Larry Carbone

Pain and Laboratory Animals: Publication Practices for Better Data Reproducibility and Better Animal Welfare.

Scientists who perform major survival surgery on laboratory animals face a dual welfare and methodological challenge: how to choose surgical anesthetics and post-operative analgesics that will best control animal suffering, knowing that both pain and the drugs that manage pain can all affect research outcomes. Scientists who publish full descriptions of animal procedures allow critical and systematic reviews of data, demonstrate their adherence to animal welfare norms, and guide other scientists on how to conduct their own studies in the field. We investigated what information on animal pain management a reasonably diligent scientist might find in planning for a successful experiment. To explore how scientists in a range of fields describe their management of this ethical and methodological concern, we scored 400 scientific articles that included major animal survival surgeries as part of their experimental methods, for the completeness of information on anesthesia and analgesia. The 400 articles (250 accepted for publication pre-2011, and 150 in 2014–15, along with 174 articles they reference) included thoracotomies, craniotomies, gonadectomies, organ transplants, peripheral nerve injuries, spinal laminectomies and orthopedic procedures in dogs, primates, swine, mice, rats and other rodents. We scored articles for Publication Completeness (PC), which was any mention of use of anesthetics or analgesics; Analgesia Use (AU) which was any use of post-surgical analgesics, and Analgesia Completeness (a composite score comprising intra-operative analgesia, extended post-surgical analgesia, and use of multimodal analgesia). 338 of 400 articles were PC. 98 of these 338 were AU, with some mention of analgesia, while 240 of 338 mentioned anesthesia only but not post-surgical analgesia. Journals’ caliber, as measured by their 2013 Impact Factor, had no effect on PC or AU. We found no effect of whether a journal instructs authors to consult the ARRIVE publishing guidelines published in 2010 on PC or AC for the 150 mouse and rat articles in our 2014–15 dataset. None of the 302 articles that were silent about analgesic use included an explicit statement that analgesics were withheld, or a discussion of how pain management or untreated pain might affect results. We conclude that current scientific literature cannot be trusted to present full detail on use of animal anesthetics and analgesics. We report that publication guidelines focus more on other potential sources of bias in experimental results, under-appreciate the potential for pain and pain drugs to skew data, and thus mostly treat pain management as solely an animal welfare concern, in the jurisdiction of animal care and use committees. At the same time, animal welfare regulations do not include guidance on publishing animal data, even though publication is an integral part of the cycle of research and can affect the welfare of animals in studies building on published work, leaving it to journals and authors to voluntarily decide what details of animal use to publish. We suggest that journals, scientists and animal welfare regulators should revise current guidelines and regulations, on treatment of pain and on transparent reporting of treatment of pain, to improve this dual welfare and data-quality deficiency.

Expertise and Advocacy in Animal-Welfare Decision Making: Considerations for a Veterinary Curriculum in Animal Welfare

An animal-welfare curriculum for veterinary students should provide learning opportunities in the application of veterinary expertise to patient management and animal-welfare policy. Real-life and hypothetical cases are presented that can allow students to develop their personal-values statement about animal welfare, explore the interaction of facts and values in deciding on a course of action, and understand the unique obligations and authority they will have as veterinarians.

Adoption Options for Laboratory Animals

Adoption programs can be enormously satisfying for all involved—not least the animals themselves—and constitute an important refinement in humane animal care and use. Most of the potential problems associated with adoption can be minimized with careful thought and planning. The authors describe adoption programs at two large academic campuses, noting differences between direct and indirect programs.

The Utility of Basic Animal Research

Justification of use of animals in research requires both that 1) it is ethically permissible to harm animals for human gain and 2) animal use actually produces useful knowledge. In this paper the author, a laboratory animal veterinarian, reviews arguments that animal research does or does not produce useful knowledge, and discusses frameworks for making such assessments. He concludes that basic animal research can in some cases produce valuable knowledge of relevance to human medicine.

