequences of actions. The text also mentions that discussions on animal research often focus on technicalities rather than overall ethical judgments, and that the focus on harm in animal ethical review bodies may contribute to this. The author emphasizes the importance of maintaining an ethical vocabulary and considering the consequences of actions, rather than solely focusing on technical details. The HBA process is seen as dynamic and requires continuous review and adaptation to ensure the ethical use of animals in research..

[Audio] The concept of utilitarianism, or consequentialism, is based on the idea that the proper course of action is the one that maximizes utility, whether that be through increasing happiness or reducing suffering. This philosophy was developed by Jeremy Bentham and John Stuart Mill and has been a significant factor in ethical decision-making surrounding the use of animals in research. Peter Singer, an Australian moral philosopher and author of the book Animal Liberation, also supports the utilitarian perspective. He believes that the interests of animals should be taken into consideration due to their ability to suffer. In the context of Harm-Benefit Analysis, it is important to have a broad representation of interests in order to minimize any potential biases caused by emotional factors. This can also help to shed light on various perspectives and views of a particular case. It is essential to understand that Harm-Benefit Analysis is not a simple task, as it challenges personal attitudes towards animal experiments and the relationship between animals and humans. Those involved in decision-making must take responsibility for their actions, rather than simply following regulations and guidelines. Furthermore, ethical responsibility is of higher importance than legal responsibility, and must be prioritized in any decision-making process. With that in mind, it is crucial to have a diverse and balanced group of individuals contributing to discussions and decisions regarding Harm-Benefit Analysis..

[Audio] It is essential to recognize the significance of performing a thorough harm-benefit analysis in understanding its impact. One of the primary advantages is the collaboration between the responsible entity and scientists to implement the 3Rs - replacement, reduction, and refinement - to the maximum extent possible. This not only reflects a commitment to animal welfare but also fosters a positive perception of animal use in research among the general public. Regulatory compliance plays a crucial role in obtaining a license to operate, although it is essential to note that these regulations are often based on outdated knowledge. While regulatory compliance is necessary, it may only contribute minimally to the actual practice of harm-benefit analysis. Different stakeholders may have varying expectations regarding HBA, potentially leading to controversies instead of solutions. Having a broad representation of legitimate interests within the decision-making group ensures transparency and fairness in the process. Combining aspects from diverse models may provide the best solution for conducting harm-benefit analysis, allowing for a more comprehensive evaluation of potential harms and benefits, ultimately leading to a more ethical and responsible use of animals in research..

[Audio] In this presentation, we will discuss the current concepts of Harm-Benefit Analysis in animal experiments, with contributions from six authors. Slide 19 shows references to the Code of Ethics of the World Medical Association, also known as the Declaration of Helsinki, which sets out ethical principles for human experimentation. The International Guiding Principles for Biomedical Research Involving Animals, published by the Council for International Organizations of Medical Sciences, provide guidance for the ethical use of animals in research. The European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, published by the Council of Europe, sets out guidelines for the use of animals in research. The United States government has also established principles for the utilization and care of vertebrate animals used in testing, research, and training. An ethical evaluation of scientific procedures, with recommendations for ethics committees, was published in 2010. A paper published in 2015 discusses the harm-benefit analysis and promotes the ethical use of animals in research..

[Audio] Brønstad et al., along with four other authors, conducted a comprehensive assessment of the harms caused by experimental, teaching, and testing procedures on live animals, which was published in the journal "Alternatives to Laboratory Animals" in 2004. Porter's study on ethical scores for animal experiments was published in Nature in 1992, focusing on the ethical concerns surrounding animal experiments and the need for a framework to assess the severity of these procedures. The European Commission Expert Working Group on Severity Assessment developed a working document outlining a framework to assess the severity of animal experiments, which was published in 2012. Peter Singer published a book in 1975 titled "Animal Liberation: A New Ethics for our Treatment of Animals", presenting an argument for the ethical treatment of animals and the concept of animal liberation. Kornerup and colleagues published a book in 1999, focusing on the need to refine the notion of reduction in animal experimentation. Sandoe and colleagues published a study in ALTEX Proceedings in 2015, discussing the harms to animals in experimentation and the need to find a common ground to limit these harms. Bateson's article in New Scientist in 1992 raised the question of whether animals can feel pain and the.

[Audio] Animal research has been extensively used throughout history, and its importance cannot be overstated. As we continue to advance in various fields such as medicine, biology, and psychology, the need for reliable data and accurate results becomes increasingly crucial. The development of the rabbit test for pregnancy, for instance, revolutionized the field of obstetrics and gynecology, allowing for more precise diagnoses and treatments. Similarly, the concept of three models of corporate social responsibility highlights the significance of considering the impact of human activities on the environment and society. Furthermore, the idea of ethical navigation in leadership training emphasizes the importance of moral sensitivity and decision-making in high-stakes situations. The moral status of invasive animal research is another topic that warrants consideration, as it raises questions about the justification and necessity of using animals in scientific inquiry. Finally, the ethics of animal use and the Danish Animal Experiments Inspectorate's guidelines provide valuable insights into the complexities surrounding animal experimentation. These examples illustrate the multifaceted nature of animal research, highlighting both its potential benefits and challenges. As we move forward, it is essential to engage in open and honest discussions about the ethics of animal research, ensuring that we prioritize the well-being of both humans and animals alike..