Time for another look

Professor Harry Harrison had been a major federal grant recipient for research on neurofibrillary tangles in the mouse brain, but his federal funding had disappeared years ago and the little research he continued to do was supported by private funding from a longtime friend of his. Harrison continued to publish review articles but none of his own research had been published for many years. Nevertheless, he continued to submit IACUC protocols for pilot studies using genetically modified mouse strains. Harrison followed his protocols to the letter. After years of approving Harrison’s studies, Dr. Larry Covelli, the chairman of the Great Eastern University IACUC, politely suggested to Harrison that he should either expand his pilot studies into publishable research or stop performing them, as they appeared to be a waste of space, money, and animal lives. But, Harrison contended that his research was important and he politely thanked the chairman for his opinion, adding that he would be continuing his studies that focused on the role of tau proteins and neurofibrillary pathology. Covelli then met with Harrison’s department chair but the latter supported Harrison. Covelli’s next stop was the institutional official, but that conversation was fruitless. Likewise, when Covelli discussed the matter with the attending veterinarian and the IACUC vice-chair, no helpful suggestions arose other than to bring the issue to the full committee. Covelli did just that but the only recommendations were to allow Harrison to continue his studies or for the IACUC to simply refuse to approve Harrison’s protocols. What do you think? Should (and can) the IACUC refuse to approve further animal studies by Harrison, is he entitled as a faculty member to continue his apparently non-publishable research, or are there other paths to be considered? ❐

Euthanasia and Laboratory Animal Welfare

Abstract The overwhelming majority of laboratory animals are killed in the laboratory. The goal of this chapter is to assist research and veterinary personnel in ensuring that most instances of killing truly qualify as euthanasia, a good death for the animal. A good death minimizes pain and distress to the animal and so requires careful assessment of how different methods may impact welfare by causing pain and/or distress. The chapter draws heavily on the 2013 American Veterinary Medical Association Guidelines for the Euthanasia of Animals, explaining the rationale for developing those guidelines, and highlighting some new guidance since the previous edition. This chapter discusses three major welfare issues for animal euthanasia: decisions about when and whether to euthanize an animal; potential animal pain and distress in the minutes to hours preceding the euthanasia process; and pain and distress induced by the euthanasia process itself. The chapter discusses the importance of setting humane endpoints to guide the decision to euthanize, as well as alternatives to euthanasia. Finally, some specific recommendations are provided for how to make the euthanasia process as free of pain and distress as possible.

Response to Protocol Review Scenario: Approve the amendment

principle involved is that it is an unfair violation to place the excessive burden on certain individuals. The Harding–Benoit proposal will save animal and staffing costs; that is appropriate but not enough to justify approval. Had this been presented from the start as a single project on the behavioral and physiological effects of estrogen, in which intact and ovariectomized rabbits are first characterized behaviorally and then evaluated for bone healing, the IACUC would have approved it and never thought of contacting the USDA. In this case, rabbit numbers (and costs) are lower in approving the rabbit-sharing proposal. No individual rabbit is subjected to greater potential pain or distress, and the IACUC should approve the amendment. But each case requires evaluation. Suppose Harding’s project required removing the ovaries in two separate surgeries, whereas Benoit only cares that by the time of the fracture, both ovaries have been removed. Combining their work might mean that the rabbits would undergo two abdominal and one orthopedic surgery. In this case, individual rabbits’ welfare costs are increased beyond that required for the science. The and the 1991 Animal Welfare Regulations (AWRs)2. The prohibition is not absolute: the AWRs3 and the Guide4 agree that such multiple procedures on a single animal may be approved but must be part of a single study and cannot be justified by cost savings. The gravity of this near-total prohibition is reflected in the facts that cost savings is explicitly disallowed as justification in the Guide only in the case of multiple major survival surgeries and that separate USDA approval is required beyond in-house IACUC approval in special circumstances where an investigator proposes to perform multiple major survival procedures on unrelated projects. Neither the AWRs nor the Guide typically explain the ethical underpinnings of their rules and guidance; on this issue, however, they clearly favor a rights-based respect for fair treatment of the individual animal over a utilitarian calculus of the greatest good (or least harm) to the greatest number. Even if performing multiple major surgeries on some individuals has a lesser overall impact than dividing the procedures among a greater number of animals, the rights of the individual rabbit set limits. The ethical ReSponSe